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.

Study Overview

• Status: Terminated
• Conditions: Developmental and Epileptic Encephalopathy
• Intervention / Treatment: Drug: gene therapy

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Colorado Child Health Research Institute
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • Buerger Center for Advanced Pediatric Care, Children's Hospital of Philadelphia
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; Participants will receive a single dose of STXBP1, administered IV	Drug: gene therapy; Intra-venous gene therapy
Experimental: Dose Level 2; Participants will receive a single dose of STXBP1, administered IV	Drug: gene therapy; Intra-venous gene therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety	Incidence of Adverse Events and Serious Adverse Events assessed through Clinical safety laboratory tests (hematology, chemistry, liver function, and urinalysis), ECG, vital sign measurements, and Physical Examinations	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bayley Scales of Infant and Toddler Development- Fourth Edition	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	Baseline, Month 6, Month 12, Month 18 and Month 24
Gross Motor Function Measure	Clinician Scores: 0 to 3; Total Score: 0 to 264; High score is a better outcome	Baseline, Month 6, Month 12, Month 18 and Month 24
Peabody Developmental Motor Scales-Third Edition	Clinician Scores: 0 to 2; High score is a better outcome	Baseline, Month 6, Month 12, Month 18 and Month 24
STXBP1-Clinical Severity Assessment-Clinician	Clinician Scores: 0 to 100; High score is a worse outcome	Baseline, Month 6, Month 12, Month 18 and Month 24
Vineland Adaptive Behavior Scales | Third Edition	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	Baseline, Month 6, Month 12, Month 18 and Month 24
Observer-Reported Communication Ability	Caregiver Scores: No or only once; Sometimes, Yes, almost all the time; Yes, almost all the time is better outcome	Baseline, Month 6, Month 12, Month 18 and Month 24
Sensory Profile-2	Caregiver Scores: 1 to 5; Total Score: 0 to 625; High score is a worse outcome	Baseline, Month 6, Month 12, Month 18 and Month 24
Quality of Life Inventory-Disability	Caregiver Scores: Never, Rarely, Sometimes, Often, Very often; Very Often is better outcome	Baseline, Week 6, Month 6, Month 12, Month 18 and Month 24
STXBP1-Clinical Severity Assessment-Caregiver	Caregiver Scores: 0 to 100; High score is a worse outcome	Baseline, Week 4, Week 8, Week 12, Month 4, Month 6, Month 12, Month 18 and Month 24
Aberrant Behavior Checklist	Caregiver Scores: 0 to 3; Total Score: 0-174; High score is a worse outcome	Baseline, Month 6, Month 12, Month 18 and Month 24
Child Behavior Checklist	Caregiver Scores: 0 to 2; Total Behavior: 0 to 224; High score is a worse outcome	Baseline, Month 6, Month 12, Month 18 and Month 24
Child's Sleep Habits	Caregiver Scores: 1 to 3; High score is a worse outcome	Baseline, Month 6, Month 12, Month 18 and Month 24
Seizure frequency	Caregiver assessment: Change from baseline in seizure experience as recorded in a seizure diary	Baseline and daily though Month 24

Collaborators and Investigators

• Sponsor: Capsida Biotherapeutics, Inc.
• Investigators: Study Director: Melanie Brandabur, MD, Capsida Biotherapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2025
• Primary Completion (Actual): March 25, 2026
• Study Completion (Actual): May 26, 2026

Study Registration Dates

• First Submitted: May 5, 2025
• First Submitted That Met QC Criteria: May 13, 2025
• First Posted (Actual): May 21, 2025

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Gene therapy; STXBP1
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Brain Diseases; Investigative Techniques; Therapeutics; Biological Therapy; Genetic Techniques; Genetic Engineering; Genetic Therapy
• Other Study ID Numbers: CAP-002-101; SYNRGY (Other Identifier: Capsida Biotherapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No