Title
A Combination Trial of Copaxone Plus Estriol in Relapsing Remitting Multiple Sclerosis (RRMS)
A Combination Trial of Copaxone Plus Estriol in RRMS
Phase
Phase 2Lead Sponsor
University of California, Los AngelesStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Relapsing Remitting Multiple SclerosisIntervention/Treatment
glatiramer acetate estriol ...Study Participants
158This 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.
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.
Injection, once a day, all subjects
Estriol 8 mg capsule, once per day, duration of treatment is 2 years
Placebo capsule, once a day, treatment duration is 2 years
Estriol Capsules (daily) plus Copaxone injections (daily). Progestin capsules given for 2 weeks every 3 months to avoid unopposed estrogens.
Inclusion Criteria: Diagnosis of relapsing remitting multiple sclerosis At least one relapse in the last two years 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
| Event Type | Organ System | Event Term | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections |
|---|
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.
Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.
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.
Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.
