Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis (MS)CombiRx
Condition: Relapsing Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Interferon beta 1-a; glatiramer acetate; placebo
Intervention description: 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).; an inactive substance
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a; Glatiramer Acetate; (T,G)-A-L
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1008.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Multiple Sclerosis; Clinical trial; treatment trial; autoimmune disease; Relapsing Remitting; MS Treatment; interferon beta-1a; glatiramer acetate

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).
    

Eligibility criteria:

        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).