A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects With Amyotrophic Lateral Sclerosis (ALS) With Superoxide Dismutase Type 1 (SOD1) Gene Mutation

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects With Amyotrophic Lateral Sclerosis (ALS) With Superoxide Dismutase Type 1 (SOD1) Gene Mutation

This is a Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) Gene Mutation

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: RAG-17; Drug: Placebo

Detailed Description

The study is a phase 1, randomized, double-blind, placebo controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RAG-17 in patients with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) gene mutation. The dose levels will be evaluated sequentially across separate cohorts using a rules-based design, wherein participants will receive RAG-17 or placebo at a ratio of 3:1.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Long-Cheng Li; Phone Number: +86 18051622388; Email: lilc@ractigen.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Tiantan Hospital
    • Contact: Yilong Wang, PhD&MD; Email: yilong528@gmail.com
  • Chengdu, China
    • Recruiting
    • West China Hospital of Sichuan University
    • Contact: Huifang Shang, PhD&MD; Email: hfshang2002@163.com
  • Hangzhou, China
    • Recruiting
    • the Second Affiliated Hospital Zhejiang University School of Medicine
    • Contact: Zhiying Wu, PhD&MD; Email: zhiyingwu@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily consents to participate in this study and provides written informed consent prior to the start of any study specific procedures.
2. ≥ 18 years of age at the time of informed consent.
3. Diagnosis of possible, laboratory supported probable, probable, or definite ALS according to the World Federation of Neurology El Escorial.
4. Documented SOD1 mutation.
5. Forced vital capacity (FVC) ≥50% of predicted value as adjusted for sex, age, and height (measured seated).
6. If taking riluzole or edaravone, subject must be on a stable dose or ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit.

Exclusion Criteria:

1. Documented p.F21C SOD1 mutation.
2. Treatment with another investigational drug, biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering ribonucleic acid, stem cell therapy, or gene therapy is allowed.
3. Current enrollment in any other interventional study.
4. History of or positive test result for human immunodeficiency virus, hepatitis C virus antibody or hepatitis B virus.
5. Pregnant or currently breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RAG-17; RAG-17 is administered by intrathecal injection to subjects with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) Gene Mutation	Drug: RAG-17; RAG-17 is a therapeutic small interfering RNA (siRNA).
Placebo Comparator: Placebo; Placebo is administered by intrathecal injection to subjects with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) Gene Mutation	Drug: Placebo; Placebo will be administered via intrathecal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events(AEs)	Assesment of Safety and Tolerability: Incidence and severity of treatment-emergent Adverse Events(AEs) and Serious Adverse Events(SAEs)	Before treatment and within 57 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Pharmacokinetic (PK) Parameter: AUC0-last	Area Under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non-zero Concentration	Before treatment and within 48 hours after treatment
Plasma Pharmacokinetic (PK) Parameter: AUC0-inf	Area Under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity	Before treatment and within 48 hours after treatment
Plasma Pharmacokinetic (PK) Parameter: Cmax	Peak Plasma Concentration	Before treatment and within 48 hours after treatment
Plasma Pharmacokinetic (PK) Parameter: Tmax	Time to reach Cmax. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value	Before treatment and within 48 hours after treatment
Plasma Pharmacokinetic (PK) Parameter: λz	Elimination Rate Constant	Before treatment and within 48 hours after treatment
Plasma Pharmacokinetic (PK) Parameter: T½	Apparent Terminal Elimination Half-life of Study Drug	Before treatment and within 48 hours after treatment
Plasma Pharmacokinetic (PK) Parameter: CL/F	Apparent Clearance	Before treatment and within 48 hours after treatment
Plasma Pharmacokinetic (PK) Parameter: Vz/F	Apparent Volume of Distribution	Before treatment and within 48 hours after treatment
Plasma Pharmacokinetic (PK) Parameter: MRT	Mean Residence Time	Before treatment and within 48 hours after treatment
CSF Pharmacokinetic (PK) Parameter: Concentration	Concentration in Cerebrospinal Fluid(CSF)	Before treatment and within 29 days after treatment
CSF Pharmacokinetic (PK) Parameter: T½	Half-life in Cerebrospinal Fluid(CSF)	Before treatment and within 29 days after treatment

Collaborators and Investigators

• Sponsor: Ractigen Therapeutics.

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: August 1, 2024
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: RGN17-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No