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THE DESIGN AND RATIONALE OF A PHASE 2B, RANDOMIZED, DOUBLE-BLINDED, AND PLACEBO-CONTROLLED TRIAL TO EVALUATE THE SAFETY AND EFFICACY OF LOMECEL-B IN OLDER ADULTS WITH FRAILTY

K. Yousefi, K.N. Ramdas, J.G. Ruiz, J. Walston, H. Arai, E. Volpi, A.B. Newman, C. Wang, B. Hitchinson, L. McClain-Moss, L. Diaz, G.A. Green, J.M. Hare, A.A. Oliva

J Frailty Aging 2022;11(2)214-223

BACKGROUND: Frailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes. OBJECTIVES: To evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate dose-range effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers. SETTING: Eight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center. PARTICIPANTS: Target enrollment is 150 subjects aged 70-85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 (“mild”) or 6 (“moderate”), a 6MWT of 200-400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL. INTERVENTION: A single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days. MEASUREMENTS: The primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial. RESULTS: The trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board. CONCLUSION: This clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.

CITATION:
K. Yousefi ; K.N. Ramdas ; J.G. Ruiz ; J. Walston ; H. Arai ; E. Volpi ; A.B. Newman ; C. Wang ; B. Hitchinson ; L. McClain-Moss ; L. Diaz ; G.A. Green ; J.M. Hare ; A.A. Oliva (2022): The Design and Rationale of a Phase 2b, Randomized, Double-Blinded, and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B in Older Adults with Frailty. The Journal of Frailty and Aging (JFA). http://dx.doi.org/10.14283/jfa.2022.2

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