Study of BBP-418 in Patients With LGMD2I

Study Overview
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Brief Summary
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BBP-418 is being developed for the treatment of patients with Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I). This is an open label study to determine the safety and tolerability of ascending dose levels of BBP-418 in the treatment of ambulatory and non-ambulatory patients with LGMD2I for which no approved therapy currently exists.

Detailed Description
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This is an open label study in ambulatory and non-ambulatory subjects with LGMD2I (also known as LGMD R9) previously enrolled in the natural history Study MLB-01-001. This is a study to determine the safety and tolerability of ascending dose levels of BBP-418 in those subjects.

Official Title
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An Open Label Phase 2 Study of BBP-418 in Patients With Limb Girdle Muscular Dystrophy Type 2I (MLB-01-003)

Conditions
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LGMD2I

Intervention / Treatment
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* Drug: BBP-418


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a body weight >30 kg Have a genetically confirmed diagnosis of LGMD2I and be clinically affected (defined as demonstrating clinical weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity) Able to complete the 10-meter walk test in ≤ 12 seconds unaided (moderate disease) or are with severe disease/non-ambulatory as defined by being unable to complete the 10-meter walk unaided in >12 seconds Willing to use an adequate method of contraception from time of consent through 12 weeks after last dose Previous enrolment in the Natural History study MLB-01-001 Exclusion Criteria: Evidence of clinically significant concomitant disease, including: Any history of a gastrointestinal condition, including surgeries, which may affect absorption after oral administration Any significant concomitant medical condition, including cardiac, pulmonary, renal, hepatic or endocrine disease other than that associated with LGMD2I Any condition other than LGMD2I requiring therapy with prescription medicine (medication for common and mild concomitant conditions may be permitted after consultation with the PI) Any other laboratory, vital sign, ECG abnormality, or 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 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. History of drug abuse including alcoholism within 2 years prior to consenting Use of ribose or other sugar alcohol-containing supplement within 60 days of Day 1 Use of a corticosteroid within 60 days of Day 1 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 60 days prior to Day 1.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Subjects must have been enrolled in the MLB-01-001 study to participate in this trial. Three ascending dose cohorts of 4-6 subjects each are planned.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Subjects will receive 6 grams of BBP-418 once daily x 90 days, then 12 grams twice daily (BID, a least 8 hours apart) of BBP-418 daily until study completion. | Drug: BBP-418<br>* BBP-418 is being developed for the treatment of patients with Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I) for which no approved therapy currently exists. It targets the molecular defect at the source by supplying excess substrate to the mutant enzyme thus boosting glycosylation of muscle α-dystroglycan. The BBP-418 drug product will be packaged in sachets and provided in a carton for in-clinic and at home use.<br>|
| Experimental: Cohort 2<br>Subjects will receive 6 grams of BBP-418 twice daily (BID, at least 8 hours apart) x 90 days, then 12 grams BID of BBP-418 daily until study completion. | Drug: BBP-418<br>* BBP-418 is being developed for the treatment of patients with Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I) for which no approved therapy currently exists. It targets the molecular defect at the source by supplying excess substrate to the mutant enzyme thus boosting glycosylation of muscle α-dystroglycan. The BBP-418 drug product will be packaged in sachets and provided in a carton for in-clinic and at home use.<br>|
| Experimental: Cohort 3<br>Subjects will receive 12 grams of BBP-418 twice daily (BID, at least 8 hours apart) x 90 days, then 12 grams BID of BBP-418 daily until study completion. | Drug: BBP-418<br>* BBP-418 is being developed for the treatment of patients with Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I) for which no approved therapy currently exists. It targets the molecular defect at the source by supplying excess substrate to the mutant enzyme thus boosting glycosylation of muscle α-dystroglycan. The BBP-418 drug product will be packaged in sachets and provided in a carton for in-clinic and at home use.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation |  | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of BBP-418 by assessment of maximum concentration (Cmax) |  | 24 months | 
| Changes in pharmacodynamic parameters by assessing changes in levels of N-terminal fragment of alpha dystroglycan (α-DG) |  | 24 months | 
| Changes in pharmacodynamic parameters by assessing muscle biopsy of the tibialis anterior |  | 24 months | 
| Pharmacokinetic profile of BBP-418 by assessment of area under the curve (AUC) |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LGMD, LGMD R9, Limb Girdle Muscular Dystrophy