Tocilizumab in Cardiac Transplantation

NCT03644667 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: DAIT RTB-004ALL INU01AI136816
• Study Type: interventional
• Target: 385
• Locations: 1 country
• Sites: 20

Brief Summary

The purpose of this research study is to see if a study drug called Tocilizumab will, when given with standard anti-rejection medicines, lead to better heart transplantation outcomes at 1 year after the transplant. Specifically, the investigators will evaluate whether taking tocilizumab leads to less rejection, less development of unwanted antibodies, and better heart function.

Conditions

Heart Transplant

Keywords

heart transplant recipients; alloimmunity; anti-inflammatory; tocilizumab; efficacy clinical trial; immunosuppression (IS)

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Positive for Event of dnDSA, ACR, AMR, Hemodynamic Compromise, Death or Re-Transplantation - By Treatment Group

  This outcome is defined by a composite 1 year post-transplant endpoint of: * detection of de novo donor-specific antibodies (dnDSA) (Core Laboratory), * acute cellular rejection (ACR) ≥ ISHLT 2R rejection (Core Laboratory), * antibody mediated rejection (AMR) ≥ ISHLT AMR 1 (Core Laboratory), * hemodynamic compromise rejection in the absence of a biopsy or histological rejection, * death, or * re-transplantation.

  From transplant through 12 months post transplant surgery (12 months)

Secondary Outcomes (22)

• Freedom of Detection of de Novo Donor-Specific Antibodies (dnDSA) - by Treatment Group

  From transplant through 12 months post transplant surgery (12 months)

• Freedom from Acute Cellular Rejection (ACR) ≥ International Society of Heart and Lung Transplantation (ISHLT) 2R Rejection - by Treatment Group

  From transplant through 12 months post transplant surgery (12 months)

• Freedom from Antibody Mediated Rejection (AMR) ≥ International Society of Heart and Lung Transplantation (ISHLT) AMR 1 - by Treatment Group

  From transplant through 12 months post transplant surgery (12 months)

• Freedom from Hemodynamic Compromise Rejection in the Absence of a Biopsy or Histological Rejection - by Treatment Group

  From transplant through 12 months post transplant surgery (12 months)

• Freedom from Any-Treated Rejection - by Treatment Group

  From transplant through 12 months post transplant surgery (12 months)

Study Arms (2)

Tocilizumab + Standard of Care Triple IS

EXPERIMENTAL

Tocilizumab plus standard of care triple immunosuppression (IS). Heart transplant recipients will receive tocilizumab (Actemra®) plus standard triple maintenance immunosuppression. Standard of care triple maintenance immunosuppression includes: * a calcineurin inhibitor (tacrolimus), * an anti-proliferative treatment (mycophenolate mofetil) or Myfortic® (enteric-coated mycophenolate sodium), and * steroids (methylprednisolone/prednisone) as prescribed by site physician investigator. Participants enrolled in the study will be followed for 24 months after their transplant surgery. Randomization will occur once a participant has weaned from cardiopulmonary bypass and has achieved hemodynamic stability without significant ongoing bleeding within the first 72 hours after transplant.

Biological: tocilizumab; Drug: Standard of Care Triple IS

Placebo + Standard of Care Triple IS

PLACEBO COMPARATOR

Placebo plus standard of care triple maintenance immunosuppression (IS). Heart transplant recipients will receive placebo plus standard triple maintenance immunosuppression. Standard of care triple maintenance immunosuppression includes: * a calcineurin inhibitor (tacrolimus), * an anti-proliferative treatment (mycophenolate mofetil) or Myfortic® (enteric-coated mycophenolate sodium), and * steroids (methylprednisolone/prednisone) as prescribed by site physician investigator. Participants enrolled in the study will be followed for 24 months after their transplant surgery. Randomization will occur once a participant has weaned from cardiopulmonary bypass and has achieved hemodynamic stability without significant ongoing bleeding within the first 72 hours after transplant.

Biological: Placebo; Drug: Standard of Care Triple IS

Interventions

tocilizumab BIOLOGICAL

6 doses: 8mg/kg (maximum of 800 mg) given once every four weeks by intravenous infusion over a 20-week period, with a minimum of 21 days between each infusion.

Also known as: Actemra®

Tocilizumab + Standard of Care Triple IS

Placebo BIOLOGICAL

The placebo is 0.9% sterile normal saline. 6 doses: 8mg/kg (maximum of 800 mg) given once every four weeks by intravenous infusion over a 20-week period, with a minimum of 21 days between each infusion.

Also known as: Placebo for tocilizumab, Placebo for Actemra®

Placebo + Standard of Care Triple IS

Standard of Care Triple IS DRUG

Standard of care triple maintenance IS includes: 1. A calcineurin inhibitor-tacrolimus (Prograf ®) per site standards by sublingual, oral or intravenous route to attain target trough levels. Exception: Should a participant be unable to tolerate tacrolimus, the site physician investigator may choose cyclosporine treatment. 2. An anti-proliferative treatment-mycophenolate mofetil or Myfortic® (enteric-coated mycophenolate sodium) will be administered, per protocol. Exception: Should a participant be unable to tolerate mycophenolate mofetil, the site physician investigator may choose an alternative treatment. 3. Steroids-methylprednisolone/prednisone dosing will be given according to the local center standard of practice early post transplantation. After 6 months, prednisone may be withdrawn at the discretion of the site physician investigator, per protocol.

Also known as: calcineurin inhibitor: (tacrolimus (Prograf ®)), anti-proliferative treatment: (mycophenolate mofetil ),, MMF, CellCept®, Myfortic®, enteric-coated mycophenolate sodium, steroids: methylprednisolone/prednisone

Placebo + Standard of Care Triple IS; Tocilizumab + Standard of Care Triple IS

Eligibility Criteria

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

You may qualify if:

• Subject must be able to understand and provide informed consent;
• Is a candidate for a primary heart transplant (listed as a heart transplant only);
• No desensitization therapy prior to 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 the above referenced 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.
• Mechanical support or investigational drug trials where the intervention ends at the time of transplantation are permitted;
• In the absence of contraindication, vaccinations should be up to date for hepatitis B, influenza, pneumococcal, zoster, and Measles, Mumps, \& Rubella (MMR); and
• Recipient of a primary heart transplant;
• Negative virtual crossmatch (according to local center criteria);
• No desensitization therapy prior to transplant;
• Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) prior to randomization; and
• 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 the above referenced 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.

You may not qualify if:

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol;
• Candidate for a multiple solid organ or tissue transplants;
• Prior history of organ or cellular transplantation requiring ongoing systemic immunosuppression;
• 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 to tocilizumab (Actemra®);
• Previous treatment with tocilizumab (Actemra®);
• Human Immunodeficiency Virus (HIV) positive;
• Hepatitis B surface antigen positive;
• Hepatitis B core antibody positive;
• Hepatitis C virus antibody positive (anti-HCV Ab+) who are either untreated or, have failed to demonstrate sustained viral remission for more than 12 months (after anti-viral treatment);
• Recipient of a Hepatitis C virus nucleic acid test (NAT) positive donor organ;
• Subjects must be tested for latent TB infection (LTBI) within a year prior to transplant:
• Subjects with a positive test for LTBI must complete appropriate therapy for LTBI.
• A Subject is considered eligible only if they have a negative test for LTBI within one year prior to transplant OR

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• PPD Development, LP: collaborator

Study Sites (20)

Cedars Sinai Medical Center (CACS)

Beverly Hills, California, 90211, United States

Location

University of California, San Diego: Sulpizio Cardiovascular Center (CASD)

La Jolla, California, 92037, United States

Location

Stanford Health Care (CASU)

Stanford, California, 94305, United States

Location

Tampa General Hospital (FLTG)

Tampa, Florida, 33606, United States

Location

Northwestern Memorial Hospital (INLM)

Chicago, Illinois, 60611, United States

Location

Tufts Medical Center (MANM)

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital (MAMG)

Boston, Massachusetts, 02114, United States

Location

St. Luke's Hospital of Kansas City (MOLH)

Kansas City, Missouri, 64111, United States

Location

University of Nebraska Medical Center (NEUN)

Omaha, Nebraska, 68198, United States

Location

Mount Sinai Medical Center (NYMS)

New York, New York, 10029, United States

Location

Columbia University Medical Center (NYCP)

New York, New York, 10032, United States

Location

Montefiore Medical Center (NYMA)

The Bronx, New York, 10467, United States

Location

Duke University Medical Center (NCDU)

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation (OHCC)

Cleveland, Ohio, 44195, United States

Location

Penn State Health: Milton S. Hershey Medical Center (PAHE)

Hershey, Pennsylvania, 17033, United States

Location

Hospital of the University of Pennsylvania (PAUP)

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital (PAAG)

Pittsburgh, Pennsylvania, 15212, United States

Location

Vanderbilt University Medical Center (TNVU)

Nashville, Tennessee, 37232, United States

Location

Baylor University Medical Center (TXTX)

Dallas, Texas, 75246, United States

Location

University of Utah (UTMC)

Salt Lake City, Utah, 84132, United States

Location

Related Links

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

MeSH Terms

Interventions

tocilizumab; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Prednisone

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jon A. Kobashigawa, MD

  Cedars Sinai Medical Center: Transplantation

  STUDY CHAIR

• Joren C. Madsen, MD, DPHIL

  Massachusetts General Hospital: Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 23, 2018
• Study Start: December 20, 2018
• Primary Completion: March 25, 2025
• Study Completion: March 25, 2025
• Last Updated: March 3, 2026

Record last verified: 2026-02

Locations

US (20)