RAPA-501 Therapy for ALS

Recruiting at 1 trial location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Rapa Therapeutics LLC

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

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for ALS using a patient's own immune cells that are modified to reduce inflammation. It targets ALS patients who have not progressed beyond certain limits. The goal is to see if this treatment is safe and effective.

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.

What data supports the effectiveness of the RAPA-501 treatment for ALS?

Research shows that regulatory T cells (Tregs), which are part of the RAPA-501 treatment, have a neuroprotective role in ALS and can slow disease progression. Additionally, studies indicate that rapamycin, a component of the treatment, can enhance the function of Tregs and prolong survival in other conditions, suggesting potential benefits for ALS patients. ^{1 2 3 4 5}

Is RAPA-501 therapy safe for humans?

The research articles provided do not contain specific safety data for RAPA-501 therapy in humans. They focus on the use of rapamycin in animal models, which showed some toxicity in dogs but little toxicity in other protocols. However, these findings may not directly translate to human safety. ^{1 3 5 6 7}

How is the RAPA-501 treatment for ALS different from other treatments?

RAPA-501 is unique because it involves a type of cell therapy using modified T cells that are designed to regulate the immune system, potentially slowing ALS progression by targeting specific immune pathways, unlike traditional treatments that may not address these immune components. ^{1 3 4 5 8}

Research Team

Daniel Fowler, M.D.

Principal Investigator

Rapa Therapeutics LLC

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• RAPA-501 (T-cell Therapy)

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.

Participant Groups

Group I: Phase 2/3 Expansion Cohort, Single-agent RAPA-501 T cells Experimental Treatment 1 Intervention

80 x 10\^6 cells per infusion (no host conditioning)

Group II: Phase 1/2 Only, Single-agent RAPA-501 T cells (dose level Arm 1) Experimental Treatment 1 Intervention

Dose level 1 is 20 x 10\^6 cells/infusion

Group III: Phase 1/2 Only, RAPA-501 + PC Regimen (Arm 3A) Experimental Treatment 1 Intervention

RAPA-501 T cell therapy preceded by the 3-day pentostatin-cyclophosphamide (PC) regimen

Group IV: : Phase 1/2 Only, Single-agent RAPA-501 T cells (dose level Arm 2) Experimental Treatment 1 Intervention

Dose level 2 is 80 x 10\^6 cells/infusion

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+

Findings from Research

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Human CD4+CD25+ T cells expressing a chimeric antigen receptor against aberrant superoxide dismutase 1 trigger antigen-specific immunomodulation. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Expanded autologous regulatory T-lymphocyte infusions in ALS: A phase I, first-in-human study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Strategies to induce marked prolongation of secondary skin allograft survival in alloantigen-primed mice. [2023]

4. England 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. [2022]

5. Netherlands 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. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Effect of rapamycin on renal allograft survival in canine recipients treated with antilymphocyte serum, donor bone marrow, and cyclosporine. [2013]

7. United States 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. [2019]

8. United States 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. [2022]