Trial record 1 of 2 for:    combirx
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Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis (MS)CombiRx

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Lublin, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00211887
First received: September 13, 2005
Last updated: March 6, 2014
Last verified: March 2014
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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:
  • ARR - PDEs [ Time Frame: Baseline to Month 36 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Confirmed Progression on the Expanded Disability Status Scale [ Time Frame: Baseline to Month 36 ] [ Designated as safety issue: Yes ]

    % 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.


  • Change in the Multiple Sclerosis Functional Composite [ Time Frame: Baseline to month 36 ] [ Designated as safety issue: Yes ]

    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


  • Change in MRI Composite Score [ Time Frame: Baseline to month 36 ] [ Designated as safety issue: Yes ]
    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)


Enrollment: 1008
Study Start Date: January 2005
Study Completion Date: March 2013
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Interferon beta 1-a

Active Interferon B1a Weekly vs. Placebo Glatiramer Acetate

Interferon b-1a (IFN) intramuscularly weekly

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 Name: IFN
Other: placebo
an inactive substance
Active Comparator: glatiramer acetate

Placebo Interferon B1a Weekly vs. Active Glatiramer Acetate

Glatiramer acetate 20mg daily

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 Name: GA
Other: placebo
an inactive substance
Active Comparator: IFN and GA
Active Interferon B1a Weekly and 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).
Other Name: IFN
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 Name: GA

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 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).

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00211887

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

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Fred Lublin, Principal Investigator, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00211887     History of Changes
Other Study ID Numbers: GCO 02-0526, 02-0526, CRC, U01NS045719
Study First Received: September 13, 2005
Results First Received: June 25, 2013
Last Updated: March 6, 2014
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:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Interferon beta 1a
Interferons
Interferon-beta
Copolymer 1
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 18, 2014