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ATX-MS-1467 in Multiple Sclerosis

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: NCT01973491
Recruitment Status : Completed
First Posted : October 31, 2013
Results First Posted : April 13, 2017
Last Update Posted : July 2, 2017
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Intervention Drug: ATX-MS-1467
Enrollment 37
Recruitment Details  
Pre-assignment Details 37 subjects were enrolled in the study and entered the 8-week Baseline Control Period. Following completion of the Baseline Control Period, eligible subjects entered the 4-week Titration Period followed by a 16-week Treatment Period.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Period Title: Baseline Control Period (8 Weeks)
Started 37
Completed 19
Not Completed 18
Reason Not Completed
Did not meet Eligibility Criteria             17
Withdrawal by Subject             1
Period Title: Titration Period(4 Weeks)
Started 19
Completed 19
Not Completed 0
Period Title: Treatment Period (16 Weeks)
Started 19
Completed 18
Not Completed 1
Reason Not Completed
Adverse Event             1
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description Subjects received ATX-MS-1467 50 mcg, 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
The Safety (SAF) Analysis Set included all subjects who received at least 1 dose of investigational medicinal product (IMP).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants
27.1  (5.45)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
15
  78.9%
Male
4
  21.1%
1.Primary Outcome
Title Change From Baseline in the Average Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) Over On-treatment Scans
Hide Description T1 CELs were measured using Magnetic Resonance Imaging (MRI) scans. Baseline value was calculated as the average number of T1 CELs during the 3 visits in the Baseline Control Period (Weeks -8, -4 and 0) and On-treatment value was calculated as the average number of T1 CELs during the 3 visits in the treatment period (Weeks 12, 16 and 20). The change from baseline in average number of T1 CELs was reported.
Time Frame Baseline (Weeks -8, -4 and 0), Treatment Period (Weeks 12, 16 and 20)
Hide Outcome Measure Data
Hide Analysis Population Description
The modified intention-to-treat (mITT) analysis set included all enrolled subjects who received at least 1 dose of IMP and had 2 or more MRI scans during the Baseline Control Period and planned on-treatment visits (Weeks 12, 16, and 20) or end of treatment visit provided it occurred within 28 days of the last dose of IMP.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: lesions
Baseline 7.4  (7.62)
Change Over Treatment Period -2.4  (4.37)
2.Secondary Outcome
Title Total Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs)
Hide Description The number of T1 CELs were measured using MRI scans.
Time Frame Weeks 12, 16, 20, 24, 28 and 36
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set. Here, “Number Analyzed” signifies those subjects who were evaluable at the specified time point.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: lesions
Week 12 3.1  (3.92)
Week 16 4.6  (6.26)
Week 20 5.6  (9.55)
Week 24 4.9  (11.07)
Week 28 2.6  (3.28)
Week 36 2.2  (2.39)
3.Secondary Outcome
Title Change From Baseline in Total Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) at Weeks 12, 16, 20, 24, 28 and 36
Hide Description T1 CELs were measured using MRI scans. Baseline was calculated as the average number of T1 CELs during the 3 visits in the Baseline Control Period (Weeks -8, -4 and 0).
Time Frame Baseline (Weeks -8, -4 and 0), Weeks 12, 16, 20, 24, 28 and 36
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set. Here, “Number Analyzed” signifies those subjects who were evaluable at the specified time point.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: lesions
Change at Week 12 -3.0  (4.90)
Change at Week 16 -2.8  (5.20)
Change at Week 20 -1.6  (5.11)
Change at Week 24 -2.2  (7.10)
Change at Week 28 -4.2  (7.06)
Change at Week 36 -4.6  (6.73)
4.Secondary Outcome
Title Change From Baseline in Total Volume of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) at Weeks 12, 16, 20, 24, 28 and 36
Hide Description T1 CELs were measured using MRI scans. Baseline was calculated as the average number of T1 CELs during the 3 visits in the Baseline Control Period (Weeks -8, -4 and 0).
Time Frame Baseline (Weeks -8, -4, 0), Week 12, 16, 20, 24, 28 and 36
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set. Here, "Number Analyzed" signifies those subjects who were evaluable at the specified time point.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: milliliter
Baseline 0.838  (1.0151)
Change at Week 12 -0.321  (0.5618)
Change at Week 16 -0.316  (0.7184)
Change at Week 20 -0.225  (0.7845)
Change at Week 24 -0.333  (0.8622)
Change at Week 28 -0.454  (0.9403)
Change at Week 36 -0.579  (0.8807)
5.Secondary Outcome
Title Total Number of New or Newly Enlarging Time Constant 2 (T2) Lesions
Hide Description T2 lesions were measured using MRI scans.
Time Frame Weeks 12, 16, 20, 24, 28 and 36
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set. Here, "Number Analyzed" signifies those subjects who were evaluable at the specified time point.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: lesions
Week 12 14.7  (20.69)
Week 16 4.5  (6.16)
Week 20 5.4  (10.07)
Week 24 4.9  (8.27)
Week 28 2.6  (3.28)
Week 36 4.2  (3.68)
6.Secondary Outcome
Title Change From Week 0 in Total Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) at Weeks 12, 16, 20, 24, 28 and 36
Hide Description T1 CELs were measured using MRI scans.
Time Frame Week 0, 12, 16, 20, 24, 28 and 36
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set. Here, "Number of participants analyzed" signifies those subjects who were evaluable for this outcome measure and "Number Analyzed" signifies those subjects who were evaluable at the specified time point.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: lesions
Week 0 7.2  (6.71)
Change at Week 12 -3.4  (6.67)
Change at Week 16 -2.3  (7.03)
Change at Week 20 -0.9  (8.57)
Change at Week 24 -1.5  (10.87)
Change at Week 28 -3.1  (5.04)
Change at Week 36 -3.5  (4.40)
7.Secondary Outcome
Title Change From Week 0 in Total Volume of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) at Weeks 12, 16, 20, 24, 28 and 36
Hide Description T1 CELs were measured using MRI scans.
Time Frame Weeks 0, 12, 16, 20, 24, 28 and 36
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set. Here, “Number of participants analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those subjects who were evaluable at the specified time point.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: milliliter
Week 0 0.815  (0.8121)
Change at Week 12 -0.420  (0.7520)
Change at Week 16 -0.264  (0.7737)
Change at Week 20 -0.157  (0.9839)
Change at Week 24 -0.271  (1.4318)
Change at Week 28 -0.341  (0.4541)
Change at Week 36 -0.473  (0.5914)
8.Secondary Outcome
Title Mean Annualized Relapse Rate
Hide Description Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. These new or worsening symptoms should be noted by the subject and must be accompanied by at least one of the following: An increase of greater than or equal to (>=) 1 grade in >=2 functional scales of the Expanded Disability Status Scale (EDSS) or an increase of >=2 grades in 1 functional scale of the EDSS or an increase of >= 0.5 or an increase of >=1.0 in EDSS if the previous EDSS was 0. Annualized Relapse Rate was calculated as = 365.25 x (Number of relapses during Treatment Period) per (Number of days on treatment during Treatment Period).
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included subset of mITT analysis set who had relapse.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: relapse per year
2.60  (0.011)
9.Secondary Outcome
Title Time to First Relapse
Hide Description Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. These new or worsening symptoms should be noted by the subject and must be accompanied by at least one of the following: An increase of greater than or equal to (>=) 1 grade in >=2 functional scales of the Expanded Disability Status Scale (EDSS) or an increase of >=2 grades in 1 functional scale of the EDSS or an increase of >= 0.5 or an increase of >=1.0 in EDSS if the previous EDSS was 0. Time to first relapse was defined as the time in days from the date of first dose of study treatment to the date of first multiple sclerosis relapse.
Time Frame Baseline up to Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set included all enrolled subjects who received at least 1 dose of IMP and had 2 or more MRI scans during the Baseline Control Period and planned on-treatment visits (Weeks 12, 16, and 20) or end of treatment visit provided it occurred within 28 days of the last dose of IMP.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
[1]
Outcome was to be assessed as time to event analysis by Kaplan-Meier estimates. However, median and 95% CI were not estimable since very few subjects had relapse during the study.
10.Secondary Outcome
Title Change From Baseline in Total Expanded Disability Status Scale (EDSS) Score at Week 20
Hide Description EDSS is an ordinal scale in half-point increments that qualifies disability in subjects with Multiple Sclerosis. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as any other neurological findings due to Multiple Sclerosis. Total EDSS score ranges from 0 (normal neurological examination) to 10 (death due to MS). Baseline was defined as the last measurement taken prior to the first dose of study drug (Week 0).
Time Frame Baseline (Week 0) and Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set. Here, "Number Analyzed" signifies those subjects who were evaluable at the specified time point.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (Week 0) 2.32  (0.803)
Change at Week 20 -0.11  (0.916)
11.Secondary Outcome
Title Change From Baseline in Total Multiple Sclerosis Functional Composite (MSFC) Score at Week 20
Hide Description The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3). Baseline was defined as the last measurement taken prior to the first dose of study drug (Week 0).
Time Frame Baseline (Week 0) and Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT analysis set. Here, "Number Analyzed" signifies those subjects who were evaluable at the specified time point.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: Z-score
Baseline (Week 0) 0.001  (0.7215)
Change at Week 20 0.187  (0.4321)
12.Secondary Outcome
Title Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation
Hide Description An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the date of first dose and within 28 days after the date of last dose in the current study. TEAEs include both Serious TEAEs and non-serious TEAEs.
Time Frame Baseline up to Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
The SAF Analysis Set included all subjects who received at least 1 dose of IMP.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 19
Measure Type: Number
Unit of Measure: subjects
TEAEs 15
Serious TEAEs 0
TEAEs Leading to Death 0
TEAEs Leading to Discontinuation 1
13.Secondary Outcome
Title Number of Subjects Experiencing Injection Site Reactions (ISRs)
Hide Description Treatment-emergent ISRs were defined as any ISR with a start date on or after the date of first dose and within 7 days after the date of last dose in the current study. Injection site reactions were identified as erythema, induration, pruritus, nodules and/or cysts, ecchymosis, pain and local edema.
Time Frame Baseline up to Week 22
Hide Outcome Measure Data
Hide Analysis Population Description
The SAF Analysis Set included all subjects who received at least 1 dose of IMP.
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description:
Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Overall Number of Participants Analyzed 19
Measure Type: Number
Unit of Measure: subjects
7
Time Frame Baseline up to Week 25
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ATX-MS-1467
Hide Arm/Group Description Subjects received ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
All-Cause Mortality
ATX-MS-1467
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
ATX-MS-1467
Affected / at Risk (%)
Total   0/19 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
ATX-MS-1467
Affected / at Risk (%)
Total   15/19 (78.95%) 
Blood and lymphatic system disorders   
Eosinophilia * 1  1/19 (5.26%) 
Neutrophilia * 1  1/19 (5.26%) 
Gastrointestinal disorders   
Diarrhoea * 1  2/19 (10.53%) 
Constipation * 1  1/19 (5.26%) 
Enterocolitis * 1  1/19 (5.26%) 
Gastritis * 1  1/19 (5.26%) 
Nausea * 1  1/19 (5.26%) 
General disorders   
Injection site erythema * 1  5/19 (26.32%) 
Injection site induration * 1  2/19 (10.53%) 
Injection site pain * 1  2/19 (10.53%) 
Injection site pruritus * 1  2/19 (10.53%) 
Injection site haemorrhage * 1  1/19 (5.26%) 
Infections and infestations   
Nasopharyngitis * 1  3/19 (15.79%) 
Cervicitis * 1  1/19 (5.26%) 
Respiratory tract infection viral * 1  1/19 (5.26%) 
Vaginitis gardnerella * 1  1/19 (5.26%) 
Viral infection * 1  1/19 (5.26%) 
Viral upper respiratory tract infection * 1  1/19 (5.26%) 
Vulvovaginal candidiasis * 1  1/19 (5.26%) 
Vulvovaginal mycotic infection * 1  1/19 (5.26%) 
Investigations   
Lymphocyte count decreased * 1  2/19 (10.53%) 
Blood bilirubin increased * 1  1/19 (5.26%) 
Blood creatine phosphokinase increased * 1  1/19 (5.26%) 
Monocyte count decreased * 1  1/19 (5.26%) 
Monocyte percentage decreased * 1  1/19 (5.26%) 
Neutrophil count increased * 1  1/19 (5.26%) 
Reticulocyte count decreased * 1  1/19 (5.26%) 
Weight decreased * 1  1/19 (5.26%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  1/19 (5.26%) 
Musculoskeletal and connective tissue disorders   
Muscle spasms * 1  1/19 (5.26%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Fibroadenoma of breast * 1  1/19 (5.26%) 
Nervous system disorders   
Headache * 1  4/19 (21.05%) 
Skin and subcutaneous tissue disorders   
Diffuse alopecia * 1  2/19 (10.53%) 
Alopecia * 1  1/19 (5.26%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merck KGaA Communication Center
Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
EMail: service@merckgroup.com
Layout table for additonal information
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT01973491    
Other Study ID Numbers: 200166-001
2013-002916-28 ( EudraCT Number )
First Submitted: October 23, 2013
First Posted: October 31, 2013
Results First Submitted: March 1, 2017
Results First Posted: April 13, 2017
Last Update Posted: July 2, 2017