Oculopharyngeal Muscular DystrophyPhase 1/2NCT06185673
A Study to Evaluate the Safety and Clinical Activity of Intramuscular Doses of BB-301 Administered to Subjects With Oculopharyngeal Muscular Dystrophy With Dysphagia
A Phase 1/2 study testing BB-301: Dose escalation phase 1b cohort 1, BB-301: Dose escalation phase 1b cohort 2 and BB-301: Dose escalation phase 1b cohort 3 in people with Oculopharyngeal Muscular Dystrophy, run by Benitec Biopharma, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 65 years
- Conditions the study is for
- Oculopharyngeal Muscular Dystrophy
- What is being tested?
- BB-301: Dose escalation phase 1b cohort 1, BB-301: Dose escalation phase 1b cohort 2 and BB-301: Dose escalation phase 1b cohort 3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Nov 2023to Nov 2040
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sophie Mukadam contact
United States1 site, 1 recruiting
- Recruiting
NYU Langone Health
New York, New York, 10016
Stratos Achlatis, M.D., (646)-754-1206, efstratios.achlatis@nyulangone.org
Milan R. Amin, M.D.
About this study
Official title: A Phase 1b/2a, Open-label, Dose Escalation Study to Evaluate the Safety and Clinical Activity of Intramuscular Doses of BB-301 Administered to Subjects With Oculopharyngeal Muscular Dystrophy With Dysphagia
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
- Being tested
- 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
- Medical subject headings
- Muscular Dystrophy, Oculopharyngeal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BB-301: Dose escalation phase 1b cohort 1Genetic
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 2Genetic
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 3Genetic
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 2aGenetic
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 group | Role | What they receive |
|---|---|---|
| BB-301 Treatment | Experimental | 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. Receives: Genetic: BB-301: Dose escalation phase 1b cohort 1; Genetic: BB-301: Dose escalation phase 1b cohort 2; Genetic: BB-301: Dose escalation phase 1b cohort 3; Genetic: BB-301: Dose expansion phase 2a |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs) in phase 1b
A DLT will be defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, as follows:
- Any Grade 2 toxicity not resolving within 14 days or any Grade 3 toxicity, assessed to be possibly related to the investigational product.
Measured: Up to 60 days
Incidence of adverse events (AEs) according to NCI CTCAE v5.0 in phase 1b and in phase 2a
For this outcome measure, AEs arising in the 360 days following administration of BB-301 will be considered. Long term AEs will be monitored for 15 years following subject dosing.
Measured: Up to 360 days
Phase 1b: Swallowing efficiency as measured by Vallecular Residue %(C2-4)^2
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The Analysis of Swallowing Physiology: Events, Kinematics and Timing (ASPEKT) method will be used to determine Vallecular Residue %(C2-4)^2.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Swallowing efficiency as measured by Pyriform Sinus Residue %(C2-4)^2
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Pyriform Sinus Residue %(C2-4)^2.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Swallowing efficiency as measured by Other Pharyngeal Residue %(C2-4)^2
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Other Pharyngeal Residue %(C2-4)^2.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Swallowing efficiency as measured by Total Pharyngeal Residue %(C2-4)^2
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Total Pharyngeal Residue %(C2-4)^2.
Measured: 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)
Videofluoroscopy will be used to characterize the area of the pharynx at the point of maximum constriction during swallowing. The PhAMPC uses the videofluoroscopy frame of maximum pharyngeal constriction, defined as the frame with the smallest amount of unobliterated air space and barium-containing bolus visible in the pharynx. The pixelated area of the frame of maximum constriction is normalized via the use of the C2-C4 length squared (i.e., [C2-4]^2) as the denominator.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Swallowing efficiency as measured by Vallecular Residue %(C2-4)^2
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Vallecular Residue %(C2-4)^2.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Swallowing efficiency as measured by Pyriform Sinus Residue %(C2-4)^2
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Pyriform Sinus Residue %(C2-4)^2.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Swallowing efficiency as measured by Other Pharyngeal Residue %(C2-4)^2
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Other Pharyngeal Residue %(C2-4)^2.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Swallowing efficiency as measured by Total Pharyngeal Residue %(C2-4)^2
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Total Pharyngeal Residue %(C2-4)^2.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Pharyngeal constrictor muscle function as estimated by PhAMPC
Videofluoroscopy will be used to characterize the area of the pharynx at the point of maximum constriction during swallowing. The PhAMPC uses the videofluoroscopy frame of maximum pharyngeal constriction, defined as the frame with the smallest amount of unobliterated air space and barium-containing bolus visible in the pharynx. The pixelated area of the frame of maximum constriction is normalized via the use of the C2-C4 length squared (i.e., [C2-4]^2) as the denominator.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Secondary outcomes (18)
Phase 1b: Global swallowing function as measured by the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale
The DIGEST scale is a validated 5-point Common Terminology Criteria for Adverse Events-compatible modified barium swallow grade, based on the interaction of pharyngeal residue and laryngeal penetration/aspiration ratings. DIGEST uses 2 component scores to quantify pharyngeal bolus transit: 1) safety profile (i.e., penetration/aspiration); and 2) efficiency profile (i.e., residue). Higher scores are indicative of more severe dysphagia, with 0 = no dysphagia, 1 = mild dysphagia, 2 = moderate dysphagia, 3 = severe dysphagia, and 4 = life-threatening dysphagia).
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Swallowing efficiency as measured by the Normalized Residue Ratio Scale (NRRS)
The NRRS is a continuous measurement for capturing residue severity using pixel-based measurements during videofluoroscopy that incorporate the ratio of residue relative to the available pharyngeal space and the residue proportionate to the size of the individual. "Pharyngeal residue" is a medical term used to describe material that remains in the pharynx post-swallow and is considered a sign of swallowing impairment.
Pharyngeal residue collects most commonly in: 1) the valleculae, bilateral spaces between the base of the tongue and the epiglottis (measured by the NRRSv); and 2) the pyriform sinuses, spaces formed on either side of the pharynx between the fibers of the inferior pharyngeal constrictor muscle and the sides of the thyroid cartilage and lined by orthogonally directed fibers of the palatopharyngeus muscle and pharyngobasilar fascia (measured by the NRRSp).
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Pharyngeal constrictor muscle function as estimated by the Pharyngeal Constriction Ratio (PCR)
The PCR was created to quantify the efficiency of the pharyngeal phase of swallowing via videofluoroscopy and was demonstrated to be a surrogate for pharyngeal muscle strength. The PCR is a pixel-based measure made on lateral view videofluoroscopy swallow study frames. The PCR is calculated by tracing the unobliterated area of the pharynx (including the bolus) at the point of maximum constriction during the swallow and then dividing that area by a corresponding area measure when the pharynx is at rest.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Maximum pharyngeal dilation as estimated by %(C2-4)^2-normalized post-swallow hyoid rest pharyngeal area (HRAN)
Maximum pharyngeal dilation will be estimated by HRAN. The post-swallow hyoid rest is defined as the earliest frame in videofluoroscopic swallowing study recordings following upper esophageal sphincter closure when the hyoid was observed to have descended and moved posteriorly to reach its original, pre-swallow position. The HRAN is the normalized (by %[C2-4]^2) area on the frame of post-swallow hyoid rest.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Dysphagia severity as measured by the cold water timed drinking test (CWDT)
The CWDT is the time in seconds a subject requires to swallow 80 mL of ice-cold water.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Maximum swallowing capacity as measured by the maximum swallowing speed (MSS)
The MSS is the time in seconds a subject requires to drink 150 mL of cold tap water as rapidly as possible.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Maximum swallowing capacity as measured by the maximum swallowing volume (MSV)
The MSV is the maximum amount of room-temperature tap water a subject is able to consume in 1 swallow.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Subject-reported oropharyngeal dysphagia as assessed by the Sydney Swallow Questionnaire (SSQ)
The SSQ is a self-report inventory assessing subjective symptoms of oropharyngeal dysphagia with strong content, construct, discriminant, and predictive validity and test-retest reliability in a range of patient populations. The SSQ is a 17-item questionnaire which was developed to measure symptomatic severity of oral-pharyngeal dysphagia as reported by the affected subject. The questionnaire uses a 100-mm long visual analogue scale for all but 1 question. Possible scores range from 0 to 1700, with higher scores indicating greater swallowing difficulty.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Subject-reported oropharyngeal dysphagia as assessed by the International Dysphagia Diet Standardization Initiative (IDDSI) Functional Diet Scale
The IDDSI Functional Diet Scale is a subject-reported oropharyngeal dysphagia functional outcome scale intended to capture the severity of oropharyngeal dysphagia, as represented by the degree of diet texture restriction recommended for the subject. The IDDSI framework consists of a continuum of 8 levels (0-7), where drinks are measured from Levels 0-4, while foods are measured from Levels 3-7. The IDDSI framework provides a common terminology to describe food textures and drink thickness. Lower scores reflect diet texture restrictions to thin liquids.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Global swallowing function as measured by the DIGEST scale
The DIGEST scale is a validated 5-point Common Terminology Criteria for Adverse Events-compatible modified barium swallow grade, based on the interaction of pharyngeal residue and laryngeal penetration/aspiration ratings. DIGEST uses 2 component scores to quantify pharyngeal bolus transit: 1) safety profile (i.e., penetration/aspiration); and 2) efficiency profile (i.e., residue). Higher scores are indicative of more severe dysphagia, with 0 = no dysphagia, 1 = mild dysphagia, 2 = moderate dysphagia, 3 = severe dysphagia, and 4 = life-threatening dysphagia).
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Swallowing efficiency as measured by the NRRS
The NRRS is a continuous measurement for capturing residue severity using pixel-based measurements during videofluoroscopy that incorporate the ratio of residue relative to the available pharyngeal space and the residue proportionate to the size of the individual. "Pharyngeal residue" is a medical term used to describe material that remains in the pharynx post-swallow and is considered a sign of swallowing impairment.
Pharyngeal residue collects most commonly in: 1) the valleculae, bilateral spaces between the base of the tongue and the epiglottis (measured by the NRRSv); and 2) the pyriform sinuses, spaces formed on either side of the pharynx between the fibers of the inferior pharyngeal constrictor muscle and the sides of the thyroid cartilage and lined by orthogonally directed fibers of the palatopharyngeus muscle and pharyngobasilar fascia (measured by the NRRSp).
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Pharyngeal constrictor muscle function as estimated by the PCR
The PCR was created to quantify the efficiency of the pharyngeal phase of swallowing via videofluoroscopy and was demonstrated to be a surrogate for pharyngeal muscle strength. The PCR is a pixel-based measure made on lateral view videofluoroscopy swallow study frames. The PCR is calculated by tracing the unobliterated area of the pharynx (including the bolus) at the point of maximum constriction during the swallow and then dividing that area by a corresponding area measure when the pharynx is at rest.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Maximum pharyngeal dilation as estimated by HRAN
Maximum pharyngeal dilation will be estimated by HRAN. The post-swallow hyoid rest is defined as the earliest frame in videofluoroscopic swallowing study recordings following upper esophageal sphincter closure when the hyoid was observed to have descended and moved posteriorly to reach its original, pre-swallow position. The HRAN is the normalized (by %[C2-4]^2) area on the frame of post-swallow hyoid rest.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Dysphagia severity as measured by the CWDT
The CWDT is the time in seconds a subject requires to swallow 80 mL of ice-cold water.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Maximum swallowing capacity as measured by the MSS
The MSS is the time in seconds a subject requires to drink 150 mL of cold tap water as rapidly as possible.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Maximum swallowing capacity as measured by the MSV
The MSV is the maximum amount of room-temperature tap water a subject is able to consume in 1 swallow.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Subject-reported oropharyngeal dysphagia as assessed by the SSQ
The SSQ is a self-report inventory assessing subjective symptoms of oropharyngeal dysphagia with strong content, construct, discriminant, and predictive validity and test-retest reliability in a range of patient populations. The SSQ is a 17-item questionnaire which was developed to measure symptomatic severity of oral-pharyngeal dysphagia as reported by the affected subject. The questionnaire uses a 100-mm long visual analogue scale for all but 1 question. Possible scores range from 0 to 1700, with higher scores indicating greater swallowing difficulty.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Subject-reported oropharyngeal dysphagia as assessed by the IDDSI Functional Diet Scale
The IDDSI Functional Diet Scale is a subject-reported oropharyngeal dysphagia functional outcome scale intended to capture the severity of oropharyngeal dysphagia, as represented by the degree of diet texture restriction recommended for the subject. The IDDSI framework consists of a continuum of 8 levels (0-7), where drinks are measured from Levels 0-4, while foods are measured from Levels 3-7. The IDDSI framework provides a common terminology to describe food textures and drink thickness. Lower scores reflect diet texture restrictions to thin liquids.
Measured: Baseline, Day 90, Day 180, Day 270, Day 360
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2023
- Study start28 Nov 2023
- Primary completionNov 2030 (estimated)
- Study completionNov 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oculopharyngeal Muscular DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Benitec Biopharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Milan R. Amin, M.D., Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06185673
- Sponsor's protocol ID
- BNTC-OPMD-BB-301-01
- Status last verified
- Dec 2025
- First submitted
- 15 Dec 2023
- Last updated
- 31 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2a, Open-label, Dose Escalation Study to Evaluate the Safety and Clinical Activity of Intramuscular Doses of BB-301 Administered to Subjects With Oculopharyngeal Muscular Dystrophy With Dysphagia
- ClinicalTrials.gov ID
- NCT06185673
- Acronym / sponsor ID
- BNTC-OPMD-BB-301-01
- Conditions
- Oculopharyngeal Muscular Dystrophy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Benitec Biopharma, Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Nov 2023 (actual)
- Primary completion
- Nov 2030 (estimated)
- Study completion
- Nov 2040 (estimated)
- First posted
- 29 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BB-301 Treatment | Experimental | Genetic: BB-301: Dose escalation phase 1b cohort 1, Genetic: BB-301: Dose escalation phase 1b cohort 2, Genetic: BB-301: Dose escalation phase 1b cohort 3, Genetic: BB-301: Dose expansion phase 2aThe 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. |
Who may qualify
- Ages
- Up to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (27 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BB-301: Dose escalation phase 1b cohort 1BB-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. | Genetic | BB-301 Treatment |
| BB-301: Dose escalation phase 1b cohort 2BB-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. | Genetic | BB-301 Treatment |
| BB-301: Dose escalation phase 1b cohort 3BB-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. | Genetic | BB-301 Treatment |
| BB-301: Dose expansion phase 2aSubjects 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). | Genetic | BB-301 Treatment |
Primary outcome
Incidence of dose-limiting toxicities (DLTs) in phase 1b
Time frame: Up to 60 days
A DLT will be defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, as follows: • Any Grade 2 toxicity not resolving within 14 days or any Grade 3 toxicity, assessed to be possibly related to the investigational product.
Incidence of adverse events (AEs) according to NCI CTCAE v5.0 in phase 1b and in phase 2a
Time frame: Up to 360 days
For this outcome measure, AEs arising in the 360 days following administration of BB-301 will be considered. Long term AEs will be monitored for 15 years following subject dosing.
Phase 1b: Swallowing efficiency as measured by Vallecular Residue %(C2-4)^2
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The Analysis of Swallowing Physiology: Events, Kinematics and Timing (ASPEKT) method will be used to determine Vallecular Residue %(C2-4)^2.
Phase 1b: Swallowing efficiency as measured by Pyriform Sinus Residue %(C2-4)^2
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Pyriform Sinus Residue %(C2-4)^2.
Phase 1b: Swallowing efficiency as measured by Other Pharyngeal Residue %(C2-4)^2
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Other Pharyngeal Residue %(C2-4)^2.
Phase 1b: Swallowing efficiency as measured by Total Pharyngeal Residue %(C2-4)^2
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Total Pharyngeal Residue %(C2-4)^2.
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
Videofluoroscopy will be used to characterize the area of the pharynx at the point of maximum constriction during swallowing. The PhAMPC uses the videofluoroscopy frame of maximum pharyngeal constriction, defined as the frame with the smallest amount of unobliterated air space and barium-containing bolus visible in the pharynx. The pixelated area of the frame of maximum constriction is normalized via the use of the C2-C4 length squared (i.e., [C2-4]^2) as the denominator.
Phase 2a: Swallowing efficiency as measured by Vallecular Residue %(C2-4)^2
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Vallecular Residue %(C2-4)^2.
Phase 2a: Swallowing efficiency as measured by Pyriform Sinus Residue %(C2-4)^2
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Pyriform Sinus Residue %(C2-4)^2.
Phase 2a: Swallowing efficiency as measured by Other Pharyngeal Residue %(C2-4)^2
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Other Pharyngeal Residue %(C2-4)^2.
Phase 2a: Swallowing efficiency as measured by Total Pharyngeal Residue %(C2-4)^2
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Pharyngeal residue in discrete anatomical locations will be assessed by applying a method that uses a common reference area across all residue locations, with residue area expressed as a percentage of the squared C2-C4 length reference scalar. The ASPEKT method will be used to determine Total Pharyngeal Residue %(C2-4)^2.
Phase 2a: Pharyngeal constrictor muscle function as estimated by PhAMPC
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Videofluoroscopy will be used to characterize the area of the pharynx at the point of maximum constriction during swallowing. The PhAMPC uses the videofluoroscopy frame of maximum pharyngeal constriction, defined as the frame with the smallest amount of unobliterated air space and barium-containing bolus visible in the pharynx. The pixelated area of the frame of maximum constriction is normalized via the use of the C2-C4 length squared (i.e., [C2-4]^2) as the denominator.
18 secondary outcomes
Phase 1b: Global swallowing function as measured by the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Swallowing efficiency as measured by the Normalized Residue Ratio Scale (NRRS)
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Pharyngeal constrictor muscle function as estimated by the Pharyngeal Constriction Ratio (PCR)
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Maximum pharyngeal dilation as estimated by %(C2-4)^2-normalized post-swallow hyoid rest pharyngeal area (HRAN)
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Dysphagia severity as measured by the cold water timed drinking test (CWDT)
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Maximum swallowing capacity as measured by the maximum swallowing speed (MSS)
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Maximum swallowing capacity as measured by the maximum swallowing volume (MSV)
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Subject-reported oropharyngeal dysphagia as assessed by the Sydney Swallow Questionnaire (SSQ)
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 1b: Subject-reported oropharyngeal dysphagia as assessed by the International Dysphagia Diet Standardization Initiative (IDDSI) Functional Diet Scale
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Global swallowing function as measured by the DIGEST scale
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Swallowing efficiency as measured by the NRRS
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Pharyngeal constrictor muscle function as estimated by the PCR
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Maximum pharyngeal dilation as estimated by HRAN
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Dysphagia severity as measured by the CWDT
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Maximum swallowing capacity as measured by the MSS
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Maximum swallowing capacity as measured by the MSV
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Subject-reported oropharyngeal dysphagia as assessed by the SSQ
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Phase 2a: Subject-reported oropharyngeal dysphagia as assessed by the IDDSI Functional Diet Scale
Time frame: Baseline, Day 90, Day 180, Day 270, Day 360
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sophie Mukadam contact
Milan R. Amin, M.D. principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BB-301: Dose escalation phase 1b cohort 1, BB-301: Dose escalation phase 1b cohort 2 and BB-301: Dose escalation phase 1b cohort 3 in people with Oculopharyngeal Muscular Dystrophy, run by Benitec Biopharma, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jerel A. Banks, M.D., Ph.D. ((510)-780-0634, jbanks@benitec.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (DLTs) in phase 1b (time frame: Up to 60 days). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2025.