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

Phase 1

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: Placebo; Drug: RAG-17

• Registration Number: NCT06556394
• Lead Sponsor: Ractigen Therapeutics.

Brief Summary

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

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 Timeline

• Study First Submitted: 2024-08-01
• Study First Submitted QC: 2024-08-13
• Study First Posted: 2024-08-16
• Study Start: 2024-12-24
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-06
• Last Update Posted: 2025-01-08
• Primary Completion: 2026-02
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo is administered by intrathecal injection to subjects with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) Gene Mutation
RAG-17	RAG-17	RAG-17 is administered by intrathecal injection to subjects with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) Gene Mutation

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Plasma Pharmacokinetic (PK) Parameter: AUC0-last	Before treatment and within 48 hours after treatment	Area Under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non-zero Concentration
Plasma Pharmacokinetic (PK) Parameter: Cmax	Before treatment and within 48 hours after treatment	Peak Plasma Concentration
Plasma Pharmacokinetic (PK) Parameter: λz	Before treatment and within 48 hours after treatment	Elimination Rate Constant
Plasma Pharmacokinetic (PK) Parameter: T½	Before treatment and within 48 hours after treatment	Apparent Terminal Elimination Half-life of Study Drug
Plasma Pharmacokinetic (PK) Parameter: Vz/F	Before treatment and within 48 hours after treatment	Apparent Volume of Distribution
Plasma Pharmacokinetic (PK) Parameter: MRT	Before treatment and within 48 hours after treatment	Mean Residence Time
CSF Pharmacokinetic (PK) Parameter: Concentration	Before treatment and within 29 days after treatment	Concentration in Cerebrospinal Fluid(CSF)
Plasma Pharmacokinetic (PK) Parameter: CL/F	Before treatment and within 48 hours after treatment	Apparent Clearance
Plasma Pharmacokinetic (PK) Parameter: AUC0-inf	Before treatment and within 48 hours after treatment	Area Under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity
Plasma Pharmacokinetic (PK) Parameter: Tmax	Before treatment and within 48 hours after treatment	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
CSF Pharmacokinetic (PK) Parameter: T½	Before treatment and within 29 days after treatment	Half-life in Cerebrospinal Fluid(CSF)

Trial Locations

Locations (3)

Beijing Tiantan Hospital; 🇨🇳 Beijing, China

West China Hospital of Sichuan University; 🇨🇳 Chengdu, China

The Second Affiliated Hospital Zhejiang University School of Medicine; 🇨🇳 Hangzhou, China