Regulatory T Cells for ALS

Recruiting at 1 trial location

Overseen By Mingqi Lu, MD., PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novabio Therapeutics

Must be taking: Riluzole, Edaravone

Must not be taking: Antipsychotics, Antiepileptics, Antiarrhythmics

Disqualifiers: Uncontrolled infection, Hypertension, Cardiology, others

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

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment for people with amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. Researchers are evaluating whether injecting regulatory T cells (a type of immune cell) is safe and effective for ALS patients. The trial seeks participants with a confirmed ALS diagnosis who have been stable on their current ALS treatments, such as Rilutek or Radicava, for over a month. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but it mentions that patients with ALS can continue treatment with riluzole and/or edaravone. It also excludes those currently using certain medications like antipsychotics and some antiarrhythmic drugs.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

A previous study found that treatments using regulatory T cells, including NP001, were generally safe and well-tolerated. Most participants did not experience serious side effects, and only a few reported unwanted effects, indicating the body's acceptance of the treatment. As this is a Phase 1 trial, the main goal is to assess safety, so safety information may still be limited. However, the initial results are promising for those considering joining the trial. ^{1 2 3 4 5}

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

Most treatments for ALS, like riluzole and edaravone, aim to slow disease progression or manage symptoms. But this new treatment, using Autologous Human Polyclonal Regulatory T Cells, works differently by harnessing the body's immune system. These regulatory T cells are specially designed to reduce inflammation in the nervous system, which might help protect motor neurons that are typically damaged in ALS. Researchers are excited because this approach could offer a new way to target the underlying mechanisms of the disease, potentially improving outcomes for patients in a way current drugs do not.

What evidence suggests that this treatment might be an effective treatment for ALS?

Research has shown that NP001 cell injection, which uses a person's own specialized immune cells, may help treat ALS. ALS affects nerve cells in the brain and spinal cord. One study found that NP001 treatment extended the lifespan of ALS patients and improved their lung function. Another study in mice with ALS demonstrated that infusions of these immune cells slowed the disease and extended the mice's lifespan. These findings suggest that NP001 might help manage ALS symptoms by reducing inflammation and protecting nerve cells. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with neurodegenerative diseases like ALS, Alzheimer's, and Multiple System Atrophy. Participants must have a confirmed diagnosis and be in stable condition to receive T cell injections.

Inclusion Criteria

Specific laboratory values within normal ranges

I can walk by myself, expected to live 3+ years, and think clearly.

I am 65 or older with Alzheimer's, on stable medication, and can consent.

Exclusion Criteria

I have had a pulmonary embolism in the last 6 months.

I am currently taking certain medications.

Seropositive for HIV, hepatitis B, or hepatitis C

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and Manufacturing

Apheresis procedure to collect cells for manufacturing the investigational product, NP001 cell injection

2-4 weeks

Treatment

Participants receive NP001 cell injection intrathecally on Days 1, 29, and 57

8 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and efficacy parameters

10 months

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Human Polyclonal Regulatory T Cells Injection (NP001 Cell Injection)

Trial Overview The study tests the safety and potential benefits of injecting patients' own regulatory T cells (NP001 cell injection) to treat various neurodegenerative conditions.

How Is the Trial Designed?

Group I: Autologous Human Polyclonal Regulatory T Cells Injection (NP001 Cell Injection) Experimental Treatment 1 Intervention

Regulatory T cell therapy, intrathecal injection

Who Is Running the Clinical Trial?

Novabio Therapeutics

Lead Sponsor

Trials

1

Recruited

10+

The First Affiliated Hospital of Zhengzhou University

Collaborator

Trials

369

Recruited

661,000+

Published Research Related to This Trial

The combination of autologous expanded regulatory T-lymphocytes (Tregs) and interleukin (IL)-2 was found to be safe and well tolerated in a phase 1 study involving ALS patients, with increased Treg suppressive function and stabilization of disease progression observed.

In a 24-week open-label extension, 6 out of 8 participants showed slow to no progression of ALS symptoms, suggesting potential efficacy, particularly in those without elevated markers of oxidative stress and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Regulatory T-Lymphocyte and IL-2 Treatment Is Safe, Tolerable, and Biologically Active for 1 Year in Persons With Amyotrophic Lateral Sclerosis. Thonhoff, JR., Berry, JD., Macklin, EA., et al.[2022]

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]

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]

In a phase I study involving 32 ALS patients, NP001 was found to be generally safe and well tolerated, indicating its potential as a treatment option.

NP001 administration resulted in a dose-dependent reduction in monocyte activation markers, suggesting it may help modulate inflammation associated with ALS progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NP001 regulation of macrophage activation markers in ALS: a phase I clinical and biomarker study. Miller, RG., Zhang, R., Block, G., et al.[2021]

T cell depletion using antilymphocyte serum (ALS) leads to the proliferation of CD4(+) regulatory T cells, which then express memory T cell markers, indicating a shift in their function after treatment.

Following ALS treatment, both CD25(+) and CD25(-) T cells showed increased suppression of immune responses initially, suggesting that ALS not only depletes T cells but also enhances the regulatory activity of remaining T cells, which may be beneficial in treating autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4+ regulatory T cells are spared from deletion by antilymphocyte serum, a polyclonal anti-T cell antibody. Minamimura, K., Gao, W., Maki, T.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06671236

NCT06671236 | Clinical Study of Regulatory T Cells (Tregs ... This is an open-label, non-randomized, multi-center clinical trial of single-agent NP001 cell injection in patients with with Neurodegenerative diseases (ALS).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11505581/

Systemic Innate Immune System Restoration as a Therapeutic ... Results presented in the current study show that NP001 treatment conveys a survival benefit in ALS patients, showing the greatest VC response.

3. withpower.com withpower.com/trial/phase-1-shy-drager-syndrome-10-2024-1c4f1

Regulatory T Cells for ALS An open, multi- center phase Ⅰ clinical study evaluating the safety and efficacy of autologous human polyclonal regulatory T cell injection (NP001 cell ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06671236/clinical-study-of-regulatory-t-cells-tregs-in-the-treatment-of-neurodegenerative-diseases?q=neurodegenerative%20diseases

Clinical Study of Regulatory T Cells (Tregs) in the ... An open, multi- center phase Ⅰ clinical study evaluating the safety and efficacy of autologous human polyclonal regulatory T cell injection ...

5. neurology.org neurology.org/doi/10.1212/NXI.0000000000000465

Expanded autologous regulatory T-lymphocyte infusions in ... In amyotrophic lateral sclerosis (ALS) mice, infusions of Tregs slow disease progression and prolong survival, and Tregs suppress the ...

6. smartpatients.com smartpatients.com/trials/NCT06671236

Clinical Study of Regulatory T Cells (Tregs) in the ... An open, multi- center phase Ⅰ clinical study evaluating the safety and efficacy of autologous human polyclonal regulatory T cell injection ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04055623

Study Details | NCT04055623 | T-regulatory Cells in ALS This early study provided evidence in a small group of patients that treatment with autologous Tregs may be effective in slowing ALS progression. Official Title.