AzTrials
AzTrials

Lung TransplantPhase 2ALL IN LUNGNCT06033196

Tocilizumab in Lung Transplantation

A Phase 2 study testing Tocilizumab in people with Lung Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 21 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a trial in which 100 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… Read more about this study

Who is it for?
Ages 12 to 75 years
Conditions the study is for
Lung Transplant
What is being tested?
Tocilizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
100 participants
Where
21 sitesUnited States
Study dates
13 Feb 2024to 8 Jan 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 12 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 20Show fewer
  • 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
  • Underwent bronchoscopy and found to have satisfactory bronchial anastomotic healing
  • No desensitization therapy prior to transplant
  • Clinically stable, without clinical evidence of untreated infection
  • Negative pregnancy test (serum or urine) for women of child-bearing potential within 48 hours prior to randomization
  • Recipient of lungs that have been supported with ex vivo lung perfusion (EVLP) devices are permitted

Who cannot join

  • 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
Show all 58Show fewer
  • Known hypersensitivity to ACTEMRA(R) (tocilizumab)
  • 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)
  • Current treatment with alkylating agents such as cyclophosphamide
  • History of gastrointestinal (GI) tract perforation
  • History of inflammatory bowel disease except fully excised ulcerative colitis
  • Any history of diverticulitis (event if not perforated) or confirmed diverticular bleeding. (Diverticulosis is not an exclusion).
  • Patients with a platelet count < 100,000/mm^3 (last measurement within 7 days prior to enrollment)
  • Patients with an absolute neutrophil count (ANC) < 2,000/mm^3 (last measurement within 7 days prior to enrollment)
  • Patients with Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) levels >3 times upper limit of normal (last measurement within 7 days prior to enrollment)
  • Patients who use illegal drugs
  • Smoking or vaping within 6 months of listing for transplant
  • Use of investigational drugs within 4 weeks prior to enrollment
  • Any condition that in the opinion of the site Principal Investigator (PI) introduces undue risk by participating in this study
  • Randomization:
  • Recipient of multi-organ or tissue transplants
  • Biopsy proven >A1 or treated rejection in the first 5 weeks post transplantation
  • Received a live virus vaccine within 30 days prior to randomization
  • Received treatment to deplete HLA antibodies before transplantation to improve the possibility of transplantation
  • Patients with known donor-specific antibody that will require intervention based on local clinical protocols
  • History of GI tract perforation
  • History of inflammatory bowel disease except fully excised ulcerative colitis
  • History of diverticulitis (diverticulosis is not an exclusion) or diverticular bleeding
  • History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies
  • Known hypersensitivity to ACTEMRA® (tocilizumab)
  • Previous treatment with ACTEMRA® (tocilizumab) within the last 3 months.
  • Recipient or donor with infection with human immunodeficiency virus (HIV)
  • Recipient with hepatitis B virus surface antigen or hepatitis B core antibody positive
  • Hepatitis B negative transplant recipient that received a transplant from a Hepatitis B core antibody positive donor unless the recipient has a Hepatitis B Surface Antigen (HBsAb) titer >10U/L
  • Recipient of a hepatitis C virus nucleic acid test (NAT) positive donor organ
  • Latent TB infection (LTBI) and has not completed appropriate therapy
  • 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 (except for non-melanoma skin cancer)
  • History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura
  • History of demyelinating disorders (e.g., multiple sclerosis, chronic inflammation demyelinating polyneuropathy)
  • Current treatment with alkylating agents such as cyclophosphamide
  • Patients with AST or ALT levels > 1.5 times upper limit of normal (last measurement within 1 day prior to randomization)
  • Patients with platelet count <100,000/mm^3 (last measurement within 1 day prior to randomization)
  • Patients with an absolute neutrophil count (ANC) <2,000/mm^3 (last measurement within 1 day prior to randomization)
  • Patients who are administered anti-thymocyte globulin as induction therapy in the immediate post- transplant period
  • Patients who have been treated in the past 3 months, or for whom it is anticipated that treatment with any immunomodulatory biological agents post-transplant are excluded
  • Use of an investigational drug after transplant
  • Smoking or vaping since enrollment
  • Any condition that in the opinion of the site PI introduces undue risk by participating in this study

Trial locations and contacts

21 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Yvonne Morrison, MS contact

301-706-9137

ymorrison@niaid.nih.gov

21 sites in 1 country

United States21 sites, 17 recruiting

  • Emory University (Site #: 71103)

    Atlanta, Georgia, 55905

    Shine Thomas, 404-712-5137, sjthom5@emory.edu

    Recruiting

  • University of Maryland Medical Center (Site #: 71138)

    Baltimore, Maryland, 21201

    Withdrawn

  • Cedars Sinai Medical Center (Site #: 71146)

    Beverly Hills, California, 90211

    Brian Gonzalez, 310-423-8474, Bryan.Gonzalez@cshs.org

    Recruiting

  • Massachusetts General Hospital (Site #: 71107)

    Boston, Massachusetts, 02114

    Idrisa Saad, 617-726-1082, Isaad1@mgh.harvard.edu

    Recruiting

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

    Boston, Massachusetts, 02215

    Withdrawn

  • Cleveland Clinic (Site #: 71101)

    Cleveland, Ohio, 44195

    Abigail Camiener, 216-390-5108, camiena3@ccf.org

    Recruiting

  • Ohio State University Medical Center (Site #: 71196)

    Columbus, Ohio, 43210

    Benjamin Hood, 614-293-4299, benjamin.hood2@osumc.edu

    Recruiting

  • University of Texas Southwestern (Site #: 71187)

    Dallas, Texas, 75390

    Alice Osuji, 214-645-6605, alice.osuji@utsouthwestern.edu

    Recruiting

  • Duke University Medical Center (Site #: 71139)

    Durham, North Carolina, 27710

    Mary Motta, 919-660-1355, mary.motta@duke.edu

    Recruiting

  • University of Florida Shands Hospital (Site #: 71131)

    Gainesville, Florida, 32610

    Duncan Lewis, 352-294-5195, duncan.lewis@medicine.ufl.edu

    Not yet recruiting

  • Houston Methodist Hospital (Site #: 71120)

    Houston, Texas, 77030

    Withdrawn

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

    Los Angeles, California, 90095

    Paul Lopez, LVN, 310-794-8595, plopez@mednet.ucla.edu

    Recruiting

  • Vanderbilt University (Site #: 71174)

    Nashville, Tennessee, 37232-0393

    Briana Swanner, 615-327-7232, briana.swanner@vumc.org

    Recruiting

  • Columbia University Medical Center (Site #: 71113)

    New York, New York, 10032

    Shreena Patel, BA, LPN, 973-722-6835, sp3646@cumc.columbia.edu

    Recruiting

  • Temple University (Site #: 71197)

    Philadelphia, Pennsylvania, 19140

    Nakeeda Earle, 215-707-1359, Nakeeda.Earle@tuhs.temple.edu

    Not yet recruiting

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

    Phoenix, Arizona, 85013

    Cheyanna Anderson, 602-819-2380, Cheyanna.Anderson@commonspirit.org

    Recruiting

  • Mayo Clinic Rochester (Site #: 71160)

    Rochester, Minnesota, 55905

    Julie Gecox Hanson, 507-293-6592, gecox.julie@mayo.edu

    Not yet recruiting

  • University of Utah Medical Center (Site #: 71126)

    Salt Lake City, Utah, 84132

    Julia Uddenberg, BS, (801) 646-6126, julia.uddenberg@hsc.utah.edu

    Recruiting

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

    San Antonio, Texas, 78229

    Renee Walruff, walruff@uthscsa.edu

    Not yet recruiting

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

    St Louis, Missouri, 63110

    Brigitte Mittler, CCRC, 314-747-1931, b.mittler@wustl.edu

    Recruiting

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

    St Louis, Missouri, 63110

    Withdrawn

Other trials in United States

About this study

Official title: Targeting Inflammation and Alloimmunity in Lung Transplant Recipients With Tocilizumab (CTOT-45)

This is a trial in which 100 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) development of de novo donor specific antibodies (DSA), c) acute cellular rejection ≥A2, d) listed for re-transplantation, and e) death

Conditions
Lung Transplant
Being tested
Tocilizumab, Placebo for Tocilizumab
Keywords
Lung Transplant, Tocilizumab, Immunosuppression, ACTEMRA

What participants receive

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

  • TocilizumabDrug

    Also called ACTEMRA

    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

  • Placebo for TocilizumabDrug

    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

Study groups in NCT06033196
Study groupRoleWhat they receive
Tocilizumab GroupExperimentalSubject in this group will receive ACTEMRA(R) (Tocilizumab) ,(six injections over 20 weeks) plus standard triple maintenance immunosuppression of Tacrolimus, Mycophenolate Mofetil, corticosteroids
Receives: Drug: Tocilizumab
Placebo GroupPlacebo comparatorSubject in this group will receive placebo for Tocilizumab (sterile normal saline) plus standard triple maintenance immunosuppression of Tacrolimus, Mycophenolate Mofetil, corticosteroids
Receives: Drug: Placebo for Tocilizumab

What is being measured

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

  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.
    1. The development of de novo donor specific antibodies (DSA)
    2. Acute cellular rejection ≥A2 (inclusive of study mandated biopsy at 12 months post-transplant and any clinically indicated biopsy up to 1 year after randomization)
    3. 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
    1. Death

    Measured: Over a period of 1 year after randomization

Secondary outcomes (24)

  1. Time to the onset of each of ACR grade ≥A2, de novo DSA, CLAD, being listed for re-transplantation, or death

    Measured: At 1 year after randomization

  2. Cumulative incidence of Chronic Lung Allograft Dysfunction (CLAD)

    Measured: At 1 year after randomization

  3. Cumulative incidence listed for re-transplantation

    Measured: At 1 year after randomization

  4. Cumulative incidence of ACR grade ≥A2

    Measured: At 1 year after randomization

  5. Cumulative incidence of de novo DSA

    Measured: At 1 year after randomization

  6. Cumulative incidence of death

    Measured: At 1 year after randomization

  7. Freedom from Acute Cellular Rejection (ACR) grade >=A1

    Transbronchial lung biopsies will be performed according to the local center standard of care using the 2007 International Society for Heart and Lung Transplantation (ISHLT) criteria.

    Acute Cellular Rejection (A grade Rejection) Scale:

    • None (A0)
    • Minimal (A1)
    • Mild (A2)
    • Moderate (A3)
    • Severe (A4)
    • Ungradable (AX)

    Measured: At 1 year after randomization

  8. Proportion of subjects free from Antibody Mediated Rejection (AMR)

    Antibody mediated rejection studies will be performed using original H\&E stained slides, trichrome/elastic trichrome stain, and C4d immunostain (5 slides per case), along with positive controls

    Measured: At 1 year after randomization

  9. Incidence of Gastrointestinal (GI) tract perforation

    Measured: At 1 year after randomization

  10. Incidence of serious infections requiring intravenous antimicrobial therapy and need for hospitalization

    Measured: At 1 year after randomization

  11. Incidence of confirmed bacterial infection requiring antimicrobial therapy

    Measured: At 1 year after randomization

  12. Incidence of confirmed Cytomegalovirus (CMV) infection requiring antimicrobial therapy

    Measured: At 1 year after randomization

  13. Incidence of confirmed mold infection requiring antimicrobial therapy

    Measured: At 1 year after randomization

  14. Incidence of confirmed mycobacterial infection requiring antimicrobial therapy

    Measured: At 1 year after randomization

  15. Incidence of discontinuation of Tocilizumab (TCZ) due to an adverse event

    Measured: At 1 year after randomization

  16. Incidence of discontinuation of Tocilizumab (TCZ) due to serious adverse event

    Measured: At 1 year after randomization

  17. Incidence of discontinuation of Tocilizumab (TCZ) placebo due to an adverse event

    Measured: At 1 year after randomization

  18. Incidence of discontinuation of Tocilizumab (TCZ) placebo due to serious adverse event

    Measured: At 1 year after randomization

  19. Incidence of malignancy excluding squamous or basal cell skin cancer

    Measured: At 1 year after randomization

  20. Incidence of Tuberculosis (TB)

    Measured: At 1 year after randomization

  21. Incidence of Post-transplant lymphoproliferative disorder (PTLD)

    Measured: At 1 year after randomization

  22. Time to the onset of Chronic Lung Allograft Dysfunction (CLAD)

    Measured: At 1 year after randomization

  23. Time to the onset of being listed for re-transplantation

    Measured: At 1 year after randomization

  24. Time to the onset of death

    Measured: At 1 year after randomization

Timeline

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

  1. First posted13 Sep 2023
  2. Study start13 Feb 2024
  3. Primary completion8 Jan 2029 (estimated)
  4. Study completion8 Jan 2029 (estimated)

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
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06033196
Sponsor's protocol ID
DAIT CTOT-45
Acronym
ALL IN LUNG
Status last verified
Sep 2026
First submitted
24 Aug 2023
Last updated
8 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tocilizumab in people with Lung Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 21 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 20 inclusion and 58 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: looking for participants now, as of the sponsor's last update on 8 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 21 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Yvonne Morrison, MS (301-706-9137, ymorrison@niaid.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of subjects who meet any one of the pre-specified events detailed in the outcome description: from Baseline up to 36 months (time frame: Over a period of 1 year after randomization). 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 NCT06033196.

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 8 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in