Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as 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
BB-301 · 1 trial · 1 indication
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| 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. |
| Name | Type | Description |
|---|---|---|
| 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). |
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 year...
BB-301 is an investigational gene therapy being developed for oculopharyngeal muscular dystrophy, a rare inherited muscle disorder that can cause swallowing difficulty. It is administered by intramuscular injection and is currently in Phase 1 clinical development. Benitec Biopharma Inc. (BNTC) is the developer.
BB-301 is being studied for oculopharyngeal muscular dystrophy, a neurological condition in which patients develop dysphagia, or difficulty swallowing, along with progressive muscle weakness. The Phase 1 study enrolls adults with oculopharyngeal muscular dystrophy who have dysphagia. BB-301 has not been approved for any use and remains investigational.
BB-301 is developed by Benitec Biopharma Inc., which trades on the Nasdaq under the ticker BNTC. The company is running the clinical program for the gene therapy in oculopharyngeal muscular dystrophy. BB-301 has received Fast Track and Orphan Drug designations from the FDA.
BB-301 is in Phase 1 clinical development. The program includes a dose escalation Phase 1b portion with three cohorts and a dose expansion Phase 2a portion. It is investigational and has not been approved by the FDA for oculopharyngeal muscular dystrophy or any other indication.
BB-301 is being evaluated in one active clinical trial, NCT06185673, titled a study to evaluate the safety and clinical activity of intramuscular doses of BB-301 administered to subjects with oculopharyngeal muscular dystrophy with dysphagia. The trial is recruiting in the United States and plans to enroll 30 participants.
Yes. BB-301 refers to the same investigational gene therapy across its clinical program. The names BB-301 dose escalation Phase 1b cohort 1, cohort 2, and cohort 3, along with BB-301 dose expansion Phase 2a, describe separate parts of the same study rather than different drugs.