ClinicalTrials.gov record NCT06739434
GCB-002 in Treatment of Patients With Rett Syndrome
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
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This open-label, single-arm dose-escalation study tests single intrathecal doses of GCB-002 in female children aged 2–10 with Rett syndrome due to MECP2 mutations. Two to three dose groups (about 6–9 participants) are planned; first participants serve as 30-day sentinels and dose escalation follows predefined safety rules, including a possible 3+3 expansion. Participants have safety and clinical assessments through 52 weeks after dosing, then enter long-term follow-up for up to 5 years. The study focuses on safety, tolerability, and initial efficacy assessments.
What it is studying. The study tests the safety, tolerability, and initial efficacy of GCB-002 — a self-complementary AAV9 carrying a full-length human MECP2 transgene — given as a single intrathecal injection in female children with Rett syndrome caused by MECP2 mutations.
What the researchers hope to learn. To evaluate drug-related adverse events through 52 weeks and to assess changes from baseline on clinician- and caregiver-rated scales: Clinical Global Impression–Improvement (CGI-I), Patient Global Impression–Improvement (PGI-I), and the Rett Syndrome Behaviour Questionnaire (RSBQ). To collect safety and initial efficacy data to inform dose escalation and longer-term monitoring.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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
- 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;
- 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;
- If none of the three subjects in a certain dose group developed DLT, the study will proceed to the next higher dose group;
- 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;
- 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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Genetic
- GCB-002
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Age range from 2 to 10 years old, female;
- The clinical diagnosis of the subject is RTT, and after genetic testing, it was found to be a pathogenic variant of the MECP2 gene;
- 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
- Has participated in or is currently participating in other RTT drug clinical trials or other AAV gene therapy clinical studies;
- The subject has a history of head injuries that can cause neurological disorders such as epilepsy, physical disabilities, etc;
- The subject has MECP2 gene mutation but does not cause RTT;
- Subjects with allergic constitution, including those allergic or hypersensitive to prednisolone, other glucocorticoids, their excipients, and local anesthetics;
- The subjects had status epilepticus in the 3 months prior to enrollment;
- Subjects require invasive or non-invasive ventilation support;
- Serum anti AAV9 neutralizing antibody titer>1:200;
- During the screening visit, subjects with the following abnormal findings: ALT, AST, and γ-glutamyl transferase (GGT) levels all ≥1.0×ULN, TBIL ≥1.0×ULN; serum creatinine (Scr) >1.0×ULN; activated partial thromboplastin time (APTT) prolonged >1.5×ULN / INR >1.5; platelet count (PLT) <100×10\^9/L or investigator judgment that PLT results are abnormal and clinically significant;
- Contraindications for lumbar puncture or intrathecal therapy exist;
- Positive for human immunodeficiency virus antibody, or hepatitis B surface antigen, or hepatitis C antibody, or Treponema pallidum antibody, or current TORCH viral infection, or current Epstein-Barr virus infection;
- Combination use of any of the following drugs within 90 days prior to administration, and planned immunotherapy therapy (cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab) other than prophylactic medication as specified in the protocol within 3 months after the start of the trial;
- The researchers believe that it is not suitable to participate in this study.
Study description and what participation involves
The registry record has no detailed description beyond the summary above.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants receive a single intrathecal injection of GCB-002 (given into the spinal fluid, typically by lumbar puncture) as part of a dose‑escalation plan with 2–3 dose groups (about 3 subjects per group; total 6–9 expected). The first subject in each group is observed for about 30 days for safety before others join, and dose groups may be expanded for additional safety observation if needed. After dosing there are regular safety visits and assessments up to 52 weeks, including clinician-rated and caregiver-rated scales (Clinical Global Impression–Improvement, Patient's Global Impression of Improvement, and the Rett Syndrome Behavior Questionnaire) and recording of adverse events. After the 52‑week period, subjects can enter a long-term follow-up phase lasting 5 years from the initial administration.
How the study is structured. Open-label (no masking), single-arm, non-randomized, sequential dose-escalation. Participants receive a single intrathecal injection of GCB-002. Two to three dose cohorts are planned; the first subject in each cohort is a sentinel with a 30-day safety observation before enrolling others. Cohorts begin with 3 subjects and may expand under a 3+3 rule if predefined adverse events occur. Safety and clinical outcome assessments occur up to 52 weeks after dosing, followed by a long-term follow-up period of up to 5 years.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry says participants are enrolled by invitation. Who decides who is invited, and how?
- The listed sites are in China. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Rett syndrome
Important dates
- Study start
- Nov 11, 2024
- Primary completion
- December 2027 (estimated)
- Study completion
- December 2030 (estimated)
- Target enrollment
- 6 participants (estimated)
- Last updated on registry
- Sep 15, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Genecombio Ltd.
- Collaborators
- Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Participating sites (1)
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200092 · China
Terms used on this page · explanations by MedicalUpdates.ai
- dose escalation
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- single-arm
- All participants receive the same treatment or follow the same plan. There is no comparison group within the study.
- intrathecal
- Given by injection into the fluid around the spinal cord, usually through a lumbar puncture.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- DLT
- A side effect, defined in advance, that is severe enough to limit how far the dose can be raised in a dose-escalation study. How many such events stop escalation is set by the study's rules.
- adverse events
- Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
- investigational drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- long-term follow-up
- Observation that continues for years after the study treatment, often required for gene and cell therapies.
- legal guardian
- A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
- informed consent form
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- prednisolone
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- screening visit
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- ULN
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- Contraindications
- A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
- lumbar puncture
- A procedure in which a needle is placed between the bones of the lower back to collect spinal fluid or to give a treatment.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
← Back to clinical trials