A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy

A Phase 1/2a, Open-Label, Multi-Center, Dose-Escalation Trial to Assess Safety, Tolerability, and Efficacy of a Single Dose of CAP-002 Gene Therapy Administered to Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy

The goal of this clinical trial is to learn about the safety of CAP-002 gene therapy in children with Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy. It will also provide information about whether CAP-002 demonstrates efficacy in treating children with STXBP1 with and without seizures.

Participants will have a single infusion of CAP-002, visit the clinic regularly for 2 years for checkups and tests and have seizures recorded in a diary by their caregiver.

This is a Phase 1/2a, FIH, open-label, multi-center, dose-escalation trial to assess the safety, tolerability, and efficacy of a single intravenous (IV) dose of CAP-002 administered to participants with syntaxin-binding protein#1 (STXBP1) encephalopathy ages ≥18 months to <8 years of age.

Approximately 12 participants will be dosed in this trial. Phase 1 is a dose escalation phase that will dose approximately 6 participants divided into 2 cohorts (Cohort 1 and Cohort 2) while Phase 2a will have 1 dose cohort and dose approximately 6 participants. Participants in Phase 1 will be dosed sequentially in each cohort. Phase 2a will allow participants to be dosed concurrently if safety and tolerability data from Phase 1 are deemed acceptable.

Participants will receive a single intravenous infusion of CAP-002 and will then be followed for 2 years with safety measures, assessments to measure changes from Baseline in development, language, cognition, motor skills and behavior, a seizure diary and structured caregiver interviews.

Upon completion of the study or at the participant's final visit they will be invited to participate in a 3 year safety follow up study.

Inclusion Criteria:

Male or female, ≥18 months to <8 years of age;

Has diagnosis of developmental encephalopathy due to an STXBP1 mutation with confirmation of a pathogenic or likely pathogenic STXBP1 gene mutation.

Has a legally authorized representative (LAR) willing and able to complete the informed consent process, willing to comply with trial procedures, and able to travel for repeat visits.

Is stable on any medication regimens (if being administered to control the signs and symptoms of underlying disease) for at least 6 weeks prior to trial entry and expected to be stable for at least 12 weeks post-CAP-002 administration.

Exclusion Criteria:

History of prior gene therapy;

Treatment with antisense oligonucleotide therapy within 6 months;

Presence of a confirmed mutation in a gene other than STXBP1 that is known to contribute to a neurodevelopmental disability or epilepsy;

Has presence of a significant non-STXBP1-related central nervous impairment/behavioral disturbance that would confound the scientific rigor or interpretation of results of the trial;

History of prematurity (defined as gestational age <35 weeks), history of low birth weight (<2.5 kg) and/or intra-uterine growth restriction, significant interventricular hemorrhage, structural brain deficit, or congenital heart disease;

Known contraindication to immunosuppression or other protocol-defined medications, including but not limited to corticosteroids or PPIs;

Clinically significant abnormalities in safety lab tests, vital signs;

Other illnesses or medications that may affect the interpretation of the study results;

Positive anti-capsid antibody test result.