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

NCT05903690 | Completed Early Phase 1 DMC

• 1 other identifier: HX-A-2023004
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the safety, tolerability and pharmacokinetics of RAG-17 in adult amyotrophic lateral sclerosis (ALS) patients with SOD1 mutation. Patients will receive drug treamtent via dose escalation which ranging from minimum of 60 mg to the maximum tolerated dose (MTD), after reaching the tolerated dose, a fixed dose of the drug is given once every two months for continuous treatment, and the total treatment cycle is 8 months. The duration of this study is two years.

Conditions

Gene Mutation

Keywords

RAG-17; SOD1 Gene Mutation; Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (14)

• Adverse events (AE) and serious adverse events (SAE)

  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

  Within 240 days after treatment

• Clinical laboratory examination index

  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.

  Before RAG-17 treatment and within 240 days after treatment

• Physiological Parameter-Vital Sign: Body Temperature

  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.

  Within 240 days after treatment

• Physiological Parameter-Vital Sign: Pulse Rate

  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.

  Within 240 days after treatment

• Physiological Parameter-Vital Sign: Respiration Rate

  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.

  Within 240 days after treatment

• Physiological Parameter-Vital Sign: Blood Pressure

  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.

  Within 240 days after treatment

• Physiological Parameter-Vital Signs: Height, Hip Circumference and Waist

  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.

  Within 240 days after treatment

• Physiological Parameter-Vital Signs: Weight

  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.

  Within 240 days after treatment

• Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R)

  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.

  Within 240 days after treatment

• Neurological examinations

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

  Within 240 days after treatment

• Heart circulatory system examinations

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

  Within 240 days after treatment

• Respiratory system examinations

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

  Within 240 days after treatment

• Abdominal examinations

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

  Within 240 days after treatment

• ECG results

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

  Within 240 days after treatment

Secondary Outcomes (9)

• SOD1 protein levels

  baseline, day 15, day 29, day 60, day 120, day 180 and day 240

• Plasma neurofilament light (NFL) levels

  baseline, day 1, day 15, day 29, day 60, day 120, day 180 and day 240

• Pharmacokinetic Changes of RAG-17

  day 1, day 15, day 29, day 60, day 120, day 180 and day 240

• Pharmacokinetic Changes of RAG-17

  day 1, day 15, day 29, day 60, day 120, day 180 and day 240

• Pharmacokinetic Changes of RAG-17

  day 1, day 15, day 29, day 60, day 120, day 180 and day 240

Other Outcomes (19)

• Lung function (including forced vital capacity)

  day 15, day 29, day 90, day 180, and day 240

• Severity of Fatigue (Fatigue Severity Scale - FSS)

  day 15, day 29, day 90, day 180, and day 240

• Muscle strength (Medical Research Council Scale - MRC Scale)

  day 15, day 29, day 90, day 180, and day 240

Study Arms (1)

RAG-17

EXPERIMENTAL

Doses of RAG-17 will range from a minimum of 60 mg to the maximum tolerated dose (MTD). Dosing once every two weeks, starting from 60 mg, with dose escalation. After reaching the tolerated dose, a fixed dose of the drug is given once every two months for continuous treatment, and the total treatment cycle is 8 months.

Drug: RAG-17

Interventions

RAG-17 DRUG

RAG-17 60mg is used

RAG-17

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are judged by professional medical staff to still be able to carry out the clinical trial project cycle;
• years old ≤ age ≤ 75 years old, males or females;
• ALS patients with confirmed SOD1 gene mutations document (known SOD1 mutation sites and related disease progression have been reported);
• Forced vital capacity ≥ 50% of predicted vital capacity during the screening period;
• Diagnosis of confirmed or probable familial or sporadic ALS in accordance with the revised EI Escorial diagnostic criteria for amyotrophic lateral sclerosis of the World Federation of Neurology;
• The patient or patient's legal representative clearly understands and voluntarily participates in the study and signs the informed consent form;
• Subjects (including male subjects) are willing to have no birth plan and voluntarily take effective contraceptive measures during the entire study period and within 3 months after the end of the study, and have no plan to donate sperm or eggs.

You may not qualify if:

• Patients with SOD1 mutations occurring at nucleotides 44 to 66 (calculated from the start of SOD1 protein translation), patients with P.F21C mutation;
• Patients who have previously received or are currently receiving Tofersen treatment;
• HIV test positive or history of positive tests;
• Positive hepatitis C virus antibody or history of positive tests;
• Active hepatitis B infection (positive hepatitis B surface antigen and/or positive hepatitis B core antibody);
• Have used other investigational drugs within 1 month or within 5 drug half-lives;
• Diseases and deformities of the lumbar spine;
• Have other conditions known to be associated with motor neuron dysfunction that may confuse or obscure an ALS diagnosis;
• Other psychiatric disorders diagnosed according to DSM-V diagnostic criteria, or significant suicide intent;
• With severe hepatic insufficiency, renal insufficiency or severe cardiac insufficiency (severe hepatic insufficiency refers to ALT value≥2.0 times the upper limit of normal value or AST value≥2.0 times the upper limit of normal value; severe renal insufficiency refers to CRE≥1.5 times the upper limit of normal value or eGFR\<40mL/min/1.73m2; severe cardiac insufficiency refers to NYHA class 3-4);
• Permanently dependent on ventilator-assisted ventilation;
• History of alcohol and drug abuse;
• Patients who are pregnant, breast-feeding, or who are likely to become pregnant and plan to become pregnant;
• Patients participating in other clinical trials or using other biological agents, drugs or devices under investigation;
• Patients who have received any vaccinations within 28 days;

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• Ractigen Therapeutics.: collaborator

Study Sites (1)

Beijing Tiantan Hospital

Beijing, 100070, China

Location

Related Publications (10)

• Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ, Sobue G. Amyotrophic lateral sclerosis. Lancet. 2022 Oct 15;400(10360):1363-1380. doi: 10.1016/S0140-6736(22)01272-7. Epub 2022 Sep 15.

  PMID: 36116464 BACKGROUND

• Chen L, Zhang B, Chen R, Tang L, Liu R, Yang Y, Yang Y, Liu X, Ye S, Zhan S, Fan D. Natural history and clinical features of sporadic amyotrophic lateral sclerosis in China. J Neurol Neurosurg Psychiatry. 2015 Oct;86(10):1075-81. doi: 10.1136/jnnp-2015-310471. Epub 2015 Jun 29.

  PMID: 26124198 BACKGROUND

• Rosenbohm A, Liu M, Nagel G, Peter RS, Cui B, Li X, Kassubek J, Rothenbacher D, Lule D, Cui L, Ludolph AC; ALS Registry Swabia Study Group. Phenotypic differences of amyotrophic lateral sclerosis (ALS) in China and Germany. J Neurol. 2018 Apr;265(4):774-782. doi: 10.1007/s00415-018-8735-9. Epub 2018 Feb 1.

  PMID: 29392461 BACKGROUND

• Amyotrophic Lateral Sclerosis (ALS) Fact Sheet. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/amyotrophic-lateral-sclerosis-als-fact-sheet#treatment. October 2022.

  BACKGROUND

• Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, Kalra S, Katz JS, Mitsumoto H, Rosenfeld J, Shoesmith C, Strong MJ, Woolley SC; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009 Oct 13;73(15):1218-26. doi: 10.1212/WNL.0b013e3181bc0141.

  PMID: 19822872 BACKGROUND

• Barrington CJ, Burruano M, Carney C, Choi J, Januska J, Lachuk L, Oskarsson B, Rodriguez C, Speicher L, Tereso G. Addressing the role of edaravone in the management of amyotrophic lateral sclerosis and gaps in care and access: expert panel recommendations. Am J Manag Care. 2021 Aug;27(12 Suppl):S231-S237. doi: 10.37765/ajmc.2021.88732.

  PMID: 34382759 BACKGROUND

• Emery AE, Holloway S. Familial motor neuron diseases. Adv Neurol. 1982;36:139-47. No abstract available.

  PMID: 7180680 BACKGROUND

• Chattopadhyay M, Valentine JS. Aggregation of copper-zinc superoxide dismutase in familial and sporadic ALS. Antioxid Redox Signal. 2009 Jul;11(7):1603-14. doi: 10.1089/ars.2009.2536.

  PMID: 19271992 BACKGROUND

• Shahrizaila N, Sobue G, Kuwabara S, Kim SH, Birks C, Fan DS, Bae JS, Hu CJ, Gourie-Devi M, Noto Y, Shibuya K, Goh KJ, Kaji R, Tsai CP, Cui L, Talman P, Henderson RD, Vucic S, Kiernan MC. Amyotrophic lateral sclerosis and motor neuron syndromes in Asia. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):821-30. doi: 10.1136/jnnp-2015-312751. Epub 2016 Apr 19.

  PMID: 27093948 BACKGROUND

• Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis. N Engl J Med. 2017 Jul 13;377(2):162-172. doi: 10.1056/NEJMra1603471. No abstract available.

  PMID: 28700839 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• YiLong Wang

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-President of Beijing Tiantan Hospital,Chief Scientist of Neurology Center

Study Record Dates

• First Submitted: May 7, 2023
• First Posted: June 15, 2023
• Study Start: May 24, 2023
• Primary Completion: July 11, 2024
• Study Completion: July 11, 2024
• Last Updated: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)