Clinical trial NCT05775848: Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients With Limb Girdle Muscular Dystrophy 2I (LGMD2I)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I)
Lead sponsor: ML Bio Solutions, Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-20
Enrollment: 81
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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").

\[NOTE: EU region will only enroll 18 to 60 years of age\]
Primary purpose: TREATMENT

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.


Eligibility criteria: 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). \[NOTE: EU region will only enroll 18 to 60 years of age\]
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, or was on BBP-418 at any time.
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.

Primary outcomes:
measure: 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
timeFrame: 36 months
measure: Frequency and severity of treatment-emergent adverse events following 36 months of treatment to assess safety of BBP-418 or placebo
timeFrame: 36 months
Secondary outcomes:
measure: Change from baseline in 10 meter walk test velocity to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9
timeFrame: 36 months
measure: 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
timeFrame: 36 months
measure: 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
timeFrame: 36 months
Other outcomes:
measure: Change from baseline in total glycosylated Alpha dystroglycan to assess biomarkers for clinical efficacy of BBP-418 in patients with LGMD2I/R9
timeFrame: 36 months
measure: 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
timeFrame: 36 months
Locations:
city: Little Rock
country: United States
facility: Arkansas Children&#39;s Hospital
state: Arkansas
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota, Twin Cities
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU) - Neurology Clinic - South Waterfront
state: Oregon
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Norfolk
country: United States
facility: Children&#39;s Hospital of the Kings Daughters
state: Virginia
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital,
state: Queensland
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Neuromuscular Clinic and Research Unit
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin and Max Delbrück Center
city: Milan
country: Italy
facility: IRCCS Ca&#39; Granda Ospedale
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord-Norge, Department of Neurology
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Newcastle Upon Tyne
country: United Kingdom
facility: International Centre for Life
Study officials:
References: