A First-in-Human Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of a Novel CRISPR RNA-editing Therapy in Patients with Mecp2 Duplication Syndrome, a Rare Orphan Disease (HERO)

NCT06615206 | Recruiting

• 1 other identifier: HG20401
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Methyl-CpG binding protein 2 (MECP2) is a dosage-sensitive, X-linked gene critical for central nervous system development and functional maintenance, which gain-of-function causes MECP2 duplication syndrome (MDS). Affecting primarily in males, this disorder is characterized by severe intellectual disability, motor dysfunction, infantile hypotonia, epilepsy, respiratory tract infections, and premature death before 25 years of age with no curative therapy. HG204 is a CRISPR RNA-editing therapy packaging novel high-fidelity Cas13Y (hfCas13Y) technology, using one single adeno-associated virus (AAV) vector to target and knock down MECP2 mRNA in the brain. Preclinical studies showed that a single intracerebroventricular injection of HG204 persistently decreased MECP2 mRNA and MECP2 protein in the cortex of the MDS mice, reversed the abnormal motor and social phenotypes, and significantly prolonged survival in MDS mouse models.

Conditions

MECP2 Duplication Syndrome

Keywords

MECP2; dupMECP2; CNS; neurodevelopmental disease; Gene-editing; HG204; CRISPR; MDS

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of systemic adverse events

  Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)

  52 weeks

Secondary Outcomes (5)

• Change from baseline in Clinical Global Impression Scale

  52 weeks

• Change from baseline in Griffiths Developmental Assessment Scale

  52 weeks

• Change from baseline in Peabody Developmental Assessment Scale

  52 weeks

• Change from baseline in Wechsler (toddler/child) Intelligence Scale (fourth version) score

  52 weeks

• Adaptive Behavior Rating Scale

  52 weeks

Study Arms (1)

HG204

EXPERIMENTAL

Once intracerebroventricular injection; The duration of the study is about 60 weeks for each subject, including a 8 weeks screening period, enrollment visit, treatment visit and 52 weeks follow-up period.

Genetic: HG204

Interventions

HG204 GENETIC

The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose

HG204

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males ≥ 2 and ≤18 years at the time of signing informed consent;
• Genetic test and clinical confirmed diagnosis of MDS;
• Stable pattern of seizures, or has had no seizures while currently receiving medical treatment (including antiepileptics) and physical therapy are stable for at least 2 months before screening;
• Willing to adhere to protocol, including biological samples collection and hospitalization for intracerebroventricular injection surgery;
• Acceptable hematology, clinical chemistry, and urine laboratory parameters.

You may not qualify if:

• MECP2 gene triplication;
• Concurrent genetic syndromes other than MDS;
• Significant brain or cerebellar atrophy, or other significant degenerative changes as shown in cranial MRI at screening;
• Prior or current hypertension, cardiomyopathy, myocardial ischemia or atrial fibrillation and other cardiovascular diseases;
• Prior central nervous system surgery within 6 months before enrolment;
• Systemic use of immunosuppressive drugs within 3 months before enrolment;
• Prior gene therapy or oligonucleotide therapy treatments;
• Any other conditions that would not allow the potential subject to complete follow-up examinations during the study and would, in the opinion of the investigator, make the potential subject unsuitable for the study.

Sponsors & Collaborators

• HuidaGene Therapeutics Co., Ltd.: lead
• Peking University First Hospital: collaborator

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Lubs X-linked mental retardation syndrome

Central Study Contacts

Study Director

CONTACT

732-318-9873; HG20401@huidagene.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, multiple doses of a single intracerebroventricular injection of HG204

Study Record Dates

• First Submitted: September 4, 2024
• First Posted: September 26, 2024
• Study Start: October 30, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)