LGMD2I
Conditions
Keywords
LGMD, LGMD R9, Limb Girdle Muscular Dystrophy
Brief summary
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
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.
Interventions
DRUGBBP-418
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.
Sponsors
ML Bio Solutions, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
12 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation | 60 months |
Secondary
| Measure | 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 |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAmy Harper, MD
Virginia Commonwealth University
Outcome results
None listed