Extended Study of RAG-17 in the Treatment of Amyotrophic Lateral Sclerosis Patients With SOD1 Gene Mutation
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 10
- Primary Endpoint
- Incidence of adverse events and serious adverse events
Study Overview
Brief Summary
This study primarily evaluates the safety, tolerability, and efficacy of RAG - 17 in adult ALS patients with SOD1 - mutated genes in the real - world setting.
Detailed Description
Based on the results of the previous investigator - initiated trial (IIT) of RAG - 17 in the treatment of SOD1 - ALS, this study further planned to conduct another small - sample real - world research. By administering regular and quantitative intrathecal injections of RAG - 17 to subjects who meet the inclusion criteria of the study, the safety, tolerability, and efficacy of RAG - 17 in adult ALS patients with SOD1 - mutated genes in the real - world setting will be evaluated.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •18 ≤ Age ≤ 75 years old, regardless of gender.
- •ALS patients with confirmed SOD1 gene mutations (known SOD1 mutation sites with reported relevant disease progression).
- •The diagnosis meets the criteria for definite or probable familial or sporadic ALS in the El Escorial diagnostic criteria for amyotrophic lateral sclerosis revised by the World Federation of Neurology.
- •The patient himself/herself or their legal representative clearly understands, voluntarily participates in this study, and signs the informed consent form.
Exclusion Criteria
- •Patients with SOD1 mutation sites occurring at nucleotides 44 - 66 (counting from the start of SOD1 protein translation) and patients with P.F21C mutation.
- •Patients diagnosed with other mental illnesses according to the DSM - V diagnostic criteria, or those with obvious suicidal intent.
- •Patients with severe hepatic insufficiency, severe renal insufficiency, or severe cardiac insufficiency. (Severe hepatic insufficiency refers to an ALT value ≥ 2.0 times the upper limit of normal or an AST value ≥ 2.0 times the upper limit of normal; severe renal insufficiency refers to a CRE ≥ 1.5 times the upper limit of normal or an eGFR < 40 mL/min/1.73m²; severe cardiac insufficiency refers to a NYHA score of 3 - 4.)
- •Patients with a history of alcohol or drug abuse.
- •Pregnant, lactating patients, those with a possibility of pregnancy, or patients planning to become pregnant.
- •Patients who have received any vaccination within 28 days.
- •Patients who are unable to cooperate with the follow - up for other reasons.
Arms & Interventions
Treatment Group
Patients who meet the inclusion and exclusion criteria are required to come to the hospital at the following time points to complete the intrathecal bolus injection of quantitative RAG - 17, relevant examinations, and evaluations by the research physicians: baseline, 60 ± 3 days, 120 ± 3 days, 180 ± 3 days, 240 ± 3 days, 300 ± 3 days, 360 ± 3 days, 450 ± 3 days, 540 ± 3 days. An online follow - up will be conducted at 570 ± 3 days.
Intervention: A sterile aqueous solution of RAG - 17 preparation (sodium salt) (Drug)
Outcomes
Primary Outcomes
Incidence of adverse events and serious adverse events
Time Frame: Baseline to 570 days
Incidence of adverse events and serious adverse events within 570 days after treating SOD1 - ALS patients with RAG - 17 in the real world, and number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V5.0.
ALSFRS-R score
Time Frame: baseline, 60±3 days, 120±3 days, 180±3 days, 240±3 days, 300±3 days, 360±3 days, 450±3 days, 540±3 days, and 570±3 days
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score (ALSFRS-R scores from 0 to 48, score decline indicates worse outcome of ALS patients, or disease progression and disability)
Secondary Outcomes
- The level of SOD1 protein in cerebrospinal fluid(baseline, 60±3 days, 120±3 days, 180±3 days, 240±3 days, 300±3 days, 360±3 days, 450±3 days, and 540±3 days)
- Plasma neurofilament light chain protein (NFL) level(baseline, 60±3 days, 120±3 days, 180±3 days, 240±3 days, 300±3 days, 360±3 days, 450±3 days, and 540±3 days)
- Invasive mechanical ventilation(From date of randomization until the date of first documented event about invasive mechanical ventilation. The assessment period is up to 30 months.)
- Gastrostomy(From date of randomization until the date of first documented event about gastrostomy. The assessment period is up to 30 months.)
- Death(From randomization date to date of death from any cause. The assessment period is up to 60 months.)
- Muscle strength (MRC Scale)(baseline, 60±3 days, 120±3 days, 180±3 days, 240±3 days, 300±3 days, 360±3 days, 450±3 days and 540±3)
- ALSAQ-40(baseline，60±3 days, 120±3 days, 180±3 days, 240±3 days, 300±3 days, 360±3 days, 450±3 days, 540±3 days and 570±3 days)
- EQ-5D-5L(baseline，60±3 days, 120±3 days, 180±3 days, 240±3 days, 300±3 days, 360±3 days, 450±3 days, 540±3 days and 570±3 days)
Investigators
yilong Wang
Vice-President of Beijing Tiantan Hospital,Chief Scientist of Neurology Center
Beijing Tiantan Hospital