Safety and Tolerance of RAG-17 in Amyotrophic Lateral Sclerosis Patients With SOD1 Gene Mutation

The incidence of adverse events (AE) and serious adverse events (SAE) within 240 days after the first injection of RAG-17, and number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V5.0

Monitor the abnormal change of clinical laboratory Index generated from general examination results before RAG-17 treatment, and within 240 days after the first injection of RAG-17, which including blood testing and urine testing. Eventually to determine the safety and tolerability of RAG-17 on adult ALS patients.

Change in vital signs are monitored within 240 days after RAG-17 treatment to determine the safety and tolerability of RAG-17 on adult ALS patients. Vital sign that is measured including body temperature in degree Celsius.

Change in vital signs are monitored within 240 days after RAG-17 treatment to determine the safety and tolerability of RAG-17 on adult ALS patients. Vital sign that is measured including pulse rate in beats per minute.

Change in vital signs are monitored within 240 days after RAG-17 treatment to determine the safety and tolerability of RAG-17 on adult ALS patients. Vital sign that is measured including respiration rate in breaths per minute.

Change in vital signs are monitored within 240 days after RAG-17 treatment to determine the safety and tolerability of RAG-17 on adult ALS patients. Vital sign that is measured including blood pressure in mmHg.

Change in vital signs are monitored within 240 days after RAG-17 treatment to determine the safety and tolerability of RAG-17 on adult ALS patients. Vital signs that are measured including height, hip circumference and waist in centimeter.

Change in vital signs are monitored within 240 days after RAG-17 treatment to determine the safety and tolerability of RAG-17 on adult ALS patients. Vital sign that is measured including body weight in kilogram.

Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) is a questionnaire-based scale that is used to measure the change in functional impairment of adult ALS patients within 240 days after RAG-17 treatment. ALSFRS-R scale measures 12 aspects of physical function, and each function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0.

Incidence rate of abnormalities in neurological examinations within 240 days after RAG-17 treatment

Incidence rate of abnormalities in heart circulatory system examinations within 240 days after RAG-17 treatment

Incidence rate of abnormalities in respiratory system examinations within 240 days after RAG-17 treatment

Incidence rate of abnormalities in abdominal examinations within 240 days after RAG-17 treatment

Incidence rate of abnormalities in ECG results within 240 days after RAG-17 treatment

Changes of SOD1 protein levels in cerebrospinal fluid from baseline on day 15, day 29, day 60, day 120, day 180 and day 240 of adult ALS patients after RAG-17 treatment

Changes in plasma neurofilament light (NFL) levels from baseline on day 1, day 15, day 29, day 60, day 120, day 180 and day 240 in adult ALS patients after RAG-17 treatment

Pharmacokinetic Parameter changes of RAG-17 in Plasma: Maximum Observed Concentration (Cmax) on day1, day15, day29, day60, day120, day180 and day240 in adult ALS patients after RAG-17 treatment

Pharmacokinetic Parameter changes of RAG-17 in Plasma: Time to Reach Maximum Observed Concentration (Tmax) on day1, day15, day29, day60, day120, day180 and day240 in adult ALS patients after RAG-17 treatment

Pharmacokinetic Parameter changes of RAG-17 in Plasma: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) on day1, day15, day29, day60, day120, day180 and day240 in adult ALS patients after RAG-17 treatment

Pharmacokinetic Parameter changes of RAG-17 in Plasma: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) on day1, day15, day29, day60, day120, day180 and day240 in adult ALS patients after RAG-17 treatment

Pharmacokinetic Parameter changes of RAG-17 in Plasma: Apparent Terminal Elimination Half-life (t1/2) on day1, day15, day29, day60, day120, day180 and day240 in adult ALS patients after RAG-17 treatment

Time to invasive mechanical ventilation in adult ALS patients treated with RAG-17

Time of death in adult ALS patients treated with RAG-17

Changes in lung function (including forced vital capacity) in adult ALS patients treated with RAG-17 on day 15, day 29, day 90, day 180, and day 240

Fatigue Severity Scale(FSS) is a questionnaire-based scale that is used to measure the change in severity of fatigue in adult ALS patients on day 15, day 29, day 90, day 180, and day 240 after RAG-17 treatment. FSS scale is 9-items questionnaire, and each item is scored on a 7 points scale from 1 (strongly disagree) to 7 (strongly agree). The minimum score in total is 9 points, and the maximum score possible is 63. The higher the score means the greater fatigue severity.

Medical Research Council Scale (MRC Scale) is an assessment that is used to measure the change in muscle strength of abductor pollicis brevis muscle, abductor digiti minimi, and tibial anterior muscle in adult ALS patients treated with RAG-17 on day 15, day 29, day 90, day 180, and day 240. MRC Scales ranges from grade 0 to grade 5, where grade 0 means no muscle contraction, grade 5 means muscle has full strength.

Electromyography(EMG) is used to determine the functional performance of muscle and the index change including compound muscle action potential（CAMP）of EMG in adult ALS patients from baseline on day 29, day 90, day 180, and day 240 after RAG-17 treatment

Changes in EMG measures (motor unit number index) from baseline on day 29, day 90, day 180, and day 240 after RAG-17 treatment in adult ALS patients

Changes in EMG measures (motor unit size index) from baseline on day 29, day 90, day 180, and day 240 after RAG-17 treatment in adult ALS patients

7T magnetic resonance imaging (7T MRI) is used to measure the change in the value of body indexes in adult ALS patients treated with RAG-17 on day 29, day 90, day 180, and day 240.

Kinetic gait analysis is used to determine the forces created by and during movement, and measurements are collected to further determine the change in gait functions of of adult ALS patients on day 15, day 29, day 90, day 180, and day 240 after RAG-17 treatment.

Kinematic gait is studied via 3D motion analysis, Construction of the coordinates and orientation of the rigid body segments allow calculation of joint angles of the proximal and distal segment, joint angular velocity, and joint acceleration. Measurements are collected for each joint in all three cardinal planes of motion, and it further measures the change in gait functions of of adult ALS patients on day 15, day 29, day 90, day 180, and day 240 after RAG-17 treatment.

Short Physical Performance Battery (SPPB) is an objective assessment that is used to measure the change in gait functions including balance, lower extremity strength, and functional capacity of of adult ALS patients on day 15, day 29, day 90, day 180, and day 240 after RAG-17 treatment. The test includes three different assessments: walking, sit-to-stand and balance. A 0- to 12-point scale is used to score the sum of the three assessments with higher point values corresponding with greater levels of physical function and lower disability, and vise versa.

Scale for the Assessment and Rating of Ataxia (SARA) is a performance based scale that has eight categories to assess different impairments. The first category - gait of SARA is used to measure the change in gait function of adult ALS patients on day 15, day 29, day 90, day 180, and day 240 after RAG-17 treatment. Gait function is scored from 0point (normal) to 8points (unable to walk).

6-meter walking test is a performance test to assess walking speed over a short distance, which determine the changes in gait function of adult ALS patients on day 15, day 29, day 90, day 180, and day 240 after RAG-17 treatment. The test will be perform in 4 trials, as the first trial is practise trial, and the average of last three trials are calculated.

The Modified Norris Test Score is a rating scale that is used to measure the change in functional ability of adult ALS patients on day 15, day 29, day 90, day 180, and day 240 after RAG-17 treatment. This scale is composed with two parts: the Limb Norris Scale (21 items) and the Norris Bulbar Scale (13 items), each item is scored from 0 point (cannot do anything) to 3 points (normal).

Amyotrophic Lateral Sclerosis Assessment Questionnaire -40 (ALSAQ-40) is a patient self-report health status PRO that is used to measure the changes in the quality of life of adult ALS patients treated with RAG-17 on day 15, day 29, day 90, day 180, and day 240. There are 40 items in ALSAQ-40 with 5 domains: physical mobility (10 items), activities of daily living and independence (10 items), eating and drinking (3 items), communication (7 items), emotional reactions (10 items), each domain has a total score of 100 points, where 0 point means the worst health condition, and 100points means the best health condition.

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 of adult ALS patients treated with RAG-17 on day 15, day 29, day 90, day 180, and day 240. 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).

Hamilton Anxiety Scale (HAM-A) is a rating scale that is used to measure the changes in severity of anxiety of adult ALS patients treated with RAG-17 on day 15, day 29, day 90, day 180, and day 240. The scale is composed of 14 items, Each item is scored on a scale of 0 (no symptom) to 4 (severe), with a total score range of 0 to 56, where <7 means no symptom of anxiety, over 24 means mild to moderate severity, >29 means extreme severity.

Hamilton Depression Scale (HAM-D) is a rating scale that is used to measure the changes in severity of depression of adult ALS patients treated with RAG-17 on day 15, day 29, day 90, day 180, and day 240. For the 17-item version, scores can range from 0 to 54. Scores between 0 and 6 indicate a normal person , scores between 7 and 17 indicate mild depression, scores between 18 and 24 indicate moderate depression, and scores over 24 indicate severe depression.

London ALS Stage is used to measure the change in clinical stages of adult ALS patients on day 15, day 29, day 90, day 180, and day 240 after RAG-17 treatment. The King's staging system consists of five disease stages, with Stage 5 being death. Stage 4 is nutritional failure.Stages 1-3 are based upon the number of El Escorial central nervous system (CNS) regions involved in the disease, measured by weakness, wasting, spasticity, dysphagia, or dysarthria.

The Milano-Torino (MiToS) Staging is used to measure the change in clinical stages of adult ALS patients on day 15, day 29, day 90, day 180, and day 240 after RAG-17 treatment. The Milano-Torino (MiToS) Staging is composed with six stages, where stage 0 is no functional impairment, stage 1 is loss of one type of function, stage 2 is loss of two type of function, stage 3 is loss of three type of function, stage 4 is loss of four type of function, and stage 5 is death.