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

A Phase 3 Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients With Limb Girdle Muscular Dystrophy 2I (LGMD2I)

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.

Study Overview

• Status: Recruiting
• Conditions: Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I)
• Intervention / Treatment: Drug: BBP-418 (ribitol); Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: ML Bio Soultions Patient Information; Phone Number: (646) 659-6642; Email: info@mlbiosolutions.com

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia
      • Recruiting
      • Royal Brisbane and Women's Hospital,
      • Principal Investigator: Robert Henderson
      • Contact: Kate Thorpe, MD; Phone Number: 36460016; Email: Kathryn.thorpe@health.qld.gov.au
• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Rigshospitalet, Neuromuscular Clinic and Research Unit
    • Contact: John Vissing, Prof, MD; Phone Number: +45 35452562; Email: john.vissing@regionh.dk
    • Principal Investigator: John Vissing, Prof, MD
• Italy
  • Milan, Italy
    • Recruiting
    • IRCCS Ca' Granda Ospedale
    • Principal Investigator: Giacomo Comi, MD
    • Contact: Giacomo Comi, Prof, MD; Phone Number: 390255033801; Email: giacomo.comi@unimi.it
• Netherlands
  • Leiden, Netherlands
    • Not yet recruiting
    • Leiden University Medical Center
    • Principal Investigator: Erik Niks, MD
    • Contact: Erik Niks, MD
• Norway
  • Tromsø, Norway
    • Recruiting
    • Universitetssykehuset Nord-Norge, Department of Neurology
    • Contact: Kjell Arne Arntzen, PhD, MD; Email: Kjell.arne.arntzen@unn.no
    • Principal Investigator: Kjell Arne Arntzen, PhD, MD
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Great Ormond Street Hospital for Children
    • Contact: Giovanni Baranello, MD
    • Principal Investigator: Giovanni Baranello, MD
  • Newcastle Upon Tyne, United Kingdom
    • Recruiting
    • International Centre for Life
    • Principal Investigator: Volker Straub, Prof MD
    • Contact: Volker Straub, Prof, MD; Phone Number: 441912418610; Email: nmd.clinicaltrials@newcastle.ac.uk
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Not yet recruiting
      • Arkansas Children's Hospital
      • Principal Investigator: Aravindhan Veerapandiyan, MD
      • Contact: Aravindhan Veerapandiyan
  • California
    • Irvine, California, United States, 92697
      • Recruiting
      • University of California Irvine
      • Principal Investigator: Mozaffar Tasheen, MD
      • Contact: Tahseen Mozaffar, MD; Email: mozaffar@hs.uci.edu
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
      • Principal Investigator: Thomas Ragole, MD
      • Contact: Thomas Ragole, MD; Phone Number: 303-724-4644; Email: NeuroResearch@cuanschutz.edu
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida
      • Contact: Carla Zingariello, MD; Phone Number: 352-273-8687; Email: czingariello@ufl.edu
      • Principal Investigator: Carla Zingariello, MD
      • Contact: Yara Mohamed; Phone Number: (352) 294-8962; Email: yaramohamed@peds.ufl.edu
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Rare Disease Research LLC
      • Principal Investigator: Han Phan, MD
      • Contact: Han Phan
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Kathryn Mathews, MD; Phone Number: 319-356-7726; Email: Katherine-Mathews@uiowa.edu
      • Principal Investigator: Kathryn Mathews, MD
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center
      • Contact: Jeffrey Statland, MD; Phone Number: 913-945-9933; Email: jstatland@kumc.edu
      • Principal Investigator: Jeffrey Statland, MD
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Kennedy Krieger Institute
      • Contact: Doris Leung, MD; Phone Number: 443-923-9525; Email: LeungD@kennedykrieger.org
      • Principal Investigator: Doris Leung, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota, Twin Cities
      • Contact: Peter Kang, MD; Phone Number: 612-626-7038; Email: pkang@umn.edu
      • Principal Investigator: Peter Kang
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Olivia Money; Phone Number: 314-273-7807; Email: moneyo@wustl.edu
      • Principal Investigator: Conrad Weihl, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University (OHSU) - Neurology Clinic - South Waterfront
      • Contact: Diana Dimitrov, PhD; Phone Number: 503-494-7269; Email: dimitrov@ohsu.edu
      • Contact: Nizar Chahin, MD; Email: chahin@ohsu.edu
      • Principal Investigator: Nizar Chahin, MD
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Withdrawn
      • Penn State
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Principal Investigator: Lauren Elman, MD
      • Contact: Lauren Elman, MD; Phone Number: 215-829-6708; Email: lauren.elman@pennmedicine.upenn.edu
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • The Children's Hospital of Philadelphia
      • Contact: John Brandsema, MD; Phone Number: 215-590-1719; Email: BrandsemaJ@chop.edu
      • Principal Investigator: John Brandsema
  • Texas
    • San Antonio, Texas, United States, 78015
      • Not yet recruiting
      • University of Texas Health Science Center at San Antonio School of Medicine
      • Contact: Matthew Wicklund
      • Principal Investigator: Matthew Wicklund
  • Virginia
    • Norfolk, Virginia, United States, 23455
      • Not yet recruiting
      • Children's Hospital of the Kings Daughters
      • Principal Investigator: Crystal Proud, MD
      • Contact: Crystal Proud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Participants must meet all the following criteria to be enrolled:

1. Have a genetically confirmed diagnosis of LGMD2I/R9 (including review of records of previous molecular genetic testing) and be clinically affected (defined as demonstrating clinical weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity).
2. Male or female participants 12 to 60 years of age (inclusive).
3. Have a body weight >30 kg.
4. The participant (or parent/guardian) who signs the ICF understands the study procedures and the participant agrees to participate in the study by giving informed consent (and assent, if <18 years of age).
5. Female participants of childbearing potential and male participants of reproductive potential must be willing to use a highly effective method of contraception from time of consent through 12 weeks after last dose.
6. Willing and able to complete all study procedures, including biopsies, according to the Schedule of Assessments (see Appendix 1).

Participants must not meet any of the following criteria to be enrolled:

1. Evidence of clinically significant concomitant disease, including:

   1. Any significant concomitant medical condition, including mental, cardiac, renal, pulmonary, hepatic, or endocrine disease other than that associated with LGMD2I/R9.
   2. Moderate to severe renal impairment (estimated glomerular filtration rate [eGFR] of < 60 mL/min/1.73 m2 based on cystatin C [CysC]), as calculated by the central laboratory.
   3. Any other laboratory, vital sign, ECG abnormality, clinical history, or finding that, in the Investigator's opinion, is likely to unfavorably alter the risk-benefit of study participation, confound study results, or interfere with study conduct or compliance.
   4. Surgery for scoliosis or other indication that will significantly impact the participant's ability to execute clinical assessments planned or expected to be required to manage curvature within 12 months following the Screening Visit.
2. A participant with a score of zero on any one or more of the primary or key secondary endpoints at the time of screening. (Participants who previously completed participation in Study MLB-01-001 and would be excluded due to this criterion may enroll in this study provided all inclusion and no other exclusion criteria are met.)
3. 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.
4. Use of ribose or other sugar alcohol-containing supplement within 90 days of the Screening Visit.
5. 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.)
6. Previously received gene therapy to treat LGMD2I/R9.
7. 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).
8. Presence of a platelet disorder, bleeding disorder, or other contraindication to muscle biopsy.
9. Actively on an experimental therapy or device or was on an experimental therapy or device within 90 days of the Screening Visit.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BBP-418; 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); 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 to provide 3 g BBP-418 per sachet. The BBP-418 Granules for Oral Solution are reconstituted in water for oral administration.; Other: Placebo; 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.
Placebo Comparator: Placebo to Match BBP-418; The placebo will be identical to the BBP-418 Granules for Oral Solution in appearance, packaging, labeling, and storage conditions.	Drug: BBP-418 (ribitol); 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 to provide 3 g BBP-418 per sachet. The BBP-418 Granules for Oral Solution are reconstituted in water for oral administration.; Other: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: ML Bio Solutions, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: March 16, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle
• Other Study ID Numbers: MLB-01-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No