Regulatory T Cells for ALS

(REGALS Trial)

Not currently recruiting at 2 trial locations

Overseen By Clinical Research Manager

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cellenkos, Inc.

Must be taking: Riluzole, Edaravone, Albrioza

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Uncontrolled infection, Cancer, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CK0803, which uses special cells from umbilical cord blood to assist people with Amyotrophic Lateral Sclerosis (ALS), a condition affecting nerve cells in the brain and spinal cord. The main goal is to determine if this treatment is safe and can slow ALS progression. Participants will receive either the CK0803 treatment or a placebo (a substance with no active treatment) for comparison. Individuals diagnosed with ALS within the last five years and on stable ALS medication might be suitable for this study. As a Phase 1 trial, this research focuses on understanding how CK0803 works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

If you are taking Riluzole, Edaravone, or Albrioza, you must be on a stable dose for at least 30 days before starting the trial. You cannot take antiplatelet or anticoagulant medications within 14 days before the trial or during the study.

Is there any evidence suggesting that CK0803 is likely to be safe for humans?

Research has shown that CK0803, a treatment using specially prepared immune cells, has promising safety results. Participants reported no serious side effects, indicating good tolerance of the treatment. However, this trial remains in an early stage, primarily focusing on confirming safety. The FDA has recognized CK0803's potential by granting it special status for treating Amyotrophic Lateral Sclerosis (ALS). While this is a positive sign, further studies are necessary to fully understand the treatment's safety and effectiveness. ^{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, focus on slowing disease progression or managing symptoms. However, CK0803 is unique because it uses cryopreserved, allogeneic, cord blood-derived T regulatory cells that express neurotropic homing markers. This innovative approach targets the immune system by harnessing Treg cells to potentially modulate inflammation in the nervous system. Researchers are excited about CK0803 because it offers a new mechanism of action that could provide more direct and effective neuroprotection compared to existing therapies.

What evidence suggests that CK0803 could be an effective treatment for ALS?

Research has shown that CK0803, a treatment made from special immune cells called T regulatory cells, may help treat ALS, a nerve disease that weakens muscles. In this trial, some participants will receive CK0803. Studies have found that infusions of these cells can slow the disease's progression and lower levels of a protein called neurofilament, which is linked to nerve damage. Scientists believe this treatment reduces inflammation and helps maintain muscle function. Early tests suggest it is safe for patients and could improve their ability to function and survive. ^{2 3 4 6 7}

Who Is on the Research Team?

Neil Shneider, MD, PhD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with ALS within the last 5 years, who meet specific criteria (Revised El Escorial Criteria). They must not be on certain medications or have participated in other trials recently. Stable doses of Riluzole, Edaravone, or Albrioza are required if used. Participants need to agree to contraception during and after the study.

Inclusion Criteria

You need to have a score between 36 and 45 on a test called ALSFRSR at the beginning of the study.

I am 18 years or older with ALS.

Agree to practice highly effective contraception during the study and continue contraception for 90 days after their last dose of study treatment

Exclusion Criteria

I am not pregnant or breastfeeding.

You have a very low platelet count or other abnormal blood test results that make you unsuitable for the study.

I am willing to follow all study procedures and cooperate with the research team.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Safety Run-in

Establish safety and tolerability of multiple doses of CK0803 in ALS patients

4 weeks

4 visits (in-person)

Phase 1b Randomized, Double Blind, Placebo Control

Extend safety and establish efficacy of CK0803 in ALS using CAFS

48 weeks

Multiple visits (in-person and virtual) at weeks 5, 8, 12, 16, 20, 24, 36, and 48

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CK0803

Trial Overview The trial tests CK0803 cells derived from umbilical cord blood as a treatment for ALS. It starts with a safety phase for 6 patients followed by a larger double-blind phase where participants randomly receive either CK0803 or an inactive substance without knowing which one they get.

How Is the Trial Designed?

Group I: CK0803 Experimental Treatment 1 Intervention

CK0803 (cryopreserved, allogeneic, cord blood derived T regulatory cells that express neurotropic homing markers) will be administered intravenously Dose: 100 million Treg cells (fixed dose) Dose regimen: * Induction: one infusion every 7 days (+/-3) x 4 doses * Consolidation: one infusion every 28 days (+/-3) x 5 doses

Group II: Placebo Placebo Group 1 Intervention

Excipient

CK0803 is already approved in United States for the following indications:

Approved in United States as CK0803 for:

• Amyotrophic Lateral Sclerosis (ALS) - Investigational

Who Is Running the Clinical Trial?

Cellenkos, Inc.

Lead Sponsor

Trials

5

Recruited

150+

Published Research Related to This Trial

The study provides detailed protocols for enriching regulatory T cells (Treg) from cord blood, achieving over 80% purity for CD25 and 50-65% for FOXP3, which are crucial markers for identifying these immune cells.

Further refinement using additional magnetic bead or flow sorting techniques can increase the purity to over 95% for CD25 and over 65% for FOXP3, allowing for effective propagation and characterization of these cells for research in autoimmune diseases and cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation, propagation and characterization of cord blood derived CD4+ CD25+ regulatory T cells. Bresatz, S., Sadlon, T., Millard, D., et al.[2017]

Regulatory T cells (Tregs) are significantly reduced in number and effectiveness in ALS patients, which correlates with faster disease progression and lower survival rates.

Tregs are emerging as a promising therapeutic target for neuroprotection in ALS, with ongoing clinical trials exploring their potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The involvement of regulatory T cells in amyotrophic lateral sclerosis and their therapeutic potential. Giovannelli, I., Heath, P., Shaw, PJ., et al.[2021]

T-regulatory cells (Tregs) are crucial for maintaining immune balance, and both deficiencies and excesses in Tregs can lead to serious health issues like autoimmunity or cancer, highlighting their potential as therapeutic targets.

Current research focuses on two main types of Tregs, FOXP3(+) Tregs and Tr1 cells, with ongoing efforts to develop therapies that can manipulate Treg function in humans, paving the way for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4+ T-regulatory cells: toward therapy for human diseases. Allan, SE., Broady, R., Gregori, S., et al.[2021]

Recent advancements in identifying regulatory T cells (T(reg) cells) at the single-cell level have been made possible through the development of transgenic mice that express fluorescent proteins driven by the Foxp3 transcription factor.

New monoclonal antibodies (mAb) have been created to specifically identify Foxp3(+) T(reg) cells, allowing researchers to quantitatively study their role in human diseases for the first time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New tools to identify regulatory T cells. Graca, L.[2005]

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 ALS patients, lower levels of regulatory T-lymphocytes (Tregs) and the FoxP3 protein are associated with faster disease progression, indicating their potential neuroprotective role.

A 3.5-year study found that early reductions in FoxP3 levels can predict rapid progression and shorter survival in ALS patients, suggesting it could be a useful biomarker for identifying those at higher risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival. Henkel, JS., Beers, DR., Wen, S., et al.[2022]

Regulatory T cells (Tregs) are crucial for maintaining immune system balance, and both CD4(+)CD25(+) and CD4(+)CD25(-) T cell populations can exhibit regulatory functions, challenging the traditional view of Tregs.

Recent discoveries highlight the importance of specific tumor necrosis factor receptor family members (GITR and TRANCE-R/RANK) and cytokines (IL-10 and IL-2) in the development and function of Tregs, which could inform new therapeutic strategies for autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4(+) regulatory T cells in autoimmunity and allergy. Curotto de Lafaille, MA., Lafaille, JJ.[2019]

CD39(+);FoxP3(+) regulatory T cells (Tregs) exhibit higher levels of CTLA-4, HLA-DR, CD45RO, and Ki-67 compared to CD39(-);FoxP3(+) Tregs, indicating they are more activated and potentially more effective in immune regulation.

These CD39(+);FoxP3(+) Tregs demonstrate significantly greater suppressive capacity on T cell proliferation and IFN-gamma secretion, suggesting they play a crucial role in modulating immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phenotypical and functional characteristic of FoxP3(+);CD39(+); regulatory T cells in humans]. Huang, HH., Wang, SY., Wang, HF., et al.[2017]

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 randomized controlled trial involving 20 ALS patients, glatiramer acetate was found to have a manageable safety profile, with injection reactions being the most common adverse event.

The treatment led to enhanced lymphocyte proliferation, indicating a potential positive immune response, which supports the need for larger trials to further explore dosing and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled phase II trial of glatiramer acetate in ALS. Gordon, PH., Doorish, C., Montes, J., et al.[2015]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05695521

NCT05695521 | Regulatory T Cells for Amyotrophic Lateral ... The goal of the phase 1b study is to extend safety and establish efficacy of CK0803 in ALS using the combined assessment of function and survival (CAFS) that ...

2. neals.org neals.org/als-trials/nct05695521

Phase 1 Safety Run-in Study and Phase 1b Randomized, ... The primary objective of the upcoming phase 1 study is to establish safety and tolerability of multiple doses of CK0803 in ALS patients.

3. prnewswire.com prnewswire.com/news-releases/cellenkos-off-the-shelf-treg-cell-therapy-shows-clinical-safety-and-preliminary-efficacy-in-als-302434750.html

Cellenkos' Off-the-Shelf Treg Cell Therapy Shows Clinical ... Cryopreserved allogeneic Treg infusions associated with slowed disease progression and decreased plasma neurofilament level in ALS.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40261116/

Clinical Safety and Preliminary Efficacy of Regulatory T ... We hypothesize that regulatory T cell (Treg) therapy can resolve inflammation and preserve function in those patients with ALS.

5. neurologylive.com neurologylive.com/view/dosing-begins-for-phase-1-study-cell-therapy-ck0803-in-als

Dosing Begins for Phase 1 Study of Cell Therapy CK0803 ... The 2-part study is intended to first establish safety and tolerability of multiple doses of CK0803, followed by efficacy analyses on several known ALS outcome ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05695521

NCT05695521 | Regulatory T Cells for Amyotrophic Lateral ... The primary objective of the upcoming phase 1 study is to establish safety and tolerability of multiple doses of CK0803 in ALS patients.

7. cgtlive.com cgtlive.com/view/ck0803-treg-therapy-safe-als-trial-set-to-treat-second-cohort

CK0803 Treg Therapy Seems Safe for ALS, Trial Set to ... The positive DSMB recommendation came after no participants were found to experience any serious adverse events from the therapy.