NCT07014020

RB001 Gene Therapy Study in Children With SHANK3-related Phelan McDermid Syndrome (PMS)

An Open-label, Single Arm, Dose-Escalation Clinical Study to Evaluating the Safety, Tolerability and Preliminary Efficacy of a Single Intracerebroventricular Injection of RB001 for the Treatment of SHANK3-related Phelan McDermid Syndrome.

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 8 (estimated)
• Sponsor: Peking University First Hospital · Academic / Other
• Sex: All
• Age: 3 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

This is a first in human, open-label, dose-escalation study to evaluate the safety, tolerability, and clinical activity of a single dose of RB001 administered via intracerebroventricular (ICV) injection in pediatric with SHANK3 related Phelan-McDermid Syndrome. Clinical data will be evaluated for safety, tolerability, and preliminary efficacy of RB001 in participants with SHANK3 related PMS.

Detailed description

SHANK3-related Phelan McDermid syndrome (PMS) is a rare neurodevelopmental disorder primarily caused by a deletion of chromosome 22q13 or a mutation of the SHANK3 gene. The syndrome is characterized by intellectual disability and language impairment. The SHANK3 protein is part of the postsynaptic density complex and participates in postsynaptic signal transduction and synaptic development, serving as a critical structural protein for central nervous system development and functional maintenance. SHANK3 deficiency leads to abnormal neuronal development and is the primary cause of PMS. The estimated global prevalence is approximately 1/15,000. Clinical manifestations include global developmental delay, particularly severe language delay, autism-like behaviors, hypotonia, and potentially epilepsy. Currently, there are no effective treatments for this condition. RB001 is developed by Shenzhen Reborngene Therapeutics Co., Ltd. for the treating of Phelan-McDermid Syndrome. RB001 utilizes the Adeno-Associated Virus (AAV) vector to deliver an optimized SHANK3-minigene via intracerebroventricular (ICV) injection. Nonclinical studies have demonstrated that a single ICV injection of RB001 could restore SHANK3 mRNA and protein expression in the target region of central nervous system of the SHANK3-mutant mouse models, as well as the restore of motor deficits, stereotypical behaviors, and reduced exploratory behaviors and neuronal function. A target of 8 pediatric participants aged 3 to 18 years will be treated. All participants will be followed for safety, tolerability and preliminary efficacy after the date of treatment with RB001.

Conditions

• Phelan-McDermid Syndrome
• SHANK3 Haploinsufficiency

Interventions

Type	Name	Description
GENETIC	RB001	The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose

Timeline

• Start date: 2025-06-16
• Primary completion: 2027-05-01
• Completion: 2027-12-31
• First posted: 2025-06-10
• Last updated: 2025-07-30

Locations

1 site across 1 country: China