Gene therapy for children and adults with SHANK3 haploinsufficiency

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

This study is testing a new gene therapy for children and possibly adults with SHANK3 haploinsufficiency to see if it is safe and helps improve their condition.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 2 Years to 9 Years
• Sex: All
• Sponsor: Jaguar Gene Therapy, LLC (Industry-sponsored)
• Drugs / interventions: immunotherapy
• Locations: 3 sites (Chicago, Illinois and 2 other locations)
• Trial ID: NCT06662188 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 open-label, dose-escalation study evaluates the safety, tolerability, and clinical activity of JAG201, a gene therapy administered via intracerebroventricular injection, in participants with SHANK3 haploinsufficiency. The study will initially enroll pediatric participants aged 2 to 9 years, with adult enrollment potentially starting later. Participants will be monitored for safety and clinical outcomes for at least five years following treatment. The study includes multiple phases, including pre-screening, treatment administration, and long-term follow-up assessments.

Who should consider this trial

Good fit: Ideal candidates are children aged 2 to 9 years with confirmed SHANK3 mutations and significant developmental delays.

Not a fit: Patients without a confirmed SHANK3 mutation or those not meeting the developmental delay criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could improve cognitive and developmental outcomes for patients with SHANK3 haploinsufficiency.

How similar studies have performed: While gene therapy approaches are being explored for various conditions, this specific application for SHANK3 haploinsufficiency is novel and has not been extensively tested in prior studies.

Eligibility criteria

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 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)
6. 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
7. 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).
8. Is a permanent legal resident of the U.S. residing within the continental U.S.

Key Exclusion Criteria:

A pediatric participant who meets any of the following criteria will be excluded from this study:

1. 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
2. Has known or suspected prion disease (e.g., Creutzfeldt-Jakob Disease)
3. 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
4. Has history of acute cerebrovascular episodes
5. 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)
6. 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)
7. 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
8. Has known allergy or hypersensitivity to prednisolone or other glucocorticosteroids, or their excipients
9. Has received any vaccine \< 6 weeks before JAG201 administration
10. Has received any gene therapy

Where this trial is running

Chicago, Illinois and 2 other locations

• Rush University — Chicago, Illinois, United States (Recruiting)
• Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
• Seaver Autism Center at Mount Sinai — New York, New York, United States (Recruiting)

Study contacts

• Study coordinator: Jaguar Gene Therapy

Conditions SHANK3 Haploinsufficiency; Phelan-McDermid Syndrome; SHANK3