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Rebif® Versus Copaxone® in the Treatment of Relapsing Remitting Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT00078338
Recruitment Status : Completed
First Posted : February 26, 2004
Results First Posted : June 27, 2018
Last Update Posted : June 27, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
EMD Serono

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsing-remitting Multiple Sclerosis
Interventions Drug: Rebif®
Drug: Copaxone®
Enrollment 764
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rebif® Copaxone®
Hide Arm/Group Description Subjects were administered with Rebif® (Recombinant interferon beta-1a) as subcutaneous (SC) injection at a dose of 44 microgram (mcg) three times weekly (tiw). Subjects were administered with Copaxone® (Glatiramer acetate) as subcutaneous (SC) injection at a dose of 20 milligram (mg) once daily (qd).
Period Title: Overall Study
Started 386 378
Safety Population 381 [1] 375 [1]
Completed 301 324
Not Completed 85 54
Reason Not Completed
Adverse Event             31             24
Lost to Follow-up             17             2
Protocol Violation             2             2
Disease Progression             4             7
Other             28             16
Subjects randomized, but not treated             3             3
[1]
Safety population=subjects who received at least 1 dose of treatment and had followup safety data.
Arm/Group Title Rebif® Copaxone® Total
Hide Arm/Group Description Subjects were administered with Rebif® (Recombinant interferon beta-1a) as subcutaneous (SC) injection at a dose of 44 microgram (mcg) three times weekly (tiw). Subjects were administered with Copaxone® (Glatiramer acetate) as subcutaneous (SC) injection at a dose of 20 milligram (mg) once daily (qd). Total of all reporting groups
Overall Number of Baseline Participants 386 378 764
Hide Baseline Analysis Population Description
The intent to treat (ITT) population consisted of all subjects who were randomized.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 386 participants 378 participants 764 participants
Less than 18 years 0 0 0
18 years to 64 years 386 378 764
Greater than 64 years 0 0 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 386 participants 378 participants 764 participants
Female
267
  69.2%
272
  72.0%
539
  70.5%
Male
119
  30.8%
106
  28.0%
225
  29.5%
1.Primary 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 subject and must be accompanied by at least 1 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. The mean time to first relapse for the 25th percentile and the 30th percentile during the 96-week treatment period was measured by Kaplan-Meier estimates and was reported.
Time Frame Baseline up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all subjects who were randomized.
Arm/Group Title Rebif® Copaxone®
Hide Arm/Group Description:
Subjects were administered with Rebif® (Recombinant interferon beta-1a) as subcutaneous (SC) injection at a dose of 44 microgram (mcg) three times weekly (tiw).
Subjects were administered with Copaxone® (Glatiramer acetate) as subcutaneous (SC) injection at a dose of 20 milligram (mg) once daily (qd).
Overall Number of Participants Analyzed 386 378
Mean (Standard Deviation)
Unit of Measure: days
25th Percentile 332.0  (10.9) 290.0  (9.5)
30th Percentile 495.0  (16.3) 432.0  (14.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rebif®, Copaxone®
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.643
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.943
Confidence Interval (2-Sided) 95%
0.74 to 1.21
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description The Safety population consisted of all subjects who received at least 1 dose of study treatment and had follow-up safety data.
 
Arm/Group Title Rebif® Copaxone®
Hide Arm/Group Description Subjects were administered with Rebif® (Recombinant interferon beta-1a) as subcutaneous (SC) injection at a dose of 44 microgram (mcg) three times weekly (tiw). Subjects were administered with Copaxone® (Glatiramer acetate) as subcutaneous (SC) injection at a dose of 20 milligram (mg) once daily (qd).
All-Cause Mortality
Rebif® Copaxone®
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rebif® Copaxone®
Affected / at Risk (%) Affected / at Risk (%)
Total   29/381 (7.61%)   27/375 (7.20%) 
Blood and lymphatic system disorders     
Neutropenia * 1  1/381 (0.26%)  0/375 (0.00%) 
Cardiac disorders     
Myocardial infarction * 1  1/381 (0.26%)  0/375 (0.00%) 
Endocrine disorders     
Hyperthyroidism * 1  1/381 (0.26%)  0/375 (0.00%) 
Eye disorders     
Glaucoma * 1  1/381 (0.26%)  0/375 (0.00%) 
Gastrointestinal disorders     
Ileus * 1  0/381 (0.00%)  2/375 (0.53%) 
Colitis ulcerative * 1  1/381 (0.26%)  0/375 (0.00%) 
Constipation * 1  0/381 (0.00%)  1/375 (0.27%) 
Diverticular perforation * 1  0/381 (0.00%)  1/375 (0.27%) 
Gastric ulcer perforation * 1  1/381 (0.26%)  0/375 (0.00%) 
Gastrooesophageal reflux disease * 1  1/381 (0.26%)  0/375 (0.00%) 
Jejunal perforation * 1  1/381 (0.26%)  0/375 (0.00%) 
Nausea * 1  0/381 (0.00%)  1/375 (0.27%) 
Pancreatitis * 1  0/381 (0.00%)  1/375 (0.27%) 
Salivary gland cyst * 1  0/381 (0.00%)  1/375 (0.27%) 
Vomiting * 1  0/381 (0.00%)  1/375 (0.27%) 
General disorders     
Chest pain * 1  2/381 (0.52%)  1/375 (0.27%) 
Face oedema * 1  0/381 (0.00%)  2/375 (0.53%) 
Adverse drug reaction * 1  0/381 (0.00%)  1/375 (0.27%) 
Asthenia * 1  0/381 (0.00%)  1/375 (0.27%) 
Hepatobiliary disorders     
Cholecystitis chronic * 1  0/381 (0.00%)  1/375 (0.27%) 
Hepatitis toxic * 1  0/381 (0.00%)  1/375 (0.27%) 
Immune system disorders     
Anaphylactic reaction * 1  0/381 (0.00%)  1/375 (0.27%) 
Drug hypersensitivity * 1  1/381 (0.26%)  0/375 (0.00%) 
Infections and infestations     
Acute sinusitis * 1  1/381 (0.26%)  1/375 (0.27%) 
Upper respiratory tract infection * 1  1/381 (0.26%)  1/375 (0.27%) 
Urinary tract infection * 1  1/381 (0.26%)  1/375 (0.27%) 
Bronchitis * 1  1/381 (0.26%)  0/375 (0.00%) 
Chronic sinusitis * 1  0/381 (0.00%)  1/375 (0.27%) 
Dental caries * 1  1/381 (0.26%)  0/375 (0.00%) 
Diverticulitis * 1  0/381 (0.00%)  1/375 (0.27%) 
Otitis media * 1  0/381 (0.00%)  1/375 (0.27%) 
Pneumonia bacterial * 1  0/381 (0.00%)  1/375 (0.27%) 
Postoperative infection * 1  1/381 (0.26%)  0/375 (0.00%) 
Pyelonephritis acute * 1  1/381 (0.26%)  0/375 (0.00%) 
Sinusitis * 1  0/381 (0.00%)  1/375 (0.27%) 
Injury, poisoning and procedural complications     
Accidental overdose * 1  0/381 (0.00%)  1/375 (0.27%) 
Concussion * 1  0/381 (0.00%)  1/375 (0.27%) 
Humerus fracture * 1  0/381 (0.00%)  1/375 (0.27%) 
Overdose * 1  1/381 (0.26%)  0/375 (0.00%) 
Tibia fracture * 1  1/381 (0.26%)  0/375 (0.00%) 
Metabolism and nutrition disorders     
Dehydration * 1  0/381 (0.00%)  1/375 (0.27%) 
Haemochromatosis * 1  0/381 (0.00%)  1/375 (0.27%) 
Hypokalaemia * 1  0/381 (0.00%)  1/375 (0.27%) 
Musculoskeletal and connective tissue disorders     
Polyarthritis * 1  1/381 (0.26%)  0/375 (0.00%) 
Spinal column stenosis * 1  1/381 (0.26%)  0/375 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Uterine leiomyoma * 1  1/381 (0.26%)  1/375 (0.27%) 
Malignant melanoma * 1  1/381 (0.26%)  0/375 (0.00%) 
Malignant melanoma stage III * 1  0/381 (0.00%)  1/375 (0.27%) 
Nervous system disorders     
Autonomic nervous system imbalance * 1  0/381 (0.00%)  1/375 (0.27%) 
Grand mal convulsion * 1  0/381 (0.00%)  1/375 (0.27%) 
Headache * 1  1/381 (0.26%)  0/375 (0.00%) 
Sciatica * 1  0/381 (0.00%)  1/375 (0.27%) 
Psychiatric disorders     
Depression * 1  2/381 (0.52%)  1/375 (0.27%) 
Affective disorder * 1  1/381 (0.26%)  0/375 (0.00%) 
Anxiety disorder * 1  1/381 (0.26%)  0/375 (0.00%) 
Delusional disorder, persecutory type * 1  1/381 (0.26%)  0/375 (0.00%) 
Panic attack * 1  0/381 (0.00%)  1/375 (0.27%) 
Paranoia * 1  1/381 (0.26%)  0/375 (0.00%) 
Reproductive system and breast disorders     
Dysfunctional uterine bleeding * 1  1/381 (0.26%)  1/375 (0.27%) 
Ovarian cyst ruptured * 1  1/381 (0.26%)  1/375 (0.27%) 
Ovarian cyst * 1  1/381 (0.26%)  0/375 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Laryngospasm * 1  0/381 (0.00%)  2/375 (0.53%) 
Dyspnoea * 1  1/381 (0.26%)  0/375 (0.00%) 
Vascular disorders     
Thrombophlebitis superficial * 1  1/381 (0.26%)  0/375 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 9.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rebif® Copaxone®
Affected / at Risk (%) Affected / at Risk (%)
Total   346/381 (90.81%)   320/375 (85.33%) 
Gastrointestinal disorders     
Nausea * 1  25/381 (6.56%)  28/375 (7.47%) 
General disorders     
Injection site erythema * 1  121/381 (31.76%)  114/375 (30.40%) 
Influenza like illness * 1  119/381 (31.23%)  5/375 (1.33%) 
Injection site pain * 1  47/381 (12.34%)  53/375 (14.13%) 
Injection site pruritus * 1  8/381 (2.10%)  75/375 (20.00%) 
Injection site bruising * 1  33/381 (8.66%)  38/375 (10.13%) 
Injection site swelling * 1  4/381 (1.05%)  42/375 (11.20%) 
Pyrexia * 1  23/381 (6.04%)  14/375 (3.73%) 
Injection site induration * 1  9/381 (2.36%)  25/375 (6.67%) 
Adverse drug reaction * 1  0/381 (0.00%)  19/375 (5.07%) 
Infections and infestations     
Nasopharyngitis * 1  34/381 (8.92%)  44/375 (11.73%) 
Sinusitis * 1  18/381 (4.72%)  29/375 (7.73%) 
Upper respiratory tract infection * 1  15/381 (3.94%)  27/375 (7.20%) 
Influenza * 1  18/381 (4.72%)  22/375 (5.87%) 
Urinary tract infection * 1  17/381 (4.46%)  20/375 (5.33%) 
Investigations     
Alanine aminotransferase increased * 1  21/381 (5.51%)  5/375 (1.33%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  25/381 (6.56%)  26/375 (6.93%) 
Arthralgia * 1  18/381 (4.72%)  22/375 (5.87%) 
Myalgia * 1  22/381 (5.77%)  8/375 (2.13%) 
Nervous system disorders     
Headache * 1  74/381 (19.42%)  35/375 (9.33%) 
Psychiatric disorders     
Depression * 1  30/381 (7.87%)  22/375 (5.87%) 
Anxiety * 1  21/381 (5.51%)  11/375 (2.93%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  4/381 (1.05%)  22/375 (5.87%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 9.0
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
Name/Title: Merck KGaA Communication Center
Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00078338     History of Changes
Other Study ID Numbers: 24735
First Submitted: February 23, 2004
First Posted: February 26, 2004
Results First Submitted: September 15, 2017
Results First Posted: June 27, 2018
Last Update Posted: June 27, 2018