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Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis (MS)CombiRx
This study is ongoing, but not recruiting participants.
First Received: September 13, 2005   Last Updated: May 8, 2009   History of Changes
Sponsor: Mount Sinai School of Medicine
Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by: Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00211887
  Purpose

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).


Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis
Drug: Interferon beta 1-a
Drug: glatiramer acetate
Other: placebo
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Safety/Efficacy Study
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Relapse Rate [ Time Frame: Baseline to Month 36 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Confirmed Progression on the Expanded Disability Status Scale [ Time Frame: Baseline to Month 36 ] [ Designated as safety issue: Yes ]
  • Change in the Multiple Sclerosis Functional Composite [ Time Frame: Baseline to month 36 ] [ Designated as safety issue: Yes ]
  • Change in MRI composite score [ Time Frame: Baseline to month 36 ] [ Designated as safety issue: Yes ]

Enrollment: 1008
Study Start Date: January 2005
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Active Comparator
Active Interferon B1a Weekly vs. Placebo Glatiramer Acetate
Drug: Interferon beta 1-a
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).
Other: placebo
an inactive substance
2: Active Comparator
Placebo Interferon B1a Weekly vs. Active Glatiramer Acetate
Drug: glatiramer acetate
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).
Other: placebo
an inactive substance
3: Active Comparator
Active Interferon B1a Weekly vs. Active Glatiramer Acetate
Drug: Interferon beta 1-a
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).
Drug: glatiramer acetate
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).

Detailed Description:

This is a multicenter, double blind, randomized trial examining combination therapy versus single agent therapy with three-year follow-up on the last patient randomized. All patients will remain on therapy until the last patient completes the study. All patients will then be transitioned, based on the findings, to open label of combination with continued follow-up or some recommendation about single agent therapy. While the study design benefits from having two arms of single agent therapy to examine the important question of whether there are differences between the single agents, the primary interest is in combination therapy. 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 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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00211887

  Show 71 Study Locations
Sponsors and Collaborators
Mount Sinai School of Medicine
Investigators
Principal Investigator: Fred Lublin, MD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Mount Sinai School of Medicine ( Fred Lublin, MD, Principal Investigator, CombiRx Clinical Coordinating Center )
Study ID Numbers: NS045719, 02-0526, CRC, U01 NS45719
Study First Received: September 13, 2005
Last Updated: May 8, 2009
ClinicalTrials.gov Identifier: NCT00211887     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:
Multiple Sclerosis
Clinical trial
treatment trial
autoimmune disease
Relapsing Remitting
MS Treatment
interferon beta-1a
glatiramer acetate

Additional relevant MeSH terms:
Anti-Infective Agents
Interferon Type I, Recombinant
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Multiple Sclerosis
Therapeutic Uses
Interferon beta 1a
Growth Inhibitors
Angiogenesis Modulating Agents
Autoimmune Diseases of the Nervous System
Autoimmune Diseases
Immune System Diseases
Demyelinating Diseases
Growth Substances
Interferons
Nervous System Diseases
Adjuvants, Immunologic
Interferon-beta
Sclerosis
Immunosuppressive Agents
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Copolymer 1
Demyelinating Autoimmune Diseases, CNS

ClinicalTrials.gov processed this record on February 08, 2010