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Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis (MS)CombiRx

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ClinicalTrials.gov Identifier: NCT00211887
Recruitment Status : Completed
First Posted : September 21, 2005
Results First Posted : April 3, 2014
Last Update Posted : April 3, 2014
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Fred Lublin, Icahn School of Medicine at Mount Sinai

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Relapsing Remitting Multiple Sclerosis
Interventions Drug: Interferon beta 1-a
Drug: glatiramer acetate
Other: placebo
Enrollment 1008
Recruitment Details The trial enrolled participants from January 2005 through April 2009. The trial was conducted in 68 sites, both private practice and academic, in the USA and Canada.
Pre-assignment Details 1129 participants assessed for eligibility. 121 excluded due to recent activity (16), <2 exacerbations (14), other medical exclusions (14), inconclusive for RRMS (12), abnormal lab value (10), cannot have Gd (5), EDSS>5.5 (2), and other reason (46).
Arm/Group Title IFN + GA Interferon Beta 1a Glatiramer Acetate
Hide Arm/Group Description Interferon beta-1a 30µg intramuscularly weekly and glatiramer acetate (GA) 20mg daily Interferon beta-1a 30µg intramuscularly weekly glatiramer acetate 20mg daily
Period Title: Overall Study
Started 499 250 259
Completed 397 194 223
Not Completed 102 56 36
Reason Not Completed
Adverse Event             8             4             6
Death             1             1             1
Lost to Follow-up             28             13             9
Non-medical reason             31             14             8
Other medical reason             15             11             7
Side effects             19             13             5
Arm/Group Title IFN + GA IFB-1a Glatiramer Total
Hide Arm/Group Description Interferon beta-1a intramuscularly weekly and glatiramer acetate daily Interferon beta-1a glatiramer acetate Total of all reporting groups
Overall Number of Baseline Participants 499 250 259 1008
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 499 participants 250 participants 259 participants 1008 participants
37.1  (9.4) 37.6  (10.2) 39.0  (9.5) 37.7  (9.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 499 participants 250 participants 259 participants 1008 participants
Female
372
  74.5%
173
  69.2%
185
  71.4%
730
  72.4%
Male
127
  25.5%
77
  30.8%
74
  28.6%
278
  27.6%
1.Primary Outcome
Title ARR - PDEs
Hide Description Annualized relapse rate of protocol-defined exacerbations Protocol defined relapse – an relapse seen within 7 days of onset, verified by the treating physician and independently observed as a change in EDSS by the examining physician. This relapse is defined as: the appearance of a new symptom or worsening of an old symptom, attributable to MS; accompanied by a change in the neurologic examination (defined as a 0.5 or greater increase in the EDSS over the last scheduled or unscheduled visit or a 2 point change in one functional system or a 1 point change in two functional systems, except bladder and cognitive changes); lasting at least 24 hours in the absence of fever; and preceded by stability or improvement for at least 30 days.
Time Frame Baseline to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title IFN + GA IFB-1a Glatiramer
Hide Arm/Group Description:
Interferon beta-1a intramuscularly weekly and glatiramer acetate daily
Interferon beta-1a
glatiramer acetate
Overall Number of Participants Analyzed 499 250 259
Measure Type: Number
Unit of Measure: relapses per year
0.12 0.16 0.11
2.Secondary Outcome
Title Confirmed Progression on the Expanded Disability Status Scale
Hide Description

% with EDSS progression

Confirmed progression in a participant was defined as a 1.0 increase in the EDSS from baseline, when baseline <=5.0; or an increase of 0.5 from baseline, when baseline >=5.5, sustained for 6 months (2 successive quarterly visits), as assessed by the blinded EDSS examiner and confirmed centrally.

Time Frame Baseline to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title IFN + GA IFB-1a Glatiramer
Hide Arm/Group Description:
Interferon beta-1a intramuscularly weekly and glatiramer acetate daily
Interferon beta-1a
glatiramer acetate
Overall Number of Participants Analyzed 499 250 259
Measure Type: Number
Unit of Measure: percentage of participants
23.9 21.6 24.8
3.Secondary Outcome
Title Change in the Multiple Sclerosis Functional Composite
Hide Description

positive indicates improvement

The Multiple Sclerosis Functional Composite (MSFC) is a scale measuring pyramidal functions, sensory functions, cerebellar functions, bowel & bladder functions,brain stem functions, mental functions, and visual functions from 0 to 6.

0= normal 6= severe loss

Time Frame Baseline to month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Due to participant dropouts, there were less participants analyzed for this particular outcome measure.
Arm/Group Title IFN + GA IFB-1a Glatiramer
Hide Arm/Group Description:
Interferon beta-1a intramuscularly weekly and glatiramer acetate daily
Interferon beta-1a
glatiramer acetate
Overall Number of Participants Analyzed 472 241 246
Median (Full Range)
Unit of Measure: units on a scale
0.1
(-3.5 to 2.3)
0.1
(-2.0 to 1.8)
0.2
(-3.0 to 2.4)
4.Secondary Outcome
Title Change in MRI Composite Score
Hide Description MRI composite score (Z4 score) - the unweighted sum of the individual Z scores for enhanced tissue volume, T2 lesion burden, equivalence of the T1 hypointense lesion burden, normalized CSF (an inverse measure of atrophy with the appropriate sign so that all scores are directionally compatible – larger is worse) MRI enhancement status at baseline (0, 1-4, and 5 or more enhancing lesions)
Time Frame Baseline to month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Due to participant dropouts, there were less participants analyzed for this particular outcome measure.
Arm/Group Title IFN + GA IFB-1a Glatiramer
Hide Arm/Group Description:
Interferon beta-1a intramuscularly weekly and glatiramer acetate daily
Interferon beta-1a
glatiramer acetate
Overall Number of Participants Analyzed 381 185 211
Mean (Standard Deviation)
Unit of Measure: z score
-0.02  (1.30) 0.05  (1.27) 0.10  (2.09)
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse events were only collected with regard to the affected organ system.
 
Arm/Group Title IFN + GA IFB-1a Glatiramer
Hide Arm/Group Description Interferon beta-1a intramuscularly weekly and glatiramer acetate daily Interferon beta-1a glatiramer acetate
All-Cause Mortality
IFN + GA IFB-1a Glatiramer
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
IFN + GA IFB-1a Glatiramer
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   70/499 (14.03%)      38/250 (15.20%)      30/259 (11.58%)    
Cardiac disorders       
Cardiac disorders   3/499 (0.60%)  3 3/250 (1.20%)  3 3/259 (1.16%)  3
Gastrointestinal disorders       
Gastrointestinal disorders   7/499 (1.40%)  7 3/250 (1.20%)  3 2/259 (0.77%)  2
Hepatobiliary disorders       
Hepato-biliary disorders   4/499 (0.80%)  4 1/250 (0.40%)  1 3/259 (1.16%)  3
Infections and infestations       
Infections and infestations   11/499 (2.20%)  11 4/250 (1.60%)  4 1/259 (0.39%)  1
Musculoskeletal and connective tissue disorders       
Musculoskeletal, connective tissue and bone disorders   4/499 (0.80%)  4 1/250 (0.40%)  1 2/259 (0.77%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Neoplasms benign and malignant   1/499 (0.20%)  1 6/250 (2.40%)  6 3/259 (1.16%)  3
Nervous system disorders       
Nervous system disorders   17/499 (3.41%)  17 11/250 (4.40%)  11 5/259 (1.93%)  5
Psychiatric disorders       
Psychiatric disorders   15/499 (3.01%)  15 4/250 (1.60%)  4 8/259 (3.09%)  8
Renal and urinary disorders       
Renal and urinary disorders   3/499 (0.60%)  3 3/250 (1.20%)  3 0/259 (0.00%)  0
Reproductive system and breast disorders       
Reproductive system and breast disorders   3/499 (0.60%)  3 2/250 (0.80%)  2 0/259 (0.00%)  0
Surgical and medical procedures       
Surgical and medical procedures   9/499 (1.80%)  9 5/250 (2.00%)  5 6/259 (2.32%)  6
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IFN + GA IFB-1a Glatiramer
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   197/499 (39.48%)      102/250 (40.80%)      98/259 (37.84%)    
Gastrointestinal disorders       
constipation   23/499 (4.61%)  29 19/250 (7.60%)  20 18/259 (6.95%)  19
Diarrhea   32/499 (6.41%)  36 21/250 (8.40%)  27 20/259 (7.72%)  20
GI Upset   41/499 (8.22%)  44 11/250 (4.40%)  12 13/259 (5.02%)  15
Nausea/Vomiting   23/499 (4.61%)  25 17/250 (6.80%)  21 9/259 (3.47%)  9
General disorders       
Fatigue   81/499 (16.23%)  99 40/250 (16.00%)  53 42/259 (16.22%)  51
Injection Site Reaction   64/499 (12.83%)  86 15/250 (6.00%)  16 26/259 (10.04%)  35
Insomnia   25/499 (5.01%)  26 22/250 (8.80%)  27 22/259 (8.49%)  24
Infection   139/499 (27.86%)  213 69/250 (27.60%)  101 75/259 (28.96%)  122
Sinusitis   79/499 (15.83%)  120 32/250 (12.80%)  44 46/259 (17.76%)  68
Sore Throat   34/499 (6.81%)  39 14/250 (5.60%)  14 19/259 (7.34%)  22
URI   99/499 (19.84%)  148 53/250 (21.20%)  86 51/259 (19.69%)  84
UTI   64/499 (12.83%)  106 37/250 (14.80%)  64 37/259 (14.29%)  56
Immune system disorders       
Allergies (Environmental or Seasonal)   29/499 (5.81%)  39 19/250 (7.60%)  21 18/259 (6.95%)  20
Bronchitis   44/499 (8.82%)  54 14/250 (5.60%)  17 22/259 (8.49%)  30
Cold   197/499 (39.48%)  358 102/250 (40.80%)  172 98/259 (37.84%)  172
Cough   21/499 (4.21%)  24 17/250 (6.80%)  18 12/259 (4.63%)  13
Flu/Flu Like Symptoms   98/499 (19.64%)  122 51/250 (20.40%)  62 44/259 (16.99%)  52
GI Virus   33/499 (6.61%)  35 21/250 (8.40%)  24 30/259 (11.58%)  32
Injury, poisoning and procedural complications       
Fall   46/499 (9.22%)  63 20/250 (8.00%)  27 25/259 (9.65%)  46
Musculoskeletal and connective tissue disorders       
Back Pain   47/499 (9.42%)  58 36/250 (14.40%)  37 32/259 (12.36%)  40
Joint Pain/Stiffness   40/499 (8.02%)  44 20/250 (8.00%)  25 27/259 (10.42%)  29
Nervous system disorders       
Cognitive Difficulties   26/499 (5.21%)  33 5/250 (2.00%)  5 18/259 (6.95%)  21
Dizziness   37/499 (7.41%)  43 20/250 (8.00%)  21 17/259 (6.56%)  22
Extremity Pain/Soreness/Stiffness   81/499 (16.23%)  105 41/250 (16.40%)  61 51/259 (19.69%)  68
Extremity Weakness   26/499 (5.21%)  34 10/250 (4.00%)  16 18/259 (6.95%)  22
Headaches   88/499 (17.64%)  116 40/250 (16.00%)  50 47/259 (18.15%)  65
Paresthesias   39/499 (7.82%)  46 28/250 (11.20%)  42 18/259 (6.95%)  18
Unspecified Neuropathic Symptoms   103/499 (20.64%)  146 58/250 (23.20%)  92 45/259 (17.37%)  67
Psychiatric disorders       
Anxiety/Panic Attacks   41/499 (8.22%)  48 20/250 (8.00%)  23 22/259 (8.49%)  24
Depression   88/499 (17.64%)  103 40/250 (16.00%)  50 43/259 (16.60%)  51
Renal and urinary disorders       
Urinary/Bladder Issues   44/499 (8.82%)  57 27/250 (10.80%)  30 22/259 (8.49%)  25
Skin and subcutaneous tissue disorders       
Dental Abcess/Extraction/Procedure   43/499 (8.62%)  53 18/250 (7.20%)  24 33/259 (12.74%)  40
Rash   57/499 (11.42%)  74 20/250 (8.00%)  22 22/259 (8.49%)  25
Indicates events were collected by systematic assessment
absence of a comparative randomized placebo only group
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Fred D. Lublin
Organization: Icahn School of Medicine at Mount Sinai
Phone: 212-241-6854
Responsible Party: Fred Lublin, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT00211887     History of Changes
Other Study ID Numbers: GCO 02-0526
02-0526
CRC
U01NS045719 ( U.S. NIH Grant/Contract )
First Submitted: September 13, 2005
First Posted: September 21, 2005
Results First Submitted: June 25, 2013
Results First Posted: April 3, 2014
Last Update Posted: April 3, 2014