JAG201 Gene Therapy Study in Children & Adults with SHANK3 Haploinsufficiency

ID#: NCT06662188

Age: 2 - 9 years

Gender: All

Healthy Subjects: No

Study Phase: Phase 1/Phase 2

Recruitment Status: Recruiting

Start Date: January 07, 2024

End Date: June 01, 2031

Contact Information:
Jaguar Gene Therapy
224-303-0701
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.
Eligibility: 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)-specific Clinical Global Impression-Severity (CGI-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, and speech therapy)

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). 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 as losing a skill previously maintained consistently for ≥ 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