Randomized Trial of Minocycline for Clinically Isolated Syndrome and Early Single Relapse Multiple Sclerosis: Study Design, Participant Characteristics, and Recruitment Challenges (P1.227)

OBJECTIVE: This phase III double-blind, randomized clinical trial (NCT00666887) aims to demonstrate that minocycline reduces the conversion of clinically isolated syndrome (CIS) to multiple sclerosis (MS) by 25% compared to placebo within 6 months. Follow-up continues to 2 years. We describe the trial design, participant characteristics and recruitment challenges. BACKGROUND: Minocycline is a widely available oral drug that appears promising for relapsing remitting MS. DESIGN/METHODS: Patients from 12 Canadian MS clinics, aged 18 to 60 years who had a first focal episode of demyelination within the previous 180 days, and at least two lesions on T2-weighted brain screening magnetic resonance imaging (MRI), were randomized (1:1) to minocycline 100 mg twice daily or matching placebo. After the screening and baseline visits, follow-up occurred at 1, 3, 6, 12, 18, and 24 months. MRI scans were obtained at screening, 3, 6, 12, and 24 months. RESULTS: This trial began in 2008 and will be completed in December 2014. Over 55 months, 236 patients were screened and 143 randomized. This was 92% of the recruitment target. The majority of screen failures were due to fewer than 2 lesions on cranial MRI (57%) or reaching the 2005 McDonald criteria for MS (the study endpoint) before randomization (24%). Mean age of the randomized group was 36 years (range: 18-56), 69% were women, mean CIS duration was 65 days (range: 4-183), median EDSS was 1.5 (range: 0-4.5), and 59% were randomized to the high risk strata (2 or more enhancing lesions or dissemination in space based on 2005 McDonald criteria). These characteristics did not change over time. Ten patients remain in follow-up to month 6. Only 12 patients (8.4%) discontinued participation before reaching month 6 indicating excellent retention. CONCLUSIONS: Recruitment was challenging as the diagnostic criteria for MS changed and new therapies became available. Despite the length of the trial, participant characteristics remained comparable over the enrolment period. StudySupported by: Multiple Sclerosis Society of Canada Disclosure: Dr. Metz has received personal compensation for activities with Teva Neuroscience as a consultant, and Novartis as a scientific advisory board member. Dr. Metz has received research support from EMD Serono. Dr. Traboulsee has received personal compensation for activities with Roche Diagnostics Corp., EMD Serono, Teva Neuroscience, and Biogen Idec. Dr. Traboulsee has received research support from Bayer Pharmaceuticals Corp., and Roche Diagnostics Corp. Dr. Li has received personal compensation for activities with Opexa, Nuron, Genzyme Corp., Roche Diagnostics Corp., and Novartis. Dr. Li has received research support from EMD Serono, Genzyme Corp., and Roche Diagnostics Corp. Dr. Duquette has received personal compensation for activities with Berlex, Biogen Idec, Serono, Novartis, and Teva Neuroscience. Dr. Kremenchutzky has received research support from Bayer Pharmaceuticals Corp., Biogen Idec, EMD Serono, Genzyme Corp., Novartis, Roche Diagnostics Corp., Sanofi-Aventis Pharmaceuticals Inc., and Teva Neuroscience. Dr. Vorobeychik has received personal compensation for activities with Berlex, Biogen Idec, EMD Serono, Teva Neuroscience, Pfizer Inc., and Novartis as a member of advisory boards. Dr. Vorobeychik has received research support from Biogen Idec. Dr. Freedman has received personal compensation for activities with Actelion, Bayer, Biogen Idec, EMD Canada, Genzyme Corporation, Novartis, Opexa, Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Freedman has received research support from Bayer and Genzyme. Dr. Bhan has received personal compensation for activities with Biogen Idec, Serono Inc., Genzyme Corporation, Novartis and Teva Neuroscience. Dr. Blevinshas received personal compensation for activities with Biogen Idec, Teva Neuroscience, Serono Inc., Novartis and GlaxoSmithKline, Inc. Dr. Marriott has received personal compensation for activities with Roche Diagnostics Corp. Dr. Marriott has received research support from Roche Diagnostics Corp. Dr. Grand-Maison has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Bayer Pharmaceuticals Corp., Serono Inc., Biogen Idec, Genzyme Corp., and Novartis. Dr. Grand-Maison has received research support from Sanofi-Aventis Pharmaceuticals Inc., Bayer Pharmaceuticals Corp., Serono Inc., Biogen Idec, Genzyme Corp., and Novartis. Dr. Lee has received personal compensation for activities with Novartis, Serono Inc., and Biogen Idec as a consultant and advisory board member. Dr. Lee has received research support from Serono Inc. Dr. Thibault has nothing to disclose. Dr. Eliasziw has nothing to disclose. Dr. Yong has received personal compensation for activities with Teva Neuroscience. Dr. Yong has received research support from Teva Neuroscience and Novartis. Dr. Cerchiaro has nothing to disclose. Dr. Wiebe has nothing to disclose. Dr. Cheng has nothing to disclose. Dr. Zhao has nothing to disclose. Dr. Greenfield has nothing to disclose. Dr. Topor has nothing to disclose. Dr. Riddehough has nothing to disclose.