Safety and Efficacy of Intrathecal NTF001 Injection in ALS

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.

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.