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

Phase 1

Not yet recruiting

• Conditions: Developmental and Epileptic Encephalopathy
• Interventions: Drug: gene therapy

• Registration Number: NCT06983158
• Lead Sponsor: Capsida Biotherapeutics, Inc.

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-05
• Study First Submitted QC: 2025-05-13
• Last Update Submitted: 2025-05-13
• Study First Posted: 2025-05-21
• Last Update Posted: 2025-05-21
• Study Start: 2025-07-23
• Primary Completion: 2028-12-20
• Study Completion: 2028-12-20

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Level 1	gene therapy	Participants will receive a single dose of STXBP1, administered IV
Dose Level 2	gene therapy	Participants will receive a single dose of STXBP1, administered IV

Primary Outcome Measures

Name	Time	Method
Safety: adverse events and clinical safety	2 years	Adverse events and clinical safety

Secondary Outcome Measures

Name	Time	Method
Bayley Scales of Infant and Toddler Development- Fourth Edition	Baseline, Month 6, Month 12, Month 18 and Month 24	Clinician Scores: 0 to 2; Total Scores: Cognitive 0-162; Receptive 0-84; Expressive 0-74; Fine Motor 0-92; Gross Motor 0-116; High score is a better outcome
Gross Motor Function Measure	Baseline, Month 6, Month 12, Month 18 and Month 24	Clinician Scores: 0 to 3; Total Score: 0 to 264; High score is a better outcome
Peabody Developmental Motor Scales-Third Edition	Baseline, Month 6, Month 12, Month 18 and Month 24	Clinician Scores: 0 to 2; High score is a better outcome
STXBP1-Clinical Severity Assessment-Clinician	Baseline, Month 6, Month 12, Month 18 and Month 24	Clinician Scores: 0 to 100; High score is a worse outcome
Vineland Adaptive Behavior Scales | Third Edition	Baseline, Month 6, Month 12, Month 18 and Month 24	Caregiver Scores: 0 to 2; Total Scores: Receptive 0-78; Expressive 0-98, Written 0-76, Personal 0-110, Domestic 0-60, Community 0-116, Interpersonal 0- 86, Play and Leisure 0-72, Coping 0-66, Fine Motor 0- 68; Gross Motor 0-86: High score is a better outcome
Observer-Reported Communication Ability	Baseline, Month 6, Month 12, Month 18 and Month 24	Caregiver Scores: No or only once; Sometimes, Yes, almost all the time; Yes, almost all the time is better outcome
Sensory Profile-2	Baseline, Month 6, Month 12, Month 18 and Month 24	Caregiver Scores: 1 to 5; Total Score: 0 to 625; High score is a worse outcome
Quality of Life Inventory-Disability	Baseline, Week 6, Month 6, Month 12, Month 18 and Month 24	Caregiver Scores: Never, Rarely, Sometimes, Often, Very often; Very Often is better outcome
STXBP1-Clinical Severity Assessment-Caregiver	Baseline, Week 4, Week 8, Week 12, Month 4, Month 6, Month 12, Month 18 and Month 24	Caregiver Scores: 0 to 100; High score is a worse outcome
Aberrant Behavior Checklist	Baseline, Month 6, Month 12, Month 18 and Month 24	Caregiver Scores: 0 to 3; Total Score: 0-174; High score is a worse outcome
Child Behavior Checklist	Baseline, Month 6, Month 12, Month 18 and Month 24	Caregiver Scores: 0 to 2; Total Behavior: 0 to 224; High score is a worse outcome
Child's Sleep Habits	Baseline, Month 6, Month 12, Month 18 and Month 24	Caregiver Scores: 1 to 3; High score is a worse outcome
Seizure frequency	Baseline and daily though Month 24	Caregiver assessment: Change from baseline in seizure experience as recorded in a seizure diary

Trial Locations

Locations (4)

Colorado Child Health Research Institute; 🇺🇸 Aurora, Colorado, United States

Weill Cornell Medicine; 🇺🇸 New York, New York, United States

Robert's Centre for Pediatric Research, Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States