Open-Label Extension Study Assessing Long-Term Safety and Efficacy of Oral Ribitol (BBP-418) in Adults with Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I/R9)

The primary objective is to assess the long-term safety of BBP-418 (ribitol) in participants with Limb‑Girdle Muscular Dystrophy type 2I/R9 and to evaluate its clinical efficacy over an extended treatment period; these outcomes are critical for defining the risk‑benefit profile of chronic therapy in this rare neuromuscular disease. Secondary objectives comprise a continued evaluation of long‑term clinical efficacy and the investigation of longitudinal biomarker changes associated with BBP-418 treatment, providing additional insight into disease modulation and therapeutic impact.

The trial enrolled a total of 72 participants diagnosed with Limb Girdle Muscular Dystrophy (LGMD) Type 2I, a rare hereditary muscular disorder. Both male and female patients were included, encompassing individuals from the pediatric age group (starting at 3 years of age) through adulthood. All participants were required to have completed the preceding study MLB‑01‑005 and to provide informed consent (or assent with parental consent for minors). Eligibility mandated the ability to adhere to the study schedule and, for those of reproductive potential, the use of acceptable contraception from enrollment until 30 days after the final dose. The population comprised patients who were otherwise in stable health relative to their underlying neuromuscular condition; no specific lifestyle restrictions such as diet or physical activity were stipulated in the available information.

The study is an open‑label, single‑arm extension evaluating the long‑term safety and efficacy of BBP‑418 (ribitol) in participants with Limb Girdle Muscular Dystrophy Type 2I. After completing the prior trial, participants attend a screening visit to confirm eligibility, followed by a baseline visit that initiates daily oral administration of ribitol 24 g granules. Follow‑up visits are scheduled at regular intervals (e.g., every three months) to record treatment‑emergent adverse events, assess laboratory safety, and measure clinical endpoints such as the NSAD, 10‑meter walk test, forced vital capacity, and serum creatine kinase. The end‑of‑study visit occurs after approximately 36 months of treatment, marking the conclusion of the observation period. Participant involvement may be terminated early for reasons such as a serious adverse event, withdrawal of consent, or failure to comply with protocol requirements.

The investigational product, Ribitol, is supplied as granules for oral solution. Each dose consists of 24 g of ribitol administered orally once daily. The drug is classified as an orphan drug and is provided in a single pharmaceutical form without dose titration. Participants receive the oral solution according to a fixed dosing schedule throughout the extension period, with dosing recorded in the study diary and compliance assessed by returned sachet counts and electronic medication adherence logs.

No placebo or alternative investigational comparator is utilized in this open‑label extension. Participants may continue concomitant standard‑of‑care therapies for Limb‑Girdle Muscular Dystrophy 2I/R9 as prescribed by their treating physicians, but no additional study‑specific non‑experimental treatments are administered.

Efficacy will be evaluated by comparing each participant’s baseline values with measurements obtained at the end of treatment (EOT). The primary efficacy parameter is the change from baseline in the NSAD score. Secondary parameters include the change from baseline in the 10MWT speed (m/s), the change in FVC expressed as percent predicted in the sitting position, the change in PUL 2.0 for participants who are non‑ambulatory at OLE baseline, the change in 100MTT performance, and the change in serum CK levels.

Assessments are performed by trained personnel using validated instruments: the NSAD is administered as a standardized functional scale; the 10MWT and 100MTT are timed walking tests measured with a calibrated stopwatch; FVC is obtained via spirometry according to ATS/ERS guidelines; PUL 2.0 follows the published protocol for upper‑limb function; and serum CK is analyzed in a central laboratory using a validated enzymatic assay. Baseline data are collected prior to the first dose of BBP‑418, and all efficacy endpoints are re‑evaluated at the EOT visit. Changes from baseline will be analyzed using appropriate statistical methods to determine the magnitude and significance of treatment effects.