GCB-001 in Treatment of Patients With Type II (SMA) Spinal Muscular Atrophy

Plain-language summary

This study explores dose escalation of GCB-001 given as a single-arm, open-label, single intrathecal injection in patients with delayed-onset type 2 spinal muscular atrophy (SMA). Two dose cohorts are planned, with 3 subjects per dose for a total of 6 subjects aged 2 to 12 years; for safety, the first subject in each cohort completes a 30-day observation period and a sentinel design with a dose-limiting toxicity (DLT) observation period governs enrollment of the remaining subjects. Eligibility requires meeting the clinical diagnostic criteria for type 2 SMA with onset between 6 and 18 months, a confirmed SMN1 biallelic pathogenic mutation and 2-4 copies of the SMN2 gene.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Not Applicable

Status

Enrolling by invitation

Sponsor

Genecombio Ltd.

Intervention

GCB-001

Start date

1/15/2025

Estimated completion

12/1/2030

Countries

China

Related genes

Locations

• Hangzhou, China

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

1. Age ≥ 2 years and ≤ 12 years, gender not limited;
2. Meet the clinical diagnostic criteria for type 2 SMA, have an onset age form 6 months to 18 months, are diagnosed with SMN1 double allele pathogenic mutation, have 2-4 copies of SMN2 gene, and meet the clinical diagnostic criteria for SMA 5qSMA;
3. Capable of sitting alone but has never acquired the ability to walk independently (according to HFMSE standards, sitting alone: able to maintain a sitting position without hand support and count to 3 or more; walking independently: able to walk 4 or more steps without assistance);
4. The guardians of the subjects are able to understand and willing to comply with the requirements and procedures of protocol, voluntarily participate and sign the informed consent form.

Exclusion Criteria:

1. Researchers believe that gene replacement therapy may cause unnecessary risk of concomitant diseases, such as serious cardiovascular and cerebrovascular diseases, digestive tract diseases, liver and kidney dysfunction diseases, diabetes, known epilepsy, convulsions, convulsions or family history of psychosis;
2. Subjects who have participated in AAV gene therapy or have participated in or are currently participating in clinical trials of other SMA drugs;
3. Received treatment with Nordenafil Sodium Injection within 4 months prior to administration;
4. Received treatment with risperidone within 15 days prior to administration;
5. Subjects who have been treated with β 2 receptor agonists within 30 days prior to treatment (excluding inhaled salbutamol);
6. Subjects with allergic constitution, including those who are allergic or hypersensitive to prednisolone, other glucocorticoids or their excipients, and allergic to local anesthetics;
7. During the screening period, non-invasive ventilation support should be used for at least 12 hours per day;
8. The serum Anti-AAV9 neutralizing antibody titer is greater than 1:200.