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ALS (Amyotrophic Lateral Sclerosis)Phase 2Tregs in ALSNCT04055623

T-regulatory Cells in ALS

A Phase 2 study testing Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injections in people with ALS (Amyotrophic Lateral Sclerosis), run by The Methodist Hospital Research Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is a randomized, placebo-controlled, phase 2a trial to study the biological activity, safety, and tolerability of regulatory T Lymphocytes (Tregs) taken and expanded outside of the body and returned back to the same person whose Treg were removed, given back by IV (intravenously) and in combination with… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
ALS (Amyotrophic Lateral Sclerosis)
What is being tested?
Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injections
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
11 participants
Where
2 sitesUnited States
Study dates
14 Aug 2019to 15 Sep 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • ALS meeting El Escorial criteria for possible, probable, lab-supported probable, or definite ALS.
  • At least 18 years old.
  • Provided informed consent and authorized use of protected health information (PHI) in accordance with national and local patient privacy regulations.
  • Capable of complying with all study procedures, including the study drug delivery procedure, in the Investigator's opinion.
  • On a stable regimen of riluzole for at least 30 days at the time of screening. If not on riluzole at the time of study entry, willing to refrain from initiation of the agent for the duration of the trial.
  • Patients on edaravone willing to refrain from taking edaravone on the same day as they will receive the Tregs infusion for the duration of the trial. If not on edaravone at the time of study entry, willing to refrain from initiation of the agent for the duration of the trial.
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  • Medical record documentation of a decline in ALSFRS-R total score of at least two points in the 90 days prior to screening or at least four points over the 180 days prior to screening.
  • Forced vital capacity (FVC) ≥65% of predicted capacity for age, height, and gender at screening.
  • Patient able and willing to undergo leukapheresis.

Who cannot join

  • Presence of any of the following clinical conditions that would interfere with the safe conduct of the study, as determined by the Investigator:
  • Unstable neurological, cardiovascular, cerebrovascular, pulmonary, renal, hepatic, endocrine, or hematologic disease; active malignancy or infectious disease; or other medical illness.
  • Unstable psychiatric illness defined as psychosis (hallucinations or delusions), unstable major depression or substance abuse within 180 days prior to screening.
  • Persistent asthma, prior history of acute systemic reactions involving immunoglobulin E (IgE)-dependent mechanisms, history of angioedema, or history of anaphylactic reactions to any medication.
  • Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal (ULN) at screening.
  • Serum creatinine greater than 1.8 mg/dL or creatinine clearance less than 40 mL/min at screening.
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  • History of or positive test result for human immunodeficiency virus (HIV), hepatitis C virus, or hepatitis B virus (i.e., positive for both hepatitis B surface antigen and hepatitis B core antibody) at screening.
  • Tracheostomy.
  • If female, breastfeeding, known to be pregnant, planning to become pregnant during the study, or unwilling to use effective contraception for the duration of the trial and for 90 days after treatment.
  • If male of reproductive capacity, unwilling to use effective contraception for the duration of the trial and for 90 days after treatment.
  • Enrollment in any other interventional study.
  • Treatment with another investigational drug, biological agent, or device within 30 days or 5 half-lives of screening, whichever is longer. Patient participation in an observational/non-interventional clinical study is to be discussed with the Medical Monitor.
  • Prior gene or cell therapy treatments for ALS.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital Neurological Clinical Research Institute

    Boston, Massachusetts, 02114

  • Houston Methodist Hospital

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase 2a Study of the Expansion and Infusion of Autologous T-Regulatory Cells in Amyotrophic Lateral Sclerosis

This study is a randomized, placebo-controlled, phase 2a trial to study the biological activity, safety, and tolerability of regulatory T Lymphocytes (Tregs) taken and expanded outside of the body and returned back to the same person whose Treg were removed, given back by IV (intravenously) and in combination with low-dose IL-2 in people with Amyotrophic Lateral Sclerosis (ALS).

Read the detailed description

Based on data collected in a previous study with a small group of patients, evidence was found to show that interfering with the immune system using Treg cells slowed ALS disease progression. It is known that Treg cell numbers and function are reduced in patients with ALS and in some patients with lower Treg cells, they have a more marked rapid progression of their ALS. For this study, there are two sites (in Houston, Texas and Boston, Massachusetts) in which Tregs will be taken from participants, increased or expanded outside the body, and then re-administered back to the participants from which the Tregs came.

This study has two parts and due to the pandemic two groups [Group 1 and Group 2]:

  1. The first period is a 6-month, randomized, placebo-controlled part of the study to study the biological activity, safety, and tolerability of the monthly expanded Tregs administered intravenously (IV) OR placebo (saline) administered intravenously plus subcutaneous low-dose Interleukin-2 (IL-2) OR subcutaneous placebo (saline) injections in 12 adults with ALS. IL2 helps regulate the immune system's white blood cells. [Group 1 only.]
  2. The second period is a 6-month OPEN-LABEL part of the study (no placebo) in which all participants will receive their own expanded Treg cells administered intravenously in combination with subcutaneous low-dose IL-2 at the following schedule: single dose of Treg cells twice (once per month with three IL2 injections per week); followed by double the dose of Treg cells twice (once per month with three IL2 injections per week); followed by triple the dose of Treg cells twice (one per month with three IL2 injection per week); followed by a 1 month follow-up safety visit after the last triple dose of Tregs with was received and the last set of IL2 injections three times per week injections. [Group 1 and Group 2.]

Groups:

GROUP 1 will go through the double-blind part of the study (receive either Tregs infusions and IL2 injections OR saline infusions and saline injections) for six months and open label part of the study (receive Treg injections and IL2 injections) for six months.

GROUP 2 will receive only the open label (Tregs infusions and IL2 injections) for six months.

This study is studying whether the enhancement of Treg numbers and function will slow disease progression.

In the first study of Tregs, we completed a single-center, open-label phase I study of Tregs from people with ALS. Tregs were increased outside the body and returned back to the individual Treg owners in multiple doses every 2 to 4 weeks. This early study provided evidence in a small group of patients that treatment with autologous Tregs may be effective in slowing ALS progression.

Being tested
Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injections, Monthly placebo infusions + 3 times per week placebo injections
Keywords
Lou Gehrig's Disease
Medical subject headings
Amyotrophic Lateral Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injectionsBiological

    Also called Individualized therapy Treg cell infusions + Interleukin-2 (IL-2), Proleukin is brand name for IL-2

    For the first 6-months of the study: T-regulatory cells taken from a patient, increased in number in a lab, and returned through monthly intravenous (IV) infusions back to same patient + 3 times per week subcutaneous Interleukin-2 injections

  • Monthly placebo infusions + 3 times per week placebo injectionsOther

    Also called inactive drug

    For first 6-months of study: monthly placebo infusions + 3 times per week subcutaneous placebo injections

  • Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injectionsBiological

    Also called Individualized therapy Treg cell infusions + Interleukin-2 (IL-2), Proleukin is the brand name for IL-2

    For the second 6-months of the study: all participants will receive T-regulatory cells taken from the patient, that have been increased in number in a lab, and returned through monthly intravenous (IV) infusions back to same patient (Treg cell owner) + 3 times per week subcutaneous Interleukin-2 injections.

Study groups in NCT04055623
Study groupRoleWhat they receive
Intravenous infusion of Treg cells + Interleukin-2 injectionsExperimentalFor the first six months: T-regulatory cells taken from a participant will be increased in numbers outside the body in a lab and then returned back to the same participant through intravenous (IV) infusions once per month. The participant will also take Interleukin-2 (IL2) injections three times per week.
Receives: Biological: Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injections
Intravenous infusion w/Placebo + matching placebo injectionsPlacebo comparatorFor the first six months: Participants will receive matching placebo or inactive intravenous (IV) infusions once per month. The participant will also take a matching inactive placebo injection three times per week.
Receives: Other: Monthly placebo infusions + 3 times per week placebo injections
2nd 6-months Open Label: Treg Infusions + IL-2 injectionsExperimentalFor second six months: All participants will receive their own expanded/increased in numbers Treg cells by monthly infusion plus 3 times per week subcutaneous injections of IL-2.
Receives: Biological: Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injections

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Treg Suppressive Function in the Blood From Baseline to Week 24.

    Change in Treg suppressive function on the proliferation of T-effector cells, as measured in percentage at baseline compared to week 24. Cohort 1-participants randomized to Tregs and IL-2 or matching placebos (no Tregs and saline. Cohort 2-participants from Cohort 1 who completed 6 Treg or placebo infusions and weekly IL-2 or placebo infusions plus 2 participants who went straight into Cohort 2 - Tregs and IL-2 (no placebo).

    Measured: Baseline and week 24.

Secondary outcomes (3)

  1. Change in Treg Numbers in the Blood From Baseline to Week 24.

    Change in Treg numbers in the blood at baseline compared to week 24; measured in % of total CD4+ cells.

    Measured: Baseline and week 24

  2. Tolerability of Treg Infusions for 6 Months of Treatment

    Defined as the percentage of participants who complete the 6-month RCT.

    Measured: Baseline to week 24.

  3. Tolerability of Ascending Doses of Tregs for 6 Months of Treatment

    Defined as the percentage of participants who complete the ascending doses of Tregs.

    Measured: Baseline to week 24.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2019
  2. Study start14 Aug 2019
  3. Primary completion31 Aug 2021
  4. Study completion15 Sep 2021

Resources

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
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Group 1 entered the first 6-months is the double-blind part of the study where participants are randomized to Treg cell infusions and low dose Interleukin-2 (IL-2) injections OR placebo (inactive) infusions and placebo IL-2 injections and then went into the open label second 6-months of ascending Treg infusions and IL-2 injections. Group 2 went directly into the open label six month trial of ascending Tregs infusions. Group 2 was added due to the pandemic and limits on travel and funding.
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04055623
Sponsor's protocol ID
Pro00022167
Acronym
Tregs in ALS
Status last verified
Oct 2026
First submitted
12 Aug 2019
Last updated
28 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified data may be shared with requests directed to the research clinical investigators.

Publications

  • Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol. 2005 Apr;6(4):345-52. doi: 10.1038/ni1178.

    PubMed 15785760

  • Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med. 2004 Apr 5;199(7):971-9. doi: 10.1084/jem.20031579.

    PubMed 15067033

  • Dejaco C, Duftner C, Grubeck-Loebenstein B, Schirmer M. Imbalance of regulatory T cells in human autoimmune diseases. Immunology. 2006 Mar;117(3):289-300. doi: 10.1111/j.1365-2567.2005.02317.x.

    PubMed 16476048

  • Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S, Hellerstein MK, Herold KC, Lares A, Lee MR, Li K, Liu W, Long SA, Masiello LM, Nguyen V, Putnam AL, Rieck M, Sayre PH, Tang Q. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015 Nov 25;7(315):315ra189. doi: 10.1126/scitranslmed.aad4134.

    PubMed 26606968

  • Beers DR, Henkel JS, Zhao W, Wang J, Huang A, Wen S, Liao B, Appel SH. Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain. 2011 May;134(Pt 5):1293-314. doi: 10.1093/brain/awr074.

    PubMed 21596768

  • Zhao W, Beers DR, Liao B, Henkel JS, Appel SH. Regulatory T lymphocytes from ALS mice suppress microglia and effector T lymphocytes through different cytokine-mediated mechanisms. Neurobiol Dis. 2012 Dec;48(3):418-28. doi: 10.1016/j.nbd.2012.07.008. Epub 2012 Jul 17.

    PubMed 22820142

  • Henkel JS, Beers DR, Wen S, Rivera AL, Toennis KM, Appel JE, Zhao W, Moore DH, Powell SZ, Appel SH. Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival. EMBO Mol Med. 2013 Jan;5(1):64-79. doi: 10.1002/emmm.201201544. Epub 2012 Nov 9.

    PubMed 23143995

  • Beers DR, Zhao W, Wang J, Zhang X, Wen S, Neal D, Thonhoff JR, Alsuliman AS, Shpall EJ, Rezvani K, Appel SH. ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity. JCI Insight. 2017 Mar 9;2(5):e89530. doi: 10.1172/jci.insight.89530.

    PubMed 28289705

  • Alsuliman A, Appel SH, Beers DR, Basar R, Shaim H, Kaur I, Zulovich J, Yvon E, Muftuoglu M, Imahashi N, Kondo K, Liu E, Shpall EJ, Rezvani K. A robust, good manufacturing practice-compliant, clinical-scale procedure to generate regulatory T cells from patients with amyotrophic lateral sclerosis for adoptive cell therapy. Cytotherapy. 2016 Oct;18(10):1312-24. doi: 10.1016/j.jcyt.2016.06.012. Epub 2016 Aug 3.

    PubMed 27497700

  • Thonhoff JR, Beers DR, Zhao W, Pleitez M, Simpson EP, Berry JD, Cudkowicz ME, Appel SH. Expanded autologous regulatory T-lymphocyte infusions in ALS: A phase I, first-in-human study. Neurol Neuroimmunol Neuroinflamm. 2018 May 18;5(4):e465. doi: 10.1212/NXI.0000000000000465. eCollection 2018 Jul.

    PubMed 29845093

  • Thonhoff JR, Berry JD, Macklin EA, Beers DR, Mendoza PA, Zhao W, Thome AD, Triolo F, Moon JJ, Paganoni S, Cudkowicz M, Appel SH. Combined Regulatory T-Lymphocyte and IL-2 Treatment Is Safe, Tolerable, and Biologically Active for 1 Year in Persons With Amyotrophic Lateral Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2022 Aug 29;9(6):e200019. doi: 10.1212/NXI.0000000000200019. Print 2022 Nov.

    PubMed 36038262

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injections in people with ALS (Amyotrophic Lateral Sclerosis), run by The Methodist Hospital Research Institute at 2 sites 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 9 inclusion and 13 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: finished, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Treg Suppressive Function in the Blood From Baseline to Week 24. (time frame: Baseline and week 24.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04055623, which also lists 11 linked publications.

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 28 Oct 2026.

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