## Protocol Section
### Identification Module
**NCT ID:** NCT06421831

**Brief Title:** Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 3 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 3 Patients

#### Organization Study ID Info
**ID:** JLJY-GC101-SMA-010
#### Organization
**Class:** INDUSTRY
**Full Name:** GeneCradle Inc
### Status Module
#### Completion Date
**Date:** 2028-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2026-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-10

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-10
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** GeneCradle Inc

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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 3 (SMA 3) patients.

**Detailed Description:** The purpose of this trial is to evaluate safety and efficacy of gene therapy drug GC101 in SMA 3 patients. Open-label, dose-escalation clinical trials 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 at various time points.

The primary analysis for efficacy will be assessed at 12 months after treatment with GC101 on the changes from baseline HFMSE (Hammersmith Functional Motor Scale Expanded) and RULM（Revised Upper Limb Module) scores for patients of age ≥ 6 years old.

### Conditions Module

**Conditions:**

- Spinal Muscular Atrophy Type 3

**Keywords:**

- SMA type 3

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 21

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 1.2x10\^14 vg/person of GC101 delivered one-time intrathecally

**Intervention Names:**

- Genetic: GC101

**Label:** single dose cohort

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- single dose cohort

**Description:** Self-complementary AAV9 carrying a codon-optimized SMN coding sequence(coSMN1) driven by CMV enhancer and chicken β-actin promoter

**Name:** GC101

**Type:** GENETIC

### Outcomes Module

#### Other Outcomes

**Measure:** The proportion of patients whose Clinical Global Impression (CGI) is improved at Month 12

**Time Frame:** 52 weeks

**Measure:** The proportion of patients whose Motor Function Measure (MFM) is improved or maintained at Month 12

**Time Frame:** 52 weeks

**Measure:** Change from baseline of Forced Vital Capacity (FVC) at Month 12 ( for patients > 6 years)

**Time Frame:** 52 weeks

**Measure:** Change from baseline of Forced Expiratory Volume in 1 Second (FEV1) at Month 12 ( for patients > 6 years)

**Time Frame:** 52 weeks

**Measure:** Change from baseline of Maximal Inspiratory Pressure (MIP) at Month 12 ( for patients > 6 years)

**Time Frame:** 52 weeks

**Measure:** Change from baseline of Maximal Expiratory Pressure (MEP) at Month 12 ( for patients > 6 years)

**Time Frame:** 52 weeks

**Description:** The 6MWT is used for ambulatory participants with SMA and measures the total distance walked in 6 minutes.

**Measure:** Change from baseline of 6 minutes walk test (6MWT) at Month 12 (for ambulatory patients)

**Time Frame:** 52 weeks

**Description:** The SMA Independence Scale (SMAIS) is a self-reported questionnaire to assess the amount of assistance patients require to perform daily activities. Higher SMAIS scores indicate greater independence.

(range: 0-44).

**Measure:** Change from baseline of SMA Independence Scale (SMAIS) at Month 12

**Time Frame:** 52 weeks

#### Primary Outcomes

**Description:** Frequency of treatment-related adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests

**Measure:** Incidence of Treatment-Emergent Adverse Events

**Time Frame:** 52 weeks

**Description:** HFMSE consists of 33 activities that can be scored one of three ways: 0 for unable to perform, 1 for performs with modification/adaptation, and 2 for performs without modification.

**Measure:** Change from baseline on Hammersmith Functional Motor Scale - Expanded (HFMSE) scores at Month 12

**Time Frame:** 52 weeks

#### Secondary Outcomes

**Description:** HFMSE ≥3 points：minimal clinically important differences (MCID) were considered for the outcomes:

**Measure:** The proportion of patients whose HFMSE improvement ≥ 3 points at Month 12

**Time Frame:** 52 weeks

**Description:** RULM is a 20-item evaluation of upper limb function primarily used for those with SMA who are non-ambulatory (young children through adults).

**Measure:** Change from baseline on Revised Upper Limb Module (RULM) scores at Month 12

**Time Frame:** 52 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* ≥2 years of age on the day of signing the informed consent form;
* Genetic and clinical diagnosis of type 3 SMA with bi-allelic deletion of SMN1 of 5qSMA;
* Hammersmith Functional Motor Scale - Expanded (HFMSE) score is between 10 and 54 at screening;
* Female patients of childbearing age who are pregnant or lactating, as well as all enrolled patients （both male and female), should take effective contraceptive measures within 6 months after the treatment;
* Patients or 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 any previous gene therapy research trials;
* Patient who has AAV9 neutralizing antibody titer ≥1:200;
* Patient who has received Nusinersen within 120 days and Risdiplam within 15 days before treatment;
* Patient who requires invasive or non-invasive ventilatory support averaging≥16 hours/day at screening;
* SMN2 copy numbers \>4；
* Patient who needs nasal or gastric tube feeding for eating;
* Patient who is positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
* Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
* Severe contractures at screening that interfere with either the ability to attain/demonstrate functional measures or with the ability to receive intrathecal (IT) dosing;
* Patient who has other serious diseases, such as severe cardiovascular and cerebrovascular diseases, digestive system diseases, urinary system diseases, endocrine system diseases, hematological diseases, immune system diseases, nervous system diseases (including but not limited to epilepsy, meningitis, history of convulsions or seizures, cerebrospinal fluid circulation disorders), and mental illnesses, etc.;
* Patient with previous injuries (such as upper or lower limb fractures) or surgical operations that have not fully recovered or reached a stable state;
* Vaccination no longer than 2 weeks before treatment;
* Patient who has any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in the study.

**Minimum Age:** 2 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ind@bj-genecradle.com

**Name:** GeneCradle, Inc China

**Phone:** +8613501380583

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Contacts:**

***Contact 1:***

- **Name:** Kang Zhang

- **Role:** CONTACT

***Contact 2:***

- **Name:** Zaiqiang Zhang

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 3:***

- **Name:** Yajie Wang

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** Beijing Tiantan Hospital, Capital Medical University

**State:** Beijing

**Status:** RECRUITING

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020763

- Term: Pathological Conditions, Anatomical

- ID: D000020879

- Term: Neuromuscular Manifestations

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000013118

- Term: Spinal Cord Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000016472

- Term: Motor Neuron Disease

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M4589

- Name: Atrophy

- Relevance: HIGH

- As Found: Atrophy

- ID: M12090

- Name: Muscular Atrophy

- Relevance: HIGH

- As Found: Muscular Atrophy

- ID: M12091

- Name: Muscular Atrophy, Spinal

- Relevance: HIGH

- As Found: Spinal Muscular Atrophy

- ID: M22519

- Name: Pathological Conditions, Anatomical

- Relevance: LOW

- As Found: Unknown

- ID: M22619

- Name: Neuromuscular Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M15915

- Name: Spinal Cord Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M18879

- Name: Motor Neuron Disease

- Relevance: LOW

- As Found: Unknown

- ID: M4024

- Name: Amyotrophic Lateral Sclerosis

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T5342

- Name: Spinal Muscular Atrophy

- Relevance: HIGH

- As Found: Spinal Muscular Atrophy

- ID: T5347

- Name: Spinal Muscular Atrophy Type 3

- Relevance: HIGH

- As Found: Spinal Muscular Atrophy Type 3

- ID: T349

- Name: Amyotrophic Lateral Sclerosis

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009133

- Term: Muscular Atrophy

- ID: D000009134

- Term: Muscular Atrophy, Spinal

- ID: D000001284

- Term: Atrophy

### Misc Info Module

- Version Holder: 2024-05-31
