RIBITOL for Limb girdle muscular dystrophy 2I (LGMD2I/R9)

Inclusion criteria

• {"criterion_text":"- 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)."}
• {"criterion_text":"- Male or female participants 18 to 60 years of age (inclusive)."}
• {"criterion_text":"- Have a body weight >30 kg."}
• {"criterion_text":"- The participant who signs the informed consent form (ICF) understands the study procedures and the participant agrees to participate in the study by giving informed consent."}
• {"criterion_text":"- Women of childbearing potential (WOCBP) 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."}
• {"criterion_text":"- Willing and able to complete all study procedures, including biopsies, according to the Schedule of Assessments."}

Exclusion criteria

• {"criterion_text":"- Evidence of clinically significant concomitant disease, including: Any significant concomitant medical condition, including cardiac, renal, pulmonary, hepatic, or endocrine disease other than that associated with LGMD2I/ R9; Moderate to severe renal impairment (eGFR < 60 mL/min/1.73 m2 based on cystatin C[CysC], as calculated by central laboratory; 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; 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."}
• {"criterion_text":"- Previously received gene therapy to treat LGMD2I/ R9."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Presence of a platelet disorder, bleeding disorder, or other contraindication to muscle biopsy."}
• {"criterion_text":"- Actively on an experimental therapy or device, was on an experimental therapy or device within 90 days prior to the Screening Visit, or was on BBP-418 at any time"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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 enrol in this study provided all inclusion and no other exclusion criteria are met.)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Use of ribose or other sugar alcohol-containing supplement within 90 days of the Screening Visit."}
• {"criterion_text":"- 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.)"}

Primary endpoints

• {"endpoint_text":"- Change from baseline in NSAD at 36 months","definition_or_measurement_approach":"Change from baseline measured using the NSAD (North Star Assessment for LGMD) score at 36 months."}
• {"endpoint_text":"- Frequency and severity of TEAEs and TESAEs","definition_or_measurement_approach":"Assessment and reporting of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs), including counts and severity grading."}
• {"endpoint_text":"- Results of physical examinations including vital signs","definition_or_measurement_approach":"Standard physical examinations and vital signs assessments per Schedule of Assessments."}
• {"endpoint_text":"- Chemistry and hematology laboratory analyses","definition_or_measurement_approach":"Central and/or local laboratory chemistry and hematology tests as defined in the protocol."}
• {"endpoint_text":"- 12-lead ECG, including QTc intervals","definition_or_measurement_approach":"Standard 12-lead electrocardiogram assessments including measurement/reporting of QTc intervals."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in 10MWT (velocity, m/s) at 36 months","definition_or_measurement_approach":"Change from baseline in 10-meter walk test velocity (m/s) measured at 36 months."}
• {"endpoint_text":"- Change from baseline in pulmonary function as measured by FVC (percent predicted, performed in a sitting position) at 36 months","definition_or_measurement_approach":"Change from baseline in forced vital capacity (FVC) percent predicted measured in sitting position at 36 months."}
• {"endpoint_text":"- Change from baseline in the PUL2.0 at 36 months","definition_or_measurement_approach":"Change from baseline measured by the PUL2.0 assessment at 36 months."}
• {"endpoint_text":"- Change from baseline in NSAD at 36 months","definition_or_measurement_approach":"Change from baseline in NSAD score at 36 months (appears also as a secondary endpoint)."}
• {"endpoint_text":"- Change from baseline in total glycosylated αDG expression","definition_or_measurement_approach":"Change from baseline in total glycosylated alpha-dystroglycan (αDG) expression measured by assay specified in protocol."}
• {"endpoint_text":"- Change from baseline in glycosylated αDG/ total αDG ratio","definition_or_measurement_approach":"Change from baseline in the ratio of glycosylated αDG to total αDG as measured by protocol-specified assays."}
• {"endpoint_text":"- Change from baseline in pre-functional assessment serum CK","definition_or_measurement_approach":"Change from baseline in serum creatine kinase (CK) measured prior to functional assessments."}

Netherlands

Earliest CTIS Part Ii Submission Date

15-01-2024

Latest Decision Or Authorization Date

21-11-2025

Processing Time Days

676

Number Of Sites

1

Number Of Participants

7

Germany

Earliest CTIS Part Ii Submission Date

04-12-2023

Latest Decision Or Authorization Date

11-12-2025

Processing Time Days

738

Number Of Sites

2

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

15-11-2023

Latest Decision Or Authorization Date

10-12-2025

Processing Time Days

756

Number Of Sites

1

Number Of Participants

4

Denmark

Earliest CTIS Part Ii Submission Date

13-12-2023

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

833

Number Of Sites

1

Number Of Participants

15

Norway

Earliest CTIS Part Ii Submission Date

22-12-2023

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

824

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

ML Bio Solutions Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Fortrea Inc.

Responsibilities

Operational and sponsor support duties (sponsorDuties codes listed in record), contact MLBio8482684@fortrea.com

Name

DLRC Limited

Responsibilities

Local/site support duties (sponsorDuties code 12), contact mlbioclinicaltrials@dlrcgroup.com

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Sponsor duties codes: 1,10,11,12,13,14,15,2,3,4,5,6,7,8,9 (includes item with value 'Contract Negotiation and execution'); contact: MLBio8482684@fortrea.com, +17432083351","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"DLRC Limited","duties_or_roles":"Sponsor duties codes: 12; contact: mlbioclinicaltrials@dlrcgroup.com, +441462372472","organisation_type":"Pharmaceutical company"}