GCB-002 in Treatment of Patients with Rett Syndrome (GITFPWRS)

An Open Label, Single Arm, Dose Escalation Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of GCB-002 in the Treatment of Female Subjects with MECP2 Gene Mutation in Patients with Rett Syndrome

Study Brief Summary overall design This study explored dose escalation of single-arm, open, single intrathecal injection in female RTT subjects with MECP2 gene mutations. The investigator plans to conduct 2-3 dose groups. It is expected that each dose group will enroll 3 subjects, with a total of 6-9 female RTT subjects aged 2-10 years old due to MECP2 gene mutations.

dose escalation

1. For safety reasons, each subject in the first dose group needs to complete a 30-day safety observation. After the researcher determines that it is safe and tolerable, the next subject can be enrolled in the group;
2. The follow-up dose group adopts a sentinel test design, with the first case of each dose group being a sentinel. The first subject needs to complete a 30-day safety observation, and after the researcher determines that it is safe and tolerable, the remaining subjects can be enrolled in the group;
3. If none of the three subjects in a certain dose group developed DLT, the study will proceed to the next higher dose group;
4. If there are no safety issues and no adverse events of dose escalation termination in dose group 2 (see dose termination escalation rules), the researcher and funding unit (Genecombio) will conduct a comprehensive evaluation of the safety data and efficacy trends of all subjects in dose group 2 to determine whether to escalate to dose group 3;
5. During the DLT observation period, if the subject does not observe DLT and the researcher believes that continuing treatment can bring clinical benefits to the subject, the subject will continue to receive treatment; During the DLT observation period, if there is no occurrence of DLT or ≥ grade 2 adverse events related to the investigational drug, it will be escalated to the next dose group. If the subject experiences grade ≥ 2 adverse events related to the study drug, the dose group will be expanded to 3 subjects for further observation of drug safety, and a "3+3" rule will be applied from this dose group onwards. Each subject in each dose group will be enrolled on a case by case basis.

According to the "Technical Guidelines for Long term Follow up Clinical Research of Gene Therapy Products (Trial)", in clinical studies, subjects can automatically enter the long-term follow-up research stage after the last follow-up (52 weeks after administration), and the follow-up period is 5 years after the initial administration.

Study Overview

• Status: Enrolling by invitation
• Conditions: RETT Syndrome with Proven MECP2 Mutation
• Intervention / Treatment: Genetic: GCB-002

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age range from 2 to 10 years old, female;
2. The clinical diagnosis of the subject is RTT, and after genetic testing, it was found to be a pathogenic variant of the MECP2 gene;
3. The legal guardian is able to understand the requirements and procedures of the research plan, voluntarily participate, and sign an informed consent form.

Exclusion Criteria:

1. Has participated in or is currently participating in other RTT drug clinical trials or other AAV gene therapy clinical studies;
2. The subject has a history of head injuries that can cause neurological disorders such as epilepsy, physical disabilities, etc;
3. The subject has MECP2 gene mutation but does not cause RTT;
4. Subjects with allergic constitution, including those allergic or hypersensitive to prednisolone, other glucocorticoids, their excipients, and local anesthetics;
5. The subjects had status epilepticus in the 3 months prior to enrollment;
6. Subjects require invasive or non-invasive ventilation support;
7. Serum anti AAV9 neutralizing antibody titer>1:200;

The researchers believe that it is not suitable to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose; Low dose is the first cohort of the study with a low dose level.	Genetic: GCB-002; GCB-002 is a self-complementary AAV9 carrying a full length human MECP2 transgenetic product.
Experimental: High dose; High dose is the first cohort of the study with a high dose level.	Genetic: GCB-002; GCB-002 is a self-complementary AAV9 carrying a full length human MECP2 transgenetic product.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the incidence of drug-related adverse events from baseline to 52 weeks after administration		0-52 weeks
Evaluate the changes from baseline using the Clinical Global Impression Scale - Overall Improvement (CGI-I) after 52 weeks of administration	This 7-point scale (1 = very much improved, 7 = very much worse, etc.) is used by the clinician to assess the participant's overall performance status; higher scores indicate increased severity.	0-52 weeks
Evaluate the changes in the Patient's Global Impressions of Improvement (PGI-I) scale compared to baseline after 52 weeks of drug administration	This 7-point scale (1 = very much improved, 7 = very much worse, etc.) is used by the clinician to assess the participant's overall performance status; higher scores indicate increased severity.	0-52 weeks
Evaluate the changes in Rett Syndrome Behavior Questionnaire (RSBQ) compared to baseline after 52 weeks of drug administration	The RSBQ is a 45-item questionnaire and is completed by the participant's Caregiver. Scores (0 = not true, 1 = somewhat/sometimes true, or 2 = very true) are applied to subscales including General Mood, Breathing Problems, Fear/Anxiety, Walking/Standing, etc.; higher scores indicate greater severity.	0-52 weeks

Collaborators and Investigators

• Sponsor: Genecombio Ltd.
• Collaborators: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 16, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: MECP2; Rett
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Genetic Diseases, Inborn; Disease; Neurobehavioral Manifestations; Heredodegenerative Disorders, Nervous System; Mental Retardation, X-Linked; Intellectual Disability; Genetic Diseases, X-Linked; Syndrome; Rett Syndrome
• Other Study ID Numbers: GCB-002-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No