Clinical trial NCT05824169: Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 1 Patients
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Spinal Muscular Atrophy
Keywords: Type 1
Lead sponsor: GeneCradle Inc
Sponsor class: INDUSTRY
First posted: 2023-04-21
Enrollment: 18
Sex: ALL
Minimum age (years): 0
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: when patient reaches 18 months of age
measure: Proportion of patients treated with GC101 who achieve motor milestone of sit unassisted for at least 10 seconds at 18 months of age
timeFrame: when patient reaches 18 months of age
Secondary outcomes:
measure: Ability to thrive
timeFrame: when patient reaches 18 months of age
measure: Changes from baseline Children's hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score
timeFrame: when patient reaches 18 months of age
measure: Proportion of event-free survival patients
timeFrame: when patient reaches 14 months of age
Other outcomes:
measure: Proportion of patients who achieve the World Health Organization (WHO) Multicenter Growth Reference Study (MGRS) motor milestones
timeFrame: when patient reaches 18 months of age
Locations:
city: Beijing
country: China
facility: Peking University， First Hospital, Department of Pediatrics
city: Beijing
country: China
facility: Bayi Children's Hospital, Seventh Medical Center, PLA general hospital
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
city: Suzhou
country: China
facility: Children's Hospital of Soochow University
Study officials:
References: