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Effect of MD1003 (high dose pharmaceutical grade biotin) in progressive MS: design and baseline data from the phase III SPI2 study
Author(s): ,
B.A.C. Cree
Affiliations:
Department of Neurology, University of California San Francisco, Weill Institute for Neurosciences, San Francisco, CA
,
G. Cutter
Affiliations:
UAB School of Public Health, Birmingham, AL
,
J.S. Wolinsky
Affiliations:
UTHealth, Houston, TX, United States
,
M.S. Freedman
Affiliations:
The University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada
,
G. Comi
Affiliations:
University of Milan San Raffaele Medical School, Milan, Italy
,
G. Giovannoni
Affiliations:
Blizard Institute, London, United Kingdom
,
H.P. Hartung
Affiliations:
Heinrich Heine University, Düsseldorf, Germany
,
F. Sedel
Affiliations:
MedDay Pharmaceuticals, Paris, France
F. Lublin
Affiliations:
Icahn School of Medicine at Mount Sinai, New York, NY, United States
ECTRIMS Online Library. Cree B.
Oct 12, 2018; 229061
Bruce A. Cree
Bruce A. Cree
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Abstract: P1221

Type: Poster Sessions

Abstract Category: Therapy - Neuroprotection and Repair

Background: A large unmet need exists for treating progressive forms of MS (PMS: PPMS and SPMS,). MS-SPI, the first trial of MD1003 in PMS, demonstrated a significant sustained improvement in disability. Here we provide the study design and baseline data for the second study, the fully-recruited, ongoing Phase III trial SPI2.
Objective: The primary objective of SPI2 is to confirm that treatment with MD1003 results in clinically meaningful sustained improvement in disability in 660 patients (pts) with PMS.
Methods: SPI2 inclusion required documented, non-fluctuating, relapse-free, disability progression in EDSS over 2 years. The primary endpoint is a composite of: 1) a decrease in EDSS and/or 2) improved timed 25-foot walk (TW25) of ≥20% from baseline to month (M) 12, confirmed at M15. Secondary endpoints are time to confirmed EDSS progression, clinical global impression (CGI/SGI), and change in TW25. Exploratory endpoints include change in brain volume, passive activity monitoring (Fitbit Flex®), symbol digit modalities test (SDMT), and quality of life scores (MSQOL54, CAREQOL-MS).
Results: SPI2 is fully enrolled (N=660 pts). As of March 2, 2018 (final results in the poster/presentation), 433 pts with PPMS (32%) or SPMS (67%) were randomised 1:1 to MD1003 300 mg/day or placebo. At baseline, mean age in years (SD) was 53.6 (6.9) for PPMS pts and 52.5 (7.8) for SPMS pts (P>0.15). Compared to SPMS, the PPMS group had more males than females (59% vs 42%, P=0.001), shorter mean time since diagnosis (7.4 [6.1] vs 15.9 [7.8], P< 0.0001), and lower mean TW25 score (10.5 [7.6] vs 12.2 [7.2], P=0.029) (median, PPMS 6.0 vs SPMS 6.0) and mean SDMT (PPMS 39.6 [11.6] vs SPMS 41.9 [13.3], P=0.098) scores were similar. Baseline MRI measurement of mean cortical gray matter volume (GMV; P=0.072), T2 volume (P=0.45), T1 volume (P=0.12), and number of gadolinium (Gd)-enhancing lesions (PPMS 0.07 [0.29] vs SPMS 0.14 [1.01], P=0.44) did not significantly differ between PPMS and SPMS groups. Mean whole brain volume (WBV) was 1.2% smaller in the SPMS vs PPMS group (P=0.021).
Conclusion: In SPI2, SPMS pts had a longer mean time since diagnosis and less WBV compared to PPMS pts at baseline. The groups did not meaningfully differ in EDSS, SDMT, TW25, cortical GMV, T1 or T2 volume, or number of Gd-enhancing lesions. SPI2 seeks to confirm that MD1003 improves disability in pts with worsening PMS without relapses. Final results are expected by late 2019.
Disclosure: Bruce Cree has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, GeNeuro, Novartis and Sanofi Genzyme.
Gary Cutter was on Data and Safety Monitoring Boards for AMO Pharmaceuticals, Biolinerx, Horizon Pharmaceuticals, Merck, Merck/Pfizer, Opko Biologics, Neurim, Ophazyme, Sanofi-Aventis, Reata Pharmaceuticals, Receptos/Celgene, Teva pharmaceuticals, NHLBI (Protocol Review Committee), and NICHD (OPRU oversight committee); and was on Consulting or Advisory Boards for Atara Biotherapeutics, Axon, Biogen, Biotherapeutics, Argenix, Brainstorm Cell Therapeutics, Charleston Labs Inc, Click Therapeutics, Genzyme, Genentech, GW Pharma, Klein-Buendel Incorporated, Medimmune, Medday, Novartis, Roche, Scifluor, Somahlution, Teva pharmaceuticals, TG Therapeutics, and UT Houston; Dr Cutter is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc. a private consulting company located in Birmingham AL.
Jerry Wolinsky received compensation for consulting, scientific advisory boards, speaking, or other activities with AbbVie, Acetilon, Alkermes, Biogen, Bionest, Celgene, Clene Nanomedicine, EMD Serono, Forward Pharma A/S, GeNeuro, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, Sanofi Genzyme; royalties are received for out-licensed monoclonal antibodies through UTHealth from Millipore Corporation.
Mark S Freedman received research or educational grants from Genzyme Canada and honoraria or consultation fees from Actelion, BayerHealthcare, BiogenIdec, Chugai, Clene Nanomedicine, EMD Canada, Genzyme, Merck Serono, Novartis, Hoffman La-Roche, Sanofi-Aventis, and Teva Canada Innovation; he is a member of the advisory board, board of directors or other similar group for Actelion, BayerHealthcare, BiogenIdec, Clene Nanomedicine, Hoffman La-Roche, Merck Serono, MedDay, Novartis, Sanofi-Aventis; and he participated in Sanofi-Genzyme's sponsored speaker's bureau.
Over the last 3 years, Professor Giovannoni has received personal compensation for participating in advisory boards in relation to clinical trial design, trial steering committees, and data and safety monitoring committees from Abbvie, Atara Bio, Biogen, Sanofi-Genzyme, Genentech, GSK, MedDay, Merck-Serono, Novartis, Roche, and Teva.
Giancarlo Comi was a Consultant for Almirall, Biogen, Celgene Corporation, EXCEMED, Forward Pharm, Genzyme, Merck, Novartis, Receptos, Roche, Sanofi, and Teva.
Hans Peter Hartung received fees for consulting, serving on steering or data monitoring committees or speaking at scientific symposia from BayerHealthcae, Biogen, Genzyme, Geneuro, MedDay, Merck, Novartis, Receptos Celgene, Roche, and Teva with approval by the Rector of HHU.
Frédéric Sedel is an employee of MedDay Pharmaceuticals.
Fred Lublin received funding for research from Novartis Pharmaceuticals Corp, Teva Neuroscience, Inc., Actelion, Transparency Life Sciences, and NMSS; and had consulting Agreements with or was on Advisory Boards/DSMB for Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Novartis, Teva, Actelion, Sanofi/Genzyme, Acorda, Roche/Genentech, MedImmune, Receptos/Celgene, Forward Pharma, TG Therapeutics, Abbvie, Regeneron, Toyama, MedDay, Atara Biotherapeutics, Polpharma, Mapi Pharma, Innate Immunotherapeutics, and Apitope.
This study is sponsored by MedDay Pharmaceuticals.

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