ALS (Amyotrophic Lateral Sclerosis)
Conditions
Keywords
Amyotrophic lateral sclerosis, RAG-17, SOD1
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.
Interventions
DRUGA sterile aqueous solution of RAG - 17 preparation (sodium salt)
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 RAG - 17 for 150 mg: 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.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events and serious adverse events | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | The time of occurrence of invasive mechanical ventilation after treating SOD1-ALS patients with RAG-17 in the real world |
| Gastrostomy | From date of randomization until the date of first documented event about gastrostomy. The assessment period is up to 30 months. | The time of occurrence of gastrostomy after treating SOD1-ALS patients with RAG-17 in the real world |
| Death | From randomization date to date of death from any cause. The assessment period is up to 60 months. | The time of occurrence of death after treating SOD1-ALS patients with RAG-17 in the real world |
| 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 | The level of SOD1 protein in the cerebrospinal fluid of ALS patients is positively correlated with the disease severity. Changes in the level of SOD1 protein in cerebrospinal fluid relative to the baseline at 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 after treating SOD1 - ALS patients with RAG - 17 in the real - world setting |
| 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 | Change in Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) score (from 40 to 200, score decline indicates worse outcome of ALS patients, or disease progression and disability). Changes in ALSAQ-40 relative to the baseline at 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 after treating SOD1 - ALS patients with RAG - 17 in the real world |
| 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 | The EuroQol 5 Dimension 5 Level (EQ-5D-5L) is a self-report survey that is used to measure the changes in the quality of life. EQ-5D-5L contains 5 domains including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, and each domain is scored on a 5-level severity from Level1(no difficulty) to Level5 (extreme difficulty). Changes in EQ-5D-5L relative to the baseline at 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 after treating SOD1 - ALS patients with RAG - 17 in the real world. |
| 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 | Medical Research Council Scale (MRC Scale) is an assessment that is used to measure the change in muscle strength. MRC Scales ranges from grade 0 to grade 5, where grade 0 means no muscle contraction, grade 5 means muscle has full strength. Changes in muscle strength relative to the baseline at 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 after treating SOD1-ALS patients with RAG-17 in the real world |
| 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 | The level of neurofilament light chain (NFL) in blood of ALS patients. Value increase indicates neuroinflammation or nerve damage. Changes in plasma neurofilament light chain protein (NFL) levels relative to the baseline at 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 after treating SOD1 - ALS patients with RAG - 17 in the real world |
Contacts
Primary ContactWang YiLong
Backup ContactChen WeiQI
Outcome results
None listed