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A Phase 2 Study of Atacicept in Subjects With Relapsing Multiple Sclerosis (ATAMS) (ATAMS)

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: NCT00642902
Recruitment Status : Terminated (Sponsor voluntarily decided to terminate trial due to increased MS disease activity in atacicept arms as compared to placebo during a routine IDMC review.)
First Posted : March 25, 2008
Results First Posted : May 24, 2016
Last Update Posted : May 24, 2016
Sponsor:
Information provided by (Responsible Party):
EMD Serono

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Relapsing Multiple Sclerosis
Interventions Drug: Atacicept
Drug: Placebo matched to atacicept
Enrollment 255
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Atacicept 25 mg Atacicept 75 mg Atacicept 150 mg
Hide Arm/Group Description Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks. Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks. Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks. Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Period Title: Overall Study
Started 63 63 64 65
Treated 63 63 63 65
Completed 23 21 21 25
Not Completed 40 42 43 40
Reason Not Completed
Adverse Event             0             1             3             1
Lost to Follow-up             1             1             0             0
Lack of Efficacy             0             3             3             0
Death             1             0             0             0
Premature termination of clinical trial             37             32             35             35
Randomized, but not treated             0             0             1             0
Other             1             5             1             4
Arm/Group Title Placebo Atacicept 25 mg Atacicept 75 mg Atacicept 150 mg Total
Hide Arm/Group Description Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks. Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks. Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks. Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks. Total of all reporting groups
Overall Number of Baseline Participants 63 63 64 65 255
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 63 participants 63 participants 64 participants 65 participants 255 participants
37.7  (10.5) 37.5  (8.5) 38.0  (10.1) 37.5  (10.5) 37.7  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 63 participants 64 participants 65 participants 255 participants
Female
45
  71.4%
34
  54.0%
44
  68.8%
46
  70.8%
169
  66.3%
Male
18
  28.6%
29
  46.0%
20
  31.3%
19
  29.2%
86
  33.7%
1.Primary Outcome
Title Mean Number of Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions Per Participant Per Scan
Hide Description Analysis of T1 Gd-enhancing lesions was done using magnetic resonance imaging (MRI) scans. Only post-baseline scans were included in the calculation of this endpoint (excluding the Study Day 1 scan which had been conducted before first dosing).
Time Frame Weeks 12 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title Placebo Atacicept 25 mg Atacicept 75 mg Atacicept 150 mg
Hide Arm/Group Description:
Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Overall Number of Participants Analyzed 63 63 64 65
Mean (95% Confidence Interval)
Unit of Measure: lesions/participant/scan
3.07
(1.40 to 6.77)
2.26
(0.97 to 5.27)
2.30
(1.08 to 4.92)
2.49
(1.18 to 5.27)
2.Secondary Outcome
Title Number of New T1 Gd-enhancing Lesions Per Participant
Hide Description Analysis of new T1 Gd-enhancing lesions was done using MRI scans.
Time Frame Weeks 12, 24, 36
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants. 'n' signifies participants who were evaluable for this measure at given time points for each group, respectively.
Arm/Group Title Placebo Atacicept 25 mg Atacicept 75 mg Atacicept 150 mg
Hide Arm/Group Description:
Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Overall Number of Participants Analyzed 63 63 64 65
Mean (Standard Deviation)
Unit of Measure: lesions/participant
Week 12 (n=55, 45, 50, 55) 2.55  (7.95) 2.71  (7.67) 3.20  (6.41) 2.96  (6.58)
Week 24 (n=41, 34, 37, 41) 0.83  (1.70) 1.50  (2.79) 1.54  (2.96) 1.54  (2.94)
Week 36 (n=23, 22, 24, 26) 0.43  (0.90) 1.68  (5.09) 1.38  (1.93) 0.54  (1.07)
3.Secondary Outcome
Title Percentage of Participants Free From Relapses
Hide Description A relapse was defined as the fulfillment of all the following criteria: a) neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both i) neurological abnormality separated by at least 30 days from onset of a preceding clinical event, and ii) neurological abnormality lasting for at least 24 hours; b) absence of fever or known infection (fever with temperature [axillary, orally, or intrauriculary] greater than (>) 37.5 degrees Celsius or 99.5 degrees Fahrenheit); and c) objective neurological impairment, correlating with the participant’s reported symptoms, defined as either i) increase in at least 1 of the functional systems of the Expanded Disability Status Scale (EDSS), or ii) increase of the total EDSS score. Percentage of participants free from relapses during 36-week treatment period was reported.
Time Frame Baseline up to Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title Placebo Atacicept 25 mg Atacicept 75 mg Atacicept 150 mg
Hide Arm/Group Description:
Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Overall Number of Participants Analyzed 63 63 64 65
Measure Type: Number
Unit of Measure: percentage of participants
81.0 69.8 71.9 61.5
4.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Hide Description An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An 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. Treatment-emergent are events between first dose of study drug up to 12 weeks after the last dose of the study drug that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with TEAEs included subjects with both non serious and serious TEAEs.
Time Frame From the first dose of study drug administration up to 12 weeks after the last dose of the study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of treatment (either active or placebo).
Arm/Group Title Placebo Atacicept 25 mg Atacicept 75 mg Atacicept 150 mg
Hide Arm/Group Description:
Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks.
Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
Overall Number of Participants Analyzed 63 63 63 65
Measure Type: Number
Unit of Measure: participants
TEAEs 46 40 39 52
Serious TEAEs 1 3 3 1
Time Frame From the first dose of study drug administration up to 12 weeks after the last dose of the study drug
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Atacicept 25 mg Atacicept 75 mg Atacicept 150 mg
Hide Arm/Group Description Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks. Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks. Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks. Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.
All-Cause Mortality
Placebo Atacicept 25 mg Atacicept 75 mg Atacicept 150 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Atacicept 25 mg Atacicept 75 mg Atacicept 150 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/63 (1.59%)   3/63 (4.76%)   3/63 (4.76%)   1/65 (1.54%) 
Cardiac disorders         
Myocardial infarction * 1  1/63 (1.59%)  0/63 (0.00%)  0/63 (0.00%)  0/65 (0.00%) 
Endocrine disorders         
Hypothyroidism * 1  0/63 (0.00%)  0/63 (0.00%)  1/63 (1.59%)  0/65 (0.00%) 
General disorders         
Asthenia * 1  0/63 (0.00%)  0/63 (0.00%)  1/63 (1.59%)  0/65 (0.00%) 
Infections and infestations         
Lung abscess * 1  0/63 (0.00%)  0/63 (0.00%)  1/63 (1.59%)  0/65 (0.00%) 
Pyothorax * 1  0/63 (0.00%)  0/63 (0.00%)  1/63 (1.59%)  0/65 (0.00%) 
Pneumonia * 1  0/63 (0.00%)  0/63 (0.00%)  1/63 (1.59%)  0/65 (0.00%) 
Otitis media acute * 1  0/63 (0.00%)  0/63 (0.00%)  0/63 (0.00%)  1/65 (1.54%) 
Injury, poisoning and procedural complications         
Hip fracture * 1  0/63 (0.00%)  1/63 (1.59%)  0/63 (0.00%)  0/65 (0.00%) 
Humerus fracture * 1  0/63 (0.00%)  1/63 (1.59%)  0/63 (0.00%)  0/65 (0.00%) 
Investigations         
Body temperature decreased * 1  0/63 (0.00%)  0/63 (0.00%)  1/63 (1.59%)  0/65 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Parathyroid tumour benign * 1  0/63 (0.00%)  0/63 (0.00%)  1/63 (1.59%)  0/65 (0.00%) 
Psychiatric disorders         
Acute psychosis * 1  0/63 (0.00%)  1/63 (1.59%)  0/63 (0.00%)  0/65 (0.00%) 
Anxiety * 1  0/63 (0.00%)  0/63 (0.00%)  1/63 (1.59%)  0/65 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Pleurisy * 1  0/63 (0.00%)  0/63 (0.00%)  1/63 (1.59%)  0/65 (0.00%) 
Bronchopleural fistula * 1  0/63 (0.00%)  0/63 (0.00%)  1/63 (1.59%)  0/65 (0.00%) 
Pneumothorax * 1  0/63 (0.00%)  0/63 (0.00%)  2/63 (3.17%)  0/65 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Atacicept 25 mg Atacicept 75 mg Atacicept 150 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   33/63 (52.38%)   30/63 (47.62%)   34/63 (53.97%)   44/65 (67.69%) 
Gastrointestinal disorders         
Diarrhoea * 1  1/63 (1.59%)  1/63 (1.59%)  3/63 (4.76%)  5/65 (7.69%) 
Nausea * 1  2/63 (3.17%)  3/63 (4.76%)  1/63 (1.59%)  4/65 (6.15%) 
General disorders         
Injection site reaction * 1  8/63 (12.70%)  19/63 (30.16%)  24/63 (38.10%)  32/65 (49.23%) 
Fatigue * 1  0/63 (0.00%)  1/63 (1.59%)  3/63 (4.76%)  4/65 (6.15%) 
Injection site pain * 1  2/63 (3.17%)  2/63 (3.17%)  0/63 (0.00%)  4/65 (6.15%) 
Infections and infestations         
Nasopharyngitis * 1  6/63 (9.52%)  4/63 (6.35%)  7/63 (11.11%)  13/65 (20.00%) 
Urinary tract infection * 1  3/63 (4.76%)  4/63 (6.35%)  7/63 (11.11%)  3/65 (4.62%) 
Upper respiratory tract infection * 1  3/63 (4.76%)  1/63 (1.59%)  4/63 (6.35%)  8/65 (12.31%) 
Bronchitis * 1  1/63 (1.59%)  2/63 (3.17%)  1/63 (1.59%)  5/65 (7.69%) 
Influenza * 1  5/63 (7.94%)  1/63 (1.59%)  1/63 (1.59%)  2/65 (3.08%) 
Musculoskeletal and connective tissue disorders         
Back pain * 1  4/63 (6.35%)  0/63 (0.00%)  3/63 (4.76%)  3/65 (4.62%) 
Pain in extremity * 1  4/63 (6.35%)  3/63 (4.76%)  1/63 (1.59%)  1/65 (1.54%) 
Nervous system disorders         
Headache * 1  11/63 (17.46%)  8/63 (12.70%)  3/63 (4.76%)  6/65 (9.23%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Sponsor voluntarily decided to prematurely terminate this trial due to an increase in multiple sclerosis (MS) disease activity observed in atacicept arms as compared to placebo during a routine independent data monitoring committee (IDMC) review.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Prior to publishing results, Institution and Principal Investigator (PI) must first provide Sponsor with a copy of proposed publication for review at least 30 days prior to submission. If Institution and PI do not agree to modification, they shall so notify Sponsor and postpone submission for additional 60 days to allow Sponsor to seek legal remedies or file patent applications. There is a need for coordinated approach to any publication of results from sites for any multi-site study.
Results Point of Contact
Name/Title: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00642902     History of Changes
Other Study ID Numbers: 28063
First Submitted: March 21, 2008
First Posted: March 25, 2008
Results First Submitted: April 15, 2016
Results First Posted: May 24, 2016
Last Update Posted: May 24, 2016