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).
Therefore, a two-group combination versus single agent concept was used - splitting the
population into single agent and combination therapy equally. The single agent arm is
divided into two groups, IFN and GA providing for 3 treatment arms: IFN intramuscularly (IM)
and GA subcutaneously (SC) (50% of the patients), IFN IM and placebo SC (25% of the
patients) and GA SC and placebo IM (25% of the patients).
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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:
- Alanine transaminase (ALT) or aspartate transaminase (AST) greater than two
times the upper limit of normal (i. e., >2 × ULN)
- Total white blood cell count <2,300/mm3
- Platelet count <80,000/mm3
- Creatinine >2 × ULN
- Participation in another experimental clinical trial, without formal approval.
- History of alcohol or drug abuse within the 2 years prior to randomization.
- Female subjects who are currently pregnant, breast-feeding, or plan to become
pregnant.
- For female subjects, unless postmenopausal or surgically sterile, unwillingness to
practice effective contraception, as defined by the investigator, during the study.
The rhythm method is not to be used as the sole method of contraception.
- Unwillingness or inability to comply with the requirements of this protocol including
the presence of any condition that is likely to affect the subject's returning for
scheduled follow-up visits on schedule (any physical, mental, or social condition).
University of Alabama - Birmingham, Birmingham, Alabama, United States
Foothills Medical Centre, Calgary, Alberta, Canada
Capital Health and the University of Alberta, Edmonton, Alberta, Canada
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
Albany Medical College, Albany, New York, United States
Neuro Associates of Albany, PC, Albany, New York 12208, United States
The Jacobs Neurological Institute, Buffalo, New York, United States
Winthrop Neurology Faculty Practice, Mineola, New York, United States
Columbia University Medical Center, New York, New York 10032, United States
Icahn School of Medicine at Mount Sinai, New York, New York 10029, 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
Ottawa Hospital, Ottawa, Ontario, Canada
St. Michael's Hospital-Multiple Sclerosis Research Center, Toronto, Ontario, Canada
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