RAPA-501 Therapy for ALS

Recruiting at 1 trial location

Overseen By Michele Donato, M.D

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Rapa Therapeutics LLC

Disqualifiers: Uncontrolled infection, Hypertension, Cardiac pathology, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 18 weeks

41 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RAPA-501, a type of T cell therapy, for individuals with amyotrophic lateral sclerosis (ALS), a condition affecting nerve cells in the brain and spinal cord. The research aims to determine if using special cells from the participant's own immune system can help manage ALS symptoms. It specifically seeks participants who have experienced ALS symptoms for less than two years. Participants should maintain stable ALS medication routines and have no recent major surgeries or experimental treatments. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking ALS treatment advancements.

Will I have to stop taking my current medications?

The trial allows participants to continue taking riluzole, edaravone, and sodium phenylbutyrate/taurusodial if they have been on a stable dose for at least 30 days before the screening. The protocol does not specify about other medications, so it's best to discuss your specific situation with the trial team.

Is there any evidence suggesting that RAPA-501 therapy is likely to be safe for humans?

Research has shown that RAPA-501 therapy is safe for people with ALS. In one study, participants reported no harmful effects related to the treatment, indicating they did not experience negative side effects from the therapy itself. RAPA-501 uses T stem cells, which are specially modified to help reduce inflammation. The treatment's progression to phase 2/3 trials suggests that earlier tests demonstrated it is generally well-tolerated. This is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ALS?

Unlike standard treatments for ALS, which often focus on symptom management and slowing disease progression, RAPA-501 uses a novel approach by employing autologous T stem cells. These cells are derived from the patient's own body, reducing the risk of immune rejection. Researchers are excited about RAPA-501 because it targets the disease more directly by potentially repairing damaged neurons and restoring function. This could mean a more effective treatment with fewer side effects compared to conventional therapies.

What evidence suggests that RAPA-501 might be an effective treatment for ALS?

Research has shown that RAPA-501 therapy, developed for ALS, helps reduce inflammation, potentially lessening the disease's effects on patients. This trial will study RAPA-501 Autologous T stem cells, which use special T cells, known as TREG/Th2 cells, to fight inflammation. These cells are enhanced outside the body to improve their function before being reintroduced to patients. Early results suggest this method could slow ALS by targeting inflammation, a major aspect of the disease. Although more data is needed, the aim is to decrease both the severity and progression of ALS symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Daniel Fowler, M.D.

Principal Investigator

Rapa Therapeutics LLC

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with ALS within the last 24 months. They can still take certain ALS medications if doses have been stable for 30 days. Participants need normal kidney function, a specific range of ALSFRS-R scores, and adequate breathing capacity. Exclusions include uncontrolled hypertension, recent heart or pulmonary issues, active infections, positive HIV/Hepatitis tests, pregnancy/breastfeeding, and unwillingness to use contraception.

Inclusion Criteria

It has been over 2 weeks since my last major surgery or experimental treatment.

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

My ALS symptoms started less than 24 months ago.

Exclusion Criteria

I have had a blood clot in my lungs within the last 6 months.

I have had heart surgery or angioplasty and will undergo a heart check.

I am of childbearing age and not willing to use contraception.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and Cell Manufacturing

Apheresis procedure to collect cells for manufacturing the investigational product, RAPA-501 T cells

1-2 weeks

1 visit (in-person)

Treatment

Participants receive up to 4 infusions of RAPA-501 T cells, each separated by six weeks

18 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits at 24 and 30 weeks, followed by remote monitoring for two years

2 years

2 visits (in-person), remote monitoring

What Are the Treatments Tested in This Trial?

Interventions

• RAPA-501

Trial Overview The RAPA-501-ALS study is testing a new therapy using patients' own modified T cells (RAPA-501) to treat ALS. It's in phase 2/3 which means it's looking at both effectiveness and safety in a larger group after initial promising results.

How Is the Trial Designed?

Group I: RAPA-501 Autologous T stem cells Experimental Treatment 1 Intervention

Phase 2/3 Expansion Cohort, Single-agent RAPA-501 T stem cells 80 x 10EE6 cells per infusion (no host conditioning)

Who Is Running the Clinical Trial?

Rapa Therapeutics LLC

Lead Sponsor

Trials

6

Recruited

200+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Hackensack Meridian Health

Collaborator

Trials

141

Recruited

42,900+

Published Research Related to This Trial

In a study involving canine renal allograft recipients, a combination treatment of rapamycin (Rapa) with antilymphocyte serum (ALS), donor bone marrow cells (BMC), and cyclosporine (CsA) significantly improved graft survival, with some dogs surviving over 470 days post-transplant.

The combination therapy showed reduced toxicity from Rapa, suggesting that this approach not only enhances the effectiveness of the treatment but also makes it safer for the recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rapamycin on renal allograft survival in canine recipients treated with antilymphocyte serum, donor bone marrow, and cyclosporine. Hartner, WC., Van der Werf, WJ., Lodge, JP., et al.[2013]

Rapamycin (Rapa) significantly prolongs graft survival in skin allografted mice when used alongside antilymphocyte serum (ALS) and donor bone marrow cells (BMC), with up to 26% of recipients achieving indefinite graft survival with the highest dose.

Rapa can be administered flexibly, either as a single dose or spaced doses, and is effective even when given after initial signs of rejection, indicating its potential as a versatile immunosuppressive agent in transplant settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late adjunctive therapy with single doses of rapamycin in skin-allografted mice treated with antilymphocyte serum and donor bone marrow cells. De Fazio, SR., Plowey, JM., Hartner, WC., et al.[2019]

A short course of rapamycin (Rapa) significantly enhances the survival of rat skin xenografts in mice treated with anti-lymphocyte serum, achieving a median survival time of 47 days.

Intrathymic injection of donor splenocytes did not improve skin graft survival in the presence of Rapa and anti-lymphocyte serum, suggesting that while Rapa is effective, the additional IT injection may not provide further benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marked prolongation of rat skin xenografts induced by intrathymic injection of xenogeneic splenocytes and a short course of rapamycin in antilymphocyte serum-treated mice. Dono, K., Wood, ML., Ozato, H., et al.[2019]

Polyclonal anti-T-cell antibody (ALS) significantly prolonged skin allograft survival in both naïve and alloantigen-primed mice, indicating its efficacy in preventing rejection.

Combining high-dose ALS with rapamycin (RAPA) or targeting specific T cell pathways can enhance graft survival, especially in alloantigen-primed mice, suggesting potential strategies for achieving tolerance in sensitized individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies to induce marked prolongation of secondary skin allograft survival in alloantigen-primed mice. Minamimura, K., Sato, K., Yagita, H., et al.[2023]

Infusions of expanded regulatory T lymphocytes (Tregs) were found to be safe and well tolerated in three ALS patients, with no adverse effects reported during the study.

The treatment not only slowed disease progression in both early and later stages of ALS but also showed a correlation between increased Treg suppressive function and reduced progression rates, suggesting a potential therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded autologous regulatory T-lymphocyte infusions in ALS: A phase I, first-in-human study. Thonhoff, JR., Beers, DR., Zhao, W., et al.[2022]

A chimeric antigen receptor (CAR) was successfully developed for human regulatory T cells (Tregs) to target the aggregated G93A-hSOD1 protein associated with ALS, enhancing their ability to modulate the immune response in this disease.

The study found that gene-modified Tregs produced anti-inflammatory IL-10 and inhibited harmful factors like tumor necrosis factor alpha when interacting with ALS-related proteins, suggesting a promising therapeutic approach for ALS through targeted immunomodulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human CD4+CD25+ T cells expressing a chimeric antigen receptor against aberrant superoxide dismutase 1 trigger antigen-specific immunomodulation. Graber, DJ., Cook, WJ., Sentman, ML., et al.[2023]

In a small study of seven ALS patients, T-cell vaccination (TCV) combined with autologous adult neural stem cells slowed or stopped disease progression, extending median survival from 3.5 years to 6 years.

Neurological improvements were observed for at least one year post-treatment, indicating that TCV may be a safe and effective long-term therapy for ALS, as confirmed by an independent neurologist using the ALS Functional Rating Scale-Revised.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, safety, and preliminary proof of principles of autologous neural stem cell treatment combined with T-cell vaccination for ALS patients. Moviglia, GA., Moviglia-Brandolino, MT., Varela, GS., et al.[2022]

Regulatory T cells (Tregs) are crucial for immune balance, and their dysfunction is linked to faster progression of amyotrophic lateral sclerosis (ALS), suggesting that enhancing Treg function could slow disease progression.

A new method was developed to expand Tregs from ALS patients, resulting in a significant increase in their numbers (25- to 200-fold) and restoration of their ability to regulate immune responses, paving the way for potential clinical trials using these enhanced Tregs as a therapy for ALS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A robust, good manufacturing practice-compliant, clinical-scale procedure to generate regulatory T cells from patients with amyotrophic lateral sclerosis for adoptive cell therapy. Alsuliman, A., Appel, SH., Beers, DR., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04220190

Study Details | NCT04220190 | RAPA-501 Therapy for ALS 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).

2. reporter.nih.gov reporter.nih.gov/project-details/10834469

Project Details RAPA has developed an autologous T cell therapy (RAPA-501) that reduces inflammation, with the goal of reducing ALS morbidity and mortality.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06169176?cond=ALS&intr=RAPA-501%20Autologous%20T%20cells&rank=1

RAPA-501 Therapy of ALS Expanded Access Protocol RAPA-501 cells are manufactured ex vivo using epigenetic reprogramming to yield a T stem cell population that is enriched for a dual anti-inflammatory phenotype ...

4. neals.org neals.org/als-trials/nct04220190

Phase 2/3 Trial of Autologous Hybrid TREG/Th2 Cell ... This is an open-label, non-randomized, multi-center phase 2/3 study evaluating RAPA-501 T cell therapy in pwALS on an expansion cohort.

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06169176

RAPA-501 Therapy of ALS Expanded Access Protocol RAPA-501-ALS is an Intermediate-Size Expanded Access Trial of RAPA-501 autologous hybrid TREG/Th2 T stem cells in patients living with amyotrophic lateral ...

6. als.net als.net/als-trial-navigator/468/

Trial: RAPA-501 Therapy for ALS 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.