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

Study Purpose:

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


Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Biological: RAPA-501 Autologous T cells

Study Status:



Phase I

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

Daniel Fowler, M.D., Rapa Therapeutics LLC ID (11 digit #):


Neals Affiliated?


Coordinating Center Contact Information

Rapa Therapeutics LLC
Daniel Fowler Chief Medical Officer / .(JavaScript must be enabled to view this email address) / 301-518-3104
.(JavaScript must be enabled to view this email address) United States

Full Study Summary:

This is an open-label, non-randomized, multicenter Phase 1 study evaluating RAPA-501 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 cells.

This study consists of three cohorts. Cohorts 1 and 2 will evaluate a 6-month regimen of four (4) cycles of RAPA-501 cell therapy without the pentostatin-cyclophosphamide host conditioning regimen (PC regimen). Cohorts 1 and 2 will evaluate two different doses: Cohort 1 - 40 x 10^6 cells/infusion and Cohort 2 - 160 x 10^6 cells/infusion. Both cohorts will evaluate a 6-month regimen of four cycles of the RAPA-501 cell therapy.

Cohort 3 will evaluate the highest safe dose of RAPA-501 cells (from Cohort 1 and Cohort 2) in combination with the PC regimen. Cohort 3 will evaluate a 6-month regimen of 4 cycles of RAPA-501 cells administered after the PC regimen. The PC regimen will be 7 days in duration and the RAPA-501 cell therapy will take place on Day 8.

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

Participant Duration:

Estimated Enrollment:


Estimated Study Start Date:


Estimated Study Completion Date:


Posting Last Modified Date:


Date Study Added to

  • Eligibility Criteria


    Female, Male

    Minimum Age:


    Maximum Age:


    Min Vital Capacity (% predicted normal):


    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?


    Inclusion Criteria:

    1. Male or female patients ≥ 18 years of age.
    2. Patients with sporadic or familial ALS diagnosed as laboratory-supported possible, probable, or definite according to World Federation of Neurology El Escorial Criteria.
    3. Must have a potential 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®) 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. To assess study immune secondary endpoints, the potential study participant must have at least two separate blood samples evaluated for immune parameters during screening.
    8. Ejection fraction by multigated acquisition (MUGA) scan or 2-D echocardiogram within institution normal limits (applies only to study participants on cohort 3).
    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.
    11. Bilirubin ≤ 1.5 (except if due to Gilbert's disease).
    12. Pulmonary vital capacity ≥ 50% 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 participant at any time without prejudice to future care.

    Exclusion Criteria:

    1. On edaravone (Radicava®) therapy.
    2. Active uncontrolled infection.
    3. Hypertension not adequately controlled by ≤ 3 medications.
    4. History of documented pulmonary embolus within 6 months of enrollment.
    5. Clinically significant cardiac pathology: myocardial infarction within 6 months prior to enrollment, Class III or IV heart failure according to the New York Heart Association (NYHA), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
    6. Patients with history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.
    7. HIV, hepatitis B, or hepatitis C seropositive.
    8. Pregnant or breastfeeding patients.
    9. Patients of childbearing age, or males who have a partner of childbearing potential, who are unwilling to practice contraception.
    10. 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.

  • Site Contact Information

    Massachusetts General Hospital
    Kelly Fisher / .(JavaScript must be enabled to view this email address) / 617-726-9094
    Ann Hu / .(JavaScript must be enabled to view this email address) / 617-724-7113
    Boston, Massachusetts 02114
    United States

    Hackensack University Medical Center
    Michele Donato / .(JavaScript must be enabled to view this email address) / 551-996-5855
    Hackensack, New Jersey 07601
    United States