Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis (MS)CombiRx
A Multi-Center, Double-Blind, Randomized Study Comparing the Combined Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Patients With Relapsing-Remitting Multiple Sclerosis (CombiRx)
4 other identifiers
interventional
1,008
2 countries
71
Brief Summary
This is for a randomized clinical trial (RCT) to determine if the combined use of interferon beta-1a (IFN) and glatiramer acetate (GA) is a measurably better therapy than either agent used individually in patients with relapsing-remitting (RR) multiple sclerosis (MS).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2005
Longer than P75 for phase_3
71 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2005
CompletedFirst Submitted
Initial submission to the registry
September 13, 2005
CompletedFirst Posted
Study publicly available on registry
September 21, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2013
CompletedResults Posted
Study results publicly available
April 3, 2014
CompletedApril 3, 2014
March 1, 2014
7.3 years
September 13, 2005
June 25, 2013
March 6, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
ARR - PDEs
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.
Baseline to Month 36
Secondary Outcomes (3)
Confirmed Progression on the Expanded Disability Status Scale
Baseline to Month 36
Change in the Multiple Sclerosis Functional Composite
Baseline to month 36
Change in MRI Composite Score
Baseline to month 36
Study Arms (3)
Interferon beta 1-a
ACTIVE COMPARATORActive Interferon B1a Weekly vs. Placebo Glatiramer Acetate Interferon b-1a (IFN) intramuscularly weekly
glatiramer acetate
ACTIVE COMPARATORPlacebo Interferon B1a Weekly vs. Active Glatiramer Acetate Glatiramer acetate 20mg daily
IFN and GA
ACTIVE COMPARATORActive Interferon B1a Weekly and Active Glatiramer Acetate
Interventions
The single agent arm is divided into two groups, IFN and GA providing for 3 treatment arms: IFN IM and GA SC (50% of the patients), IFN IM and placebo SC (25% of the patients) and GA SC and placebo IM (25% of the patients).
The single agent arm is divided into two groups, IFN and GA providing for 3 treatment arms: IFN IM and GA SC (50% of the patients), IFN IM and placebo SC (25% of the patients) and GA SC and placebo IM (25% of the patients).
Eligibility Criteria
You may qualify if:
- Male and female subjects between the ages of 18 and 60 years, inclusive.
- Diagnosis of relapsing-remitting MS by either the Poser or McDonald criteria.
- Expanded Disability Status Scale (EDSS) score between 0 and 5.5, inclusive.
- At least 2 exacerbations in the prior three years; one exacerbation may utilize the McDonald MRI criteria for dissemination in time (a new gadolinium \[Gd\]-enhancing lesion demonstrated on a scan done at least 3 months following onset of a clinical attack or a new T2 lesion or Gd-enhancing lesion on a follow-up scan after an additional 3 months).
- Give written informed consent prior to any testing under this protocol, including screening tests and evaluations that are not considered part of the subject's routine care.
You may not qualify if:
- Any prior use of interferon beta or glatiramer acetate.
- Acute exacerbation within 30 days of screening.
- Steroids for acute exacerbations (\>100 mg/day) within 30 days of study entrance or chronic systemic steroid use.
- Evidence of progressive MS.
- Use IVIg, azathioprine, methotrexate, cyclosporine, mitoxantrone, cyclophosphamide, mycophenolate (CellCept) or plasma exchange in the twelve weeks prior to study drug dosing.
- Any previous treatment with natalizumab (Tysabri, Antegren), cladribine, T cell vaccine, Campath, daclizumab, rituximab, altered peptide ligand or total lymphoid irradiation.
- Treatment with 4 aminopyridines in the four weeks prior to study drug dosing.
- Prior treatment with any other investigational drug, unless approved by the Clinical Coordinating Center (Dr. Lublin).
- Inability to perform the baseline MSFC (timed 25-foot walk, 9-hole peg test \[9HPT\], and Paced Auditory Serial Addition Test 3 \[PASAT3\]).
- Inability to undergo baseline MRI scan.
- History of any significant cardiac, hepatic, pulmonary, or renal disease, immune deficiency, or other medical conditions that would preclude therapy with interferon beta, glatiramer acetate, or participation in this study.
- Known history of sensitivity to gadopentetate dimeglumine or mannitol.
- History of a seizure within the 3 months prior to randomization.
- History of suicidal ideation or an episode of severe depression within the 3 months prior to randomization.
- Abnormal screening blood tests exceeding any of the limits defined below:
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (71)
University of Alabama - Birmingham
Birmingham, Alabama, United States
Barrow Neurology Clinic
Phoenix, Arizona, United States
Mayo Clinic - Scottsdale
Scottsdale, Arizona, United States
Northwest Neurospecialists PLLC
Tucson, Arizona, 85741, United States
Sutter East Bay Medical Group
Berkeley, California, United States
Neurology Center North Orange County
La Habra, California, United States
VA West Los Angeles Healthcare Center
Los Angeles, California, United States
University of California - Davis Medical Center
Sacramento, California, 95817, United States
Alpine Clinical Research Center
Boulder, Colorado, United States
Patricia Fodor P.C.
Colorado Springs, Colorado, United States
University of Colorado Health Sciences Center
Denver, Colorado, United States
Yale University School of Medicine
New Haven, Connecticut, United States
Neurology Associates, PA
Maitland, Florida, United States
University of Miami - Neurology
Miami, Florida, 33124, United States
MS Center of Atlanta
Atlanta, Georgia, United States
Shepherd Center
Atlanta, Georgia, United States
Northwest University
Chicago, Illinois, United States
Consultants in Neurology - Multiple Sclerosis Center
Northbrook, Illinois, United States
University of Illinois College of Medicine
Peoria, Illinois, United States
Ruan Neurology Clinic and Research Center
Des Moines, Iowa, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Maryland Center for MS
Baltimore, Maryland, United States
Tufts-New England Medical Center
Boston, Massachusetts, United States
University of Massachusetts Memorial Medical Center
Boston, Massachusetts, United States
Lahey Clinic
Burlington, Massachusetts, United States
Wayne State University
Detroit, Michigan, United States
Michigan State University
East Lansing, Michigan, United States
Minneapolis Clinic - MS Center
Golden Valley, Minnesota, United States
Mayo Clinic - Rochester
Rochester, Minnesota, United States
St. Louis University - St. Louis VA
St Louis, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Northern Rockies MS Center
Billings, Montana, United States
Dartmouth Medical School
Lebanon, New Hampshire, United States
CentraState Medical Center
Freehold, New Jersey, United States
University of New Mexico
Albuquerque, New Mexico, United States
Neuro Associates of Albany, PC
Albany, New York, 12208, United States
Albany Medical College
Albany, New York, United States
The Jacobs Neurological Institute
Buffalo, New York, United States
Winthrop Neurology Faculty Practice
Mineola, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Columbia University Medical Center
New York, New York, 10032, United States
NYU Hospital For Joint Diseases
New York, New York, United States
South Shore Neurologic Associates Inc.
Patchogue, New York, United States
University of Rochester
Rochester, New York, United States
SUNY Upstate Medical University
Syracuse, New York, United States
CMC-Neuroscience & Spine Institute, Division of Neurology, MS Center
Charlotte, North Carolina, United States
Meritcare Neuroscience
Fargo, North Dakota, United States
NeuroCare Center, Inc.
Canton, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
Ohio State University
Columbus, Ohio, United States
Neurology Specialists
Dayton, Ohio, 45415, United States
Medical College Of Ohio
Toledo, Ohio, United States
Oak Clinic for Multiple Sclerosis
Uniontown, Ohio, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Allegheny MS Treatment Center
Pittsburgh, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Baylor College of Medicine
Houston, Texas, United States
University of Texas - Houston
Houston, Texas, United States
University of Utah
Salt Lake City, Utah, United States
Neurological Research Center, Inc.
Bennington, Vermont, United States
Fletcher Allen Health Care
Burlington, Vermont, United States
Neurological Associates, Inc.
Richmond, Virginia, United States
Virginia Commonwealth University
Richmond, Virginia, United States
MS Center at Evergreen
Seattle, Washington, United States
Virginia Mason Medical Center
Seattle, Washington, United States
Marshfield Clinic
Marshfield, Wisconsin, United States
Regional MS Center at St. Luke's Medical Center
Milwaukee, Wisconsin, United States
Foothills Medical Centre
Calgary, Alberta, Canada
Capital Health and the University of Alberta
Edmonton, Alberta, Canada
Ottawa Hospital
Ottawa, Ontario, Canada
St. Michael's Hospital-Multiple Sclerosis Research Center
Toronto, Ontario, Canada
Related Publications (12)
Lublin FD, Cofield SS, Cutter GR, Conwit R, Narayana PA, Nelson F, Salter AR, Gustafson T, Wolinsky JS; CombiRx Investigators. Randomized study combining interferon and glatiramer acetate in multiple sclerosis. Ann Neurol. 2013 Mar;73(3):327-40. doi: 10.1002/ana.23863. Epub 2013 Mar 11.
PMID: 23424159RESULTKoch MW, Moral E, Brieva L, Mostert J, Strijbis EM, Comtois J, Repovic P, Bowen JD, Wolinsky JS, Lublin FD, Cutter G. Relapse recovery in relapsing-remitting multiple sclerosis: An analysis of the CombiRx dataset. Mult Scler. 2023 Dec;29(14):1776-1785. doi: 10.1177/13524585231202320. Epub 2023 Oct 13.
PMID: 37830451DERIVEDSatyanarayan S, Cutter G, Krieger S, Cofield S, Wolinsky JS, Lublin F. The impact of relapse definition and measures of durability on MS clinical trial outcomes. Mult Scler. 2023 Apr;29(4-5):568-575. doi: 10.1177/13524585231157211.
PMID: 37119208DERIVEDZhang Y, Cofield S, Cutter G, Krieger S, Wolinsky JS, Lublin F. Predictors of Disease Activity and Worsening in Relapsing-Remitting Multiple Sclerosis. Neurol Clin Pract. 2022 Aug;12(4):e58-e65. doi: 10.1212/CPJ.0000000000001177.
PMID: 36382118DERIVEDKoch MW, Mostert J, Repovic P, Bowen JD, Wolinsky JS, Lublin FD, Strijbis E, Cutter G. Early first-line treatment response and subsequent disability worsening in relapsing-remitting multiple sclerosis. Eur J Neurol. 2022 Apr;29(4):1106-1116. doi: 10.1111/ene.15220. Epub 2021 Dec 26.
PMID: 34927308DERIVEDBen-Zacharia AB, Janal MN, Brody AA, Wolinsky J, Lublin F, Cutter G. The Effect of Body Mass Index on Brain Volume and Cognitive Function in Relapsing-Remitting Multiple sclerosis: A CombiRx Secondary Analysis. J Cent Nerv Syst Dis. 2021 Nov 6;13:11795735211042173. doi: 10.1177/11795735211042173. eCollection 2021.
PMID: 34759712DERIVEDPetracca M, Cutter G, Cocozza S, Freeman L, Kangarlu J, Margoni M, Moro M, Krieger S, El Mendili MM, Droby A, Wolinsky JS, Lublin F, Inglese M. Cerebellar pathology and disability worsening in relapsing-remitting multiple sclerosis: A retrospective analysis from the CombiRx trial. Eur J Neurol. 2022 Feb;29(2):515-521. doi: 10.1111/ene.15157. Epub 2021 Nov 17.
PMID: 34695274DERIVEDKoch MW, Mostert JP, Wolinsky JS, Lublin FD, Uitdehaag B, Cutter GR. Comparison of the EDSS, Timed 25-Foot Walk, and the 9-Hole Peg Test as Clinical Trial Outcomes in Relapsing-Remitting Multiple Sclerosis. Neurology. 2021 Oct 19;97(16):e1560-e1570. doi: 10.1212/WNL.0000000000012690. Epub 2021 Aug 25.
PMID: 34433679DERIVEDKoch MW, Mostert J, Zhang Y, Wolinsky JS, Lublin FD, Strijbis E, Cutter G. Association of Age With Contrast-Enhancing Lesions Across the Multiple Sclerosis Disease Spectrum. Neurology. 2021 Sep 28;97(13):e1334-e1342. doi: 10.1212/WNL.0000000000012603. Epub 2021 Aug 10.
PMID: 34376508DERIVEDSalter A, Kowalec K, Fitzgerald KC, Cutter G, Marrie RA. Comorbidity is associated with disease activity in MS: Findings from the CombiRx trial. Neurology. 2020 Aug 4;95(5):e446-e456. doi: 10.1212/WNL.0000000000010024. Epub 2020 Jun 17.
PMID: 32554770DERIVEDFitzgerald KC, Kim K, Smith MD, Aston SA, Fioravante N, Rothman AM, Krieger S, Cofield SS, Kimbrough DJ, Bhargava P, Saidha S, Whartenby KA, Green AJ, Mowry EM, Cutter GR, Lublin FD, Baranzini SE, De Jager PL, Calabresi PA. Early complement genes are associated with visual system degeneration in multiple sclerosis. Brain. 2019 Sep 1;142(9):2722-2736. doi: 10.1093/brain/awz188.
PMID: 31289819DERIVEDBhanushali MJ, Gustafson T, Powell S, Conwit RA, Wolinsky JS, Cutter GR, Lublin FD, Cofield SS. Recruitment of participants to a multiple sclerosis trial: the CombiRx experience. Clin Trials. 2014 Apr;11(2):159-66. doi: 10.1177/1740774513517184.
PMID: 24686106DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
absence of a comparative randomized placebo only group
Results Point of Contact
- Title
- Dr. Fred D. Lublin
- Organization
- Icahn School of Medicine at Mount Sinai
Study Officials
- PRINCIPAL INVESTIGATOR
Fred Lublin, MD
Icahn School of Medicine at Mount Sinai
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
September 13, 2005
First Posted
September 21, 2005
Study Start
January 1, 2005
Primary Completion
April 1, 2012
Study Completion
March 1, 2013
Last Updated
April 3, 2014
Results First Posted
April 3, 2014
Record last verified: 2014-03