ALS - Amyotrophic Lateral Sclerosis, ALS (Amyotrophic Lateral Sclerosis)
Conditions
Keywords
Neuron-derived Neurotrophic Factor, Amyotrophic Lateral Sclerosis, NTF001, Gene Therapy, Adeno-associated Virus, Intrathecal Injection
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.
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.
Interventions
GENETICNTF001 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.
Sponsors
Ruijin Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events | From administration of NTF001 through Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in ALS Functional Rating Scale-Revised Score | Baseline through Week 52 | 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. |
| Change From Baseline in ALS Quality of Life Assessment | Baseline through Week 52 | 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. |
| Change From Baseline in ALSAQ-40 Score | Baseline through Week 52 | 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. |
| Change From Baseline in Norris Scale Score | Baseline through Week 52 | 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. |
Countries
China
Outcome results
None listed