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A Phase IV Study of Rebif ® 44mcg Administered Three Times Per Week by Subcutaneous Injection Compared With no Treatment in the Therapy of Relapsing Multiple Sclerosis After Mitoxantrone (REMAIN)

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ClinicalTrials.gov Identifier: NCT01142466
Recruitment Status : Completed
First Posted : June 11, 2010
Results First Posted : June 10, 2011
Last Update Posted : February 27, 2014
Sponsor:
Collaborator:
Gesellschaft für Therapieforschung mbH
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Sclerosis, Relapsing-Remitting
Intervention Drug: Interferon beta-1a (Rebif)
Enrollment 30
Recruitment Details Participants were enrolled at multiple centres in Germany.
Pre-assignment Details A total of 36 participants were screened and 30 were randomized to the study treatment. 6 participants were not treated (4 participants were screening failures and 2 participants did not meet the inclusion and exclusion criteria).
Arm/Group Title Rebif 44 Mcg No Treatment
Hide Arm/Group Description Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week. Participants in this group did not receive any treatment.
Period Title: Overall Study
Started 15 15
Completed 12 13
Not Completed 3 2
Reason Not Completed
Adverse Event             2             1
Withdrawal by Subject             1             1
Arm/Group Title Rebif 44 Mcg No Treatment Total
Hide Arm/Group Description Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week. Participants in this group did not receive any treatment. Total of all reporting groups
Overall Number of Baseline Participants 14 15 29
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 15 participants 29 participants
43.8  (7.0) 44.3  (6.5) 44.1  (6.6)
[1]
Measure Description: One participant of the safety population discontinued the study after 25 days due to an adverse event (AE) without providing any baseline data and hence was not included in this analysis.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 15 participants 29 participants
Female
11
  78.6%
9
  60.0%
20
  69.0%
Male
3
  21.4%
6
  40.0%
9
  31.0%
[1]
Measure Description: One participant of the safety population discontinued the study after 25 days due to an adverse event (AE) without providing any baseline data and hence was not included in this analysis.
Expanded Disability Status Scale (EDSS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on Scale
Number Analyzed 14 participants 15 participants 29 participants
4.1  (1.4) 4.3  (1.0) 4.2  (1.2)
[1]
Measure Description: EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. One participant of the safety population discontinued the study after 25 days due to an adverse event (AE) without providing any baseline data and hence was not included in this analysis.
1.Primary Outcome
Title Time From Baseline to First Multiple Sclerosis Relapse (in Weeks)
Hide Description A qualifying relapse was defined as a new or worsening neurological symptom, in the absence of fever, lasting for >= 48 hours, and accompanied by an objective change in the relevant (i.e. symptomatic) Kurtzke Functional Systems (KFS).
Time Frame Baseline through Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants who received at least 1 treatment dose (only for Rebif group) and had at least 1 post-baseline efficacy endpoint assessment. Time to relapse was documented for participants who had at least 1 relapse during the study period.
Arm/Group Title Rebif 44 Mcg No Treatment
Hide Arm/Group Description:
Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.
Participants in this group did not receive any treatment.
Overall Number of Participants Analyzed 4 8
Mean (Standard Deviation)
Unit of Measure: weeks
35.5  (40.8) 40.9  (28.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rebif 44 Mcg, No Treatment
Comments Two-sided log rank test with alpha equal to 0.05 was used as the appropriate nonparametric method to compare the two groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1384
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Number of Relapse-free Participants
Hide Description A qualifying relapse was defined as a new or worsening neurological symptom, in the absence of fever, lasting for >= 48 hours, and accompanied by an objective change in the relevant (i.e. symptomatic) Kurtzke Functional Systems (KFS).
Time Frame Baseline through Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least 1 treatment dose (only for Rebif group) and had at least 1 post-baseline efficacy endpoint assessment.
Arm/Group Title Rebif 44 Mcg No Treatment
Hide Arm/Group Description:
Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.
Participants in this group did not receive any treatment.
Overall Number of Participants Analyzed 14 15
Measure Type: Number
Unit of Measure: participants
10 7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rebif 44 Mcg, No Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2635
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Absolute Changes in the Number of T1 Lesions From Baseline to Week 24, 48, 72 and 96
Hide Description Analysis of T1 lesions was done using magnetic resonance imaging (MRI) scans.
Time Frame Baseline to Week 24, 48, 72, and 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least 1 treatment dose (only for Rebif group) and had at least 1 post-baseline efficacy endpoint assessment. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the time point for each group respectively.
Arm/Group Title Rebif 44 Mcg No Treatment
Hide Arm/Group Description:
Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.
Participants in this group did not receive any treatment.
Overall Number of Participants Analyzed 14 15
Mean (Standard Deviation)
Unit of Measure: T1 lesions
Week 24 (n= 13,15) -0.5  (4.4) -0.9  (8.9)
Week 48 (n= 13,13) -0.8  (4.3) 1.5  (11.2)
Week 72 (n= 12,12) -0.8  (9.2) -3.6  (12.0)
Week 96 (n= 12,12) -1.8  (5.5) -2.3  (11.6)
4.Secondary Outcome
Title Absolute Changes in the Number of T1-Gadolinium (T1-Gd) Lesions From Baseline to Week 24, 48, 72 and 96
Hide Description Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans.
Time Frame Baseline to Week 24, 48, 72, and 96
Hide Outcome Measure Data
Hide Analysis Population Description
The data was not evaluated due to the small sample size available for this parameter.
Arm/Group Title Rebif 44 Mcg No Treatment
Hide Arm/Group Description:
Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.
Participants in this group did not receive any treatment.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Absolute Changes in the Number of T2 Lesions From Baseline to Week 24, 48, 72 and 96
Hide Description Analysis of T2 lesions was done using magnetic resonance imaging (MRI) scans.
Time Frame Baseline to Week 24, 48, 72, and 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least 1 treatment dose (only for Rebif group) and had at least 1 post-baseline efficacy endpoint assessment. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the time point for each group respectively.
Arm/Group Title Rebif 44 Mcg No Treatment
Hide Arm/Group Description:
Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.
Participants in this group did not receive any treatment.
Overall Number of Participants Analyzed 14 15
Mean (Standard Deviation)
Unit of Measure: T2 lesions
Week 24 (n= 13,15) -1.2  (4.0) 1.0  (6.0)
Week 48 (n= 13,13) 0.2  (8.5) 3.2  (10.1)
Week 72 (n= 12,13) -1.8  (3.3) 3.1  (14.1)
Week 96 (n= 12,12) -3.1  (7.6) 2.1  (15.4)
6.Secondary Outcome
Title Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96
Hide Description EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. EDSS progression was defined as increase by at least 1 point if last value of EDSS was equal to 5.5, and by at least 0.5 points if last EDSS was more than 5.5.
Time Frame Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who received at least 1 treatment dose (only for Rebif group) and had at least 1 post-baseline efficacy endpoint assessment. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the time point for each group respectively.
Arm/Group Title Rebif 44 Mcg No Treatment
Hide Arm/Group Description:
Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.
Participants in this group did not receive any treatment.
Overall Number of Participants Analyzed 14 15
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Week 12 (n= 14, 15) -0.1  (0.5) -0.1  (0.4)
Week 24 (n= 14, 15) 0.3  (0.6) 0.1  (0.4)
Week 36 (n= 13, 14) 0.5  (0.8) -0.2  (0.4)
Week 48 (n= 14, 14) 0.5  (0.8) 0.2  (0.7)
Week 60 (n= 10, 11) 0.4  (0.8) 0.0  (1.0)
Week 72 (n= 12, 13) 0.3  (0.6) 0.2  (0.9)
Week 84 (n= 12, 13) 0.5  (0.9) 0.2  (0.9)
Week 96 (n= 12, 13) 0.1  (0.8) 0.3  (1.0)
7.Secondary Outcome
Title Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Hide Description AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.
Time Frame Baseline to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants all randomized participants of the active treatment group who received at least 1 injection and all randomized participants of the 'No Treatment' group, provided that any post-baseline data was available.
Arm/Group Title Rebif 44 Mcg No Treatment
Hide Arm/Group Description:
Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.
Participants in this group did not receive any treatment.
Overall Number of Participants Analyzed 15 15
Measure Type: Number
Unit of Measure: participants
Adverse Events 15 14
Serious Adverse Events 5 1
Time Frame Baseline to Week 96 or premature termination or unscheduled visit.
Adverse Event Reporting Description An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
 
Arm/Group Title Rebif 44 Mcg No Treatment
Hide Arm/Group Description Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week. Participants in this group did not receive any treatment.
All-Cause Mortality
Rebif 44 Mcg No Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Rebif 44 Mcg No Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/15 (33.33%)      1/15 (6.67%)    
Eye disorders     
Angle Closure Glaucoma * 1  1/15 (6.67%)  1 0/15 (0.00%)  0
Gastrointestinal disorders     
Haemorrhoid Operation * 1  1/15 (6.67%)  1 0/15 (0.00%)  0
Gastroenteritis salmonella * 1  1/15 (6.67%)  1 0/15 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis chronic * 1  1/15 (6.67%)  1 0/15 (0.00%)  0
Cholelithiasis * 1  1/15 (6.67%)  1 0/15 (0.00%)  0
Nervous system disorders     
Convulsion * 1  1/15 (6.67%)  1 0/15 (0.00%)  0
Status Epilepticus * 1  1/15 (6.67%)  1 0/15 (0.00%)  0
Depression * 1  0/15 (0.00%)  0 1/15 (6.67%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rebif 44 Mcg No Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/15 (100.00%)      14/15 (93.33%)    
Ear and labyrinth disorders     
Vertigo * 1  1/15 (6.67%)  1 1/15 (6.67%)  1
Gastrointestinal disorders     
Diarrhoea * 1  0/15 (0.00%)  0 3/15 (20.00%)  4
Vomiting * 1  1/15 (6.67%)  2 2/15 (13.33%)  2
Nausea * 1  0/15 (0.00%)  0 2/15 (13.33%)  2
Oral herpes * 1  1/15 (6.67%)  1 1/15 (6.67%)  1
General disorders     
Influenza like illness * 1  3/15 (20.00%)  3 2/15 (13.33%)  2
Injection site erythema * 1  2/15 (13.33%)  4 1/15 (6.67%)  1
Fatigue * 1  1/15 (6.67%)  1 1/15 (6.67%)  1
Injection site pain * 1  2/15 (13.33%)  2 0/15 (0.00%)  0
Pyrexia * 1  2/15 (13.33%)  3 0/15 (0.00%)  0
Infections and infestations     
Nasopharyngitis * 1  6/15 (40.00%)  9 4/15 (26.67%)  5
Infection * 1  3/15 (20.00%)  5 0/15 (0.00%)  0
Rhinitis * 1  3/15 (20.00%)  5 0/15 (0.00%)  0
Bronchitis * 1  0/15 (0.00%)  0 2/15 (13.33%)  2
Skin reaction * 1  2/15 (13.33%)  2 0/15 (0.00%)  0
Injury, poisoning and procedural complications     
Fall * 1  2/15 (13.33%)  2 1/15 (6.67%)  1
Wound * 1  1/15 (6.67%)  1 1/15 (6.67%)  1
Investigations     
Blood bilirubin increased * 1  1/15 (6.67%)  1 1/15 (6.67%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  2/15 (13.33%)  2 1/15 (6.67%)  1
Back Pain * 1  2/15 (13.33%)  2 1/15 (6.67%)  1
Pain in extremity * 1  1/15 (6.67%)  1 1/15 (6.67%)  1
Nervous system disorders     
Headache * 1  4/15 (26.67%)  4 2/15 (13.33%)  3
Muscle Spasticity * 1  2/15 (13.33%)  2 1/15 (6.67%)  1
Paresthesia * 1  1/15 (6.67%)  1 1/15 (6.67%)  1
Renal and urinary disorders     
Urinary tract infection * 1  2/15 (13.33%)  6 2/15 (13.33%)  4
Respiratory, thoracic and mediastinal disorders     
Cough * 1  2/15 (13.33%)  5 1/15 (6.67%)  1
Upper respiratory tract infection * 1  2/15 (13.33%)  3 1/15 (6.67%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
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.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Responsible
Organization: Merck Serono GmbH, Germany, an affiliate 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: NCT01142466    
Obsolete Identifiers: NCT00283140
Other Study ID Numbers: IMP 25874
First Submitted: June 10, 2010
First Posted: June 11, 2010
Results First Submitted: April 7, 2011
Results First Posted: June 10, 2011
Last Update Posted: February 27, 2014