Tocilizumab in Lung Transplantation

NCT06033196 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DAIT CTOT-45
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 21

Brief Summary

This is a trial in which 350 primary lung transplant recipients will be randomized (1:1) to receive either Tocilizumab (six doses over 20 weeks) plus standard triple maintenance immunosuppression or placebo (sterile normal saline) plus standard triple maintenance immunosuppression (Tacrolimus, Mycophenolate Mofetil, corticosteroids). The primary objective is to test the hypothesis that treatment with triple maintenance immunosuppression plus Tocilizumab (TCZ) is superior to triple maintenance immunosuppression plus placebo (saline) as defined by a composite endpoint of a) CLAD, b) listed for re-transplantation, and c) death

Conditions

Lung Transplant

Keywords

Lung Transplant; Tocilizumab; Immunosuppression; ACTEMRA

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects who meet any one of the pre-specified events detailed in the outcome description: from Baseline up to 36 months

  1. The development of Chronic Lung Allograft Dysfunction (CLAD) * The development of any form of CLAD will be defined according to the standard 2019 The International Society for Heart and Lung Transplantation (ISHLT) criteria. 2. Listed for re-transplantation * Re-transplantation defined as the subject has been formally registered on the United Network for Organ Sharing (UNOS) waiting list to undergo a second lung transplant surgery 3. Death * Primary analysis will be conducted according to an Intent-to-treat (ITT) principle and therefore will include all randomized subjects who receive Tocilizumab(TCZ) or placebo. The time from randomization to development of CLAD will be compared between the two treatment groups (TCZ vs. placebo) using a Pearson's chi-square test.

  Over a period of 3 years after randomization

Secondary Outcomes (24)

• Time to the onset of CLAD, being listed for re-transplantation, or death

  At 3 years after randomization

• Cumulative incidence of Chronic Lung Allograft Dysfunction (CLAD)

  At 3 years after randomization

• Cumulative incidence listed for re-transplantation

  At 3 years after randomization

• Cumulative incidence of death

  At 3 years after randomization

• Freedom from Acute Cellular Rejection (ACR) grade >=A2

  At 3 years after randomization

Study Arms (2)

Tocilizumab Group

EXPERIMENTAL

Subject in this group will receive ACTEMRA(R) (Tocilizumab) ,(six injections over 20 weeks) plus standard triple maintenance immunosuppression of Tacrolimus, Mycophenolate Mofetil, corticosteroids

Drug: Tocilizumab

Placebo Group

PLACEBO COMPARATOR

Subject in this group will receive placebo for Tocilizumab (sterile normal saline) plus standard triple maintenance immunosuppression of Tacrolimus, Mycophenolate Mofetil, corticosteroids

Drug: Placebo for Tocilizumab

Interventions

Tocilizumab DRUG

The initial dose of tocilizumab will be administered in the operating room before reperfusion of the first lung during the lung transplant surgery. 6 doses will be given once every four weeks over a 20-week period. The dose is approved for pediatric patients who weigh 30 kg or more

Also known as: ACTEMRA

Tocilizumab Group

Placebo for Tocilizumab DRUG

Placebo 0.9% Sodium Chloride Injection USP (Normal Saline) Placebo will be given as a single intravenous dose, volume matched to tocilizumab. Placebo will be administered over a period of approximately 60 minutes; once every four weeks over a 20-week period. The first placebo dose will be during the transplant surgery before reperfusion of the first lung allograft, with 5 subsequent monthly doses

Placebo Group

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Study Entry:
• Subject and/or parent guardian must be able to understand the purpose of the study and willing to participate and sign informed consent/assent
• Greater than or equal to 30 kg body weight
• Listed or received for a primary lung transplant
• No previous or planned desensitization therapy prior to transplant
• Serum Immunoglobulin G (IgG) level greater than 400 mg/dL. Patients treated with intravenous immune globulin (IVIG) for hypogammaglobulinemia are eligible for enrollment if their serum IgG level is greater than 400 mg/dL 14 or more days after the most recent IVIG treatment
• For women of child-bearing potential, willingness to use highly-effective contraception; according to the Food and Drug Administration (FDA) Office of Women's Health (http://www.fda.gov/birthcontrol).
• Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for the duration of the study. Those who choose oral contraception must agree to use a second form of contraception after administration of study drug for a period of 1 year after the last dose of study drug
• Tested negative for latent TB infection (LTBI) using a PPD or interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB) within 1 year prior to transplant or has completed appropriate LTBI therapy within the 1 year prior to transplant
• Vaccinations must be up to date per the Division of Allergy, Immunology, and Transplantation (DAIT) Guidance for Patients in Transplant Trials
• Randomization:
• Provide written informed consent for the study participation, and agree to continue in the study
• Received a single or bilateral lung transplant
• Agreement to use contraception; according to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for the duration of the study. Those who choose oral contraception must agree to use a second form of contraception after administration of study drug for a period of 1 year after the last dose of study drug
• Negative physical crossmatch at the time of transplant or a crossmatch result that did not require specific treatment per the site's clinical protocol

You may not qualify if:

• Study Entry:
• Listed for multi-organ transplant (e.g., heart-lung, liver-lung, kidney-lung)
• Prior history of allogeneic organ or cellular transplantation
• Received treatment to deplete Human Leukocyte Antigens (HLA) antibodies before transplantation
• Currently breast-feeding a child or plans to become pregnant during the timeframe of the study follow up period
• History of severe allergic and/or anaphylactic reactions to humanized or murine monoclonal antibodies
• Known hypersensitivity or previous treatment with ACTEMRA(R) (tocilizumab) within the last 3 months
• Infection with human immunodeficiency virus (HIV)
• Hepatitis B virus surface antigen or core antibody positive
• Hepatitis C virus PCR positive (HCV+) patients who have failed to demonstrate sustained viral remission (2 consecutive PCR or Nucleic Acid Tests (NAT) negative tests at least 24 weeks apart), with or without anti-viral treatment;
• Chronic infection with Burkholderia cenocepacia or Burkholderia gladioli
• Non-tuberculous mycobacterial (NTM) pulmonary disease; if there is a history of NTM pulmonary disease, culture conversion is necessary for eligibility
• Presence of active malignancy or history of malignancy less than 5 years in remission, excluding adequately treated in-situ cervical carcinoma, low grade prostate carcinoma, or adequately treated basal or squamous cell carcinoma of the skin
• History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura
• History of demyelinating disorders (e.g., multiple sclerosis, chronic inflammation demyelinating polyneuropathy)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (21)

St. Joseph's Hospital and Medical Center (Site #: 71192)

Phoenix, Arizona, 85013, United States

RECRUITING

Cedars Sinai Medical Center (Site #: 71146)

Beverly Hills, California, 90211, United States

RECRUITING

David Geffen School of Medicine at UCLA (Site #: 71123)

Los Angeles, California, 90095, United States

RECRUITING

University of Florida Shands Hospital (Site #: 71131)

Gainesville, Florida, 32610, United States

NOT YET RECRUITING

Emory University (Site #: 71103)

Atlanta, Georgia, 55905, United States

NOT YET RECRUITING

University of Maryland Medical Center (Site #: 71138)

Baltimore, Maryland, 21201, United States

WITHDRAWN

Massachusetts General Hospital (Site #: 71107)

Boston, Massachusetts, 02114, United States

RECRUITING

Boston Children's Hospital and Harvard Medical School (Site #: 71001)

Boston, Massachusetts, 02215, United States

WITHDRAWN

Mayo Clinic Rochester (Site #: 71160)

Rochester, Minnesota, 55905, United States

NOT YET RECRUITING

Barnes Jewish Hospital/ Washington University SOM (Site #: 71191)

St Louis, Missouri, 63110, United States

RECRUITING

St. Louis Children's Hospital of Washington University (Site #: 71006)

St Louis, Missouri, 63110, United States

WITHDRAWN

Columbia University Medical Center (Site #: 71113)

New York, New York, 10032, United States

RECRUITING

Duke University Medical Center (Site #: 71139)

Durham, North Carolina, 27710, United States

RECRUITING

Cleveland Clinic (Site #: 71101)

Cleveland, Ohio, 44195, United States

RECRUITING

Ohio State University Medical Center (Site #: 71196)

Columbus, Ohio, 43210, United States

NOT YET RECRUITING

Temple University (Site #: 71197)

Philadelphia, Pennsylvania, 19140, United States

NOT YET RECRUITING

Vanderbilt University (Site #: 71174)

Nashville, Tennessee, 37232-0393, United States

NOT YET RECRUITING

University of Texas Southwestern (Site #: 71187)

Dallas, Texas, 75390, United States

RECRUITING

Houston Methodist Hospital (Site #: 71120)

Houston, Texas, 77030, United States

WITHDRAWN

University of Texas Health Science at San Antonio (Site #: 71198)

San Antonio, Texas, 78229, United States

NOT YET RECRUITING

University of Utah Medical Center (Site #: 71126)

Salt Lake City, Utah, 84132, United States

RECRUITING

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• NIAID Transplant Programs website

MeSH Terms

Interventions

tocilizumab

Study Officials

• Joren Madsen, MD, D.Phil.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Ramsey Hachem, MD

  University of Utah Medical Center

  STUDY CHAIR

• Daniel Kreisel, M.D.

  Washington University School of Medicine

  STUDY CHAIR

Central Study Contacts

Yvonne Morrison, MS

CONTACT

301-706-9137; ymorrison@niaid.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2023
• First Posted: September 13, 2023
• Study Start: February 13, 2024
• Primary Completion (Estimated): January 8, 2029
• Study Completion (Estimated): January 8, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

US (21)