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A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Duchenne Muscular Dystrophy

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ClinicalTrials.gov Identifier: NCT02310763
Recruitment Status : Terminated (Termination Date 30AUG2018: Reason for termination: Lack of Efficacy)
First Posted : December 8, 2014
Results First Posted : July 23, 2019
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Duchenne Muscular Dystrophy
Interventions Biological: PF-06252616
Drug: Placebo
Enrollment 121
Recruitment Details  
Pre-assignment Details A total of 162 subjects were screened, 121 subjects were enrolled in the study and assigned to 1 of 3 sequences. Only 120 subjects received the study treatment and 1 subject withdrew prior to dosing.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3
Hide Arm/Group Description Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Period Title: Period 1 (Weeks 1 to 48)
Started 41 39 40
Completed 38 37 38
Not Completed 3 2 2
Reason Not Completed
Withdrawal by Subject             1             1             1
Unable to comply with study procedures             0             1             1
Lost to Follow-up             1             0             0
Adverse Event             1             0             0
Period Title: Period 2 (Weeks 49 to 96)
Started 38 37 38
Completed 22 21 22
Not Completed 16 16 16
Reason Not Completed
Study terminated by sponsor             16             16             16
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). Total of all reporting groups
Overall Number of Baseline Participants 41 39 40 120
Hide Baseline Analysis Population Description
Baseline analysis population included all participants who received at least 1 dose of study treatment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 40 participants 120 participants
<=18 years
41
 100.0%
39
 100.0%
40
 100.0%
120
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 39 participants 40 participants 120 participants
8.3  (1.9) 8.5  (1.5) 9.3  (2.3) 8.7  (2.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 40 participants 120 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
41
 100.0%
39
 100.0%
40
 100.0%
120
 100.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 40 participants 120 participants
White 33 33 35 101
Black 1 0 1 2
Asian 6 5 4 15
Other 1 1 0 2
1.Primary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49
Hide Description An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator.
Time Frame Study Day 1 to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
All-causalities TEAE
38
  95.0%
66
  82.5%
57
  73.1%
59
  77.6%
Treatment-related TEAE
14
  35.0%
18
  22.5%
14
  17.9%
16
  21.1%
All-causalities serious TEAE
0
   0.0%
1
   1.3%
1
   1.3%
1
   1.3%
Treatment-related serious TEAE
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.3%
All-causalities severe TEAE
2
   5.0%
2
   2.5%
3
   3.8%
2
   2.6%
Treatment-related severe TEAE
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.3%
2.Primary Outcome
Title Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49
Hide Description An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.
Time Frame Study Day 1 to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
All-causalities TEAE
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.3%
Treatment-related TEAE
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.3%
3.Primary Outcome
Title Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49
Hide Description An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.
Time Frame Study Day 1 to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
All-causalities TEAE
8
  20.0%
4
   5.0%
4
   5.1%
0
   0.0%
Treatment-related TEAE
3
   7.5%
0
   0.0%
1
   1.3%
0
   0.0%
4.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology
Hide Description Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils, absolute monocytes and absolute myelocytes.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin <0.8*lower limit of normal (LLN) Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Hematocrit <0.8*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
RBC count <0.8*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Platelets <0.5*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
1
   2.5%
1
   1.3%
1
   1.3%
1
   1.3%
Platelets >1.75*upper limit of normal (ULN) Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
RBC Morphology >0 Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
1
   1.3%
1
   1.3%
WBC count <0.6*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
WBC count >1.5*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
1
   1.3%
1
   1.3%
0
   0.0%
Absolute Lymphocytes <0.8*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
2
   2.5%
2
   2.6%
0
   0.0%
Absolute lymphocytes >1.2*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
1
   2.5%
1
   1.3%
0
   0.0%
0
   0.0%
Absolute atypical lymphocytes >0 (10*3/uL) Number Analyzed 0 participants 1 participants 0 participants 1 participants
1
 100.0%
1
 100.0%
Absolute total neutrophils <0.8*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
1
   2.5%
0
   0.0%
0
   0.0%
0
   0.0%
Absolute total neutrophils >1.2*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
13
  32.5%
8
  10.0%
5
   6.4%
5
   6.6%
Absolute total neutrophils count <1.35 (10*3/uL) Number Analyzed 40 participants 80 participants 78 participants 76 participants
2
   5.0%
0
   0.0%
2
   2.6%
1
   1.3%
Absolute total neutrophils count >8.15 (10*3/uL) Number Analyzed 40 participants 80 participants 78 participants 76 participants
20
  50.0%
13
  16.3%
12
  15.4%
9
  11.8%
Absolute band cells >0.27 (10*3/uL) Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Absolute basophils >1.2*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
2
   5.0%
1
   1.3%
1
   1.3%
2
   2.6%
Absolute eosinophils >1.2*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
6
  15.0%
2
   2.5%
6
   7.7%
6
   7.9%
Absolute monocytes >1.2*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
1
   2.5%
1
   1.3%
2
   2.6%
2
   2.6%
Absolute myelocytes >0 (10*3/uL) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
5.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation
Hide Description Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT).
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
aPTT >1.1*ULN
1
   2.5%
1
   1.3%
1
   1.3%
2
   2.6%
PT >1.1*ULN
13
  32.5%
6
   7.5%
3
   3.8%
7
   9.2%
6.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function
Hide Description Liver function evaluation included: total/direct/indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
Total bilirubin >1.5*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Direct bilirubin >1.5*ULN Number Analyzed 1 participants 0 participants 0 participants 1 participants
0
   0.0%
0
   0.0%
Indirect bilirubin >1.5*ULN Number Analyzed 1 participants 0 participants 0 participants 1 participants
0
   0.0%
0
   0.0%
AST >3*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
39
  97.5%
80
 100.0%
76
  97.4%
74
  97.4%
ALT >3*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
40
 100.0%
80
 100.0%
78
 100.0%
75
  98.7%
GGT >3*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Alkaline phosphatase >3*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Total protein <0.8*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Total protein >1.2*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Albumin <0.8*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Albumin >1.2*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Glutamate dehydrogenase >1.0*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
8
  20.0%
8
  10.0%
6
   7.7%
5
   6.6%
7.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function
Hide Description Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
BUN >1.3*ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Creatinine >1.3*ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Uric acid >1.2*ULN
0
   0.0%
1
   1.3%
3
   3.8%
3
   3.9%
8.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes
Hide Description Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate, bicarbonate, ferritin, transferrin saturation, iron, iron binding capacity and unsaturated iron binding capacity. Number of participants with iron abnormalities was reported in different age groups.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
Sodium <0.95*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sodium >1.05*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Potassium <0.9*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Potassium >1.1*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Chloride <0.9*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Chloride >1.1*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Calcium <0.9*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Calcium >1.1*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Phosphate <0.8*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Phosphate >1.2*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Bicarbonate <0.9*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
8
  20.0%
2
   2.5%
3
   3.8%
4
   5.3%
Bicarbonate >1.1*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
1
   2.5%
0
   0.0%
0
   0.0%
0
   0.0%
Iron (1 Year<=Age<11 Years) <50 (ug/dL) Number Analyzed 31 participants 69 participants 68 participants 65 participants
19
  61.3%
23
  33.3%
14
  20.6%
11
  16.9%
Iron (1 Year<=Age<11 Years) >120 (ug/dL) Number Analyzed 31 participants 69 participants 68 participants 65 participants
12
  38.7%
29
  42.0%
33
  48.5%
39
  60.0%
Iron (11 Years<=Age<18 Years) <50 (ug/dL) Number Analyzed 11 participants 11 participants 12 participants 11 participants
2
  18.2%
4
  36.4%
2
  16.7%
2
  18.2%
Iron (11 Years<=Age<18 Years) >170 (ug/dL) Number Analyzed 11 participants 11 participants 12 participants 11 participants
0
   0.0%
1
   9.1%
1
   8.3%
0
   0.0%
Ferritin <15 (ug/L) Number Analyzed 40 participants 80 participants 78 participants 76 participants
20
  50.0%
32
  40.0%
38
  48.7%
42
  55.3%
Ferritin >140 (ug/L) Number Analyzed 40 participants 80 participants 78 participants 76 participants
1
   2.5%
1
   1.3%
0
   0.0%
0
   0.0%
Iron binding capacity <37.6 (ug/dL) Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unsaturated iron binding capacity<130 (ug/dL) Number Analyzed 40 participants 80 participants 78 participants 76 participants
3
   7.5%
7
   8.8%
6
   7.7%
10
  13.2%
Unsaturated iron binding capacity >375 (ug/dL) Number Analyzed 40 participants 80 participants 78 participants 76 participants
1
   2.5%
0
   0.0%
0
   0.0%
0
   0.0%
Transferrin saturation <20% Number Analyzed 40 participants 80 participants 78 participants 76 participants
26
  65.0%
34
  42.5%
26
  33.3%
20
  26.3%
Transferrin saturation >50% Number Analyzed 40 participants 80 participants 78 participants 76 participants
4
  10.0%
9
  11.3%
19
  24.4%
18
  23.7%
9.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones
Hide Description Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
Free T4 <0.8*LLN Number Analyzed 40 participants 77 participants 75 participants 72 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Free T4 >1.2*ULN Number Analyzed 40 participants 77 participants 75 participants 72 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
TSH <0.8*LLN Number Analyzed 40 participants 78 participants 75 participants 72 participants
0
   0.0%
2
   2.6%
0
   0.0%
1
   1.4%
TSH >1.2*ULN Number Analyzed 40 participants 78 participants 75 participants 72 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
LH (15 Days<=Age<7 Years) <0.3 (mIU/mL) Number Analyzed 2 participants 4 participants 2 participants 0 participants
1
  50.0%
2
  50.0%
0
   0.0%
LH (15 Days<=Age<7 Years) >2.8 (mIU/mL) Number Analyzed 2 participants 4 participants 2 participants 0 participants
0
   0.0%
0
   0.0%
0
   0.0%
LH (7 Years<=Age<9 Years) <0.3 (mIU/mL) Number Analyzed 10 participants 35 participants 29 participants 24 participants
6
  60.0%
23
  65.7%
21
  72.4%
14
  58.3%
LH (7 Years<=Age<9 Years) >2.8 (mIU/mL) Number Analyzed 10 participants 35 participants 29 participants 24 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
LH (9 Years<=Age<11 Years) <0.3 (mIU/mL) Number Analyzed 22 participants 27 participants 33 participants 38 participants
17
  77.3%
17
  63.0%
23
  69.7%
27
  71.1%
LH (9 Years<=Age<11 Years) >2.8 (mIU/mL) Number Analyzed 22 participants 27 participants 33 participants 38 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
LH (11 Years<=Age<12 Years) <0.3 (mIU/mL) Number Analyzed 3 participants 3 participants 5 participants 3 participants
2
  66.7%
2
  66.7%
3
  60.0%
1
  33.3%
LH (11 Years<=Age<12 Years) >1.8 (mIU/mL) Number Analyzed 3 participants 3 participants 5 participants 3 participants
1
  33.3%
1
  33.3%
0
   0.0%
0
   0.0%
LH (12 Years<=Age<13 Years) <0.3 (mIU/mL) Number Analyzed 4 participants 3 participants 3 participants 2 participants
1
  25.0%
1
  33.3%
2
  66.7%
2
 100.0%
LH (12 Years<=Age<13 Years) >4.0 (mIU/mL) Number Analyzed 4 participants 3 participants 3 participants 2 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
LH (13 Years<=Age<14 Years) <0.3 (mIU/mL) Number Analyzed 5 participants 4 participants 2 participants 4 participants
3
  60.0%
1
  25.0%
0
   0.0%
1
  25.0%
LH (13 Years<=Age<14 Years) >6.0 (mIU/mL) Number Analyzed 5 participants 4 participants 2 participants 4 participants
0
   0.0%
1
  25.0%
1
  50.0%
1
  25.0%
FSH (4 Years<=Age<7 Years) >6.70 (mIU/mL) Number Analyzed 2 participants 4 participants 2 participants 0 participants
0
   0.0%
0
   0.0%
0
   0.0%
FSH (7 Years<=Age<9 Years) >4.10 (mIU/mL) Number Analyzed 10 participants 35 participants 29 participants 24 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (9 Years<=Age<11 Years) >4.50 (mIU/mL) Number Analyzed 22 participants 27 participants 33 participants 38 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (11 Years<=Age<12 Years) <0.40 (mIU/mL) Number Analyzed 3 participants 3 participants 5 participants 3 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (11 Years<=Age<12 Years) >8.90 (mIU/mL) Number Analyzed 3 participants 3 participants 5 participants 3 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (12 Years<=Age<13 Years) <0.50 (mIU/mL) Number Analyzed 4 participants 3 participants 3 participants 2 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (12 Years<=Age<13 Years) >10.50 (mIU/mL) Number Analyzed 4 participants 3 participants 3 participants 2 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (13 Years<=Age<14 Years) <0.70 (mIU/mL) Number Analyzed 5 participants 4 participants 2 participants 4 participants
0
   0.0%
1
  25.0%
0
   0.0%
2
  50.0%
FSH (13 Years<=Age<14 Years) >10.80 (mIU/mL) Number Analyzed 5 participants 4 participants 2 participants 4 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Androstenedione (1 Year<=Age<7 Years) <8 (ng/dL) Number Analyzed 2 participants 5 participants 2 participants 0 participants
1
  50.0%
2
  40.0%
1
  50.0%
Androstenedione (1 Year<=Age<7Years) >50(ng/dL) Number Analyzed 2 participants 5 participants 2 participants 0 participants
0
   0.0%
0
   0.0%
0
   0.0%
Androstenedione (7 Years<=Age<10Years)<3(ng/dL) Number Analyzed 20 participants 49 participants 46 participants 44 participants
5
  25.0%
11
  22.4%
10
  21.7%
7
  15.9%
Androstenedione(7Years<=Age<10Years) >31(ng/dL) Number Analyzed 20 participants 49 participants 46 participants 44 participants
1
   5.0%
0
   0.0%
4
   8.7%
4
   9.1%
Androstenedione(10Years<=Age<12Years) <7(ng/dL) Number Analyzed 20 participants 16 participants 20 participants 23 participants
13
  65.0%
8
  50.0%
8
  40.0%
10
  43.5%
Androstenedione (10Years<=Age<12Years)>41 (ng/dL) Number Analyzed 20 participants 16 participants 20 participants 23 participants
3
  15.0%
0
   0.0%
0
   0.0%
0
   0.0%
Androstenedione (12Years<=Age<14Years)<11 (ng/dL) Number Analyzed 6 participants 7 participants 5 participants 6 participants
3
  50.0%
4
  57.1%
2
  40.0%
2
  33.3%
Androstenedione(12 Years<=Age<14Years)>64 (ng/dL) Number Analyzed 6 participants 7 participants 5 participants 6 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
10.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry
Hide Description Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, and amylase.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
Glucose <0.6*LLN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Glucose >1.5*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
1
   1.3%
0
   0.0%
2
   2.6%
CK >2.0*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
40
 100.0%
80
 100.0%
78
 100.0%
76
 100.0%
Troponin I >3.0*ULN Number Analyzed 40 participants 79 participants 74 participants 72 participants
11
  27.5%
12
  15.2%
10
  13.5%
13
  18.1%
Amylase >1.5*ULN Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.3%
11.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis
Hide Description Urinalysis included: urine pH, qualitative urine glucose, qualitative urine ketones, qualitative urine protein, qualitative blood/hemoglobin, urine nitrite, urine leukocytes, urine RBC, urine WBC, urine granular casts, urine hyaline casts, urine urate (uric acid) acidic crystal, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 80 78 76
Measure Type: Count of Participants
Unit of Measure: Participants
Qualitative urine glucose (dipstick) >=1 Number Analyzed 40 participants 80 participants 78 participants 76 participants
1
   2.5%
0
   0.0%
0
   0.0%
0
   0.0%
Qualitative urine ketones(dipstick) >=1 Number Analyzed 40 participants 80 participants 78 participants 76 participants
3
   7.5%
3
   3.8%
5
   6.4%
6
   7.9%
Qualitative urine protein (dipstick) >=1 Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
1
   1.3%
0
   0.0%
0
   0.0%
Qualitative urine blood/hemoglobin (dipstick) >=1 Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
2
   2.5%
1
   1.3%
0
   0.0%
Urine nitrite (dipstick) >=1 Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine leukocytes (dipstick): +1 Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
1
   1.3%
1
   1.3%
Urine RBC >=20 (/high power field[HPF]) Number Analyzed 14 participants 28 participants 30 participants 22 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine WBC >=20 (/HPF) Number Analyzed 25 participants 42 participants 43 participants 38 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine granular casts >1 (/low power field [LPF]) Number Analyzed 1 participants 0 participants 0 participants 0 participants
1
 100.0%
Urine hyaline casts >1 (/LPF) Number Analyzed 2 participants 0 participants 0 participants 0 participants
2
 100.0%
Urine urate (uric acid) acidic crystal: Present Number Analyzed 4 participants 2 participants 2 participants 2 participants
4
 100.0%
2
 100.0%
2
 100.0%
2
 100.0%
Urine calcium oxalate crystals: Present Number Analyzed 19 participants 24 participants 23 participants 24 participants
19
 100.0%
24
 100.0%
23
 100.0%
24
 100.0%
Urine amorphous crystals: Present Number Analyzed 7 participants 7 participants 6 participants 11 participants
7
 100.0%
7
 100.0%
6
 100.0%
11
 100.0%
Urine bacteria >20 (/HPF) Number Analyzed 5 participants 4 participants 5 participants 5 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine microscopic exam: Positive Number Analyzed 31 participants 55 participants 52 participants 46 participants
31
 100.0%
50
  90.9%
49
  94.2%
45
  97.8%
Urine pH (dipstick) <4.5 Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine pH (dipstick) >8 Number Analyzed 40 participants 80 participants 78 participants 76 participants
0
   0.0%
1
   1.3%
1
   1.3%
1
   1.3%
12.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal
Hide Description Number of participants with blood detected in fecal samples is presented.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug and had at least 1 fecal evaluation.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 79 78 74
Measure Type: Count of Participants
Unit of Measure: Participants
2
   5.0%
8
  10.1%
2
   2.6%
3
   4.1%
13.Primary Outcome
Title Categorical Summary of Liver Iron Accumulation by Week 49
Hide Description Magnetic resonance imaging (MRI) of Liver was obtained to quantify liver iron accumulation for safety monitoring. MRIs were sent to an independent central radiology imaging facility for calculation of the average transverse relaxation rate (R2*) value which was used to monitor for iron accumulation in the liver. Number of participants meeting the following criteria is presented as follows: 1) normal: R2*<=75Hz at 1.5T or <=139 Hz at 3.0T; 2) above normal: R2*>75Hz and <=190Hz at 1.5T or R2* >139Hz and <=369Hz at 3.0T; 3) mild overload: R2*>190Hz at 1.5T or R2*>360Hz at 3.0T.
Time Frame Screening, Weeks 13, 29 and 45
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3
Hide Arm/Group Description:
Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study.
Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study.
Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 41 39 40
Measure Type: Count of Participants
Unit of Measure: Participants
Normal, Screening Number Analyzed 41 participants 39 participants 40 participants
41
 100.0%
39
 100.0%
40
 100.0%
Above normal, Screening Number Analyzed 41 participants 39 participants 40 participants
0
   0.0%
0
   0.0%
0
   0.0%
Mild overload, Screening Number Analyzed 41 participants 39 participants 40 participants
0
   0.0%
0
   0.0%
0
   0.0%
Normal, Week 13 Number Analyzed 27 participants 24 participants 26 participants
27
 100.0%
24
 100.0%
26
 100.0%
Above normal, Week 13 Number Analyzed 27 participants 24 participants 26 participants
0
   0.0%
0
   0.0%
0
   0.0%
Mild overload, Week 13 Number Analyzed 27 participants 24 participants 26 participants
0
   0.0%
0
   0.0%
0
   0.0%
Normal, Week 29 Number Analyzed 23 participants 21 participants 21 participants
23
 100.0%
21
 100.0%
21
 100.0%
Above normal, Week 29 Number Analyzed 23 participants 21 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
Mild overload, Week 29 Number Analyzed 23 participants 21 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
Normal, Week 45 Number Analyzed 37 participants 37 participants 38 participants
37
 100.0%
37
 100.0%
38
 100.0%
Above normal, Week 45 Number Analyzed 37 participants 37 participants 38 participants
0
   0.0%
0
   0.0%
0
   0.0%
Mild overload, Week 45 Number Analyzed 37 participants 37 participants 38 participants
0
   0.0%
0
   0.0%
0
   0.0%
14.Primary Outcome
Title Number of Participants With Physical Examination Findings Reported as SAEs by Week 49
Hide Description Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A targeted nose and throat mucosal exam were also performed to monitor for any signs of mucosal telangiectasias. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which physical examination findings were reported as SAEs.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3
Hide Arm/Group Description:
Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study.
Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study.
Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 41 39 40
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
15.Primary Outcome
Title Summary of Tanner Stage Rating by Week 49
Hide Description Tanner staging was performed before the first dose of each dose escalation to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition.
Time Frame Baseline, Weeks 17, 33 and 49
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Measure Type: Count of Participants
Unit of Measure: Participants
Pubic hair, Stage 1, Baseline Number Analyzed 40 participants 78 participants
35
  87.5%
70
  89.7%
Pubic hair, Stage 2, Baseline Number Analyzed 40 participants 78 participants
4
  10.0%
7
   9.0%
Pubic hair, Stage 3, Baseline Number Analyzed 40 participants 78 participants
0
   0.0%
1
   1.3%
Pubic hair, Stage 4, Baseline Number Analyzed 40 participants 78 participants
1
   2.5%
0
   0.0%
Pubic hair, Stage 5, Baseline Number Analyzed 40 participants 78 participants
0
   0.0%
0
   0.0%
Pubic hair, Stage 1, Week 17 Number Analyzed 40 participants 77 participants
30
  75.0%
64
  83.1%
Pubic hair, Stage 2, Week 17 Number Analyzed 40 participants 77 participants
9
  22.5%
11
  14.3%
Pubic hair, Stage 3, Week 17 Number Analyzed 40 participants 77 participants
0
   0.0%
2
   2.6%
Pubic hair, Stage 4, Week 17 Number Analyzed 40 participants 77 participants
1
   2.5%
0
   0.0%
Pubic hair, Stage 5, Week 17 Number Analyzed 40 participants 77 participants
0
   0.0%
0
   0.0%
Pubic hair, Stage 1, Week 33 Number Analyzed 36 participants 75 participants
23
  63.9%
60
  80.0%
Pubic hair, Stage 2, Week 33 Number Analyzed 36 participants 75 participants
11
  30.6%
13
  17.3%
Pubic hair, Stage 3, Week 33 Number Analyzed 36 participants 75 participants
1
   2.8%
1
   1.3%
Pubic hair, Stage 4, Week 33 Number Analyzed 36 participants 75 participants
1
   2.8%
1
   1.3%
Pubic hair, Stage 5, Week 33 Number Analyzed 36 participants 75 participants
0
   0.0%
0
   0.0%
Pubic hair, Stage 1, Week 49 Number Analyzed 37 participants 72 participants
21
  56.8%
52
  72.2%
Pubic hair, Stage 2, Week 49 Number Analyzed 37 participants 72 participants
11
  29.7%
15
  20.8%
Pubic hair, Stage 3, Week 49 Number Analyzed 37 participants 72 participants
3
   8.1%
4
   5.6%
Pubic hair, Stage 4, Week 49 Number Analyzed 37 participants 72 participants
1
   2.7%
1
   1.4%
Pubic hair, Stage 5, Week 49 Number Analyzed 37 participants 72 participants
1
   2.7%
0
   0.0%
Penis, Stage 1, Baseline Number Analyzed 40 participants 78 participants
30
  75.0%
70
  89.7%
Penis, Stage 2, Baseline Number Analyzed 40 participants 78 participants
9
  22.5%
7
   9.0%
Penis, Stage 3, Baseline Number Analyzed 40 participants 78 participants
0
   0.0%
1
   1.3%
Penis, Stage 4, Baseline Number Analyzed 40 participants 78 participants
1
   2.5%
0
   0.0%
Penis, Stage 5, Baseline Number Analyzed 40 participants 78 participants
0
   0.0%
0
   0.0%
Penis, Stage 1, Week 17 Number Analyzed 40 participants 77 participants
29
  72.5%
68
  88.3%
Penis, Stage 2, Week 17 Number Analyzed 40 participants 77 participants
10
  25.0%
8
  10.4%
Penis, Stage 3, Week 17 Number Analyzed 40 participants 77 participants
0
   0.0%
1
   1.3%
Penis, Stage 4, Week 17 Number Analyzed 40 participants 77 participants
1
   2.5%
0
   0.0%
Penis, Stage 5, Week 17 Number Analyzed 40 participants 77 participants
0
   0.0%
0
   0.0%
Penis, Stage 1, Week 33 Number Analyzed 36 participants 75 participants
22
  61.1%
58
  77.3%
Penis, Stage 2, Week 33 Number Analyzed 36 participants 75 participants
11
  30.6%
16
  21.3%
Penis, Stage 3, Week 33 Number Analyzed 36 participants 75 participants
3
   8.3%
1
   1.3%
Penis, Stage 4, Week 33 Number Analyzed 36 participants 75 participants
0
   0.0%
0
   0.0%
Penis, Stage 5, Week 33 Number Analyzed 36 participants 75 participants
0
   0.0%
0
   0.0%
Penis, Stage 1, Week 49 Number Analyzed 37 participants 72 participants
21
  56.8%
57
  79.2%
Penis, Stage 2, Week 49 Number Analyzed 37 participants 72 participants
9
  24.3%
14
  19.4%
Penis, Stage 3, Week 49 Number Analyzed 37 participants 72 participants
5
  13.5%
1
   1.4%
Penis, Stage 4, Week 49 Number Analyzed 37 participants 72 participants
2
   5.4%
0
   0.0%
Penis, Stage 5, Week 49 Number Analyzed 37 participants 72 participants
0
   0.0%
0
   0.0%
Testes, Stage 1, Baseline Number Analyzed 40 participants 78 participants
34
  85.0%
67
  85.9%
Testes, Stage 2, Baseline Number Analyzed 40 participants 78 participants
4
  10.0%
10
  12.8%
Testes, Stage 3, Baseline Number Analyzed 40 participants 78 participants
1
   2.5%
1
   1.3%
Testes, Stage 4, Baseline Number Analyzed 40 participants 78 participants
1
   2.5%
0
   0.0%
Testes, Stage 5, Baseline Number Analyzed 40 participants 78 participants
0
   0.0%
0
   0.0%
Testes, Stage 1, Week 17 Number Analyzed 40 participants 77 participants
29
  72.5%
66
  85.7%
Testes, Stage 2, Week 17 Number Analyzed 40 participants 77 participants
10
  25.0%
10
  13.0%
Testes, Stage 3, Week 17 Number Analyzed 40 participants 77 participants
0
   0.0%
1
   1.3%
Testes, Stage 4, Week 17 Number Analyzed 40 participants 77 participants
1
   2.5%
0
   0.0%
Testes, Stage 5, Week 17 Number Analyzed 40 participants 77 participants
0
   0.0%
0
   0.0%
Testes, Stage 1, Week 33 Number Analyzed 36 participants 75 participants
24
  66.7%
59
  78.7%
Testes, Stage 2, Week 33 Number Analyzed 36 participants 75 participants
9
  25.0%
15
  20.0%
Testes, Stage 3, Week 33 Number Analyzed 36 participants 75 participants
1
   2.8%
1
   1.3%
Testes, Stage 4, Week 33 Number Analyzed 36 participants 75 participants
2
   5.6%
0
   0.0%
Testes, Stage 5, Week 33 Number Analyzed 36 participants 75 participants
0
   0.0%
0
   0.0%
Testes, Stage 1, Week 49 Number Analyzed 37 participants 71 participants
19
  51.4%
53
  74.6%
Testes, Stage 2, Week 49 Number Analyzed 37 participants 71 participants
11
  29.7%
15
  21.1%
Testes, Stage 3, Week 49 Number Analyzed 37 participants 71 participants
4
  10.8%
3
   4.2%
Testes, Stage 4, Week 49 Number Analyzed 37 participants 71 participants
3
   8.1%
0
   0.0%
Testes, Stage 5, Week 49 Number Analyzed 37 participants 71 participants
0
   0.0%
0
   0.0%
16.Primary Outcome
Title Number of Participants With Vital Signs Findings Reported as SAEs by Week 49
Hide Description Vital signs evaluation included supine systolic and diastolic blood pressure (BP), pulse rate, and respiratory rate. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which vital signs findings were reported as SAEs.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
17.Primary Outcome
Title Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49
Hide Description Number of participants with ECG data meeting the following criteria are presented: 1) corrected QT interval using Fridericia’s formula (QTcF interval) <450msec; 2) QTcF interval >=450 and <480msec; 3) QTcF interval >=480 and <500msec; 4) QTcF interval>=500msec; 5) QTcF interval increase from baseline<30msec; 6) QTcF interval increase from baseline >=30 and <60msec; 7) QTcF interval increase from baseline >=60msec.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Domagrozumab 5 mg/kg Domagrozumab 20 mg/kg Domagrozumab 40 mg/kg
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).
Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).
Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Overall Number of Participants Analyzed 40 70 67 69
Measure Type: Count of Participants
Unit of Measure: Participants
QTcF interval <450msec
40
 100.0%
70
 100.0%
67
 100.0%
68
  98.6%
QTcF interval>=450 and <480msec
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
QTcF interval >=480 and <500msec
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QTcF interval>=500msec
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QTcF interval increase <30msec
40
 100.0%
66
  94.3%
65
  97.0%
63
  91.3%
QTcF interval increase >=30 and <60msec
0
   0.0%
4
   5.7%
2
   3.0%
6
   8.7%
QTcF interval increase >=60msec
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
18.Primary Outcome
Title Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49
Hide Description The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance image (MRI) or echocardiogram. The same method of cardiac imaging was used consistently within a single participant. Cardiac MRIs were read by a central imaging vendor and echocardiograms were read locally at each site. The LVEF values measured by cardiac MRI and echocardiogram are combined in the following presentation. The analysis of covariance (ANCOVA) model was used to analyze the change from baseline for domagrozumab compared to placebo on LVEF. The baseline result, age, use of angiotensin receptor blocker (ARB)/beta blocker/angiotensin converting enzyme (ACE) inhibitor and treatment were included as fixed effects in the model.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 35 72
Least Squares Mean (Standard Error)
Unit of Measure: Ratio of blood
-0.063  (0.8464) -1.356  (0.5620)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2088
Comments The significance level is 0.05.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.293
Confidence Interval (2-Sided) 95%
-0.7343 to 3.3200
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.0220
Estimation Comments Least square mean difference was calculated by placebo minus domagrozumab.
19.Primary Outcome
Title Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49
Hide Description Bone mineral density (BMD) was evaluated by Dual energy X-ray Absorptiometry (DXA). The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was “below the expected range for age”. If the Z-score was above -2 standard deviations, the result was “within the expected range for age”.
Time Frame Screening and Week 49
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Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3
Hide Arm/Group Description:
Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study.
Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study.
Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 41 39 40
Mean (Standard Deviation)
Unit of Measure: Standard deviations
Screening Number Analyzed 41 participants 37 participants 37 participants
-0.545151  (1.2845570) -0.622784  (1.0778788) -0.572650  (1.0283031)
Week 49 Number Analyzed 37 participants 35 participants 36 participants
-0.683750  (1.0673420) -0.401631  (1.0758951) -0.489513  (1.0057285)
20.Primary Outcome
Title Bone Age to Chronological Age Ratio by Week 49
Hide Description Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date-date of birth+1)/365.25.
Time Frame Screening, Weeks 17, 33 and 49
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Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Mean (Standard Deviation)
Unit of Measure: Ratio
Screening Number Analyzed 40 participants 80 participants
0.809  (0.1656) 0.762  (0.1650)
Week 17 Number Analyzed 40 participants 76 participants
0.805  (0.1567) 0.749  (0.1654)
Week 33 Number Analyzed 39 participants 76 participants
0.790  (0.1614) 0.750  (0.1589)
Week 49 Number Analyzed 32 participants 68 participants
0.770  (0.1604) 0.761  (0.1778)
21.Primary Outcome
Title Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49
Hide Description An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. AEs of suicide ideation or behavior were determined by the investigator.
Time Frame Baseline to Week 49 visit
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Measure Type: Count of Participants
Unit of Measure: Participants
Suicidal ideation
0
   0.0%
0
   0.0%
Suicidal behavior
0
   0.0%
0
   0.0%
22.Primary Outcome
Title Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49
Hide Description The 4SC quantified the time required for a participant to ascend 4 standard steps. Mixed effect model for repeated measures (MMRM) was used to analyze the change from baseline on 4SC for domagrozumab compared to placebo. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time Frame Baseline, Weeks 17, 33 and 49
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timeponts.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Least Squares Mean (Standard Error)
Unit of Measure: Seconds
Week 17 Number Analyzed 39 participants 74 participants
1.6896  (0.6776) 1.6051  (0.4814)
Week 33 Number Analyzed 33 participants 70 participants
3.6407  (1.5837) 4.2244  (1.1209)
Week 49 Number Analyzed 32 participants 63 participants
8.0122  (3.03) 8.2835  (2.1507)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 17
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9191
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0845
Confidence Interval (2-Sided) 95%
-1.7354 to 1.5663
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 33
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7642
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.5837
Confidence Interval (2-Sided) 95%
-3.2978 to 4.4652
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 49
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9423
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2712
Confidence Interval (2-Sided) 95%
-7.3799 to 7.9223
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
23.Secondary Outcome
Title Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49
Hide Description FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time Frame Baseline, Weeks 17, 33 and 49
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Week 17 Number Analyzed 40 participants 78 participants
0.0578  (0.0327) 0.0578  (0.0250)
Week 33 Number Analyzed 37 participants 76 participants
0.1008  (0.0385) 0.0749  (0.0286)
Week 49 Number Analyzed 38 participants 74 participants
0.1513  (0.0367) 0.1092  (0.0278)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 17
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9993
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0
Confidence Interval (2-Sided) 95%
-0.0693 to 0.0693
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 33
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5464
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0259
Confidence Interval (2-Sided) 95%
-0.1107 to 0.0589
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 49
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3041
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0420
Confidence Interval (2-Sided) 95%
-0.1227 to 0.0386
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
24.Secondary Outcome
Title Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49
Hide Description The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time Frame Baseline, Weeks 17, 33 and 49
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 17 Number Analyzed 38 participants 77 participants
-1.9  (0.8) -1.1  (0.6)
Week 33 Number Analyzed 38 participants 75 participants
-4.5  (0.8) -2.0  (0.6)
Week 49 Number Analyzed 37 participants 73 participants
-5.2  (0.9) -3.6  (0.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 17
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3522
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.9 to 2.5
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 33
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0061
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.5
Confidence Interval (2-Sided) 95%
0.7 to 4.2
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Week 49
Statistical Test of Hypothesis P-Value 0.1268
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.6
Confidence Interval (2-Sided) 95%
-0.5 to 3.8
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
25.Secondary Outcome
Title Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49
Hide Description ROM was evaluated by using goniometry to evaluate the loss of motion in the ankles. MMRM was used to analyze the change from baseline on ROM for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time Frame Baseline, Weeks 17, 33 and 49
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Least Squares Mean (Standard Error)
Unit of Measure: Degrees of passive dorsiflexion
Left ankle, Week 17 Number Analyzed 40 participants 78 participants
-1.0  (1.2) -1.4  (0.9)
Left ankle, Week 33 Number Analyzed 37 participants 76 participants
-1.9  (1.2) -1.7  (0.9)
Left ankle, Week 49 Number Analyzed 38 participants 75 participants
-2.3  (1.3) -3.7  (1.0)
Right ankle, Week 17 Number Analyzed 40 participants 78 participants
-2.1  (1.3) -1.3  (1.0)
Right ankle, Week 33 Number Analyzed 37 participants 76 participants
-4.1  (1.3) -1.3  (0.9)
Right ankle, Week 49 Number Analyzed 38 participants 75 participants
-3.6  (1.4) -3.6  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Left ankle, Week 17
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7337
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-2.9 to 2.1
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Left ankle, Week 33
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8893
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-2.4 to 2.7
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Left ankle, Week 49
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2939
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-4.3 to 1.3
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Right ankle, Week 17
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5995
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-2.1 to 3.6
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Right ankle, Week 33
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0385
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
0.2 to 5.6
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Right ankle, Week 49
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9927
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0
Confidence Interval (2-Sided) 95%
-3.3 to 3.2
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
26.Secondary Outcome
Title Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49
Hide Description The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0–1 and 0–6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time Frame Baseline, Weeks 17, 33 and 49
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 17 Number Analyzed 39 participants 78 participants
-0.7  (0.6) -1.0  (0.4)
Week 33 Number Analyzed 37 participants 76 participants
-2.7  (1.1) -0.9  (0.8)
Week 49 Number Analyzed 38 participants 74 participants
-1.3  (0.5) -1.4  (0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 17
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6049
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-1.7 to 1.0
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 33
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2065
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
-1.0 to 4.4
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 49
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9391
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0
Confidence Interval (2-Sided) 95%
-1.3 to 1.2
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
27.Secondary Outcome
Title Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49
Hide Description 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time Frame Baseline, Weeks 17, 33 and 49
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Least Squares Mean (Standard Error)
Unit of Measure: Meters
Week 17 Number Analyzed 36 participants 74 participants
-32.0  (9.1) -30.2  (6.9)
Week 33 Number Analyzed 31 participants 70 participants
-52.3  (9.9) -43.4  (7.4)
Week 49 Number Analyzed 30 participants 61 participants
-56.5  (12.7) -58.0  (9.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 17
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8499
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
-16.7 to 20.3
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 33
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4008
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.9
Confidence Interval (2-Sided) 95%
-12.0 to 29.8
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Week 49
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9160
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-30.0 to 27.0
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
28.Secondary Outcome
Title Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49
Hide Description Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time Frame Baseline, Weeks 17, 33 and 49
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Least Squares Mean (Standard Error)
Unit of Measure: Kilograms
Left elbow extension, Week 17 Number Analyzed 40 participants 76 participants
-0.182  (0.183) -0.067  (0.141)
Left elbow extension, Week 33 Number Analyzed 35 participants 76 participants
-0.213  (0.187) -0.376  (0.141)
Left elbow extension, Week 49 Number Analyzed 37 participants 74 participants
-0.353  (0.200) -0.479  (0.150)
Right elbow extension, Week 17 Number Analyzed 40 participants 77 participants
-0.064  (0.209) -0.086  (0.158)
Right elbow extension, Week 33 Number Analyzed 35 participants 75 participants
-0.052  (0.197) -0.491  (0.148)
Right elbow extension, Week 49 Number Analyzed 37 participants 74 participants
-0.396  (0.192) -0.562  (0.145)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Left elbow extension, Week 17
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5726
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.115
Confidence Interval (2-Sided) 95%
-0.287 to 0.517
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Left elbow extension, Week 33
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4334
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.163
Confidence Interval (2-Sided) 95%
-0.574 to 0.248
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Left elbow extension, Week 49
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5767
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.126
Confidence Interval (2-Sided) 95%
-0.573 to 0.321
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Right elbow extension, Week 17
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9274
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.022
Confidence Interval (2-Sided) 95%
-0.489 to 0.446
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Right elbow extension, Week 33
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0469
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.439
Confidence Interval (2-Sided) 95%
-0.872 to -0.006
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Right elbow extension, Week 49
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4362
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.166
Confidence Interval (2-Sided) 95%
-0.587 to 0.255
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
29.Secondary Outcome
Title Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49
Hide Description Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time Frame Baseline, Weeks 17, 33 and 49
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Placebo Domagrozumab
Hide Arm/Group Description:
Participants received placebo from Week 1 to Week 48.
Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Overall Number of Participants Analyzed 40 80
Least Squares Mean (Standard Error)
Unit of Measure: Kilograms
Left elbow flexion, Week 17 Number Analyzed 40 participants 76 participants
-0.096  (0.237) -0.252  (0.181)
Left elbow flexion, Week 33 Number Analyzed 35 participants 76 participants
-0.194  (0.244) -0.497  (0.183)
Left elbow flexion, Week 49 Number Analyzed 37 participants 74 participants
-0.573  (0.205) -0.734  (0.159)
Right elbow flexion, Week 17 Number Analyzed 40 participants 77 participants
-0.035  (0.220) -0.118  (0.168)
Right elbow flexion, Week 33 Number Analyzed 35 participants 75 participants
-0.057  (0.234) -0.418  (0.175)
Right elbow flexion, Week 49 Number Analyzed 37 participants 74 participants
-0.495  (0.199) -0.684  (0.152)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Left elbow flexion, Week 17
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5557
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.156
Confidence Interval (2-Sided) 95%
-0.679 to 0.367
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Domagrozumab
Comments Left elbow flexion, Week 33
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2669
Comments The significance level is 0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.303
Confidence Interval (2-Sided) 95%
-0.841 to 0.235
Estimation Comments Mean difference was calculated by domagrozumab minus placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview