A Combination Trial of Copaxone Plus Estriol in Relapsing Remitting Multiple Sclerosis (RRMS)

Phase 2

Completed

Brief Summary: This is a double-blinded, placebo controlled study of estriol pills versus placebo pills in relapsing remitting multiple sclerosis. The study treatment will be an added on to Copaxone injections in all subjects. The primary outcome measure is a reduction in relapses.

Detailed Description: Multiple sclerosis (MS) relapses are known to be significantly decreased during pregnancy. This proposal will establish whether oral treatment with estriol, the major estrogen of pregnancy, induces a decrease in relapses in relapsing remitting multiple sclerosis (RRMS) subjects when used in combination with injectable Copaxone. Previously, in a pilot study, it has been demonstrated that treatment of RRMS subjects with oral estriol for six months resulted in a significant reduction in gadolinium enhancing lesions on serial brain MRIs (Annals of Neurology, 2002; 52:421-428) and caused a favorable shift in immune responses (Journal of Immunology, 2003; 171:6267-6274). This is an add-on study aiming to extend these previous findings by treating longer and focusing on clinical outcomes. The combination of Copaxone injection plus estriol pill (8 mg per day) will be compared to Copaxone injection plus placebo pill in a double blind trial. The duration of treatment will be two years and the primary outcome measure will be relapse rate. Other outcomes will include disability measures and brain MRI outcomes. Safety measures (blood tests and gynecologic evaluations) will also be followed and correlations will be made between serum estriol levels with efficacy and safety. The overall goal of this study will be the development of a new oral treatment, estriol, for RRMS.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Patients treated in the past with total lymphoid irradiation, monoclonal antibody, T cell vaccination, cladribine, bone marrow transplantation, azathioprine, cyclophosphamide, methotrexate, mitoxantrone, cyclosporin or Tysabri
Clinically significant diseases other than multiple sclerosis

Arm && Interventions

Group	Intervention	Description
Placebo plus Copaxone injections QD	Placebo	Placebo Capsules (daily) plus Copaxone injections (daily). A second placebo capsule given for 2 weeks every 3 months.
Estriol plus Copaxone injections QD	Copaxone	Estriol Capsules (daily) plus Copaxone injections (daily). Progestin capsules given for 2 weeks every 3 months to avoid unopposed estrogens.
Estriol plus Copaxone injections QD	Estriol	Estriol Capsules (daily) plus Copaxone injections (daily). Progestin capsules given for 2 weeks every 3 months to avoid unopposed estrogens.
Placebo plus Copaxone injections QD	Copaxone	Placebo Capsules (daily) plus Copaxone injections (daily). A second placebo capsule given for 2 weeks every 3 months.

Primary Outcome Measures

Name	Time	Method
Confirmed Relapse, Annualized Relapse Rate	24 months	A confirmed relapse was defined as new neurological symptoms or worsening of pre-existing symptoms, lasting at least 48 hours in a subject who had been neurologically stable or improving in the previous 30 days, accompanied by objective change in the neurological examination (worsening of 0.5 points on the EDSS or worsening by 1.0 or more points on the pyramidal, cerebellar, brainstem or visual functional system scores), not due to fatigue alone and not associated with fever or infection.

Secondary Outcome Measures

Name	Time	Method
Relapse Event, Annualized Relapse Rate	24 months	Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.
Confirmed Relapse, Probability of First Relapse	24 months
Relapse Event, Probability of First Relapse Event	24 months

Locations (16): Western Institute for Biomedical Research
🇺🇸
Salt Lake City, Utah, United States
University of Texas Southwestern
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Dallas, Texas, United States
Dartmouth Medical School
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Lebanon, New Hampshire, United States
University of Chicago
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Chicago, Illinois, United States
University of Kansas
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Kansas City, Kansas, United States
University of New Mexico
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Albuquerque, New Mexico, United States
Mayo Clinic
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Scottsdale, Arizona, United States
University of Colorado
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Aurora, Colorado, United States
University of California, Los Angeles
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Los Angeles, California, United States
University of Minnesota
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Minneapolis, Minnesota, United States
Johns Hopkins University
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Baltimore, Maryland, United States
Washington University
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Saint Louis, Missouri, United States
UMDNJ-Robert Wood Johnson Medical Center
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New Brunswick, New Jersey, United States
University of Pennsylvania
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Philadelphia, Pennsylvania, United States
Montreal Neurological Institute
🇨🇦
Montreal, Canada
Ohio State University
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Columbus, Ohio, United States