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

Study Purpose:

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).

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Enrolling

Phase:

Phase II

Study Chair(s)/Principal Investigator(s):

Stanley H. Appel, MD The Methodist Hospital System
James D. Berry, MD Massachusetts General Hospital

Clinicaltrials.gov ID (11 digit #):

NCT04055623

Neals Affiliated?

Yes

Coordinating Center Contact Information

Houston Methodist Hospital
Rachel G Applegate, BS,CCRC / .(JavaScript must be enabled to view this email address) / 713-441-9120
Patricia A Mendoza, BSN,CCRC / .(JavaScript must be enabled to view this email address) / 713-441-5855
Houston, Texas 77030 United States

Full Study Summary:

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.

Study Sponsor:

The Methodist Hospital System

Participant Duration:

Estimated Enrollment:

12

Estimated Study Start Date:

09/01/2019

Estimated Study Completion Date:

11/30/2024

Posting Last Modified Date:

11/11/2019

Date Study Added to alsconsortium.org:

08/16/2019
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    N/A

    Min Vital Capacity (% predicted normal):

    65

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?

    Yes


    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.

  • Site Contact Information

    Massachusetts General Hospital
    Ella Collins / .(JavaScript must be enabled to view this email address) / 617-726-0981
    Boston, Massachusetts 02114
    United States

    Houston Methodist Hospital
    Rachel Applegate / .(JavaScript must be enabled to view this email address) / 713-441-9120
    Patricia Mendoza / .(JavaScript must be enabled to view this email address) / 713-441-5855
    Houston, Texas 77030
    United States