NCT04220190

RAPA-501 Therapy for ALS

Phase 2/3 Trial of Autologous Hybrid TREG/Th2 (RAPA-501) T Stem Cell Therapy for Amyotrophic Lateral Sclerosis

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 41 (estimated)
• Sponsor: Rapa Therapeutics LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RAPA-501-ALS is a phase 2/3 expansion cohort study of RAPA-501 autologous hybrid TREG/Th2 cells in patients living with amyotrophic lateral sclerosis (pwALS).

Detailed description

This is an open-label, non-randomized, multi-center phase 2/3 study evaluating RAPA-501 T stem cell therapy in pwALS on an expansion cohort. Amyotrophic lateral sclerosis (ALS) is a rare disease that is also considered an orphan disease according to the Orphan Drug Act. After a subject consents to the study, an apheresis procedure will be performed to collect cells to manufacture the investigational product, RAPA-501 T stem cells. RAPA-501 T stem cells are manufactured ex vivo using epigenetic reprogramming to yield a T stem cell population that is enriched for a dual anti-inflammatory phenotype based on hybrid TREG and Th2 differentiation. RAPA-501 cells express both the TREG and Th2 transcription factors FOXP3 and GATA3, are enriched for expression of the ATP ectonucleotidase molecules CD39 and CD73, are enriched for the T cell homing molecule CD103, and suppress both effector T cell inflammatory molecules and CNS microglial cell inflammatory molecules. This study consists of a phase 2/3 expansion cohort that is evaluating RAPA-501 T stem cell therapy at the dose of 80 x 10EE6 cells per infusion, with up to 4 infusions separated by six weeks between doses (infusion at time 0, and then after week 6, 12, and 18). Study subjects are then followed at the treatment site at 24 weeks and 30 weeks on-study; then, subjects are followed remotely using surveys for two years to capture major clinical events and assess survival. The primary objective in the expansion cohort is to determine the feasibility and safety of the highest established safe dose of RAPA-501 (80 x 10EE6 cells per infusion) in patients with standard-risk ALS (as defining by study entry values of: SVC greater than or equal to 70% of predicted normal; time interval since first ALS symptom, 24 months or less; and ALSFRS-R score between 34 and 45). Secondary study objectives relate to assessing the potential efficacy of RAPA-501 therapy through monitoring of ALSFRS-R scores, SVC values, time to King's stage transition, and survival.

Conditions

• Amyotrophic Lateral Sclerosis

Interventions

Type	Name	Description
BIOLOGICAL	RAPA-501 Autologous T stem cells	Experimental: Phase 2/3 Expansion Cohort, Single-agent RAPA-501 T stem cells 80 x 10EE6 cells per infusion (no host conditioning)

Timeline

• Start date: 2025-01-02
• Primary completion: 2026-07-01
• Completion: 2027-06-01
• First posted: 2020-01-07
• Last updated: 2025-06-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study