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A Study to Assess the Efficacy and Safety of BIVV009 (Sutimlimab) in Participants With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion (Cardinal Study)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03347396
Recruitment Status : Completed
First Posted : November 20, 2017
Results First Posted : October 31, 2022
Last Update Posted : October 31, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Bioverativ, a Sanofi company )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Agglutinin Disease, Cold
Intervention Drug: BIVV009
Enrollment 24
Recruitment Details The study was conducted at 16 active sites in 8 countries. Out of 42 screened participants, a total of 24 participants were enrolled from 05 March 2018 to 10 Jan 2019. This was a single arm study that consisted of 2 Parts: Part A and Part B.
Pre-assignment Details Participants were stratified based on baseline body weight to receive BIVV009 6.5 grams (g) (if <75 kg) or 7.5 g (if >=75 kg). As planned, data presented as: 1) Dose-wise (2 dose cohorts: BIVV009 6.5 g & BIVV009 7.5 g) for sections, 'disposition, baseline characteristics, safety endpoints & AEs' and 2) combined population (BIVV009) for efficacy endpoints.
Arm/Group Title BIVV009 6.5 g BIVV009 7.5 g
Hide Arm/Group Description Participants with primary cold agglutinin disease (CAD) and body weight less than (<)75 kg with a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an intravenous (IV) infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All participants who completed Part A elected to continue in Part B. Participants with primary CAD and body weight greater than or equal to (>=)75 kg with a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Period Title: Part A (26 Weeks)
Started 17 7
Completed 16 6
Not Completed 1 1
Reason Not Completed
Adverse Event             1             0
Death             0             1
Period Title: Part B (149 Weeks)
Started 16 6
Completed 14 5
Not Completed 2 1
Reason Not Completed
Adverse Event             1             1
Death             1             0
Arm/Group Title BIVV009 6.5 g BIVV009 7.5 g Total
Hide Arm/Group Description Participants with primary CAD and body weight <75 kg with a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All participants who completed Part A elected to continue in Part B. Participants with primary CAD and body weight >=75 kg with a recent history of transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B. Total of all reporting groups
Overall Number of Baseline Participants 17 7 24
Hide Baseline Analysis Population Description
Analysis was performed on all enrolled participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 7 participants 24 participants
71.8  (9.05) 70.1  (6.01) 71.3  (8.18)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 7 participants 24 participants
Female
11
  64.7%
4
  57.1%
15
  62.5%
Male
6
  35.3%
3
  42.9%
9
  37.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 7 participants 24 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
  17.6%
0
   0.0%
3
  12.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
2
  11.8%
1
  14.3%
3
  12.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
12
  70.6%
6
  85.7%
18
  75.0%
1.Primary Outcome
Title Part A: Percentage of Participants With Response to Treatment
Hide Description A participant was considered a responder: if he or she did not receive a blood transfusion from Week 5 through Week 26 (end of treatment in Part A) and did not receive treatment for CAD beyond what was permitted per protocol. Additionally, the participant's hemoglobin (Hgb) level must meet either of the following criteria: Hgb level >= 12 grams per deciliter (g/dL) at the treatment assessment endpoint (defined as the average of the values from the Week 23, 25, and 26 visits), or Hgb increased >= 2 g/dL from baseline (defined as the last Hgb value before administration of the first dose of study drug) at treatment assessment endpoint. Percentage of responders was calculated together with a 95% exact Clopper-Pearson confidence interval (CI).
Time Frame From Week 5 through Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part A-full analysis set (FAS) which included all participants who received at least 1 dose (including partial dose) of study drug. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 24
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
54.2
(32.8 to 74.4)
2.Primary Outcome
Title Part B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Hide Description An Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TESAEs was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the treatment-emergent (TE) period (from the first investigational medicinal product [IMP] administration in Part B to the last IMP administration + 9 weeks follow up period).
Time Frame Part B, 6.5 g cohort: From first dose (Week 27) up to 143 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 179); Part B, 7.5 g cohort: From first dose (Week 27) up to 149 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 185)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B safety analysis set (SAS) which included all participants who received at least 1 dose (including partial dose) of study drug in Part B. Data for this outcome measures was planned to be collected and analyzed for dose-wise reporting groups (BIVV009 6.5g and BIVV009 7.5 g).
Arm/Group Title BIVV009 6.5 g BIVV009 7.5 g
Hide Arm/Group Description:
Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All participants who completed Part A elected to continue in Part B.
Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 16 6
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
16
 100.0%
6
 100.0%
TESAEs
10
  62.5%
2
  33.3%
3.Secondary Outcome
Title Part A: Mean Change From Baseline in Bilirubin Levels at the Treatment Assessment Timepoint
Hide Description Mean change from baseline in bilirubin levels at the treatment assessment timepoint was reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. Least squares (LS) mean and 95% confidence interval (CI) was assessed by Mixed Model for Repeated Measures (MMRM) approach using heterogeneous Toeplitz (TOEPH) covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.
Time Frame Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: micromoles per Liter (mcmol/L)
-38.18
(-42.52 to -33.84)
4.Secondary Outcome
Title Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Treatment Assessment Timepoint
Hide Description FACIT-Fatigue scale consists of 13 questions assessed using a 5-point scale (0=not at all; 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much). Responses to each question were added to obtain a total score. Total score ranged from 0 to 52, with higher score indicating more fatigue. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.
Time Frame Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 17
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
10.85
(8.00 to 13.70)
5.Secondary Outcome
Title Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint
Hide Description Mean change from baseline in LDH at the treatment assessment timepoint is reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.
Time Frame Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 17
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units per liter
-126.95
(-218.47 to -35.42)
6.Secondary Outcome
Title Part A: Number of Blood Transfusions Per Participant
Hide Description A participant was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was <9 g/dL and the participant had symptoms of anemia or Hgb was <7 g/dL and the participant was asymptomatic. Number of transfusions after the first 5 weeks of study drug administration and up to Week 26 are reported in this outcome measure.
Time Frame From Week 5 up to Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: blood transfusions per participant
0.9  (2.75)
7.Secondary Outcome
Title Part A: Number of Blood Units Transfused Per Participant
Hide Description A participant was to receive a transfusion if his or her Hgb level met either of the following criteria: -Hgb was <9 g/dL and the participant had symptoms of anemia or Hgb was <7 g/dL and the participant was asymptomatic. Number of blood units transfused after the first 5 weeks of study drug administration and up to Week 26 are reported in this outcome measure.
Time Frame From Week 5 up to Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = number of participants with at least 1 transfusion. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: blood units transfused per participant
5.8  (8.47)
8.Secondary Outcome
Title Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint
Hide Description Mean change from baseline (Week 0) in Hgb at treatment assessment timepoint is reported in this outcome measure. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug.
Time Frame Baseline, treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part A-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 17
Least Squares Mean (95% Confidence Interval)
Unit of Measure: g/dL
2.60
(0.74 to 4.46)
9.Secondary Outcome
Title Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points
Hide Description Change From Hgb level from baseline (Week 0) at each specified time points (i.e., Weeks 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175 and early termination/safety follow up [ET/SFU] Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame Baseline, Weeks 27,29,31,33,35,37,39,41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS which included all participants who enrolled in Part B study and received at least 1 dose (including partial dose) of study drug. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: g/dL
Week 27 Number Analyzed 22 participants
2.76  (2.20)
Week 29 Number Analyzed 22 participants
2.77  (2.20)
Week 31 Number Analyzed 22 participants
2.74  (1.96)
Week 33 Number Analyzed 22 participants
2.87  (1.97)
Week 35 Number Analyzed 21 participants
2.82  (2.10)
Week 37 Number Analyzed 21 participants
2.71  (2.08)
Week 39 Number Analyzed 21 participants
2.72  (2.26)
Week 41 Number Analyzed 21 participants
2.76  (2.24)
Week 43 Number Analyzed 21 participants
2.73  (2.06)
Week 45 Number Analyzed 21 participants
2.84  (2.21)
Week 47 Number Analyzed 21 participants
2.74  (1.95)
Week 49 Number Analyzed 21 participants
2.73  (2.09)
Week 51 Number Analyzed 22 participants
2.71  (1.97)
Week 53 Number Analyzed 22 participants
2.66  (1.97)
Week 55 Number Analyzed 21 participants
2.73  (1.96)
Week 57 Number Analyzed 21 participants
3.01  (2.36)
Week 59 Number Analyzed 21 participants
2.81  (2.10)
Week 61 Number Analyzed 21 participants
2.88  (2.37)
Week 63 Number Analyzed 21 participants
2.99  (2.33)
Week 65 Number Analyzed 21 participants
2.53  (2.18)
Week 67 Number Analyzed 20 participants
2.52  (2.20)
Week 69 Number Analyzed 20 participants
2.96  (2.08)
Week 71 Number Analyzed 19 participants
2.86  (2.31)
Week 73 Number Analyzed 20 participants
2.79  (2.25)
Week 75 Number Analyzed 21 participants
2.70  (2.18)
Week 77 Number Analyzed 21 participants
2.93  (2.59)
Week 79 Number Analyzed 19 participants
3.13  (2.23)
Week 83 Number Analyzed 20 participants
2.89  (2.47)
Week 87 Number Analyzed 18 participants
2.63  (2.36)
Week 91 Number Analyzed 20 participants
3.23  (2.17)
Week 95 Number Analyzed 19 participants
3.12  (2.06)
Week 99 Number Analyzed 20 participants
2.98  (2.01)
Week 103 Number Analyzed 21 participants
2.92  (2.09)
Week 107 Number Analyzed 21 participants
2.60  (2.10)
Week 111 Number Analyzed 21 participants
2.82  (2.17)
Week 115 Number Analyzed 19 participants
2.96  (2.25)
Week 119 Number Analyzed 20 participants
2.79  (2.57)
Week 123 Number Analyzed 20 participants
2.82  (2.35)
Week 127 Number Analyzed 19 participants
2.89  (1.99)
Week 131 Number Analyzed 19 participants
3.03  (2.19)
Week 135 Number Analyzed 19 participants
3.35  (1.99)
Week 139 Number Analyzed 13 participants
3.42  (2.14)
Week 143 Number Analyzed 11 participants
3.43  (2.31)
Week 147 Number Analyzed 8 participants
3.75  (2.38)
Week 151 Number Analyzed 8 participants
3.43  (1.91)
Week 155 Number Analyzed 8 participants
3.74  (1.94)
Week 159 Number Analyzed 6 participants
5.20  (1.65)
Week 163 Number Analyzed 4 participants
4.18  (1.14)
Week 167 Number Analyzed 2 participants
4.80  (0.42)
Week 171 Number Analyzed 1 participants
4.80
Week 175 Number Analyzed 1 participants
4.40
ET/SFU Visit Number Analyzed 20 participants
1.21  (1.56)
10.Secondary Outcome
Title Part B: Change From Baseline in Bilirubin Levels at Each Specified Time Points
Hide Description Change from baseline (Week 0) in bilirubin levels at each specified time point (i.e., Weeks 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame Baseline, Weeks 27,29,31,33,35,37,39,41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: mcmol/L
Week 27 Number Analyzed 19 participants
-34.96  (18.31)
Week 29 Number Analyzed 19 participants
-34.92  (15.78)
Week 31 Number Analyzed 19 participants
-32.58  (17.07)
Week 33 Number Analyzed 19 participants
-32.67  (17.52)
Week 35 Number Analyzed 19 participants
-32.25  (22.39)
Week 37 Number Analyzed 19 participants
-33.24  (15.53)
Week 39 Number Analyzed 13 participants
-35.92  (13.17)
Week 41 Number Analyzed 18 participants
-35.03  (13.71)
Week 43 Number Analyzed 16 participants
-36.46  (17.25)
Week 45 Number Analyzed 18 participants
-34.81  (15.76)
Week 47 Number Analyzed 18 participants
-34.57  (16.53)
Week 49 Number Analyzed 18 participants
-32.36  (19.50)
Week 51 Number Analyzed 16 participants
-34.88  (15.90)
Week 53 Number Analyzed 19 participants
-35.25  (18.32)
Week 55 Number Analyzed 18 participants
-34.79  (16.70)
Week 57 Number Analyzed 18 participants
-36.32  (16.54)
Week 59 Number Analyzed 18 participants
-35.77  (17.73)
Week 61 Number Analyzed 18 participants
-36.39  (16.14)
Week 63 Number Analyzed 17 participants
-38.25  (15.43)
Week 65 Number Analyzed 17 participants
-35.46  (16.84)
Week 67 Number Analyzed 17 participants
-35.74  (18.37)
Week 69 Number Analyzed 17 participants
-33.88  (16.83)
Week 71 Number Analyzed 17 participants
-32.54  (23.01)
Week 73 Number Analyzed 14 participants
-33.03  (21.82)
Week 75 Number Analyzed 16 participants
-30.55  (21.68)
Week 77 Number Analyzed 18 participants
-30.95  (22.83)
Week 79 Number Analyzed 17 participants
-35.51  (14.79)
Week 83 Number Analyzed 16 participants
-38.60  (13.90)
Week 87 Number Analyzed 15 participants
-37.45  (16.29)
Week 91 Number Analyzed 16 participants
-35.19  (16.07)
Week 95 Number Analyzed 15 participants
-33.57  (15.93)
Week 99 Number Analyzed 15 participants
-28.71  (21.98)
Week 103 Number Analyzed 18 participants
-32.04  (22.45)
Week 107 Number Analyzed 18 participants
-34.46  (15.27)
Week 111 Number Analyzed 15 participants
-37.67  (14.28)
Week 115 Number Analyzed 16 participants
-36.41  (16.76)
Week 119 Number Analyzed 16 participants
-34.65  (13.71)
Week 123 Number Analyzed 17 participants
-29.99  (24.96)
Week 127 Number Analyzed 17 participants
-35.57  (17.83)
Week 131 Number Analyzed 16 participants
-35.03  (18.72)
Week 135 Number Analyzed 15 participants
-36.88  (14.71)
Week 139 Number Analyzed 11 participants
-37.60  (14.59)
Week 143 Number Analyzed 8 participants
-44.50  (15.96)
Week 147 Number Analyzed 6 participants
-44.82  (15.12)
Week 151 Number Analyzed 6 participants
-46.53  (10.80)
Week 155 Number Analyzed 6 participants
-50.32  (12.63)
Week 159 Number Analyzed 5 participants
-46.30  (13.90)
Week 163 Number Analyzed 4 participants
-46.13  (11.86)
Week 167 Number Analyzed 2 participants
-36.30  (12.59)
Week 171 Number Analyzed 1 participants
-32.50
Week 175 Number Analyzed 1 participants
-29.10
ET/SFU Visit Number Analyzed 17 participants
-9.98  (18.11)
11.Secondary Outcome
Title Part B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and Early Termination (ET) Visit/Safety Follow-up Visit
Hide Description FACIT-Fatigue scale consists of 13 questions assessed using a 5-point scale (0=not at all; 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much). Responses to each question were added to obtain a total score. The Total score ranged from 0 to 52, with higher score indicating more fatigue. Baseline (Week 0) was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and ET Visit/SFU visit (i.e., up to Week 185)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: score on a scale
Week 39 Number Analyzed 19 participants
9.37  (16.00)
Week 51 Number Analyzed 20 participants
10.50  (12.05)
Week 63 Number Analyzed 19 participants
10.21  (11.88)
Week 75 Number Analyzed 19 participants
11.00  (11.51)
Week 87 Number Analyzed 18 participants
10.39  (13.41)
Week 99 Number Analyzed 17 participants
9.94  (8.19)
Week 111 Number Analyzed 18 participants
9.11  (12.35)
Week 123 Number Analyzed 19 participants
6.79  (11.28)
Week 135 Number Analyzed 14 participants
11.71  (13.85)
Week 147 Number Analyzed 7 participants
13.29  (13.39)
Week 159 Number Analyzed 4 participants
24.75  (10.24)
Week 171 Number Analyzed 1 participants
32.00
ET/SFU Visit Number Analyzed 19 participants
1.05  (8.15)
12.Secondary Outcome
Title Part B: Change From Baseline in 12-Item Short-Form Survey (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Each Specified Time Points
Hide Description SF-12: 12 item-questionnaire assessed health-related quality of life (HRQOL) contained 12 items, categorized into 8 domains (subscales) of functioning and well-being: physical functioning, role-physical, role emotional, mental health, bodily pain, general health, vitality and social functioning, with each domain score ranged from 0 (poor health) to 100 (better health). Higher scores = good health condition. These 8 domains were further summarized into 2 summary scores, PCS and MCS for which, score ranged 0 (poor health) to 100 (better health). Higher scores = better HRQOL. Baseline (Week 0) was defined as the last non-missing value prior to first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Change from baseline in SF-12 PCS and MCS scores is reported in this outcome measure.
Time Frame Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135 and ET Visit/SFU visit (i.e., up to Week 185)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: score on a scale
Week 39-PCS Number Analyzed 16 participants
7.813  (10.486)
Week 39-MCS Number Analyzed 16 participants
5.859  (10.249)
Week 51-PCS Number Analyzed 18 participants
6.677  (9.925)
Week 51-MCS Number Analyzed 18 participants
3.912  (9.493)
Week 63-PCS Number Analyzed 19 participants
8.318  (7.148)
Week 63-MCS Number Analyzed 19 participants
2.385  (9.777)
Week 75-PCS Number Analyzed 18 participants
6.580  (9.214)
Week 75-MCS Number Analyzed 18 participants
3.102  (9.881)
Week 87-PCS Number Analyzed 18 participants
6.398  (9.021)
Week 87-MCS Number Analyzed 18 participants
1.611  (10.336)
Week 99-PCS Number Analyzed 14 participants
9.054  (5.803)
Week 99-MCS Number Analyzed 14 participants
2.581  (9.169)
Week 111-PCS Number Analyzed 8 participants
11.958  (3.832)
Week 111-MCS Number Analyzed 8 participants
2.523  (12.585)
Week 123-PCS Number Analyzed 6 participants
4.743  (6.900)
Week 123-MCS Number Analyzed 6 participants
3.810  (14.071)
Week 135-PCS Number Analyzed 1 participants
10.450
Week 135-MCS Number Analyzed 1 participants
27.900
ET/SFU Visit-PCS Number Analyzed 1 participants
-8.920
ET/SFU Visit-MCS Number Analyzed 1 participants
-1.180
13.Secondary Outcome
Title Part B: Change From Baseline in 5-level European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) Health State Utility Index and VAS Scores at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and ET Visit/SFU Visit
Hide Description EQ-5D-5L:standardized, participant-rated questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state utility index (descriptive system) and Visual Analog Scale (VAS). EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response option: no problems, slight problems, moderate problems, severe problems, and extreme problems measured with Likert scale. EQ-5D-5L responses relating to 5 dimensions are converted into a single index utility score between 0 to 1, where higher score=better health state. The EQ-5D-5L VAS rated participant's current health state on a scale from 0=worst imaginable health state to 100 =best imaginable health state. Baseline (Week 0): last non-missing value prior to first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame Baseline, Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and ET Visit/SFU visit (i.e., up to Week 185)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: score on a scale
Week 39 - Index score Number Analyzed 18 participants
0.067  (0.264)
Week 39 - VAS score Number Analyzed 18 participants
18.111  (20.642)
Week 51 - Index score Number Analyzed 20 participants
0.078  (0.194)
Week 51 - VAS score Number Analyzed 20 participants
14.500  (19.050)
Week 63 - Index score Number Analyzed 19 participants
0.092  (0.166)
Week 63 - VAS score Number Analyzed 19 participants
18.053  (16.844)
Week 75 - Index score Number Analyzed 19 participants
0.069  (0.211)
Week 75 - VAS score Number Analyzed 19 participants
17.842  (16.604)
Week 87 - Index score Number Analyzed 19 participants
0.022  (0.226)
Week 87 - VAS score Number Analyzed 19 participants
14.421  (20.815)
Week 99 - Index Score Number Analyzed 17 participants
0.060  (0.136)
Week 99 - VAS Score Number Analyzed 17 participants
14.059  (13.818)
Week 111 - Index score Number Analyzed 18 participants
0.099  (0.174)
Week 111 - VAS score Number Analyzed 18 participants
18.889  (15.408)
Week 123 - Index Score Number Analyzed 19 participants
0.009  (0.190)
Week 123 - VAS score Number Analyzed 19 participants
8.842  (18.765)
Week 135 - Index score Number Analyzed 15 participants
0.085  (0.233)
Week 135 - VAS score Number Analyzed 15 participants
17.067  (21.608)
Week 147 - Index score Number Analyzed 7 participants
0.143  (0.131)
Week 147 - VAS score Number Analyzed 7 participants
17.857  (20.178)
Week 159 - Index Score Number Analyzed 4 participants
0.250  (0.145)
Week 159 - VAS score Number Analyzed 4 participants
36.250  (14.930)
Week 171 - Index score Number Analyzed 1 participants
0.535
Week 171 - VAS score Number Analyzed 1 participants
35.000
ET/SFU Visit - Index score Number Analyzed 19 participants
-0.025  (0.173)
ET/SFU Visit - VAS score Number Analyzed 19 participants
1.263  (19.287)
14.Secondary Outcome
Title Part B: Number of Participants With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU Visit
Hide Description The PGIS is a self-reported scale. The PGIS is a 1-item questionnaire designed to assess participant's impression of disease severity using a 5-point scale ranging from 1 to 5, where 1=none, 2= mild, 3=moderate, 4=severe, 5=very severe. Higher scores indicated greater severity. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame At Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU visit (i.e., up to Week 185)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS population. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
Week 39 - None Number Analyzed 18 participants
5
  27.8%
Week 39 - Mild Number Analyzed 18 participants
8
  44.4%
Week 39 - Moderate Number Analyzed 18 participants
4
  22.2%
Week 39 - Severe Number Analyzed 18 participants
1
   5.6%
Week 39 - Very severe Number Analyzed 18 participants
0
   0.0%
Week 51 - None Number Analyzed 21 participants
5
  23.8%
Week 51 - Mild Number Analyzed 21 participants
13
  61.9%
Week 51 - Moderate Number Analyzed 21 participants
3
  14.3%
Week 51 - Severe Number Analyzed 21 participants
0
   0.0%
Week 51 - Very severe Number Analyzed 21 participants
0
   0.0%
Week 63 - None Number Analyzed 20 participants
4
  20.0%
Week 63 - Mild Number Analyzed 20 participants
12
  60.0%
Week 63 - Moderate Number Analyzed 20 participants
3
  15.0%
Week 63 - Severe Number Analyzed 20 participants
1
   5.0%
Week 63 - Very severe Number Analyzed 20 participants
0
   0.0%
Week 75 - None Number Analyzed 20 participants
3
  15.0%
Week 75 - Mild Number Analyzed 20 participants
12
  60.0%
Week 75 - Moderate Number Analyzed 20 participants
5
  25.0%
Week 75 - Severe Number Analyzed 20 participants
0
   0.0%
Week 75 - Very severe Number Analyzed 20 participants
0
   0.0%
Week 87 - None Number Analyzed 19 participants
5
  26.3%
Week 87 - Mild Number Analyzed 19 participants
9
  47.4%
Week 87 - Moderate Number Analyzed 19 participants
3
  15.8%
Week 87 - Severe Number Analyzed 19 participants
2
  10.5%
Week 87 - Very severe Number Analyzed 19 participants
0
   0.0%
Week 99 - None Number Analyzed 18 participants
4
  22.2%
Week 99 - Mild Number Analyzed 18 participants
10
  55.6%
Week 99 - Moderate Number Analyzed 18 participants
4
  22.2%
Week 99 - Severe Number Analyzed 18 participants
0
   0.0%
Week 99 - Very severe Number Analyzed 18 participants
0
   0.0%
Week 111 - None Number Analyzed 19 participants
7
  36.8%
Week 111 - Mild Number Analyzed 19 participants
6
  31.6%
Week 111 - Moderate Number Analyzed 19 participants
6
  31.6%
Week 111 - Severe Number Analyzed 19 participants
0
   0.0%
Week 111 - Very severe Number Analyzed 19 participants
0
   0.0%
Week 123 - None Number Analyzed 20 participants
4
  20.0%
Week 123 - Mild Number Analyzed 20 participants
7
  35.0%
Week 123 - Moderate Number Analyzed 20 participants
7
  35.0%
Week 123 - Severe Number Analyzed 20 participants
2
  10.0%
Week 123 - Very severe Number Analyzed 20 participants
0
   0.0%
Week 135 - None Number Analyzed 15 participants
4
  26.7%
Week 135 - Mild Number Analyzed 15 participants
8
  53.3%
Week 135 - Moderate Number Analyzed 15 participants
3
  20.0%
Week 135 - Severe Number Analyzed 15 participants
0
   0.0%
Week 135 - Very severe Number Analyzed 15 participants
0
   0.0%
Week 147 - None Number Analyzed 7 participants
3
  42.9%
Week 147 - Mild Number Analyzed 7 participants
3
  42.9%
Week 147 - Moderate Number Analyzed 7 participants
1
  14.3%
Week 147 - Severe Number Analyzed 7 participants
0
   0.0%
Week 147 - Very severe Number Analyzed 7 participants
0
   0.0%
Week 159 - None Number Analyzed 4 participants
3
  75.0%
Week 159 - Mild Number Analyzed 4 participants
1
  25.0%
Week 159 - Moderate Number Analyzed 4 participants
0
   0.0%
Week 159 - Severe Number Analyzed 4 participants
0
   0.0%
Week 159 - Very severe Number Analyzed 4 participants
0
   0.0%
Week 171 - None Number Analyzed 1 participants
0
   0.0%
Week 171 - Mild Number Analyzed 1 participants
1
 100.0%
Week 171 - Moderate Number Analyzed 1 participants
0
   0.0%
Week 171 - Severe Number Analyzed 1 participants
0
   0.0%
Week 171 - Very severe Number Analyzed 1 participants
0
   0.0%
ET/SFU Visit - None Number Analyzed 20 participants
4
  20.0%
ET/SFU Visit - Mild Number Analyzed 20 participants
6
  30.0%
ET/SFU Visit - Moderate Number Analyzed 20 participants
4
  20.0%
ET/SFU Visit - Severe Number Analyzed 20 participants
5
  25.0%
ET/SFU Visit - Very severe Number Analyzed 20 participants
1
   5.0%
15.Secondary Outcome
Title Part B: Number of Participants With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU Visit
Hide Description PGIC is a self-administered questionnaire to evaluate the improvement or worsening compared to the start of the study. PGIC was assessed on a 7-point Likert scale ranged from 1 (greatly improved) to 7 (greatly worsened). Categories were defined based on the PGIC scores as follows: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse and 7=very much worsen. Higher scores indicated greater severity. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame At Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU visit (i.e., up to Week 185)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
Week 39 - Very much improved Number Analyzed 19 participants
9
  47.4%
Week 39 - Much improved Number Analyzed 19 participants
5
  26.3%
Week 39 - Minimally improved Number Analyzed 19 participants
3
  15.8%
Week 39 - No change Number Analyzed 19 participants
1
   5.3%
Week 39 - Minimally worse Number Analyzed 19 participants
0
   0.0%
Week 39 - Much worse Number Analyzed 19 participants
1
   5.3%
Week 39 - Very much worse Number Analyzed 19 participants
0
   0.0%
Week 51 - Very much improved Number Analyzed 21 participants
6
  28.6%
Week 51 - Much improved Number Analyzed 21 participants
13
  61.9%
Week 51 - Minimally improved Number Analyzed 21 participants
2
   9.5%
Week 51 - No change Number Analyzed 21 participants
0
   0.0%
Week 51 - Minimally worse Number Analyzed 21 participants
0
   0.0%
Week 51 - Much worse Number Analyzed 21 participants
0
   0.0%
Week 51- Very much worse Number Analyzed 21 participants
0
   0.0%
Week 63 - Very much improved Number Analyzed 20 participants
8
  40.0%
Week 63 - Much improved Number Analyzed 20 participants
9
  45.0%
Week 63 - Minimally improved Number Analyzed 20 participants
1
   5.0%
Week 63 - No change Number Analyzed 20 participants
1
   5.0%
Week 63 - Minimally worse Number Analyzed 20 participants
1
   5.0%
Week 63 - Much worse Number Analyzed 20 participants
0
   0.0%
Week 63 - Very much worse Number Analyzed 20 participants
0
   0.0%
Week 75 - Very much improved Number Analyzed 20 participants
5
  25.0%
Week 75 - Much improved Number Analyzed 20 participants
11
  55.0%
Week 75 - Minimally improved Number Analyzed 20 participants
1
   5.0%
Week 75 - No change Number Analyzed 20 participants
2
  10.0%
Week 75 - Minimally worse Number Analyzed 20 participants
1
   5.0%
Week 75 - Much worse Number Analyzed 20 participants
0
   0.0%
Week 75 - Very much worse Number Analyzed 20 participants
0
   0.0%
Week 87 - Very much improved Number Analyzed 19 participants
5
  26.3%
Week 87 - Much improved Number Analyzed 19 participants
11
  57.9%
Week 87 - Minimally improved Number Analyzed 19 participants
2
  10.5%
Week 87 - No change Number Analyzed 19 participants
1
   5.3%
Week 87 - Minimally worse Number Analyzed 19 participants
0
   0.0%
Week 87 - Much worse Number Analyzed 19 participants
0
   0.0%
Week 87 - Very much worse Number Analyzed 19 participants
0
   0.0%
Week 99 - Very much improved Number Analyzed 18 participants
4
  22.2%
Week 99 - Much improved Number Analyzed 18 participants
10
  55.6%
Week 99 - Minimally improved Number Analyzed 18 participants
3
  16.7%
Week 99 - No Change Number Analyzed 18 participants
1
   5.6%
Week 99 - Minimally worse Number Analyzed 18 participants
0
   0.0%
Week 99 - Much worse Number Analyzed 18 participants
0
   0.0%
Week 99 - Very much worse Number Analyzed 18 participants
0
   0.0%
Week 111 - Very much improved Number Analyzed 19 participants
7
  36.8%
Week 111 - Much improved Number Analyzed 19 participants
7
  36.8%
Week 111 - Minimally improved Number Analyzed 19 participants
5
  26.3%
Week 111 - No change Number Analyzed 19 participants
0
   0.0%
Week 111 - Minimally worse Number Analyzed 19 participants
0
   0.0%
Week 111 - Much worse Number Analyzed 19 participants
0
   0.0%
Week 111 - Very much worse Number Analyzed 19 participants
0
   0.0%
Week 123 - Very much improved Number Analyzed 20 participants
8
  40.0%
Week 123 - Much improved Number Analyzed 20 participants
6
  30.0%
Week 123 - Minimally improved Number Analyzed 20 participants
6
  30.0%
Week 123 - No change Number Analyzed 20 participants
0
   0.0%
Week 123 - Minimally worse Number Analyzed 20 participants
0
   0.0%
Week 123 - Much worse Number Analyzed 20 participants
0
   0.0%
Week 123 - Very much worse Number Analyzed 20 participants
0
   0.0%
Week 135 - Very much improved Number Analyzed 15 participants
5
  33.3%
Week 135 - Much improved Number Analyzed 15 participants
6
  40.0%
Week 135 - Minimally improved Number Analyzed 15 participants
2
  13.3%
Week 135 - No change Number Analyzed 15 participants
1
   6.7%
Week 135 - Minimally worse Number Analyzed 15 participants
1
   6.7%
Week 135 - Much worse Number Analyzed 15 participants
0
   0.0%
Week 135 - Very much worse Number Analyzed 15 participants
0
   0.0%
Week 147 - Very much improved Number Analyzed 7 participants
4
  57.1%
Week 147 - Much improved Number Analyzed 7 participants
2
  28.6%
Week 147 - Minimally improved Number Analyzed 7 participants
1
  14.3%
Week 147 - No change Number Analyzed 7 participants
0
   0.0%
Week 147 - Minimally worse Number Analyzed 7 participants
0
   0.0%
Week 147 - Much worse Number Analyzed 7 participants
0
   0.0%
Week 147 - Very much worse Number Analyzed 7 participants
0
   0.0%
Week 159 - Very much improved Number Analyzed 4 participants
4
 100.0%
Week 159 - Much improved Number Analyzed 4 participants
0
   0.0%
Week 159 - Minimally improved Number Analyzed 4 participants
0
   0.0%
Week 159 - No change Number Analyzed 4 participants
0
   0.0%
Week 159 - Minimally worse Number Analyzed 4 participants
0
   0.0%
Week 159 - Much worse Number Analyzed 4 participants
0
   0.0%
Week 159 - Very much worse Number Analyzed 4 participants
0
   0.0%
Week 171 - Very much improved Number Analyzed 1 participants
1
 100.0%
Week 171 - Much improved Number Analyzed 1 participants
0
   0.0%
Week 171 - Minimally improved Number Analyzed 1 participants
0
   0.0%
Week 171 - No Change Number Analyzed 1 participants
0
   0.0%
Week 171 - Minimally worse Number Analyzed 1 participants
0
   0.0%
Week 171 - Much worse Number Analyzed 1 participants
0
   0.0%
Week 171 - Very much worse Number Analyzed 1 participants
0
   0.0%
ET/SFU Visit - Very much improved Number Analyzed 20 participants
3
  15.0%
ET/SFU Visit - Much improved Number Analyzed 20 participants
8
  40.0%
ET/SFU Visit - Minimally improved Number Analyzed 20 participants
2
  10.0%
ET/SFU Visit - No Change Number Analyzed 20 participants
4
  20.0%
ET/SFU Visit - Minimally worse Number Analyzed 20 participants
2
  10.0%
ET/SFU Visit - Much worse Number Analyzed 20 participants
0
   0.0%
ET/SFU Visit - Very much worse Number Analyzed 20 participants
1
   5.0%
16.Secondary Outcome
Title Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points
Hide Description Mean change from baseline in LDH levels at each specified time points (i.e., Weeks 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175 and ET/SFU Visit) is reported in this outcome measure. Baseline (Week 0) was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185).
Time Frame Baseline, Weeks 27,29,31,33,35,37,39,41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: units per liter
Week 27 Number Analyzed 22 participants
-111.59  (327.80)
Week 29 Number Analyzed 21 participants
-129.76  (331.91)
Week 31 Number Analyzed 22 participants
-95.27  (319.25)
Week 33 Number Analyzed 21 participants
-82.19  (330.04)
Week 35 Number Analyzed 22 participants
-126.64  (346.75)
Week 37 Number Analyzed 21 participants
-151.57  (307.15)
Week 39 Number Analyzed 15 participants
-49.27  (172.53)
Week 41 Number Analyzed 21 participants
-116.10  (305.11)
Week 43 Number Analyzed 19 participants
-150.26  (271.72)
Week 45 Number Analyzed 21 participants
-85.48  (308.01)
Week 47 Number Analyzed 21 participants
-79.81  (286.13)
Week 49 Number Analyzed 21 participants
-104.38  (313.66)
Week 51 Number Analyzed 19 participants
-76.84  (344.60)
Week 53 Number Analyzed 21 participants
-87.00  (299.09)
Week 55 Number Analyzed 21 participants
-68.29  (305.09)
Week 57 Number Analyzed 21 participants
-101.71  (273.44)
Week 59 Number Analyzed 21 participants
-97.71  (296.74)
Week 61 Number Analyzed 21 participants
-89.48  (298.05)
Week 63 Number Analyzed 20 participants
-94.20  (288.34)
Week 65 Number Analyzed 20 participants
-91.05  (305.75)
Week 67 Number Analyzed 19 participants
-106.32  (327.48)
Week 69 Number Analyzed 19 participants
-75.00  (333.47)
Week 71 Number Analyzed 18 participants
-52.39  (378.82)
Week 73 Number Analyzed 17 participants
-70.35  (348.56)
Week 75 Number Analyzed 19 participants
-18.68  (323.02)
Week 77 Number Analyzed 21 participants
-64.67  (335.73)
Week 79 Number Analyzed 20 participants
-54.10  (338.58)
Week 83 Number Analyzed 19 participants
-87.21  (344.88)
Week 87 Number Analyzed 18 participants
-89.17  (392.80)
Week 91 Number Analyzed 19 participants
-78.47  (349.15)
Week 95 Number Analyzed 16 participants
-132.75  (301.36)
Week 99 Number Analyzed 18 participants
-13.83  (155.04)
Week 103 Number Analyzed 20 participants
-106.40  (309.44)
Week 107 Number Analyzed 20 participants
-85.45  (312.50)
Week 111 Number Analyzed 19 participants
-107.58  (286.18)
Week 115 Number Analyzed 19 participants
-107.84  (293.61)
Week 119 Number Analyzed 19 participants
-63.68  (310.56)
Week 123 Number Analyzed 20 participants
-58.90  (339.49)
Week 127 Number Analyzed 18 participants
-57.72  (400.26)
Week 131 Number Analyzed 19 participants
-113.63  (344.53)
Week 135 Number Analyzed 17 participants
-97.06  (339.41)
Week 139 Number Analyzed 13 participants
-1.00  (256.65)
Week 143 Number Analyzed 10 participants
180.70  (318.62)
Week 147 Number Analyzed 7 participants
-10.29  (196.90)
Week 151 Number Analyzed 8 participants
-24.13  (146.79)
Week 155 Number Analyzed 8 participants
-17.38  (146.80)
Week 159 Number Analyzed 4 participants
-126.00  (150.38)
Week 163 Number Analyzed 4 participants
-31.50  (35.49)
Week 167 Number Analyzed 2 participants
-48.50  (68.59)
Week 171 Number Analyzed 1 participants
-23.00
Week 175 Number Analyzed 1 participants
6.00
ET/SFU visit Number Analyzed 20 participants
-107.50  (249.28)
17.Secondary Outcome
Title Part B: Number of Blood Transfusions Per Participant
Hide Description A participant was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was <9 g/dL and the participant had symptoms of anemia or Hgb was <7 g/dL and the participant was asymptomatic.
Time Frame From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part-B FAS. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: blood transfusions per participant
2.86  (6.58)
18.Secondary Outcome
Title Part B: Number of Blood Units Transfused Per Participant
Hide Description A participant was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was <9 g/dL and the participant had symptoms of anemia or Hgb was <7 g/dL and the participant was asymptomatic.
Time Frame From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS. Here, 'overall number of participants analyzed' = number of participants with at least 1 transfusion. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: blood units transfused per participants
16.57  (16.85)
19.Secondary Outcome
Title Part B: Change From Baseline in Haptoglobin Values at Each Specified Time Points
Hide Description Change in Haptoglobin values from baseline at each specified time points (i.e., Weeks 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175 and ET/SFU Visit) is reported in this outcome measure. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Haptoglobin values <0.2 were imputed as 0.2.
Time Frame Baseline, Weeks 27,29,31,33,35,37,39,41,43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175, ET/SFU (up to Week 185)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS. Here, 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: grams per liter
Week 27 Number Analyzed 22 participants
0.21  (0.38)
Week 29 Number Analyzed 21 participants
0.21  (0.45)
Week 31 Number Analyzed 22 participants
0.21  (0.43)
Week 33 Number Analyzed 22 participants
0.28  (0.53)
Week 35 Number Analyzed 22 participants
0.25  (0.41)
Week 37 Number Analyzed 21 participants
0.14  (0.28)
Week 39 Number Analyzed 17 participants
0.27  (0.49)
Week 41 Number Analyzed 20 participants
0.39  (0.59)
Week 43 Number Analyzed 18 participants
0.29  (0.47)
Week 45 Number Analyzed 21 participants
0.16  (0.26)
Week 47 Number Analyzed 20 participants
0.15  (0.35)
Week 49 Number Analyzed 21 participants
0.21  (0.41)
Week 51 Number Analyzed 19 participants
0.20  (0.37)
Week 53 Number Analyzed 22 participants
0.23  (0.46)
Week 55 Number Analyzed 20 participants
0.26  (0.45)
Week 57 Number Analyzed 20 participants
0.26  (0.43)
Week 59 Number Analyzed 21 participants
0.29  (0.44)
Week 61 Number Analyzed 21 participants
0.23  (0.43)
Week 63 Number Analyzed 20 participants
0.38  (0.50)
Week 65 Number Analyzed 20 participants
0.25  (0.41)
Week 67 Number Analyzed 19 participants
0.25  (0.42)
Week 69 Number Analyzed 20 participants
0.24  (0.47)
Week 71 Number Analyzed 19 participants
0.19  (0.33)
Week 73 Number Analyzed 19 participants
0.13  (0.29)
Week 75 Number Analyzed 20 participants
0.13  (0.24)
Week 77 Number Analyzed 21 participants
0.17  (0.29)
Week 79 Number Analyzed 20 participants
0.09  (0.22)
Week 83 Number Analyzed 20 participants
0.14  (0.25)
Week 87 Number Analyzed 18 participants
0.35  (0.53)
Week 91 Number Analyzed 19 participants
0.17  (0.28)
Week 95 Number Analyzed 20 participants
0.19  (0.33)
Week 99 Number Analyzed 18 participants
0.21  (0.37)
Week 103 Number Analyzed 21 participants
0.15  (0.25)
Week 107 Number Analyzed 21 participants
0.26  (0.40)
Week 111 Number Analyzed 19 participants
0.22  (0.33)
Week 115 Number Analyzed 18 participants
0.21  (0.35)
Week 119 Number Analyzed 19 participants
0.16  (0.31)
Week 123 Number Analyzed 20 participants
0.19  (0.45)
Week 127 Number Analyzed 20 participants
0.14  (0.23)
Week 131 Number Analyzed 19 participants
0.18  (0.38)
Week 135 Number Analyzed 18 participants
0.18  (0.35)
Week 139 Number Analyzed 13 participants
0.10  (0.17)
Week 143 Number Analyzed 11 participants
0.07  (0.16)
Week 147 Number Analyzed 8 participants
0.06  (0.16)
Week 151 Number Analyzed 8 participants
0.12  (0.24)
Week 155 Number Analyzed 8 participants
0.09  (0.22)
Week 159 Number Analyzed 5 participants
0.15  (0.34)
Week 163 Number Analyzed 4 participants
0.30  (0.35)
Week 167 Number Analyzed 2 participants
0.00  (0.00)
Week 171 Number Analyzed 1 participants
0.00
Week 175 Number Analyzed 1 participants
0.00
ET/SFU visit Number Analyzed 20 participants
0.02  (0.13)
20.Secondary Outcome
Title Part B: Number of Healthcare Visits by Type
Hide Description In this outcome measure, number of healthcare visits which included non-study healthcare resource utilization visit (consisted mainly of extra visits to the office of the study doctor, or visit to a generalist doctor, or visit to a specialist doctor) and hospitalization visit and visit to hospital emergency is reported.
Time Frame From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on Part B-FAS. Data for this outcome measure was planned to be collected and analyzed for combined population (i.e., all participants who received BIVV009 [either at 6.5 g or 7.5 g]).
Arm/Group Title BIVV009
Hide Arm/Group Description:
Participants with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
Overall Number of Participants Analyzed 22
Measure Type: Number
Unit of Measure: visits
Non-study healthcare resource utilization visits 16
Hospitalization 8
Visit to a hospital emergency room 3
Time Frame Part A (both 6.5 g and 7.5 g cohorts): From first dose (Day 0) up to Week 26; Part B, 6.5 g cohort: From first dose (Week 27) up to 143 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 179). Part B, 7.5 g cohort: From first dose (Week 27) up to 149 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 185)
Adverse Event Reporting Description Reported AEs and SAEs including fatal AEs were TEAEs that developed/worsened or became serious during on-treatment period. Analysis was performed on SAS.
 
Arm/Group Title Part A: BIVV009 6.5 g Part A: BIVV009 7.5 g Part B: BIVV009 6.5 g Part B: BIVV009 7.5 g
Hide Arm/Group Description Participants with primary CAD and body weight <75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants with primary CAD and body weight >=75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All participants who completed Part A elected to continue in Part B. Participants who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All participants who completed Part A elected to continue in Part B.
All-Cause Mortality
Part A: BIVV009 6.5 g Part A: BIVV009 7.5 g Part B: BIVV009 6.5 g Part B: BIVV009 7.5 g
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/17 (0.00%)      1/7 (14.29%)      2/16 (12.50%)      0/6 (0.00%)    
Hide Serious Adverse Events
Part A: BIVV009 6.5 g Part A: BIVV009 7.5 g Part B: BIVV009 6.5 g Part B: BIVV009 7.5 g
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/17 (23.53%)      3/7 (42.86%)      10/16 (62.50%)      2/6 (33.33%)    
Blood and lymphatic system disorders         
Anaemia  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Cold Type Haemolytic Anaemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Haemolytic Anaemia  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Cardiac disorders         
Angina Pectoris  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Coronary Artery Stenosis  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Stress Cardiomyopathy  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Eye disorders         
Iridocyclitis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Retinal Detachment  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  2
Uveitis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Vitreous Haemorrhage  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 1/6 (16.67%)  1
Gastrointestinal disorders         
Abdominal Pain Upper  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Gastrointestinal Haemorrhage  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Haemorrhoids  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Inguinal Hernia  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
General disorders         
Inflammation  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Non-Cardiac Chest Pain  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Hepatobiliary disorders         
Biliary Colic  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Cholecystitis Acute  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Cholelithiasis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Infections and infestations         
Appendicitis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Asymptomatic Covid-19  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Covid-19 Pneumonia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Erysipelas  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Escherichia Sepsis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Herpes Zoster  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Pneumococcal Sepsis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Pneumonia Klebsiella  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Respiratory Tract Infection  1  1/17 (5.88%)  2 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Streptococcal Sepsis  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Urinary Tract Infection Bacterial  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  2 0/6 (0.00%)  0
Urosepsis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Viral Infection  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Wound Infection Staphylococcal  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Injury, poisoning and procedural complications         
Femoral Neck Fracture  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Hepatic Cancer  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Meningioma  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Renal Cell Carcinoma  1  1/17 (5.88%)  1 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Tubular Breast Carcinoma  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Nervous system disorders         
Parkinsonism  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Transient Global Amnesia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Renal and urinary disorders         
Urinary Retention  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Vascular disorders         
Cyanosis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 2/16 (12.50%)  3 0/6 (0.00%)  0
Peripheral Artery Thrombosis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Peripheral Vascular Disorder  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  2 0/6 (0.00%)  0
1
Term from vocabulary, MedDRA 24.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A: BIVV009 6.5 g Part A: BIVV009 7.5 g Part B: BIVV009 6.5 g Part B: BIVV009 7.5 g
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/17 (88.24%)      6/7 (85.71%)      16/16 (100.00%)      6/6 (100.00%)    
Blood and lymphatic system disorders         
Anaemia  1  0/17 (0.00%)  0 1/7 (14.29%)  3 5/16 (31.25%)  11 2/6 (33.33%)  2
Cold Type Haemolytic Anaemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 2/16 (12.50%)  2 0/6 (0.00%)  0
Haemolysis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 1/6 (16.67%)  3
Haemolytic Anaemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Increased Tendency To Bruise  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Leukopenia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Monoclonal B-Cell Lymphocytosis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Thrombocytopenia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Cardiac disorders         
Aortic Valve Incompetence  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Aortic Valve Sclerosis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Aortic Valve Stenosis  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Atrial Fibrillation  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Atrioventricular Block First Degree  1  0/17 (0.00%)  0 0/7 (0.00%)  0 2/16 (12.50%)  2 0/6 (0.00%)  0
Cardiac Failure  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Coronary Artery Disease  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Mitral Valve Incompetence  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Sinus Bradycardia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Stress Cardiomyopathy  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Supraventricular Extrasystoles  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Tricuspid Valve Incompetence  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Ventricular Extrasystoles  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Ear and labyrinth disorders         
Meniere's Disease  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  2
Tinnitus  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Vertigo  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Eye disorders         
Cataract  1  0/17 (0.00%)  0 0/7 (0.00%)  0 2/16 (12.50%)  2 0/6 (0.00%)  0
Dry Eye  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Macular Degeneration  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Ocular Discomfort  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Photopsia  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Visual Field Defect  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Visual Impairment  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Gastrointestinal disorders         
Abdominal Distension  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Abdominal Pain  1  0/17 (0.00%)  0 1/7 (14.29%)  1 1/16 (6.25%)  1 0/6 (0.00%)  0
Abdominal Pain Upper  1  1/17 (5.88%)  1 1/7 (14.29%)  1 2/16 (12.50%)  3 1/6 (16.67%)  8
Abdominal Tenderness  1  1/17 (5.88%)  2 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Ascites  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Constipation  1  1/17 (5.88%)  1 0/7 (0.00%)  0 3/16 (18.75%)  3 1/6 (16.67%)  1
Dental Caries  1  1/17 (5.88%)  1 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Diarrhoea  1  1/17 (5.88%)  1 1/7 (14.29%)  1 2/16 (12.50%)  4 3/6 (50.00%)  4
Dyspepsia  1  1/17 (5.88%)  1 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Dysphagia  1  1/17 (5.88%)  1 0/7 (0.00%)  0 2/16 (12.50%)  3 0/6 (0.00%)  0
Gastritis  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Gastritis Erosive  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Gastrooesophageal Reflux Disease  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Haemorrhoidal Haemorrhage  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Haemorrhoids  1  2/17 (11.76%)  2 0/7 (0.00%)  0 1/16 (6.25%)  2 0/6 (0.00%)  0
Nausea  1  1/17 (5.88%)  1 0/7 (0.00%)  0 3/16 (18.75%)  3 2/6 (33.33%)  5
Oral Mucosal Blistering  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Periodontal Disease  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Stomatitis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Vomiting  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
General disorders         
Asthenia  1  1/17 (5.88%)  1 0/7 (0.00%)  0 1/16 (6.25%)  4 1/6 (16.67%)  1
Catheter Site Haematoma  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Chest Discomfort  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Device Related Thrombosis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Drug Intolerance  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Facial Pain  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Fatigue  1  1/17 (5.88%)  1 0/7 (0.00%)  0 3/16 (18.75%)  3 3/6 (50.00%)  5
Feeling Cold  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Influenza Like Illness  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Malaise  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 1/6 (16.67%)  1
Mucosal Inflammation  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Non-Cardiac Chest Pain  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 1/6 (16.67%)  1
Oedema Peripheral  1  1/17 (5.88%)  1 1/7 (14.29%)  1 2/16 (12.50%)  2 1/6 (16.67%)  2
Peripheral Swelling  1  1/17 (5.88%)  2 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Pyrexia  1  0/17 (0.00%)  0 1/7 (14.29%)  1 3/16 (18.75%)  4 2/6 (33.33%)  4
Temperature Intolerance  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Hepatobiliary disorders         
Biliary Colic  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Cholelithiasis  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Immune system disorders         
Allergy To Arthropod Bite  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Autoinflammatory Disease  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Seasonal Allergy  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Infections and infestations         
Abdominal Infection  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Asymptomatic Covid-19  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Bacteriuria  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Bronchitis  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 1/6 (16.67%)  2
Cystitis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 2/16 (12.50%)  7 1/6 (16.67%)  1
Cystitis Bacterial  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Escherichia Urinary Tract Infection  1  0/17 (0.00%)  0 0/7 (0.00%)  0 2/16 (12.50%)  2 1/6 (16.67%)  2
Eye Infection  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Fungal Skin Infection  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Gastroenteritis  1  2/17 (11.76%)  2 0/7 (0.00%)  0 1/16 (6.25%)  3 0/6 (0.00%)  0
Herpes Simplex Viraemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Infection  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Nasopharyngitis  1  2/17 (11.76%)  2 0/7 (0.00%)  0 4/16 (25.00%)  6 0/6 (0.00%)  0
Oral Herpes  1  1/17 (5.88%)  2 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Otitis Externa  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Otitis Externa Bacterial  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Pneumonia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Rash Pustular  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Respiratory Tract Infection Viral  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Root Canal Infection  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Skin Candida  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Skin Infection  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Tinea Pedis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  3 0/6 (0.00%)  0
Tooth Infection  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  2 0/6 (0.00%)  0
Upper Respiratory Tract Infection  1  2/17 (11.76%)  4 0/7 (0.00%)  0 1/16 (6.25%)  1 1/6 (16.67%)  2
Urinary Tract Infection  1  1/17 (5.88%)  1 0/7 (0.00%)  0 3/16 (18.75%)  13 2/6 (33.33%)  6
Urinary Tract Infection Bacterial  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 1/6 (16.67%)  1
Viral Infection  1  0/17 (0.00%)  0 1/7 (14.29%)  1 1/16 (6.25%)  2 0/6 (0.00%)  0
Viral Upper Respiratory Tract Infection  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Injury, poisoning and procedural complications         
Ankle Fracture  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Arthropod Bite  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Back Injury  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Bone Contusion  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Concussion  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Contusion  1  0/17 (0.00%)  0 1/7 (14.29%)  1 1/16 (6.25%)  1 0/6 (0.00%)  0
Exposure To Extreme Temperature  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Eye Contusion  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Fall  1  1/17 (5.88%)  3 1/7 (14.29%)  1 1/16 (6.25%)  1 1/6 (16.67%)  1
Hand Fracture  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Infusion Related Reaction  1  1/17 (5.88%)  1 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Joint Injury  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Limb Injury  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Procedural Pain  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Road Traffic Accident  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Skin Abrasion  1  1/17 (5.88%)  2 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Spinal Column Injury  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Stress Fracture  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Tendon Rupture  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Investigations         
Alanine Aminotransferase Increased  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Blood Creatinine Increased  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Blood Immunoglobulin G Decreased  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Blood Pressure Increased  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
C-Reactive Protein Increased  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Chest X-Ray Abnormal  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Computerised Tomogram Head Abnormal  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Serum Ferritin Decreased  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Weight Increased  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Metabolism and nutrition disorders         
Cachexia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Decreased Appetite  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Gout  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Hypercholesterolaemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Hypertriglyceridaemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 2/16 (12.50%)  2 0/6 (0.00%)  0
Hypoalbuminaemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Hypocalcaemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Hypokalaemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Hyponatraemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Hypophosphataemia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Iron Deficiency  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Magnesium Deficiency  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Malnutrition  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Vitamin B12 Deficiency  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia  1  1/17 (5.88%)  1 0/7 (0.00%)  0 2/16 (12.50%)  2 2/6 (33.33%)  3
Back Pain  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  2
Coccydynia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Intervertebral Disc Calcification  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Muscle Spasms  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Myalgia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Neck Pain  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Osteoarthritis  1  1/17 (5.88%)  1 0/7 (0.00%)  0 2/16 (12.50%)  3 0/6 (0.00%)  0
Osteoporosis  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Pain In Extremity  1  0/17 (0.00%)  0 0/7 (0.00%)  0 2/16 (12.50%)  3 0/6 (0.00%)  0
Rotator Cuff Syndrome  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Systemic Scleroderma  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Temporomandibular Joint Syndrome  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Tendonitis  1  0/17 (0.00%)  0 1/7 (14.29%)  2 0/16 (0.00%)  0 1/6 (16.67%)  1
Trigger Finger  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Basal Cell Carcinoma  1  1/17 (5.88%)  1 1/7 (14.29%)  1 1/16 (6.25%)  1 0/6 (0.00%)  0
Bowen's Disease  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Myelodysplastic Syndrome  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Seborrhoeic Keratosis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Nervous system disorders         
Brain Oedema  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Carotid Artery Stenosis  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Cerebrovascular Disorder  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Dizziness  1  0/17 (0.00%)  0 0/7 (0.00%)  0 3/16 (18.75%)  3 1/6 (16.67%)  1
Dizziness Postural  1  0/17 (0.00%)  0 0/7 (0.00%)  0 2/16 (12.50%)  2 0/6 (0.00%)  0
Headache  1  1/17 (5.88%)  1 1/7 (14.29%)  1 2/16 (12.50%)  2 2/6 (33.33%)  3
Multiple Sclerosis Relapse  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Paraesthesia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 2/16 (12.50%)  2 0/6 (0.00%)  0
Parkinsonism  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Seizure  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Syncope  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Psychiatric disorders         
Adjustment Disorder  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Anxiety Disorder  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Confusional State  1  1/17 (5.88%)  1 1/7 (14.29%)  1 1/16 (6.25%)  3 0/6 (0.00%)  0
Insomnia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Mental Fatigue  1  1/17 (5.88%)  1 0/7 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0
Renal and urinary disorders         
Acute Kidney Injury  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Chronic Kidney Disease  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Dysuria  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Haemoglobinuria  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Renal Failure  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Renal Impairment  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Reproductive system and breast disorders         
Benign Prostatic Hyperplasia  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Intermenstrual Bleeding  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Ovarian Cyst  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0
Pelvic Pain  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Respiratory, thoracic and mediastinal disorders         
Bronchial Irritation  1  0/17 (0.00%)  0 1/7 (14.29%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0
Chronic Obstructive Pulmonary Disease  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1
Cough  1  1/17 (5.88%)  1 1/7 (14.29%)  1 2/16 (12.50%)  2 0/6 (0.00%)  0
Dyspnoea  1  0/17 (0.00%)  0 0/7 (0.00%)  0 1/16 (6.25%)  1 2/6 (33.33%)  2
Dyspnoea Exertional  1  0/17 (0.00%)  0 0/7 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  2
Epistaxis  1