MLB-01-002: A Phase 1 Randomized, Blinded, Placebo-Controlled Study of the Safety, Tolerability, and PK of BBP-418 (ribitol) in Healthy Subjects


Clinical Trials

Poster Number: 64


Doug Sproule, MD, MSc, ML Bio Solutions, Hector Rodriguez, PhD, BridgeBio Pharma, Athiwat Hutchaleelaha, PhD, BridgeBio Pharma, Uma Sinha, PhD, BridgeBio Pharma, Marissa Lynn, MD, ML Bio Solutions, George Mclendon, PhD, ML Bio Solutions, Karen Kelley, ML Bio Solutions

Introduction: LGMD Type 2I/R9 is caused by bi-allelic loss-of-function of the Fukutin-Related Protein (FKRP) gene, which results in hypoglycosylation of alpha-dystroglycan (?DG). BBP-418 (Ribitol) is an oral-administered substrate supplementation therapy intended to saturate the FKRP enzyme to drive increased glycosylation of the ?DG, thus addressing the root cause of disease in LGMD Type 2I/R9.

Objectives: The MLB-01-002 Phase 1 study is intended to explore safety and tolerability of single (SAD) and multiple (MAD) ascending doses of BBP-418 following administration to healthy subjects. Investigators sought to characterize single dose and steady state pharmacokinetics (PK) of BBP-418 and evaluate the effect of a standardized high calorie meal on the PK profile of BBP-418
Methods: This is a randomized, blinded, placebo-controlled study of the administration of BBP-418 to 85 healthy subjects. The SAD part of this study includes 1 food effect (FE) cohort. Vital signs, ECGs, evaluation of AEs and blood draws for PK and safety laboratory tests were obtained serially. SAD dosing was assessed across 7 cohorts to a maximum dose of 15 g. Five MAD cohorts were enrolled to a maximum dose of 9 g BID.
Results: All studied doses were well-tolerated with no dose-limiting toxicity. PK assessment showed dose proportional exposure following both single (0.5 g to 15 g) and multiple dose administrations (1.5 g QD to 9 g BID). The geometric mean (%CV) for Cmax and AUC(0-?) following a single 15 g dose were 221 (12.6%) µg/mL and 543 (12.3%) µg*hr/mL, respectively. Effective half-life was ~4-5 hours. No clinically significant differences in exposure occurred when administered under fed conditions.

Conclusions: Phase 1 study of BBP-418 in healthy volunteers demonstrated broad tolerability across a wide range of dosing, including doses beyond expected therapeutic range. No dose limiting toxicity was observed. A phase 2 “first in patient” study is currently ongoing.