Amyotrophic Lateral SclerosisPhase 2/3NCT04220190
RAPA-501 Therapy for ALS
A Phase 2/3 study testing RAPA-501 Autologous T stem cells in people with Amyotrophic Lateral Sclerosis, run by Rapa Therapeutics LLC at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- RAPA-501 Autologous T stem cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jan 2025to 1 Jul 2028
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- . Less than or equal to 24 months since ALS symptom onset.
- Total ALSFRS-R score between 34 and 45.
- 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.
- 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.
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- Patients must be ≥ 2 two weeks removed from major surgery or investigational therapy.
- Patients must have recovered from clinical toxicities ([resolution of CTCAE(v5) [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 (ULN).
- Bilirubin ≤ 1.5 (except if due to Gilbert's disease).
- Pulmonary slow vital capacity (SVC) ≥ 70% of predicted normal.
- No history of abnormal bleeding tendency.
- 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.
Who cannot join
- 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.
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- Pregnancy or breastfeeding patients.
- Patients of Subjects of childbearing age, or males who have a partner of childbearing potential, who are unwilling to practice contraception.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Daniel Fowler, M.D. Chief Medical Officer, RAPA Therapeutics, LLC contact
Jennifer Sunga, M.S. Senior Regulatory Affairs Associate, RAPA Therapeutics, LLC contact
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Megan Okoro, 617-643-6252, rapa501healey@mgb.org
James Berry, M.D.
About this study
Official title: Phase 2/3 Trial of Autologous Hybrid TREG/Th2 (RAPA-501) T Stem Cell Therapy for Amyotrophic Lateral Sclerosis
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).
Read the 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. 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
- Being tested
- RAPA-501 Autologous T stem cells
- Keywords
- Amyotrophic Lateral Sclerosis, RAPA-501, Autologous TREG/Th2 T stem cell therapy, Orphan Disease, rare disease
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAPA-501 Autologous T stem cellsBiological
Also called RAPA-501 cells
Experimental: Phase 2/3 Expansion Cohort, Single-agent RAPA-501 T stem cells 80 x 10EE6 cells per infusion (no host conditioning)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Biological: RAPA-501 Autologous T stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
In the expansion cohort enrolling standard-risk pwALS, determine the feasibility and safety of the highest established safe dose of RAPA-501 (80 x 10^6 cells per infusion).
Measured: Through 30 Weeks On-Study
Secondary outcomes (4)
Characterize immune system parameters pre- and post-therapy.
Specifically, relative to pretreatment patient peripheral blood values, determine whether study interventions: (a) increase circulating Th2 and TREG cells; (b) reduce circulating Th1 cells; (c) increase T cell expression of programmed death-1 (PD-1); and (d) reduce inflammatory cytokines IL-1-beta, IL-6, and TNF-alpha.
Measured: Through 30 Weeks On-Study
Relative to pretreatment values, characterize the potential effect of RAPA-501 therapy on serum markers of neurodegeneration (neurofilament light, NfL).
Measured: Through 30 Weeks On-Study
Relative to pretreatment values, characterize the potential effect of RAPA-501 therapy on pulmonary function, as measured by slow vital capacity measurements (SVC, percent of predicted normal).
Measured: Through 30 Weeks On-Study
Relative to pretreatment values, characterize the potential effect of RAPA-501 therapy on hand grip strength using hand-held dynamometry.
Measured: Through 30 Weeks On-Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2020
- Study start2 Jan 2025
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rapa Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Massachusetts General Hospital
- Responsible party
- Sponsor
- Investigators
- Daniel Fowler, M.D., Study director, Rapa Therapeutics LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04220190
- Sponsor's protocol ID
- RAPA-501-ALS
- Status last verified
- Sep 2026
- First submitted
- 3 Jan 2020
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2/3 Trial of Autologous Hybrid TREG/Th2 (RAPA-501) T Stem Cell Therapy for Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT04220190
- Acronym / sponsor ID
- RAPA-501-ALS
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Amyotrophic Lateral Sclerosis, RAPA-501, Autologous TREG/Th2 T stem cell therapy, Orphan Disease, rare disease
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Rapa Therapeutics LLCIndustry (pharma, biotech, devices)
- Collaborators
- Massachusetts General Hospital
- Study start
- 2 Jan 2025 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2028 (estimated)
- First posted
- 7 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAPA-501 Autologous T stem cells | Experimental | Biological: RAPA-501 Autologous T stem cellsPhase 2/3 Expansion Cohort, Single-agent RAPA-501 T stem cells 80 x 10EE6 cells per infusion (no host conditioning) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
- . Less than or equal to 24 months since ALS symptom onset.
- Total ALSFRS-R score between 34 and 45.
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAPA-501 Autologous T stem cellsAlso: RAPA-501 cellsExperimental: Phase 2/3 Expansion Cohort, Single-agent RAPA-501 T stem cells 80 x 10EE6 cells per infusion (no host conditioning) | Biological | RAPA-501 Autologous T stem cells |
Primary outcome
In the expansion cohort enrolling standard-risk pwALS, determine the feasibility and safety of the highest established safe dose of RAPA-501 (80 x 10^6 cells per infusion).
Time frame: Through 30 Weeks On-Study
4 secondary outcomes
Characterize immune system parameters pre- and post-therapy.
Time frame: Through 30 Weeks On-Study
Relative to pretreatment values, characterize the potential effect of RAPA-501 therapy on serum markers of neurodegeneration (neurofilament light, NfL).
Time frame: Through 30 Weeks On-Study
Relative to pretreatment values, characterize the potential effect of RAPA-501 therapy on pulmonary function, as measured by slow vital capacity measurements (SVC, percent of predicted normal).
Time frame: Through 30 Weeks On-Study
Relative to pretreatment values, characterize the potential effect of RAPA-501 therapy on hand grip strength using hand-held dynamometry.
Time frame: Through 30 Weeks On-Study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel Fowler, M.D. Chief Medical Officer, RAPA Therapeutics, LLC contact
Jennifer Sunga, M.S. Senior Regulatory Affairs Associate, RAPA Therapeutics, LLC contact
Daniel Fowler, M.D. study director
Rapa Therapeutics LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing RAPA-501 Autologous T stem cells in people with Amyotrophic Lateral Sclerosis, run by Rapa Therapeutics LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daniel Fowler, M.D. Chief Medical Officer, RAPA Therapeutics, LLC ((301) 518-3104, dan@rapatherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
In the expansion cohort enrolling standard-risk pwALS, determine the feasibility and safety of the highest established safe dose of RAPA-501 (80 x 10^6 cells per infusion). (time frame: Through 30 Weeks On-Study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026; AzTrials last refreshed its copy on 27 Oct 2026.