Phase I Trial of Autologous Hybrid TREG/Th2 Cell (RAPA-501) Therapy for Amyotrophic Lateral Sclerosis

Study Purpose:

RAPA-501-ALS is an open-label, dose escalation, Phase 1/2 study of RAPA-501 autologous T cells in adults with amyotrophic lateral sclerosis (ALS).

Study Status:



Amyotrophic Lateral Sclerosis

Study Type:


Type of Intervention:


Intervention Name:

RAPA-501 Autologous T cells




Phase 1/Phase 2

Study Chair(s)/Principal Investigator(s):

Daniel Fowler, M.D., Rapa Therapeutics LLC ID:


Neals Affiliated?


Coordinating Center Contact Information

Rapa Therapeutics LLC

Daniel Fowler Chief Medical Officer / email hidden; JavaScript is required / 3015183104

United States

Full Study Summary:

This is an open-label, non-randomized, multi-center Phase 1/2 study evaluating RAPA-501 T cells in subjects with amyotrophic lateral sclerosis.

After a subject consents to the study, an apheresis procedure will be performed to collect cells to manufacture the investigational product, RAPA-501 T cells.

This study consists of three cohorts. Cohorts 1 and 2 will evaluate a 6-month regimen of between one (1) and four (4) cycles of RAPA-501 T cell therapy without the pentostatin- cyclophosphamide host conditioning regimen (PC regimen). Cohorts 1 and 2 will evaluate two different doses: Cohort 1 - 20 x 10^6 cells/infusion and Cohort 2 - 80 x 10^6 cells/infusion.

Cohorts 3A and 3B will evaluate the Cohort 1 dose of RAPA-501 cells when administered in combination with the PC regimen, with between one and four cycles of therapy to be administered. For Cohort 3A, the PC regimen will be 3 days of chemotherapy, with RAPA-501 cell administration occurring after two rest days not involving chemotherapy; for Cohort 3B, the PC regimen will be intensified to 5 days of chemotherapy, with RAPA-501 cell administration occurring after two rest days not involving chemotherapy.

All subjects who complete active treatment on each cohort will then complete the follow-up portion of the study (approximately 6-months in duration).

Study Sponsor:

Rapa Therapeutics LLC

Estimated Enrollment:


Estimated Study Start Date:

12 / 15 / 2020

Estimated Study Completion Date:

12 / 15 / 2023

Posting Last Modified Date:

03 / 16 / 2022

Date Study Added to

01 / 07 / 2020

Minimum Age:

18 Years

Maximum Age:


Can participants use Riluzole?


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. Must have a source of autologous T cells potentially sufficient to manufacture RAPA-501 cells, as defined by a peripheral CD3+ T cell count ≥ 800 cells per μl.

4. Patients may continue riluzole (Rilutek®) and/or edaravone (Radicava®) therapy if on a stable dose for ≥ one month prior to study entry.

5. Patients must be ≥ two weeks from major surgery, from edaravone therapy, and from participation in investigational trials.

6. Patients must have recovered from clinical toxicities (resolution of CTCAE [version 5] toxicity to a value of ≤ 2).

7. Serum creatinine ≤ less than or equal to 2.0 mg/dL.

8. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal.

9. Bilirubin ≤ 1.5 (except if due to Gilbert's disease).

10. Pulmonary slow vital capacity (SVC) ≥ 50% of predicted normal.

11. No history of abnormal bleeding tendency.

12. 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 participant at any time without prejudice to future care.

For accrual to Cohort 3, additional eligibility inclusion criteria are as follows:

13. Ejection fraction by MUGA or 2-D echocardiogram within institution normal limits (applies only to study participants on cohort).

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 childbearing age, or males who have a partner of childbearing potential, who are unwilling to practice contraception.

9. Patients may be excluded at the discretion of the PI or if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.

For accrual to Cohort 3, additional eligibility exclusion criteria are as follows:

10. Calculated creatinine clearance value of < 70 mL/min, as calculated by the Cockcroft-Gault formula.

11. Diagnosis of malignancy (active).

12. Urinary obstruction.

13. Hypersensitivity to the agents in the PC regimen (pentostatin, cyclophosphamide).

Massachusetts General Hospital | Recruiting

Kelly Fisher / 617-726-9094 / email hidden; JavaScript is required

Jacqueline Topping / 617-643-6036 / email hidden; JavaScript is required

Principal Investigator : James Berry, M.D.

Boston, Massachusetts 02114
United States

Hackensack University Medical Center | Recruiting

Michele Donato Principal Investigator / 551-996-5855 / email hidden; JavaScript is required

Principal Investigator : Michele Donato

Hackensack, New Jersey 07601
United States