BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double‐Blind Randomised Interventional Phase 2b Trial
ABSTRACT 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 activ...
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2025-04-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
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| Online Access: | https://doi.org/10.1002/jcsm.13750 |
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| author | Roger A. Fielding Michael M. Dao Kevin Cannon Moise Desvarieux Sam S. Miller Michael Paul Gimness Donald M. Brandon Dennis T. Villareal Olivier Bruyere Ivan Bautmans Kyle Rickner Robert Perry Stephen B. Kritchevsky Nicolas Musi Joe M. Chehade Judith L. Kirstein Evelien Gielen Paul Pickrell Pierre Dilda Rene Lafont Carole Margalef Yves Rolland Susanna Del Signore Jean Mariani Samuel Agus Cendrine Tourette Waly Dioh Rob vanMaanen Stanislas Veillet |
| author_facet | Roger A. Fielding Michael M. Dao Kevin Cannon Moise Desvarieux Sam S. Miller Michael Paul Gimness Donald M. Brandon Dennis T. Villareal Olivier Bruyere Ivan Bautmans Kyle Rickner Robert Perry Stephen B. Kritchevsky Nicolas Musi Joe M. Chehade Judith L. Kirstein Evelien Gielen Paul Pickrell Pierre Dilda Rene Lafont Carole Margalef Yves Rolland Susanna Del Signore Jean Mariani Samuel Agus Cendrine Tourette Waly Dioh Rob vanMaanen Stanislas Veillet |
| author_sort | Roger A. Fielding |
| collection | DOAJ |
| description | ABSTRACT 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. |
| format | Article |
| id | doaj-art-445da26fd008498c9b0048a47cdc2ef9 |
| institution | DOAJ |
| issn | 2190-5991 2190-6009 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
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| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj-art-445da26fd008498c9b0048a47cdc2ef92025-08-20T03:10:42ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-04-01162n/an/a10.1002/jcsm.13750BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double‐Blind Randomised Interventional Phase 2b TrialRoger A. Fielding0Michael M. Dao1Kevin Cannon2Moise Desvarieux3Sam S. Miller4Michael Paul Gimness5Donald M. Brandon6Dennis T. Villareal7Olivier Bruyere8Ivan Bautmans9Kyle Rickner10Robert Perry11Stephen B. Kritchevsky12Nicolas Musi13Joe M. Chehade14Judith L. Kirstein15Evelien Gielen16Paul Pickrell17Pierre Dilda18Rene Lafont19Carole Margalef20Yves Rolland21Susanna Del Signore22Jean Mariani23Samuel Agus24Cendrine Tourette25Waly Dioh26Rob vanMaanen27Stanislas Veillet28Nutrition, Exercise Physiology, and Sarcopenia Laboratory Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University Boston Massachusetts USAAMD Medical Group and National Institute of Clinical Research Inc. Garden Grove California USAPMG Research of Wilmington Wilmington North Carolina USADepartment of Epidemiology, Mailman School of Public Health Columbia University New York New York USASAM CLINICAL RESEARCH CENTER/Science Advancing Medicine San Antonio Texas USAFamily Medical Specialists of Florida Plant City Florida USACalifornia Research Foundation San Diego California USACenter for Translational Research on Inflammatory Diseases Michael E DeBakey Veterans Affairs (VA) Medical Center Houston Texas USAResearch Unit in Public Health, Epidemiology and Health Economics University of Liège Liège BelgiumFrailty & Resilience in Ageing Research Unit (FRIA), Vitality Research Group, and Gerontology Department Vrije Universiteit Brussel Brussels BelgiumTekton Research Yukon Oklahoma USAPanax Clinical Research Miami Lakes Florida USASection on Gerontology and Geriatric Medicine, Department of Internal Medicine Wake Forest University School of Medicine Winston‐Salem North Carolina USADepartment of Medicine Cedars‐Sinai Medical Center Los Angeles California USADepartment of Medicine University of Florida College of Medicine Jacksonville Florida USAVelocity Clinical Research Banning California USADepartment of Geriatric Medicine, UZ Leuven, & Department of Primary Care and Public Health, Division of Gerontology and Geriatrics KU Leuven Leuven BelgiumTekton Research Austin Texas USABIOPHYTIS SA Sorbonne Université Paris FranceBIOPHYTIS SA Sorbonne Université Paris FranceBIOPHYTIS SA Sorbonne Université Paris FranceIHU HealthAge, Centre Hospitalo‐Universitaire de Toulouse; CERPOP UMR 1295 University of Toulouse III Toulouse FranceBluecompanion Ltd London UKBIOPHYTIS SA Sorbonne Université Paris FranceBIOPHYTIS SA Sorbonne Université Paris FranceBIOPHYTIS SA Sorbonne Université Paris FranceBIOPHYTIS SA Sorbonne Université Paris FranceBIOPHYTIS SA Sorbonne Université Paris FranceBIOPHYTIS SA Sorbonne Université Paris FranceABSTRACT 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.https://doi.org/10.1002/jcsm.1375020‐hydroxyecdysoneBIO101clinical trialgait speedmobility disabilitysarcopenia |
| spellingShingle | Roger A. Fielding Michael M. Dao Kevin Cannon Moise Desvarieux Sam S. Miller Michael Paul Gimness Donald M. Brandon Dennis T. Villareal Olivier Bruyere Ivan Bautmans Kyle Rickner Robert Perry Stephen B. Kritchevsky Nicolas Musi Joe M. Chehade Judith L. Kirstein Evelien Gielen Paul Pickrell Pierre Dilda Rene Lafont Carole Margalef Yves Rolland Susanna Del Signore Jean Mariani Samuel Agus Cendrine Tourette Waly Dioh Rob vanMaanen Stanislas Veillet BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double‐Blind Randomised Interventional Phase 2b Trial Journal of Cachexia, Sarcopenia and Muscle 20‐hydroxyecdysone BIO101 clinical trial gait speed mobility disability sarcopenia |
| title | BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double‐Blind Randomised Interventional Phase 2b Trial |
| title_full | BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double‐Blind Randomised Interventional Phase 2b Trial |
| title_fullStr | BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double‐Blind Randomised Interventional Phase 2b Trial |
| title_full_unstemmed | BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double‐Blind Randomised Interventional Phase 2b Trial |
| title_short | BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double‐Blind Randomised Interventional Phase 2b Trial |
| title_sort | bio101 in sarcopenic seniors at risk of mobility disability results of a double blind randomised interventional phase 2b trial |
| topic | 20‐hydroxyecdysone BIO101 clinical trial gait speed mobility disability sarcopenia |
| url | https://doi.org/10.1002/jcsm.13750 |
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