Safety and Efficacy of Intrathecal NTF001 Injection in ALS (NTF-ALS)

A Study of the Safety and Efficacy of Intrathecal NTF001 Injection in the Treatment of Amyotrophic Lateral Sclerosis

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.

Study Overview

• Status: Active, not recruiting
• Conditions: ALS (Amyotrophic Lateral Sclerosis); ALS - Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Genetic: NTF001 Injection

Detailed Description

This is a single-arm, open-label, early-phase clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of NTF001 injection in patients with amyotrophic lateral sclerosis (ALS). NTF001 is an investigational AAV-mediated gene therapy product designed to express human neuron-derived neurotrophic factor (NDNF). The investigational product will be administered once by intrathecal injection.

12 patients with ALS will be enrolled in this study. All eligible participants will receive a single intrathecal administration of NTF001 and will undergo scheduled safety and efficacy assessments during a 52-week follow-up period after treatment.

The primary objective of this study is to assess the safety and tolerability of intrathecal NTF001 injection, primarily by evaluating the occurrence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), clinically significant laboratory abnormalities, vital signs, neurological examinations, and other safety-related findings.

The secondary objective is to explore the preliminary efficacy of NTF001 in patients with ALS. Efficacy assessments will include changes in the ALS Functional Rating Scale-Revised (ALSFRS-R), quality-of-life assessments, neurological function, and other exploratory clinical indicators.

This study is expected to provide preliminary clinical evidence regarding the safety, tolerability, and potential therapeutic effects of intrathecal NTF001 injection in patients with ALS, and to support further clinical development of AAV-mediated neurotrophic factor gene therapy for ALS.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200025
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.
• Meet the diagnostic and exclusion criteria for amyotrophic lateral sclerosis according to the Chinese Expert Consensus on the Diagnosis and Treatment of Amyotrophic Lateral Sclerosis 2022 issued by the Neurology Branch of the Chinese Medical Association.
• Have a history of amyotrophic lateral sclerosis of no more than 5 years.

Exclusion Criteria:

• 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.
• History of alcohol dependence or drug addiction, and inability to stop alcohol consumption as instructed during the study.
• Female participants who are pregnant or breastfeeding.
• Participants considered unsuitable for enrollment by the investigator.
• Patients requiring ventilator-assisted ventilation.
• Patients allergic to the investigational intervention.
• Patients with obvious signs of dementia.
• Patients with other psychiatric disorders that may affect disease assessment.
• Severely obese patients, defined as BMI > 35 kg/m².

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose NTF001; Participants in this cohort will receive a single intrathecal administration of low-dose NTF001 （2E+14 vg）injection.	Genetic: NTF001 Injection; 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.
Experimental: High-dose NTF001; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in ALS Functional Rating Scale-Revised Score	The ALS Functional Rating Scale-Revised (ALSFRS-R) will be used to assess functional status in patients with ALS. The total score ranges from 0 to 48, with higher scores indicating better functional status.	Baseline through Week 52
Change From Baseline in ALS Quality of Life Assessment	Quality of life will be assessed using an ALS-specific quality-of-life questionnaire. Changes from baseline will be evaluated during the follow-up period, with higher or lower scores interpreted according to the scoring rules of the selected questionnaire.	Baseline through Week 52
Change From Baseline in ALSAQ-40 Score	The Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) will be used to assess disease-specific quality of life. The questionnaire evaluates multiple domains of daily functioning and well-being in patients with ALS, with higher scores generally indicating worse quality of life.	Baseline through Week 52
Change From Baseline in Norris Scale Score	The Norris Scale will be used to assess neurological function and disease severity in patients with amyotrophic lateral sclerosis. Changes from baseline in the Norris Scale score will be evaluated during the follow-up period, with lower scores indicating greater functional impairment.	Baseline through Week 52

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: May 25, 2026
• First Submitted That Met QC Criteria: May 25, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; Gene Therapy; Intrathecal Injection; Adeno-associated Virus; Neuron-derived Neurotrophic Factor; NTF001
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: NTF-ALS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No