RAPA-501 Therapy for ALS
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04220190 |
Recruitment Status :
Recruiting
First Posted : January 7, 2020
Last Update Posted : March 16, 2022
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Condition or disease | Intervention/treatment | Phase |
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Amyotrophic Lateral Sclerosis | Biological: RAPA-501 Autologous T cells | Phase 1 Phase 2 |
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 Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 21 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Masking Description: | No masking |
Primary Purpose: | Treatment |
Official Title: | Phase I Trial of Autologous Hybrid TREG/Th2 Cell (RAPA-501) Therapy for Amyotrophic Lateral Sclerosis |
Actual Study Start Date : | December 15, 2020 |
Estimated Primary Completion Date : | December 15, 2023 |
Estimated Study Completion Date : | December 15, 2023 |

Arm | Intervention/treatment |
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Experimental: Single agent RAPA-501 T cells (dose level Arm 1)
Dose level 1 is 20 x 10^6 cells/infusion
|
Biological: RAPA-501 Autologous T cells
TREG/Th2 cells
Other Name: RAPA-501 cells |
Experimental: Single agent RAPA-501 T cells (dose level Arm 2)
Dose level 2 is 80 x 10^6 cells/infusion
|
Biological: RAPA-501 Autologous T cells
TREG/Th2 cells
Other Name: RAPA-501 cells |
Experimental: RAPA-501 + PC Regimen (Arm 3A)
Arm 3A) RAPA-501 T cell therapy preceded by the 3-day pentostatin- cyclophosphamide (PC) regimen
|
Biological: RAPA-501 Autologous T cells
TREG/Th2 cells
Other Name: RAPA-501 cells |
Experimental: RAPA-501 + PC Regimen (Arm 3B)
Arm 3B) RAPA-501 T cell therapy preceded by the 5-day pentostatin- cyclophosphamide (PC) regimen
|
Biological: RAPA-501 Autologous T cells
TREG/Th2 cells
Other Name: RAPA-501 cells |
- Dose safety of single-agent RAPA-501 T cells [ Time Frame: 30 days after the first infusion of RAPA-501 T cells. ]To determine the safety of single-agent RAPA-501 T cells administered intravenously (i.v.) at dose level 1 and dose level 2.
- Highest tolerated dose of RAPA-501 T cells [ Time Frame: 30 days after the first infusion of RAPA-501 T cells. ]Determine the safety of dose level 1 of RAPA-501 T cells in combination with the 3-day and 5-day pentostatin and cyclophosphamide host conditioning (PC regimen).
- Effect of therapy on disease status [ Time Frame: One year after treatment initiation. ]To determine the ALS disease activity score (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised and Rasch Overall ALS Disability Scale [ROADS]) for each study cohort pre-therapy, during study interventions, and after the post-therapy observation interval.
- Characterize immune system parameters [ Time Frame: One year after treatment initiation. ]Determine whether therapy increases the number of circulating Th2 and TREG cells, as measured by T cells that express the transcription factors GATA3 and FOXP3 by flow cytometry, respectively. The absolute number of GATA3+ and FOXP3+ T cells will be determined pre- and post-therapy (unit of measurement for both GATA3 and FOP3: absolute number of positive cells per microliter of blood).
- Characterize immune system parameters [ Time Frame: One year after treatment initiation. ]Determine whether therapy reduces the number of circulating Th1 cells, as measured by T cells that express the transcription factor TBET by flow cytometry, respectively. The absolute number of TBET+ cells will be determined pre- and post-therapy (unit of measure for TBET: number of positive cells per microliter of blood).
- Characterize pulmonary function test parameters [ Time Frame: One year after treatment initiation. ]Determine whether therapy increases pulmonary function, as determined by measurement of pre- and post-therapy measures of Slow Vital Capacity (SVC) (unit of measurement: percent of age-predicted value).
- Characterize hand grip strength [ Time Frame: One year after treatment initiation. ]Characterize hand grip strength pre- and post-therapy using hand-held dynamometry.
- Cerebrospinal fluid assessment [ Time Frame: Six months after treatment initiation. ]To assess cerebrospinal fluid pre- and post- therapy for content of inflammation molecules and neurodegeneration molecules.
- Neuroinflammation assessment [ Time Frame: Six months after treatment initiation. ]Assess neuroinflammation in vivo using PET scan that incorporates a translocator protein radiotracer.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male or female patients ≥ 18 years of age.
- 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.
- 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.
- Patients may continue riluzole (Rilutek®) and/or edaravone (Radicava®) therapy if on a stable dose for ≥ one month prior to study entry.
- Patients must be ≥ two weeks from major surgery, from edaravone therapy, and from participation in investigational trials.
- Patients must have recovered from clinical toxicities (resolution of CTCAE [version 5] toxicity to a value of ≤ 2).
- Serum creatinine ≤ less than or equal to 2.0 mg/dL.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal.
- Bilirubin ≤ 1.5 (except if due to Gilbert's disease).
- Pulmonary slow vital capacity (SVC) ≥ 50% of predicted normal.
- No history of abnormal bleeding tendency.
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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:
- Ejection fraction by MUGA or 2-D echocardiogram within institution normal limits (applies only to study participants on cohort).
Exclusion Criteria:
- Active uncontrolled infection.
- Hypertension not adequately controlled by ≤ 3 medications.
- History of documented pulmonary embolus within 6 months of enrollment.
- 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.
- Patients with history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.
- HIV, hepatitis B, or hepatitis C seropositive.
- Pregnancy or breastfeeding patients.
- Patients of childbearing age, or males who have a partner of childbearing potential, who are unwilling to practice contraception.
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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:
- Calculated creatinine clearance value of < 70 mL/min, as calculated by the Cockcroft-Gault formula.
- Diagnosis of malignancy (active).
- Urinary obstruction.
- Hypersensitivity to the agents in the PC regimen (pentostatin, cyclophosphamide).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04220190
Contact: Daniel Fowler Chief Medical Officer | 3015183104 | dan@rapatherapeutics.com |
United States, Massachusetts | |
Massachusetts General Hospital | Recruiting |
Boston, Massachusetts, United States, 02114 | |
Contact: Kelly Fisher 617-726-9094 kefisher@mgh.harvard.edu | |
Principal Investigator: James Berry, M.D. | |
United States, New Jersey | |
Hackensack University Medical Center | Recruiting |
Hackensack, New Jersey, United States, 07601 | |
Contact: Michele Donato Principal Investigator 551-996-5855 michele.donato@hackensackmeridian.org | |
Principal Investigator: Michele Donato |
Study Director: | Daniel Fowler, M.D. | Rapa Therapeutics LLC |
Responsible Party: | Rapa Therapeutics LLC |
ClinicalTrials.gov Identifier: | NCT04220190 |
Other Study ID Numbers: |
RAPA-501-ALS |
First Posted: | January 7, 2020 Key Record Dates |
Last Update Posted: | March 16, 2022 |
Last Verified: | March 2022 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Amyotrophic Lateral Sclerosis Autologous TREG/Th2 cell therapy RAPA-501 |
Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases |
Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases |