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T-regulatory Cells in ALS (Tregs in ALS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04055623
Recruitment Status : Active, not recruiting
First Posted : August 14, 2019
Last Update Posted : March 3, 2020
Sponsor:
Collaborators:
Massachusetts General Hospital
The Center for Clinical and Translational Sciences (CCTS) Clinical Research Unit at The University of Texas Health Science Center at Houston
North East Amyotrophic Lateral Sclerosis Consortium
Information provided by (Responsible Party):
Jason R. Thonhoff, The Methodist Hospital System

Brief 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 low-dose IL-2 in people with Amyotrophic Lateral Sclerosis (ALS).

Condition or disease Intervention/treatment Phase
ALS (Amyotrophic Lateral Sclerosis) Biological: Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injections Other: Monthly placebo infusions + 3 times per week placebo injections Phase 2

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, TX and Boston, MA) 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:

  1. the first period is a 6-month phase 2a, 2-center, randomized, placebo-controlled clinical trial studying the biological activity, safety, and tolerability of the increased / expanded Tregs administered intravenously (IV) with subcutaneous low-dose Interleukin-2 (IL-2) in 12 adults with ALS. IL2 helps regulate the immune system's white blood cells.
  2. The second period is a 6-month open-label extension in which all participants will receive their own expanded Treg cells administered intravenously in combination with subcutaneous low-dose IL-2.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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. This is followed by a second 6-months of Treg infusions and IL-2 injections for all participants.
Masking: Double (Participant, Care Provider)
Masking Description: The study drugs for the first 6-months of the study are (1) Treg cell intravenous (IV) infusions or matching placebo / inactive infusion and (2) subcutaneous interleukin-2 (IL-2) injections or matching placebo / inactive injections; followed by 6-months of Treg infusions and IL-2 injections for all participants.
Primary Purpose: Treatment
Official Title: Phase 2a Study of the Expansion and Infusion of Autologous T-Regulatory Cells in Amyotrophic Lateral Sclerosis
Actual Study Start Date : August 7, 2019
Estimated Primary Completion Date : September 1, 2024
Estimated Study Completion Date : November 30, 2024


Arm Intervention/treatment
Experimental: Intravenous infusion of Treg cells + Interleukin-2 injections
For 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.
Biological: Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injections
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
Other Names:
  • Individualized therapy Treg cell infusions + Interleukin-2 (IL-2)
  • Proleukin is brand name for IL-2

Placebo Comparator: Intravenous infusion w/Placebo + matching placebo injections
For 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.
Other: Monthly placebo infusions + 3 times per week placebo injections
For first 6-months of study: monthly placebo infusions + 3 times per week subcutaneous placebo injections
Other Name: inactive drug

Experimental: 2nd 6-months Open Label: Treg Infusions + IL-2 injections
For 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.
Biological: Monthly autologous Treg cells infusions + 3 times per week Interleukin-2 injections
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.
Other Names:
  • Individualized therapy Treg cell infusions + Interleukin-2 (IL-2)
  • Proleukin is the brand name for IL-2




Primary Outcome Measures :
  1. Treg suppressive function change as measured in the blood, at baseline and week 24. [ Time Frame: Baseline and week 24. ]
    Change in T-regulatory suppressive cell function of T-effector cells in the blood, as measured in percentage at baseline compared to week 24. A correlation between the rate of disease progression and Treg percentage will be determined by Spearman's correlation analysis.


Secondary Outcome Measures :
  1. Treg cell numbers measured in the blood at baseline and week 24. [ Time Frame: Baseline and week 24 ]
    Change in T-regulatory cells in the blood at baseline compared to week 24; measured in %.

  2. Appel Amyotrophic Lateral Sclerosis Score/Grading measured at baseline and week 24. [ Time Frame: Baseline and week 24 ]
    Change in the Appel ALS Score at baseline compared to week 24; measures overall progression of disability or altered function.

  3. Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) score measured at baseline and week 24. [ Time Frame: Baseline and week 24 ]
    Change in the ALSFRS-R score measured at baseline & week 24; assesses the progression of disability or altered function.

  4. Forced Vital Capacity (FVC) measured at baseline and week 24. [ Time Frame: Baseline and week 24 ]
    Change in FVC (strength of muscles used with expiration) at baseline compared to week 24, where the highest number is the strongest measurement.

  5. Maximum Inspiratory Pressure (MIP) measured at Baseline and Week 24. [ Time Frame: Baseline and week 24 ]
    Change in MIP (strength of muscles used with inspiration) at baseline & week 24, where the highest number is the strongest measurement.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04055623


Locations
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United States, Massachusetts
Massachusetts General Hospital (MGH) Neurological Clinical Research Institute
Boston, Massachusetts, United States, 02114
United States, Texas
Houston Methodist Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
The Methodist Hospital System
Massachusetts General Hospital
The Center for Clinical and Translational Sciences (CCTS) Clinical Research Unit at The University of Texas Health Science Center at Houston
North East Amyotrophic Lateral Sclerosis Consortium
Investigators
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Study Director: Stanley H. Appel, MD The Methodist Hospital System
Principal Investigator: Jason R. Thonhoff, MD, PhD The Methodist Hospital System
Principal Investigator: James D. Berry, MD, MPH Massachusetts General Hospital
Publications of Results:
Other Publications:

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Responsible Party: Jason R. Thonhoff, Principal Investigator, Houston Methodist Neurological Institute, The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT04055623    
Other Study ID Numbers: Pro00022167
First Posted: August 14, 2019    Key Record Dates
Last Update Posted: March 3, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified data may be shared with requests directed to the research clinical investigators.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: At the end of the study via data management plan for duration of Treg studies.
Access Criteria: Request to PI.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jason R. Thonhoff, The Methodist Hospital System:
Lou Gehrig's Disease
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Aldesleukin
Interleukin-2
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents