RAPA-501 therapy for ALS

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

This study is testing a new treatment called RAPA-501 to see if it can help slow down the progression of ALS in patients.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Rapa Therapeutics LLC (Industry-sponsored)
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT04220190 on ClinicalTrials.gov

What this trial studies

This is an open-label, non-randomized, multi-center phase 2/3 study evaluating the efficacy of RAPA-501 autologous hybrid TREG/Th2 cells in patients with amyotrophic lateral sclerosis (ALS). Participants will undergo apheresis to collect cells for the manufacture of RAPA-501 T stem cells, which are designed to have anti-inflammatory properties. The study will administer up to four infusions of RAPA-501, with follow-up assessments at 24 and 30 weeks, and remote monitoring for two years to track clinical events and survival. The primary objective is to evaluate the safety and efficacy of this innovative therapy in slowing disease progression.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of sporadic or familial ALS and a specific range of ALSFRS-R scores.

Not a fit: Patients with advanced ALS symptoms or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly slow the progression of ALS and improve quality of life for patients.

How similar studies have performed: While this approach is novel, other studies have explored T cell therapies for ALS, but results have been mixed, indicating a need for further investigation.

Eligibility criteria

Inclusion Criteria:

1. Male or female patients ≥ 18 years of age.
2. Patients with sporadic or familial amyotrophic lateral sclerosis (ALS) diagnosed as laboratory-supported possible, probable, or definite according to World Federation of Neurology El Escorial Criteria.
3. . Less than or equal to 24 months since ALS symptom onset.
4. Total ALSFRS-R score between 34 and 45.
5. Must have a source of autologous T cells potentially sufficient to manufacture RAPA-501 cells, as defined by a peripheral CD3+ T cell count ≥ 500 cells per μl.
6. Patients may continue riluzole (Rilutek®), and/or edaravone (Radicava®), and/or sodium phenylbutyrate/taurusodial (Relyvrio™) if on a stable dose for at least 30 days prior to the screening visit.
7. Patients must be ≥ 2 two weeks removed from major surgery or investigational therapy.
8. Patients must have recovered from clinical toxicities (\[resolution of CTCAE(v5) \[version 5\] toxicity to a value of ≤ 2\].).
9. Serum creatinine ≤ less than or equal to 2.0 mg/dL.
10. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN).
11. Bilirubin ≤ 1.5 (except if due to Gilbert's disease).
12. Pulmonary slow vital capacity (SVC) ≥ 70% of predicted normal.
13. No history of abnormal bleeding tendency.
14. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient participant at any time without prejudice to future medical care.

Exclusion Criteria:

1. Active uncontrolled infection.
2. Hypertension not adequately controlled by ≤ 3 medications.
3. History of documented pulmonary embolus within 6 months of enrollment.
4. Clinically significant cardiac pathology, as defined by: myocardial infarction within 6 months prior to enrollment, Class III or IV heart failure according to NYHA, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
5. Patients with history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.
6. HIV, hepatitis B, or hepatitis C seropositive.
7. Pregnancy or breastfeeding patients.
8. Patients of Subjects of childbearing age, or males who have a partner of childbearing potential, who are unwilling to practice contraception.
9. Patients Subjects may be excluded at the Principal Investigator discretion of the PI or if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.

Where this trial is running

Boston, Massachusetts

• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Study coordinator: Daniel Fowler, M.D. Chief Medical Officer, RAPA Therapeutics, LLC

Conditions Amyotrophic Lateral Sclerosis; RAPA-501; Autologous TREG/Th2 T stem cell therapy; Orphan Disease; rare disease