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 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.

Keywords: 20‐hydroxyecdysone; BIO101; clinical trial; gait speed; mobility disability; sarcopenia.

FIGURE 1

Study design and patient disposition. (a) Initial study design, including a screening period (up to 8 weeks, study intervention (26 weeks) and safety follow‐up of 6 weeks. (b) Patients disposition. EoT, end‐of‐treatment visit; FAS, full analysis set; PD, protocol deviation; PP, per protocol. After the COVID‐19 pandemic started, participants still active in the study have been proposed to increase their participation duration up to 9 months.

FIGURE 2

Change from baseline in 400MWT gait speed (SE), based on multiple imputation for subjects without on‐site visit data at Month 6 and adjusted Bayesian imputation for non‐completers at Month 6. (a) Full analysis set. (b) Per protocol population. LS, least square; SE, standard error.

FIGURE 3

Change from baseline in 4‐m gait speed at Month 6 based on multiple imputation in the PP population. Missing data are imputed using multiple imputation. Analysis is based on mixed‐effect model for repeated measurements (MMRM) with treatment, visit, center, gender, and treatment * visit as fixed effects and baseline value as a covariate. LS, least square; SE, standard error.