A Phase 1/2, Multicenter, Open-Label, Dose-Escalation, Safety, Tolerability, and Clinical Activity Study of a Single Dose of JAG201 Gene Therapy Delivered Via Intracerebroventricular Administration in Participants With SHANK3 Haploinsufficiency
Jaguar Gene Therapy, LLC
Summary
This is a Phase 1/2, first in human, open-label, dose-escalation study to evaluate the safety, tolerability, and clinical activity of a single dose of JAG201 administered via intracerebroventricular (ICV) injection in pediatric and adult participants with SHANK3 haploinsufficiency resulting from SHANK3 loss of function mutations and chromosomal deletions encompassing the SHANK3 gene. Clinical data will be evaluated for safety, tolerability, and preliminary clinical activity of JAG201 in pediatric and adult participants with SHANK3 haploinsufficiency. The pediatric cohorts will start enrolling first and the enrollment for adult cohorts may be initiated at a later timepoint in the study.
Description
A target of 6 pediatric participants aged 2 to 9 years will be treated in Cohorts 1 and 2. In total, all participants will be followed for safety and tolerability for at least 5 years after the date of treatment with JAG201. The study will include 5 periods: Pre-Screening, Screening, Gene Therapy Administration and Perioperative Management, Initial Follow-Up, and Long-Term Follow-Up. Study participants will be evaluated for treatment eligibility during the Pre-Screening and Screening Periods. The Pre-Screening/Screening Period may be up to 90 days before treatment with JAG201 (Day 1). On Day 1…
Eligibility
- Age range
- 2–9 years
- Sex
- All
- Healthy volunteers
- No
Key Inclusion Criteria: 1. Is male or female, and 2 to 9 years of age at the time of JAG201 administration 2. Has a molecular confirmation of a loss of function mutation in SHANK3 or a 22q13.3 deletion classified as a Class I deletion 3. Has evidence of developmental/cognitive delay of at least 2 standard deviations (SD) below the mean (i.e., ≤ 70) via either Intelligence Quotient (IQ) OR Developmental Quotient (DQ) assessment (as applicable) 4. Has an overall Phelan-McDermid Syndrome (PMS) Assessment of Severity (PMSA-S) Score of 3 or greater at Screening 5. Willing to initiate structured th…
Interventions
- GeneticJAG201
Adeno-associated virus 2/9 expressing a miniature version of the human SHANK3 gene (AAV2/9-miniSHANK3)
- GeneticJAG201
Adeno-associated virus 2/9 expressing a miniature version of the human SHANK3 gene (AAV2/9-miniSHANK3)
Locations (3)
- Rush UniversityChicago, Illinois
- Boston Children's HospitalBoston, Massachusetts
- Seaver Autism Center at Mount SinaiNew York, New York