Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 1 Patients

Spinal Muscular Atrophy Clinical Trial

Official title:

A Multi-center, Open Label, Single-arm, Dose Ascending Clinical Trial for Evaluation of Safety and Efficacy of Gene Therapy Drug GC101 in the Treatment of Spinal Muscular Atrophy (SMA) Type 1 Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05824169
• Other study ID #: JLJY-GC101-SMA-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 25, 2023
• Est. completion date: December 2025

Study information

• Verified date: April 2023
• Source: GeneCradle Inc
• Contact: GeneCradle, Inc. China
• Phone: 86-13501380583
• Email: ind[@]bj-genecradle.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will evaluate safety and efficacy of intrathecal delivery of GC101 gene therapy drug as a treatment of spinal muscular atrophy Type 1 (SMA 1) patients.

Description:

The purpose of this trial is to evaluate safety and efficacy of gene therapy drug GC101 in SMA 1 patients. Open-label, dose-escalation clinical trial of GC101 will be conducted in multiple centers in China. GC101 will be administrated intrathecally. Short-term safety will be evaluated in 52 weeks and enter long-term follow-up study of 5 years at will. Patients will be tested at baseline and followed up on various time points. The primary analysis for efficacy will be assessed when all patients reach 18 months of age on the motor milestone of sit unassisted for at least 10 seconds.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Months to 6 Months

Eligibility

Inclusion Criteria:

• Six months of age and younger on day of vector infusion with Type 1 SAM as defined by

the following features:

• Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN2;
• Onset of disease before 6 months of age
• The patient's legal guardian(s) must be able to understand the purpose and risks of the study and voluntarily provide signed and dated informed consent prior to any study-related procedures being performed.

Exclusion Criteria:

• Patient who has participated in a previous gene therapy research trials;
• Patient who has received Nusinersen and Risdiplam treatment;
• Patient who has AAV9 neutralizing antibody titer =1:200;
• Patient who requires non-invasive ventilatory support averaging=16 hours/day;
• Patient with a point mutation in SMN2 (c.859G>C);
• Patient who requires non-invasive ventilatory support averaging=16 hours/day at screening;
• Patient who use invasive ventilatory support or pulse oximetry < 95% saturation while awake and calm at screening;
• Patient who is positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
• Abnormal laboratory values considered clinically significant, including gamma-glutamyl transferase(GGT), Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin > 3x upper limit of normal (ULN), Hemoglobin (Hgb)< 110 or >150 g/L, platelet <183x10^9/L or 614x10^9/L;
• Class IV patient based on Modified Ross Heart Failure Classification for Children;
• Patient with a history of glucocorticoid allergy;
• Contraindication that would interfere with the lumbar puncture procedures;
• Presence of an untreated active infection requiring systemic antiviral therapy at any time during the screening period;
• Vaccination less than 2 weeks before infusion of vector;
• Patient who has any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study. Note: Other protocol defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Intervention

Genetic:
• GC101
Self-complementary AAV9 carrying a codon-optimized SMN coding sequence(coSMN1) driven by CMV enhancer and chicken ß-actin promoter

Locations

Country	Name	City	State
China	Bayi Children's Hospital, Seventh Medical Center, PLA general hospital	Beijing
China	Peking University, First Hospital, Department of Pediatrics	Beijing
China	Shengjing Hospital of China Medical University	Shenyang
China	Children's Hospital of Soochow University	Suzhou

Sponsors (1)

Lead Sponsor	Collaborator
GeneCradle Inc

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of patients who achieve the World Health Organization (WHO) Multicenter Growth Reference Study (MGRS) motor milestones	WHO MGRS gross motor milestones and performance criteria included sitting without support for at least 10 seconds, Hands-and-knees crawling at least three in a row, standing with assistance for at least 10 seconds, walking with assistance at least five steps, standing alone for at least 10 seconds, and walking alone.	when patient reaches 18 months of age
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Frequency of treatment-related adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests	when patient reaches 18 months of age
Primary	Proportion of patients treated with GC101 who achieve motor milestone of sit unassisted for at least 10 seconds at 18 months of age		when patient reaches 18 months of age
Secondary	Ability to thrive	Ability to thrive is defined as the following at 18 months of age: does not receive nutrition through mechanical support or other non-oral method; maintains weight	when patient reaches 18 months of age
Secondary	Changes from baseline Children's hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score	CHOP INTEND score ranges from 0 to 64 with higher scores indicating higher motor function	when patient reaches 18 months of age
Secondary	Proportion of event-free survival patients		when patient reaches 14 months of age