Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients With Limb Girdle Muscular Dystrophy 2I (LGMD2I)

NCT05775848 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: MLB-01-005
• Study Type: interventional
• Target: 81
• Locations: 8 countries
• Sites: 21

Brief Summary

This study will evaluate the safety and efficacy of long-term administration of BBP-418 in patients with LGMD2I/R9. The study will include patients ages 12 to 60, consistent with the existing preclinical toxicology profile. This will encompass the significant majority of existing diagnosed patients based upon the established epidemiology of the disease.

Conditions

Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I)

Outcome Measures

Primary Outcomes (2)

• Change from baseline in North Star Assessment for Limb Girdle Muscular Dystrophy following 36 months of treatment to assess efficacy of BBP-418 or placebo

  36 months

• Frequency and severity of treatment-emergent adverse events following 36 months of treatment to assess safety of BBP-418 or placebo

  36 months

Secondary Outcomes (3)

• Change from baseline in 10 meter walk test velocity to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9

  36 months

• Change from baseline in pulmonary function as measured by FVC (percent predicted, performed in a sitting position) to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9

  36 months

• Change from baseline in the Performance of Upper Limb scale 2.0 to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9

  36 months

Other Outcomes (2)

• Change from baseline in total glycosylated Alpha dystroglycan to assess biomarkers for clinical efficacy of BBP-418 in patients with LGMD2I/R9

  36 months

• Change from baseline in glycosylated Alpha dystroglycan / total glycosylated Alpha dystroglycan ratio to assess biomarkers for clinical efficacy of BBP-418 in patients with LGMD2I/R9

  36 months

Study Arms (2)

BBP-418

ACTIVE COMPARATOR

BBP-418 Granules for Oral Solution will be supplied as granules in tri-ply PET/Aluminum/PE sachets for unit dose. The number of sachets to reconstitute will depend on the applicable dose to be delivered, 9 g BID or 12 g BID, as determined by the weight of the participant. The granules will be reconstituted in water for oral administration.

Drug: BBP-418 (ribitol); Other: Placebo

Placebo to Match BBP-418

PLACEBO COMPARATOR

The placebo will be identical to the BBP-418 Granules for Oral Solution in appearance, packaging, labeling, and storage conditions.

Drug: BBP-418 (ribitol); Other: Placebo

Interventions

BBP-418 (ribitol) DRUG

The BBP-418 drug product is provided as Granules for Oral solution consisting of BBP-418 drug substance and silicon dioxide in a multilaminate sachet with a foil barrier. Silicon dioxide is generally regarded as safe and listed in the FDA IIAD. Silicon dioxide is a compendial excipient and is commonly used in pharmaceutical dosage forms. The BBP-418 Granules for Oral Solution are provided in sachets.The BBP-418 Granules for Oral Solution are reconstituted in water for oral administration.

BBP-418; Placebo to Match BBP-418

Placebo OTHER

A placebo matched for similar taste and appearance was compounded at the clinical pharmacy with sucralose as a 0.35 mg/mL oral solution in purified water (USP) in a glass container. Sucralose is similar in taste to the compounded drug product.

BBP-418; Placebo to Match BBP-418

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may not qualify if:

• If pregnant and/or breastfeeding or planning to conceive children within the projected duration of the study through 12 weeks after the last dose of study treatment.
• Use of ribose or other sugar alcohol-containing supplement within 90 days of the Screening Visit.
• Use of a systemic corticosteroid for the treatment of muscular dystrophy within 90 days of the Screening Visit. (An inhaled corticosteroid or bronchodilator for reactive airway disease is allowed if the participant is on a stable dose for 30 days prior to study entry.)
• Previously received gene therapy to treat LGMD2I/R9.
• Participants with active suicidal ideation as measured by Columbia-Suicide Severity Rating Scale during screening with most severe suicide ideation score of 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan) or 5 (Active Suicidal Ideation with Specific Plan and Intent).
• Presence of a platelet disorder, bleeding disorder, or other contraindication to muscle biopsy.
• Actively on an experimental therapy or device or was on an experimental therapy or device within 90 days of the Screening Visit, or was on BBP-418 at any time.
• In the judgment of the Investigator or Medical Monitor, has any clinically important ongoing medical condition or laboratory abnormality or condition that might jeopardize the participant's safety, increase their risk from participation, or interfere with the study. For COVID-19 infections, Investigator should refer to local guidance.

Sponsors & Collaborators

• ML Bio Solutions, Inc.: lead

Study Sites (21)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

University of California Irvine

Irvine, California, 92697, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainsville, Florida, 32610, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

University of Minnesota, Twin Cities

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Oregon Health & Science University (OHSU) - Neurology Clinic - South Waterfront

Portland, Oregon, 97239, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of the Kings Daughters

Norfolk, Virginia, 23455, United States

Location

Royal Brisbane and Women's Hospital,

Brisbane, Queensland, Australia

Location

Rigshospitalet, Neuromuscular Clinic and Research Unit

Copenhagen, Denmark

Location

Charité Universitätsmedizin Berlin and Max Delbrück Center

Berlin, Germany

Location

IRCCS Ca' Granda Ospedale

Milan, Italy

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Universitetssykehuset Nord-Norge, Department of Neurology

Tromsø, Norway

Location

Great Ormond Street Hospital for Children

London, United Kingdom

Location

International Centre for Life

Newcastle upon Tyne, United Kingdom

Location

MeSH Terms

Conditions

Muscular Dystrophy, Limb-Girdle, Type 2I

Interventions

Ribitol

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 2:1 Randomization
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomization will be stratified by mutation status (L276I homozygous or other), age (\<12 years \[to allow for possible addition of this age group in a future protocol amendment\], 12 to \<18 years, and 18 to 60 years of age), and qualification status for the Primary Efficacy Analysis Population ("qualifies" or "does not qualify"). \[NOTE: EU region will only enroll 18 to 60 years of age\]

Study Record Dates

• First Submitted: February 16, 2023
• First Posted: March 20, 2023
• Study Start: May 31, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

AU (1); DE (1); GB (2); NO (1); DK (1); NL (1); US (13); IT (1)