JAG201 Gene Therapy Study in Children & Adults With SHANK3 Haploinsufficiency

NCT06662188 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: JAG-201-CL-101
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Phelan-McDermid Syndrome; SHANK3 Haploinsufficiency

Keywords

SHANK3 Haploinsufficiency; SHANK3; Phelan-McDermid Syndrome

Outcome Measures

Primary Outcomes (4)

• Incidence of Adverse Events (AEs)

  Incidence, type, severity, and frequency of AEs

  Enrollment to Month 60

• Incidence of Serious Adverse Events (SAEs)

  Incidence, type, severity, and frequency of SAEs

  Enrollment to Month 60

• Clinically significant abnormalities in laboratory values

  Changes in clinically significant abnormalities in laboratory values

  Enrollment to Month 60

• Incidence of immunogenicity response abnormalities

  Incidence of anti-AAV9 antibodies, anti-transgene antibodies, and T-cell reactivity to transgene over time

  Enrollment to Month 60

Secondary Outcomes (1)

• Change from Baseline in SAND

  Enrollment to Month 60

Other Outcomes (1)

• Change from baseline in Vineland Adaptive Behavior Scales

  Enrollment to Month 60

Study Arms (2)

Pediatric Cohort 1

EXPERIMENTAL

Starting Dose

Pediatric Cohort 2

EXPERIMENTAL

Escalated Dose

Genetic: JAG201

Interventions

JAG201 GENETIC

Adeno-associated virus 2/9 expressing a miniature version of the human SHANK3 gene (AAV2/9-miniSHANK3)

Eligibility Criteria

• Age: 2 Years - 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Is male or female, and 2 to 9 years of age at the time of JAG201 administration
• Has a molecular confirmation of a loss of function mutation in SHANK3 or a 22q13.3 deletion classified as a Class I deletion
• 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)
• Has an overall Phelan-McDermid Syndrome (PMS) Assessment of Severity (PMSA-S) Score of 3 or greater at Screening
• Willing to initiate structured therapies and continue for the duration of the study as determined by the specific therapist (structured therapies may include, at a minimum, physical therapy, occupational therapy, speech therapy, and applied behavior analysis)
• Is stable on any medication regimens (if being administered to control the signs and symptoms of underlying disease) for at least 3 months prior to the planned JAG201 study treatment
• If undergoing any kind of behavioral or therapeutic intervention, then the level of intervention must have remained stable for at least 3 months prior to the planned JAG201 study treatment (exclusive of school vacations/illness).
• Is a permanent legal resident of the U.S. residing within the continental U.S.

You may not qualify if:

• A pediatric participant who meets any of the following criteria will be excluded from this study:
• Has history of developmental regression defined in this study as a prolonged loss of previously acquired skills (defined as skills maintained for at least 3 months) with loss of skills persisting for at least 3 months
• Has known or suspected prion disease (e.g., Creutzfeldt-Jakob Disease)
• Has poorly-controlled epilepsy (defined as an increase in the dose or addition of new anti-epileptic medications within the past 3 months) or any history of status epilepticus or seizure-induced hospitalizations within the last 12 months
• Has history of acute cerebrovascular episodes
• Has active autoimmune disease or prior treatment with immunomodulatory therapy, immunotherapy, and/or immunosuppressive drugs within 3 months prior to study enrollment (Note: Inhaled or topical steroids are permitted in the absence of active autoimmune disease)
• Has infection (viral, bacterial, or fungal) that requires treatment \< 6 weeks before JAG201 administration (Note: JAG201 administration may be postponed until the infection has resolved and the participant is clinically stable)
• Has medical illness or other concern that would cause the Investigator to conclude that the participant will not be able to perform the study procedures or assessments or would confound interpretation of data obtained during assessments
• Has known allergy or hypersensitivity to prednisolone or other glucocorticosteroids, or their excipients
• Has received any vaccine \< 6 weeks before JAG201 administration
• Has received any gene therapy

Sponsors & Collaborators

• Jaguar Gene Therapy, LLC: lead

Study Sites (3)

Rush University

Chicago, Illinois, 60612, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Seaver Autism Center at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Telomeric 22q13 Monosomy Syndrome

Study Officials

• Dan Gallo, PhD

  Jaguar Gene Therapy

  STUDY DIRECTOR

Central Study Contacts

Jaguar Gene Therapy

CONTACT

224-303-0701; medinfo@jaguargenetherapy.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, open-label, first-in-human (FIH), single-dose, dose-escalation, safety, tolerability, and clinical activity of JAG201. A traditional 3+3 design strategy will be implemented for dose escalation from the 1st cohort to the 2nd cohort.

Study Record Dates

• First Submitted: October 16, 2024
• First Posted: October 28, 2024
• Study Start: January 7, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2031
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)