A Study to Evaluate the Safety and Clinical Activity of Intramuscular Doses of BB-301 Administered to Subjects With Oculopharyngeal Muscular Dystrophy With Dysphagia

Conditions

• Oculopharyngeal Muscular Dystrophy

Eligibility Criteria

Sex

ALL

Age

N/A - 65 Years

Healthy Volunteers

Not accepted

Interventions

• BB-301: Dose escalation phase 1b cohort 1 — GENETIC
  BB-301 is composed of an AAV9 capsid, AAV9PL, which delivers the gene of interest, comprised of a recombinant genome encoding a single RNA transcript that produces a codon-optimized, wildtype PABPN1 protein as well as 2 short hairpin (sh)RNAs directed against the disease-causing mutant PABPN1 gene. Subjects in cohort 1 in the dose escalation phase of the study will receive a fixed number of intramuscular (IM) injections of BB-301 into the respective pharyngeal constrictor muscles on the day of dosing, with a total dose of 1.2e13 vg/subject.
• BB-301: Dose escalation phase 1b cohort 2 — GENETIC
  BB-301 is composed of an AAV9 capsid, AAV9PL, which delivers the gene of interest, comprised of a recombinant genome encoding a single RNA transcript that produces a codon-optimized, wildtype PABPN1 protein as well as 2 shRNAs directed against the disease-causing mutant PABPN1 gene. Subjects in cohort 2 in the dose escalation phase of the study will receive a fixed number of IM injections of BB-301 into the respective pharyngeal constrictor muscles on the day of dosing, with a total dose of 1.8e13 vg/subject.
• BB-301: Dose escalation phase 1b cohort 3 — GENETIC
  BB-301 is composed of an AAV9 capsid, AAV9PL, which delivers the gene of interest, comprised of a recombinant genome encoding a single RNA transcript that produces a codon-optimized, wildtype PABPN1 protein as well as 2 shRNAs directed against the disease-causing mutant PABPN1 gene. Subjects in cohort 3 in the dose escalation phase of the study will receive a fixed number of IM injections of BB-301 into the respective pharyngeal constrictor muscles on the day of dosing, with a total dose per subject to be determined following the completion of cohort 1 and cohort 2.
• BB-301: Dose expansion phase 2a — GENETIC
  Subjects in the dose expansion phase of the study will receive a fixed number of IM injections of BB-301 into the respective pharyngeal constrictor muscles on the day of dosing, at the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D).

Study Details

Subjects who have enrolled in the oculopharyngeal muscular dystrophy (OPMD) natural history study (Study BNTC-OPMD-NH-001) and have completed at least 6 months of follow up in Study BNTC-OPMD-NH-001 may be eligible to participate in this study, where all subjects will be treated with a single dose of BB-301. BB-301 will be injected directly into the middle pharyngeal constrictor muscle and the inferior pharyngeal constrictor muscle of the throat through the use of an open surgical procedure conducted under general anesthesia. The primary objectives of the study are to evaluate the safety of BB-301, to identify the best dose of BB-301 to administer to patients, and to characterize how well BB-301 works to improve the symptoms of dysphagia in patients with OPMD.

Key Dates

Start date

Nov 28, 2023

Status verified

Dec 2025

Primary completion

Nov 30, 2030

Completion

Nov 30, 2040

Study Design

Enrollment

30 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: BB-301 Treatment
  The phase 1b component of the study is the dose escalation phase which will enroll up to 18 subjects in up to 3 dosing cohorts. The phase 2a component of the study is the dose expansion phase which will enroll up to 12 subjects.

Primary Outcome Measure

Incidence of dose-limiting toxicities (DLTs) in phase 1b [ Time Frame: Up to 60 days ]

Central Contacts

• Jerel A. Banks, M.D., Ph.D.
  (510)-780-0634
  [email protected]
• Sophie Mukadam
  [email protected]

Locations (1)

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