This is an open label study in ambulatory and non-ambulatory subjects with LGMD2I (also known as LGMD R9). This is a study to determine the safety and tolerability of ascending dose levels of BBP-418 in those subjects.
Subjects must have been enrolled in the MLB-01-001 study to participate in this trial. Three ascending dose cohorts of 4 subjects each are planned, but a fourth cohort may be added.
- Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation [ Time Frame: 90 days ]
- Pharmacokinetic profile of BBP-418 by assessment of maximum concentration (Cmax) [ Time Frame: Day 1 and Day 90 ]
- Changes in pharmacodynamic parameters by assessing changes in levels of N-terminal fragment of alpha dystroglycan (α-DG) [ Time Frame: Day 1 and Day 90 ]
- Changes in pharmacodynamic parameters by assessing muscle biopsy of the tibialis anterior [ Time Frame: Day 1 and Day 90 ]
- Pharmacokinetic profile of BBP-418 by assessment of area under the curve (AUC) [ Time Frame: Day 1 and Day 90 ]
Ages Eligible for Study: 12 Years to 55 Years (Child, Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
- 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 MLB-01-001 study
- 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 and the Medical Monitor)
- 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, planning to become 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.
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23219
ML Bio Solutions, Inc.
Nicholas Johnson, MD
Virginia Commonwealth University