SHANK3 HaploinsufficiencyPhase 1/2NCT06662188
JAG201 Gene Therapy Study in Children & Adults With SHANK3 Haploinsufficiency
A Phase 1/2 study testing JAG201 in people with SHANK3 Haploinsufficiency and Phelan-McDermid Syndrome, run by Jaguar Gene Therapy, LLC at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 9 years
- Conditions the study is for
- SHANK3 Haploinsufficiency, Phelan-McDermid Syndrome
- What is being tested?
- JAG201
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 3 sitesUnited States
- Study dates
- 7 Jan 2024to Jun 2031
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 9 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Anna Cronin, 617-919-3499, anna.cronin@childrens.harvard.edu
Siddharth Srivastava, MD
- Recruiting
Rush University
Chicago, Illinois, 60612
Giulia DeMarco, 312-942-9841, Giulia_DiMarco@rush.edu
Elizabeth B Kravis, MD, PhD
- Recruiting
Seaver Autism Center at Mount Sinai
New York, New York, 10029
Stella Chukwulozie, 212-241-3072, stella.chukwulozie@mssm.edu
Alex Kolevzon, MD
About this study
Official title: 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 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.
Read the detailed 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, treatment-eligible participants will receive a one-time ICV injection of JAG201. Participant safety will be monitored closely after JAG201 administration in a hospital setting. During the Initial Follow-Up Period, up to Year 2, participants will return at regularly scheduled intervals for safety and clinical activity assessments. Participants will continue the study in the Long-Term Follow-Up Period through Year 5.
- Being tested
- JAG201
- Keywords
- SHANK3 Haploinsufficiency, SHANK3, Phelan-McDermid Syndrome
- Medical subject headings
- Telomeric 22q13 Monosomy Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JAG201Genetic
Adeno-associated virus 2/9 expressing a miniature version of the human SHANK3 gene (AAV2/9-miniSHANK3)
JAG201Genetic
Adeno-associated virus 2/9 expressing a miniature version of the human SHANK3 gene (AAV2/9-miniSHANK3)
| Study group | Role | What they receive |
|---|---|---|
| Pediatric Cohort 1 | Experimental | Starting Dose Receives: Genetic: JAG201 |
| Pediatric Cohort 2 | Experimental | Escalated Dose Receives: Genetic: JAG201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events (AEs)
Incidence, type, severity, and frequency of AEs
Measured: Enrollment to Month 60
Incidence of Serious Adverse Events (SAEs)
Incidence, type, severity, and frequency of SAEs
Measured: Enrollment to Month 60
Clinically significant abnormalities in laboratory values
Changes in clinically significant abnormalities in laboratory values
Measured: 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
Measured: Enrollment to Month 60
Secondary outcomes (1)
Change from Baseline in SAND
To characterize the preliminary disease response to JAG201 by assessing the change from baseline in SAND (Sensory Assessment for Neurodevelopmental Disorders)
Measured: Enrollment to Month 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2024
- Study start7 Jan 2024
- Primary completionJun 2028 (estimated)
- Study completionJun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SHANK3 HaploinsufficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jaguar Gene Therapy, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dan Gallo, PhD, Study director, Jaguar Gene Therapy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06662188
- Sponsor's protocol ID
- JAG-201-CL-101
- Status last verified
- Sep 2026
- First submitted
- 16 Oct 2024
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No