A Combination Trial of Estriol Plus Glatimer Acetate in Relapsing-Remitting Multiple Sclerosis (I7-2.002)

OBJECTIVE: Determine the effect of oral treatment with the pregnancy hormone estriol in women with relapsing remitting multiple sclerosis. BACKGROUND: Pregnancy is known to be a period of relative protection from MS relapses. Estriol is an estrogen which naturally increases to high levels in serum during the last half of pregnancy. Beneficial effects of estrogen treatment, including estriol, have included both anti-inflammatory and neuroprotective mechanisms in MS models. A small crossover pilot trial had previously shown an 80% reduction in white matter enhancing lesions on monthly MRIs. DESIGN/METHODS: This is a randomized, double-blind, multicenter, placebo-controlled (1:1) trial of oral estriol 8 mg per day in RRMS women, age 18-50 years. Estriol was an add-on therapy. Thus, all subjects began glatimer acetate injections within 2 months or less of randomization to take either estriol versus placebo pills in combination. Treatment duration was 2 years. The primary endpoint was annualized relapse rate. Other endpoints included MSFC, EDSS, and MRI measures of white matter lesion activity. RESULTS: Baseline characteristics: 164 subjects from 15 sites across the U.S. were randomized with a mean age of 37.5 and mean disease duration of 3.0 years. 99.4% had at least one relapse in the preceding 24 months, with 29.4% having at least one enhancing lesion on a single screening MRI. The mean EDSS score was 2.2. The database will be locked and unblinded analyses will be done by the time of presentation. Results from primary and other outcomes will be shown as well as serum estriol levels and safety data. CONCLUSIONS: Effects of treatment of RRMS women with a dose of estriol to induce a pregnancy level in serum will be discussed in the context of future development of estriol as a novel treatment in MS, and insights in understanding disease protection during pregnancy will be explored. Disclosure: Dr. Voskuhl has received personal compensation for activities with Synthetic Biologics Inc. Dr. Voskuhl has received license fee payments from UCLA. Dr. Voskuhl has received research support from Synthetic Biologics, and Karo Bio. Dr. Wang has nothing to disclose. Dr. Wu has nothing to disclose. Dr. Sicotte has nothing to disclose. Dr. Bates has received personal compensation for activities with Teva Neuroscience, and Biogen Idec, Dr. Beaver has nothing to disclose. Dr. Corboy has received personal compensation for activities with ProCE as a speaker, and Celgene Therapeutics, Teva Neuroscience, and Novartis as a speaker. Dr. Corboy has received research support from Novartis, BioMS, Eli Lilly & Co., Celgene Therapeutics, and Immune Tolerance Network. Dr. Cross has received personal compensation for activities with Biogen Idec, Genzyme Corporation, GlaxoSmithKline, Inc., Hoffman-La Roche, Teva Neuroscience, Novartis, and Questcor. Dr. Cross has received research support from Hoffman-La Roche and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Dhib-Jalbut has received personal compensation for activities with Serono and Novartis as a consultant. Dr. Ford has received personal compensation for activities with Teva Neuroscience, Biogen Idec, and Novartis. Dr. Ford has received research support from Acorda Therapeutics, Biogen Idec, Genzyme Corp., Novartis, Ono Pharmaceutical, Roche Diagnostics Corp., Sanofi-Aventis Pharmaceuticals Inc., EMD Serono, and Teva Neuroscience. Dr. Giesser9s family hold stock and/or stock options in Biogen Idec and Pfizer Inc. Dr. Giesser has received research support from AVAcore Technologies. Dr. Jacobs has received personal compensation for activities with Questcor Diagnostics, and Teva Neuroscience. Dr. Lynch has received research support from Novartis, Biogen Idec, Teva Neuroscience, Genzyme Corp., Genentech Inc., Berlex, Cognition Pharmaceuticals, UCB Pharmaceuticals, Serono Inc., and Cephalon. Dr. Pachner has received personal compensation for activities with Biogen Idec, Novartis, Pfizer Inc., Sanofi-Aventis Pharmaceuticals Inc., Genzyme Corp., and EMD-Serono. Dr. Pachner has received research support from Hoffman-LaRoche, and Sanofi-Aventis Pharmaceuticals Inc. Dr. Racke has received personal compensation for activities with Biogen Idec, Revalesio, and Novartis. Dr. Racke has received personal compensation in an editorial capacity for JAMA Neurology and the Journal of Neuroimmunology. Dr. Racke has received research support from Diogenix. Dr. Ratchford has received personal compensation for activities with Biogen Idec, Genzyme Corporation, GW Pharmaceuticals, and Diogenix. Dr. Ratchford has received research support from Novartis, Biogen Idec, and Sun Pharmaceuticals. Dr. Reder has received personal compensation for activities with Bayer, Biogen Idec, Genentech, Inc., Genzyme Corporation, Merck & Co., Inc., Novartis, Questcor, Serono, Teva Neuroscience, Caremark, Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, State of Illinois, and State of Indiana. Dr. Reder has received personal compensation in an editorial capacity for Medlink/Neurobase. Dr. Rose has received research support from Teva Neuroscience, and Biogen Idec. Dr. Wingerchuk has received research support from Genentech, Inc., Genzyme Corporation, Alexion, and TerumoBCT. Dr. Burnett has received personal compensation for activities with Biogen Idec, Genzyme Corporation, Novartis, Serono Inc., Pfizer Inc., and Teva Neuroscience. Dr. Tseng has nothing to disclose. Dr. Elashoff has nothing to disclose.