Tocilizumab in Cardiac Transplantation

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.

Inclusion Criteria: Inclusion Criteria- Study Entry 1. Subject must be able to understand and provide informed consent; 2. Is a candidate for a primary heart transplant (listed as a heart transplant only); 3. No desensitization therapy prior to transplant; 4. 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. 5. Mechanical support or investigational drug trials where the intervention ends at the time of transplantation are permitted; 6. In the absence of contraindication, vaccinations should be up to date for hepatitis B, influenza, pneumococcal, zoster, and Measles, Mumps, \& Rubella (MMR); and 7. Subjects from areas of endemic coccidioidomycosis are eligible for inclusion but must be treated prophylactically with fluconazole or itraconazole. Inclusion Criteria - Randomization 1. Recipient of a primary heart transplant; 2. Negative virtual crossmatch (according to local center criteria); 3. No desensitization therapy prior to transplant; 4. Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) prior to randomization; and 5. 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. 6. Negative SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) test result performed within 48 hours of transplant (SARS-CoV-2 is the virus that causes COVID-19) Exclusion Criteria: Exclusion Criteria Study Entry 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol; 2. Candidate for a multiple solid organ or tissue transplants; 3. Prior history of organ or cellular transplantation requiring ongoing systemic immunosuppression; 4. Currently breast-feeding a child or plans to become pregnant during the timeframe of the study follow up period; 5. History of severe allergic and/or anaphylactic reactions to humanized or murine monoclonal antibodies; 6. Known hypersensitivity to tocilizumab (Actemra®); 7. Previous treatment with tocilizumab (Actemra®); 8. Human Immunodeficiency Virus (HIV) positive; 9. Hepatitis B surface antigen positive; 10. Hepatitis B core antibody positive; 11. 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); 12. Recipient of a Hepatitis C virus nucleic acid test (NAT) positive donor organ; 13. 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 \---- if they have completed appropriate LTBI therapy within one year prior to transplant. 14. Subjects with a previous history of active Tuberculosis (TB); 15. Subjects with a history of splenectomy; 16. Known active current viral, fungal, mycobacterial or other infections not including (left ventricular assist device \[LVAD\]) driveline infections; 17. History of malignancy less than 5 years in remission. --Any history of adequately treated in-situ cervical carcinoma, low grade prostate carcinoma, or adequately treated basal or squamous cell carcinoma of the skin will be permitted. 18. History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura; 19. History of demyelinating disorders such as: * multiple sclerosis, * chronic inflammation, * demyelinating polyneuropathy. 20. History of gastrointestinal perforations, active inflammatory bowel disease or diverticulitis; 21. Any previous treatment with alkylating agents such as chlorambucil or, total lymphoid irradiation; 22. Radiation therapy within 3 weeks before enrollment. --Enrollment of subjects who require concurrent radiotherapy should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy. 23. Subjects with a hemoglobin \3 x Upper Limit of Normal (ULN); 27. Subjects who are administered or intended to be administered cytolytic or anti-cluster of differentiation 25 (CD25) monoclonal antibody agents as induction therapy in the immediate post-transplant period; 28. Intent to give the recipient a live vaccine within 30 days prior to randomization; 29. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may: * pose additional risks from participation in the study, * may interfere with the participant's ability to comply with study requirements, or * that may impact the quality or interpretation of the data obtained from the study. Exclusion Criteria - Randomization 1. Recipient of multiple solid organ or tissue transplants; 2. Recipient of ex vivo preserved hearts and hearts donated after cardiac death (DCD); 3. Currently breast-feeding a child or plans to become pregnant during the timeframe of the study follow up period; 4. History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies; 5. Known hypersensitivity to tocilizumab (Actemra®); 6. Previous treatment with tocilizumab (Actemra®); 7. HIV positive; 8. Hepatitis B surface antigen positive; 9. Hepatitis B core antibody positive; 10. Hepatitis B negative transplant recipient that received a transplant from a hepatitis B core antibody positive donor; 11. HCV+ subject(s) who are either untreated or have failed to demonstrate sustained viral remission for more than 12 months after anti-viral treatment; 12. Recipient of a hepatitis C virus nucleic acid test (NAT) positive donor organ; 13. Subject's organ donor tests positive for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (SARS-CoV-2 is the virus that causes COVID-19). 14. Subjects with a previous history of active (TB); 15. 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 \---- if they have completed appropriate LTBI therapy within one year prior to transplant. 16. Subjects with a history of splenectomy; 17. Known active current viral, fungal, mycobacterial or other infections, not including (left ventricular assist device \[LVAD\]) driveline infections; 18. History of malignancy less than 5 years in remission. --Any history of adequately treated in-situ cervical carcinoma, low grade prostate carcinoma, or adequately treated basal or squamous cell carcinoma of the skin will be permitted. 19. History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura; 20. History of demyelinating disorders; 21. History of gastrointestinal perforations, active inflammatory bowel disease or diverticulitis; 22. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation; 23. Radiation therapy within 3 weeks before randomization. --Enrollment of subjects who require concurrent radiotherapy should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy. 24. Subjects with a hemoglobin \3 x ULN; 28. Subjects who are administered or intended to be administered cytolytic or anti- CD25 monoclonal antibody agents as induction therapy in the immediate post- transplant period; 29. Receipt of a live vaccine within 30 days prior to randomization; 30. Use of investigational drugs after transplantation; 31. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, * may pose additional risks from participation in the study, * may interfere with the participant's ability to comply with study requirements, or * that may impact the quality or interpretation of the data obtained from the study. 32. Subjects with known donor-specific antibody at the time of evaluation of antibodies for heart transplant surgery (within 6 months).