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

NCT06772402 | Enrolling By Invitation

• 1 other identifier: GCB-001-401
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study explored dose escalation of single-arm, open, single intrathecal injection in patients with delayed onset type 2 SMA. The investigator plans to conduct 2 cohorts. It is expected that each dose will be enrolled 3 subjects, with a total of 6 subjects aged from 2-12 years old. For safety reasons, first subject of each dose cohort needs to complete a 30-day safety observation. After the researcher determines that the dosing is safe and tolerable, the next two subjects can be enrolled in the cohort; The follow-up dose cohort adopts a sentinel test design, with the first subject of each dose group being a sentinel. 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. If the subject experiences grade ≥ 2 adverse events related to the study drug, the dose will be expanded to 3 subjects for further safety observation. Each subject in each dose cohort will be enrolled on a case by case basis.

Conditions

Spinal Muscular Atrophy Type 2

Keywords

Type II SMA; AAV; GCB-001

Outcome Measures

Primary Outcomes (6)

• The rate of adverse events from baseline to 12 months after administration Assessed by CTCAE v4.0.

  0-12 months

• AAV viral load after a single administration.

  Detect the AAV viral load by central lab.

  0-12 months

• AAV viral immunogenicity after a single administration.

  Detect the AAV viral immunogenicity by central lab.

  0-12 months

• AAV viral shedding after a single administration.

  Detect the AAV viral shedding by central lab.

  0-12 months

• The change in total HFMSE (Hammersmith Functional Motor Scale Expanded) score from baseline at 12 months after a single administration

  This 66-point scale (66 = very much improved, 0 = very much worse, etc.) is used by the clinician to assess the participant's performance status; higher scores indicate better status.

  0-12 months

• The change in total RULM (Revised Upper Limb Module) score from baseline at 12 months after a single administration

  This 38-point scale (38 = very much improved, 0 = very much worse, etc.) is used by the clinician to assess the participant's performance status of upper limb; higher scores indicate better status.

  0-12 months

Study Arms (2)

Experimental : Low dose

EXPERIMENTAL

Low dose is the first cohort of the study with a low dose level.

Genetic: GCB-001

Experimental : High dose

EXPERIMENTAL

High dose is the first cohort of the study with a high dose level.

Genetic: GCB-001

Interventions

GCB-001 GENETIC

GCB-001 is a self-complementary AAV9 carrying a full length human SMN transgenetic product.

Experimental : High dose; Experimental : Low dose

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age ≥ 2 years and ≤ 12 years, gender not limited;
• 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;
• 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);
• 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.

You may not qualify if:

• 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;
• Subjects who have participated in AAV gene therapy or have participated in or are currently participating in clinical trials of other SMA drugs;
• Received treatment with Nordenafil Sodium Injection within 4 months prior to administration;
• Received treatment with risperidone within 15 days prior to administration;
• Subjects who have been treated with β 2 receptor agonists within 30 days prior to treatment (excluding inhaled salbutamol);
• Subjects with allergic constitution, including those who are allergic or hypersensitive to prednisolone, other glucocorticoids or their excipients, and allergic to local anesthetics;
• During the screening period, non-invasive ventilation support should be used for at least 12 hours per day;
• The serum Anti-AAV9 neutralizing antibody titer is greater than 1:200.

Sponsors & Collaborators

• Genecombio Ltd.: lead
• The Children's Hospital of Zhejiang University School of Medicine: collaborator

Study Sites (1)

Children's Hospital ZheJiang Univisity School Of Medicine

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Spinal Muscular Atrophies of Childhood

Condition Hierarchy (Ancestors)

Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2025
• First Posted: January 13, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2030
• Last Updated: March 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)