[en] [en] BACKGROUND: Sarcopenia is a progressive muscle disorder that may lead to mobility disability. No pharmaceutical interventions are currently available, and treatment relies on physical exercise and nutrition. The aim of SARA-INT was to investigate whether BIO101 (20-hydroxyecdysone), an activator of the MAS receptor, is safe and improves muscle function and physical performance of community dwelling older sarcopenic patients.
METHODS: SARA-INT was a randomised three-arm interventional study (BIO101 175 mg bid /350 mg bid/placebo) with a planned 6-month treatment (up to 9 months in 50 subjects). Eligibility criteria for sarcopenia were meeting FNIH criteria for sarcopenia and Short Physical Performance Battery (SPPB) score ≤ 8/12 in men and women aged ≥ 65 years. Primary endpoint was the change from baseline (CFB) in gait speed (GS) measured by 400-m walking test (400MWT), secondary endpoints being CFB in other physical performance tests.
RESULTS: A total of 233 participants were randomised (mean age 75.5 ± 7.12; 54.3% female), of whom 232 and 156 were included in the full analysis set (FAS) and per-protocol (PP) populations, respectively. Due to COVID-19 pandemic, 55% of on-site end-of-treatment efficacy assessments were lost, reducing the studies' power. In the primary analysis (mix of 6/9 months), BIO101 350 mg bid treatment after 6/9 months was associated with an improvement in the 400MWT of 0.07 m/s versus placebo in the FAS population (not significant) and of 0.09 m/s in the PP population (p = 0.008). BIO101 350 mg bid treatment effect on the 400MWT GS was also observed in pre-defined subpopulations at higher risk of mobility disability (0.0474 m/s for slow walkers, 0.0521 m/s for obese and 0.0662 m/s for chair stand sub-score ≤ 2 from SPPB in the FAS population), with a trend for a dose response. BIO101 showed a good safety profile at both doses (number of subjects with related treatment emergent adverse events (TEAEs) of 13 (16.0%), 10 (13.3%) and 10 (13.5%) in the placebo, 175 mg and 350 mg BIO101 groups, respectively).
CONCLUSIONS: After 6 to 9 months of treatment, BIO101 350 mg bid showed strong trends consistent with a clinically relevant effect on the 400MWT GS, close to the minimal clinically important difference (MCID) in sarcopenia (0.1 m/s). This was also shown in predefined subpopulations at higher risk of mobility disability. BIO101 showed a good safety profile. Taken together, efficacy and safety data of this Phase 2 trial encourage us to pursue further development of BIO101 for the treatment of sarcopenia.
Disciplines :
Geriatrics
Author, co-author :
Fielding, Roger A; Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA
Dao, Michael M; AMD Medical Group and National Institute of Clinical Research Inc., Garden Grove, California, USA
Cannon, Kevin; PMG Research of Wilmington, Wilmington, North Carolina, USA
Desvarieux, Moise; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA ; METHODS Core, Centre de Recherche Epidémiologie et Statistique Paris Sorbonne Cité (CRESS), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1153, Paris, France
Miller, Sam S; SAM CLINICAL RESEARCH CENTER/Science Advancing Medicine, San Antonio, Texas, USA
Gimness, Michael Paul; Family Medical Specialists of Florida, Plant City, Florida, USA
Brandon, Donald M; California Research Foundation, San Diego, California, USA
Villareal, Dennis T; Center for Translational Research on Inflammatory Diseases, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, Texas, USA
Bruyère, Olivier ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Bautmans, Ivan; Frailty & Resilience in Ageing Research Unit (FRIA), Vitality Research Group, and Gerontology Department, Vrije Universiteit Brussel, Brussels, Belgium ; Department of Geriatric Physiotherapy, SOMT University of Physiotherapy, Amersfoort, The Netherlands ; Geriatrics Department, Universitair Ziekenhuis Brussel, Brussels, Belgium
Rickner, Kyle; Tekton Research, Yukon, Oklahoma, USA
Perry, Robert; Panax Clinical Research, Miami Lakes, Florida, USA
Kritchevsky, Stephen B; Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Musi, Nicolas; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
Chehade, Joe M; Department of Medicine, University of Florida College of Medicine, Jacksonville, Florida, USA
Kirstein, Judith L; Velocity Clinical Research, Banning, California, USA
Gielen, Evelien; Department of Geriatric Medicine, UZ Leuven, & Department of Primary Care and Public Health, Division of Gerontology and Geriatrics, KU Leuven, Leuven, Belgium
Pickrell, Paul; Tekton Research, Austin, Texas, USA
Dilda, Pierre; BIOPHYTIS SA, Sorbonne Université, Paris, France
Lafont, Rene; BIOPHYTIS SA, Sorbonne Université, Paris, France ; FSI, Paris-Seine Biology Institute (BIOSIPE), CNRS, Sorbonne Université, Paris, France
Margalef, Carole; BIOPHYTIS SA, Sorbonne Université, Paris, France
Rolland, Yves; IHU HealthAge, Centre Hospitalo-Universitaire de Toulouse, CERPOP UMR 1295, University of Toulouse III, Toulouse, France
Del Signore, Susanna; Bluecompanion Ltd, London, UK ; Bluecompanion France, Jambville, France
Mariani, Jean; BIOPHYTIS SA, Sorbonne Université, Paris, France ; CNRS - Institut de Biologie Paris Seine (UMR DEV2A), Sorbonne Université, Paris, France
Agus, Samuel; BIOPHYTIS SA, Sorbonne Université, Paris, France
Tourette, Cendrine ; BIOPHYTIS SA, Sorbonne Université, Paris, France
Dioh, Waly ; BIOPHYTIS SA, Sorbonne Université, Paris, France
van Maanen, Rob ; BIOPHYTIS SA, Sorbonne Université, Paris, France
Veillet, Stanislas; BIOPHYTIS SA, Sorbonne Université, Paris, France
R.A.F. is partially supported by the US Department of Agriculture (USDA), under agreement No. 58\u20108050\u20109\u2010004, and by the NIH Boston Claude D. Pepper Center (OAIC; 1P30AG031679). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the USDA. R.A.F. reports grant support from Lonza, Biophytis, National Institutes of Health and USDA; scientific advisory board membership for Biophytis, Amazentis, Inside Tracker, Rejuventate Biomed and Aging in Motion; and consultancies for Embion, Biophytis, Amazentis, Pfizer, Nestle and Rejuvenate Biomed. Y.R. reports support from CHU Toulouse, University Paul Sabatier and INSERM CERPOP1295 (employee), to be a shareholder of SARQOL SPRL, a spin\u2010off of the University of Liege; consultancy fees from Longeveron, to be a Scientific Advisory Board member to Biophytis; and have received honoraria for lectures for Pfizer. OB reports to be stakeholder of SARQOL SRL, a spin\u2010off of the University of Liege in charge of the interest of the SarQoL and reports consulting or lecture fees (in the last 5\u2009years) from Amgen, Aptissen, Biophytis, IBSA, Mylan, Novartis, Nutricia, Orifarm, Sanofi, UCB and Viatris. D.T.V. is on the scientific advisory board for Biophytis SA. E.G. reports consulting or lecture fees (in the last 5\u2009years) from Amgen, Nutricia, Orifarm and UCB. I.B. reports to be stakeholder of SARQOL SRL, a spin\u2010off of the University of Liege in charge of the interest of the SarQoL. M.M.D., M.D., D.B., S.B.K., N.M., J.M.C., K.C., D.M.B., M.P.G., P.P., S.S.M., K.R., R.P. and J.K. declare that they have no competing interests. J.M. is the President of the Scientific Advisory Board of Biophytis SA. P.D., R.L., C.T., W.D., R.V.M. and S.V. are employees of Biophytis SA. C.M., S.D.S. and S.A. are former employees of Biophytis SA.
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