Recruiting

Phase 1

Phase 2

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

Sponsor:

Benitec Biopharma, Inc.

Code:

NCT06185673

Conditions

Oculopharyngeal Muscular Dystrophy

Eligibility Criteria

Sex: All

Age: 0 - 65

Healthy Volunteers: Not accepted

Interventions

BB-301: Dose escalation phase 1b cohort 1

BB-301: Dose escalation phase 1b cohort 2

BB-301: Dose escalation phase 1b cohort 3

BB-301: Dose expansion phase 2a

Study Details

Brief summary:

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.

Conditions

Oculopharyngeal Muscular Dystrophy

Study ID

NCT06185673

Start date

Nov 28, 2023

Status verified date

Dec, 2025

Completion date

Nov, 2040

Anticipated

Primary completion date

Nov, 2030

Anticipated

Eligibility Criteria

Sex: All

Age: 0 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

Subject was previously enrolled in the BNTC-OPMD-NH-001 natural history (NH) study and completed at least 6 months of follow-up in the NH study.
Signed written informed consent prior to the initiation of any study-specific procedures.
Males or females, aged ≥50 to ≤65 years at the time of NH study enrollment, with genetically diagnosed heterozygous OPMD disease (as indicated by 1 of the following allelic classifications: GCN10/GCN12, GCN10/GCN13, GCN10/GCN14, GCN10/GCN15, GCN10/GCN16) OR
Males or females, aged ≤65 years at the time of NH study enrollment, with genetically diagnosed homozygous OPMD disease (as indicated by 1 of the following allelic classifications: GCN12/GCN12, GCN13/GCN13, GCN14/GCN14, GCN15/GCN15, GCN16/GCN16).
Subject is eligible and willing to undergo a surgical dissection of the pharyngeal region with intubation under general anesthesia to administer the study drug.
Subject has moderate dysphagia, defined as pharyngeal area at maximum constriction (PhAMPC) >2.7%(C2-4)\^2 with natural sips of thin liquid barium or PhAMPC >2.1%(C2-4)\^2 with teaspoon delivery of moderately thick liquid barium.
Subject is not of childbearing potential, i.e., is postmenopausal (absence of menstrual bleeding for ≥1 year before Baseline, without any other medical reason), or has documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy OR
Subject or their partner is of childbearing potential and agrees to use 2 highly effective forms of contraception during the study and continuing through 52 weeks after the study drug administration. The 2 authorized forms of contraception are condom used with 1 of the following methods of contraception:

bilateral tubal ligation
combined oral contraceptives (estrogens and progesterone), vaginal ring, or implanted or injectable hormonal contraceptives with a stable dose for at least 1 month prior to the day of dosing; hormonal contraceptives must inhibit ovulation
intrauterine device inserted at least 1 month prior to the day of dosing OR
Subject agrees to abstain from heterosexual intercourse during study participation and to use a highly effective form of contraception (as described above) as backup if they become sexually active during the study. Abstinence is only acceptable if this is the subject's usual lifestyle. Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.
Subjects capable of donating sperm must agree not to donate sperm beginning at Screening and continuing through 52 weeks after the study drug administration.

Exclusion Criteria:

Subject has received prior treatment with an adeno-associated virus (AAV) vector (e.g., AAV-based therapy for the treatment of hemophilia B \[including HEMGENIX®\], AAV-based therapy for the treatment of RPE65 mutation-associated retinal dystrophy \[including LUXTURNA®\]).
Subject with presence of anti-AAV9 antibody titers >1:50.
Subject is pregnant or breastfeeding.
In the investigator's opinion, the subject's pharyngeal muscle is not amenable to intramuscular (IM) injection due to clinically significant atrophy as assessed by maximum pharyngeal dilation for OPMD subjects (determined by normalized post-swallow hyoid rest pharyngeal area \[HRAN\] using videofluoroscopy) compared to relative HRAN measurements of pharyngeal dilation from a database comprising healthy control subjects as determined during the Screening Visit of the NH study.
Subject with contraindication to the videofluoroscopy procedures (e.g., allergy to any of the radiopaque contrast agents planned for use in the study).
Subject has received gene therapy (e.g., chimeric antigen receptor-positive T cell therapy for the treatment of leukemia, lymphoma, or multiple myeloma \[including ABECMA®, BREYANZI®, CARVYKTI™, KYMRIAH®, YESCARTA®, and TECARTUS™\], IMLYGIC® for the treatment of melanoma, SKYSONA® for the treatment of cerebral adrenoleukodystrophy, and ZYNTEGLO® for the treatment of β-thalassemia) within the 6 months prior to Screening.
Subject for whom any of the proposed study procedures or medications (e.g., corticosteroids) would be contraindicated.
Subject has had prior cricopharyngeal myotomy or cricopharyngeal botulinum toxin injection.
Subject has had cricopharyngeal dilation within the 12 months prior to Screening.
Subject with pre-existing clinically diagnosed and/or self-reported dysphagia has been hospitalized within the 12 months prior to Screening for treatment of pneumonia of nonpathogenic origin (e.g., aspiration pneumonitis secondary to aspiration of sterile gastric contents) or pneumonia secondary to bacterial pathogens. A subject is eligible for enrollment if diagnosed with pneumonia secondary to documented pathogenic organism(s)including: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, i.e., coronavirus disease 2019), non-SARS-CoV-2-related viral pathogens, and fungal pathogens.
Subject has been intubated within the 30 days prior to Screening.
Subject consumes a very restricted range of diet textures, defined as a score of ≤3 on the IDDSI Functional Diet Scale as determined during the Screening Visit of the NH study.
Subject presents with muscular dystrophy and/or other neuromuscular diseases distinct from OPMD, or any other disease that may significantly interfere with the characterization of dysphagia in OPMD.
Subject presents with other disorders associated with dysphagia, e.g., severe gastroesophageal reflux, esophageal stricture due to mechanical or chemical trauma, infection (e.g., esophageal moniliasis), drug-induced dysphagia (e.g., bisphosphonates), esophageal rings and webs, or spastic motility disorders of the esophagus.
Subject with any concomitant illness likely to significantly decrease life expectancy or any malignancy other than curatively treated skin cancer or in situ carcinoma of the cervix, unless adequately treated or in complete remission for ≥5 years.
Subject has received a diagnosis of head and neck cancer at any time.
Subject has any history of neck irradiation.
Subject has undergone a major surgical procedure to the mouth or neck. Subject is eligible for enrollment with a past medical history of routine dental procedures, tonsillectomy, or adenoidectomy.
Subject has abnormal liver function (serum alanine aminotransferase or aspartate aminotransferase >2.5 × upper limit of normal).
Subject is immunocompromised or is receiving immunosuppressant therapy.
Subject has evidence of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, neurologic, or allergic diseases (including drug allergies but excluding untreated, not clinically significant, seasonal allergies).
Subject has NCI CTCAE grade 3 hypertension defined as systolic blood pressure consistently ≥160 mmHg or diastolic blood pressure consistently ≥100 mmHg.
Subject has malnutrition defined as unintended weight loss of >5-10% during the 1 to 6 months prior to Screening and a body mass index (BMI) of <18.5 to 20 kg/m², or subject has cachexia defined as weight loss of >5% over the past 6 months or a BMI of <20 kg/m² and ongoing weight loss of >2%.
Subject has received treatment with an investigational drug, investigational device, or approved therapy for investigational use within the 3 months or 5 half-lives prior to Screening.
Subject has any kind of disorder that, in the investigator's opinion, compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
Subject is unwilling or unable to comply with study procedures and scheduled follow-up visits.
Subject has any other medical or social condition that, in the investigator's opinion, would not permit the subject to complete the study or sign informed consent.

Study Design

Enrollment

30 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

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.

Interventions

BB-301: Dose escalation phase 1b cohort 1

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

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

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

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).

Primary outcome measure

Incidence of dose-limiting toxicities (DLTs) in phase 1b [ Time Frame: Up to 60 days ]
Incidence of adverse events (AEs) according to NCI CTCAE v5.0 in phase 1b and in phase 2a [ Time Frame: Up to 360 days ]
Phase 1b: Swallowing efficiency as measured by Vallecular Residue %(C2-4)^2 [ Time Frame: Baseline, Day 90, Day 180, Day 270, Day 360 ]
Phase 1b: Swallowing efficiency as measured by Pyriform Sinus Residue %(C2-4)^2 [ Time Frame: Baseline, Day 90, Day 180, Day 270, Day 360 ]
Phase 1b: Swallowing efficiency as measured by Other Pharyngeal Residue %(C2-4)^2 [ Time Frame: Baseline, Day 90, Day 180, Day 270, Day 360 ]
Phase 1b: Swallowing efficiency as measured by Total Pharyngeal Residue %(C2-4)^2 [ Time Frame: Baseline, Day 90, Day 180, Day 270, Day 360 ]
Phase 1b: Pharyngeal constrictor muscle function as estimated by the pharyngeal area at maximum constriction (PhAMPC) [ Time Frame: Baseline, Day 90, Day 180, Day 270, Day 360 ]
Phase 2a: Swallowing efficiency as measured by Vallecular Residue %(C2-4)^2 [ Time Frame: Baseline, Day 90, Day 180, Day 270, Day 360 ]
Phase 2a: Swallowing efficiency as measured by Pyriform Sinus Residue %(C2-4)^2 [ Time Frame: Baseline, Day 90, Day 180, Day 270, Day 360 ]
Phase 2a: Swallowing efficiency as measured by Other Pharyngeal Residue %(C2-4)^2 [ Time Frame: Baseline, Day 90, Day 180, Day 270, Day 360 ]
Phase 2a: Swallowing efficiency as measured by Total Pharyngeal Residue %(C2-4)^2 [ Time Frame: Baseline, Day 90, Day 180, Day 270, Day 360 ]
Phase 2a: Pharyngeal constrictor muscle function as estimated by PhAMPC [ Time Frame: Baseline, Day 90, Day 180, Day 270, Day 360 ]

Central Contacts and Locations

Central contacts

Jerel A. Banks, M.D., Ph.D.

(510)-780-0634 jbanks@benitec.com

Sophie Mukadam

smukadam@benitec.com

Locations

NYU Langone Health

Recruiting

New York, New York, United States, 10016

Contacts

Stratos Achlatis, M.D.

(646)-754-1206 efstratios.achlatis@nyulangone.org

Principal Investigator:

Milan R. Amin, M.D.

More Information

Sponsor

Benitec Biopharma, Inc.

Last update posted

Dec 31, 2025

Last verified

Dec, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Benitec Biopharma, Inc. on 2025-12-31.