NCT07080801

Study on the Safety and Efficacy of RAG-21 in the Treatment of Amyotrophic Lateral Sclerosis Patients With FUS Gene Mutations

• Status: Not Yet Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Sponsor: Beijing Tiantan Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Amyotrophic lateral sclerosis (ALS) is a chronic progressive neurodegenerative disease that remains incurable, with limited existing therapies or drugs available. Familial ALS can be caused by mutations in various genes. In Asia, mutations in the FUS gene are relatively common among early-onset familial ALS patients. Reducing the levels of toxic FUS protein may be an effective therapeutic approach for such ALS patients without causing side effects. RAG-21 is a small interfering ribonucleic acid (siRNA) with a molecular weight of 20 kDa. Through the RNA interference mechanism, it targets the FUS gene, recognizes the corresponding mRNA, and mediates its degradation, thereby downregulating FUS gene expression and reducing toxic FUS protein levels. Accordingly, this project plans to conduct a single-center, dose-escalation clinical study aimed at evaluating the safety, tolerability, and pharmacokinetics of intrathecal bolus administration of RAG-21 in ALS patients carrying FUS gene mutations.

Conditions

• Amyotrophic Lateral Sclerosis (ALS)

Interventions

Type	Name	Description
DRUG	RAG-21	Intrathecal bolus administration of RAG-21 will be initiated at a dose of 120 mg, prepared with a dedicated solvent into a 10 mL sterile aqueous solution. Dosing will occur every 2 weeks, with the dose escalating to 180 mg after 3 administrations. Subsequently, the dosing interval will be extended to every 4 weeks. The investigator will then select an optimal dose from the completed dose cohorts or continue dose escalation until the maximum tolerated dose (MTD) is reached, with a predefined maximum dose of 210 mg. For continued treatment, the investigator-determined optimal dose will be administered as a fixed dose every 4 weeks, with a total treatment duration of 6 months (8 administrations).

Timeline

• Start date: 2025-08-01
• Primary completion: 2026-08-01
• Completion: 2026-12-01
• First posted: 2025-07-23
• Last updated: 2025-07-23