Safety and Efficacy of Intrathecal NTF001 Injection in ALS

NCT07618585 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: NTF-ALS
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, early-phase clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of intrathecal NTF001 injection, an AAV-mediated human neuron-derived neurotrophic factor gene therapy, in patients with amyotrophic lateral sclerosis (ALS). 12 patients with ALS will be enrolled. Each participant will receive a single intrathecal administration of NTF001 and will be followed for 52 weeks after treatment. The primary outcome measures include treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Secondary outcome measures include changes in the ALS Functional Rating Scale-Revised (ALSFRS-R), quality-of-life assessments, and neurological function. This study aims to provide preliminary clinical evidence regarding the safety and potential efficacy of intrathecal NTF001 injection in patients with ALS.

Conditions

ALS (Amyotrophic Lateral Sclerosis)

Keywords

Neuron-derived Neurotrophic Factor; Amyotrophic Lateral Sclerosis; NTF001; Gene Therapy; Adeno-associated Virus; Intrathecal Injection

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events

  Safety and tolerability will be assessed by evaluating the incidence, severity, seriousness, and relationship to the investigational product of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Safety assessments will also include clinical laboratory tests, vital signs, physical examinations, neurological examinations, and other clinically significant safety findings.

  From administration of NTF001 through Week 52

Secondary Outcomes (4)

• Change From Baseline in ALS Functional Rating Scale-Revised Score

  Baseline through Week 52

• Change From Baseline in ALS Quality of Life Assessment

  Baseline through Week 52

• Change From Baseline in ALSAQ-40 Score

  Baseline through Week 52

• Change From Baseline in Norris Scale Score

  Baseline through Week 52

Study Arms (2)

Low-dose NTF001

EXPERIMENTAL

Participants in this cohort will receive a single intrathecal administration of low-dose NTF001 （2E+14 vg）injection.

Genetic: NTF001 Injection

High-dose NTF001

EXPERIMENTAL

Participants in this cohort will receive a single intrathecal administration of high-dose NTF001(4-5 E+14 vg) injection after safety evaluation of the low-dose cohort.

Genetic: NTF001 Injection

Interventions

NTF001 Injection GENETIC

NTF001 is an investigational AAV-mediated gene therapy product designed to express human neuron-derived neurotrophic factor (NDNF). It will be administered once by intrathecal injection to patients with amyotrophic lateral sclerosis (ALS). Participants will receive NTF001 according to the assigned dose cohort and will be followed for safety, tolerability, and preliminary efficacy.

High-dose NTF001; Low-dose NTF001

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in this study and sign the informed consent form.
• Agree to comply with study procedures and cooperate with all study-related assessments throughout the study.
• Male or female patients aged 18 to 65 years.

You may not qualify if:

• Have a history of amyotrophic lateral sclerosis of no more than 5 years.
• Mini-Mental State Examination (MMSE) score \< 24.
• Patient Health Questionnaire-9 (PHQ-9) score ≥ 16.
• Abnormal liver or renal function, defined as AST or ALT \> 1.5 × upper limit of normal (ULN), or serum creatinine (Cr) \> 1.5 × ULN.
• Abnormal coagulation function or current use of anticoagulants.
• Positive infectious disease screening, including positive HBsAg or HBV-DNA, positive HCV-RNA, positive HIV test, or positive syphilis serology.
• Currently receiving antiviral treatment for hepatitis B or hepatitis C.
• Unstable or severe systemic diseases, including active tuberculosis, cardiovascular, respiratory, gastrointestinal, urinary, psychiatric or neurological disorders, such as epilepsy, hematological disorders, immune system diseases, or abnormal laboratory findings that, in the opinion of the investigator, make the participant unsuitable for this study.
• Current or previous history of malignant tumor.
• History of severe allergic reactions, allergy to contrast agents, or inability to undergo surgical anesthesia.
• Currently participating in another clinical trial, or participation in another clinical trial within 3 months before screening.
• Previous receipt of gene therapy before screening.
• Receipt of stem cell therapy within 6 months before screening.
• Use of other investigational drugs within 4 weeks before screening or within 5 half-lives of the investigational drug, whichever is longer, or use of any medication that, in the opinion of the investigator, may affect this study.
• Receipt of a live vaccine within 2 months before screening, or any vaccination within 30 days before screening.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be assigned sequentially to different dose cohorts of NTF001 injection. Each participant will receive a single intrathecal administration and will be followed for 52 weeks after treatment.

Study Record Dates

• First Submitted: May 25, 2026
• First Posted: June 1, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)