Clinical trial NCT04800874: Study of BBP-418 in Patients With LGMD2I
Official title: An Open Label Phase 2 Study of BBP-418 in Patients With Limb Girdle Muscular Dystrophy Type 2I (MLB-01-003)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: LGMD2I
Keywords: LGMD
LGMD R9
Limb Girdle Muscular Dystrophy
Lead sponsor: ML Bio Solutions, Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-16
Enrollment: 14
Sex: ALL
Minimum age (years): 12
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation
timeFrame: 60 months
Secondary outcomes:
measure: Pharmacokinetic profile of BBP-418 by assessment of maximum concentration (Cmax)
timeFrame: 24 months
measure: Changes in pharmacodynamic parameters by assessing changes in levels of N-terminal fragment of alpha dystroglycan (α-DG)
timeFrame: 24 months
measure: Changes in pharmacodynamic parameters by assessing muscle biopsy of the tibialis anterior
timeFrame: 24 months
measure: Pharmacokinetic profile of BBP-418 by assessment of area under the curve (AUC)
timeFrame: 24 months
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Amy Harper, MD
role: PRINCIPAL_INVESTIGATOR
References: