Principal Investigator: Josef Stehlik
Keywords: Heart Transplant , Cardiology Department: Cardiovascular Medicine
IRB Number: 00115352
Specialty: Cardiology, Cardiology
Sub Specialties: Heart Transplant
Recruitment Status: Recruiting

Contact Information

Habeeb Mohammad
habeeb.mohammad@hsc.utah.edu
801-213-1334

Simple Summary

Targeting Inflammation and Alloimmunity in Heart Transplant Recipients with Tocilizumab

Inclusion Criteria

4.1 Inclusion Criteria- Study Entry

Individuals who meet all the following criteria are eligible for enrollment as study participants:

1. Subject must be able to understand and provide informed consent;

2. Male or female, 18 to 75 years of age;

3. Candidate for a primary heart transplant (listed as a heart transplant only);

4. No desensitization therapy prior to transplant;

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 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;

6. Mechanical support or investigational drug trials where the intervention ends at the time of transplantation are permitted;

7. In the absence of contraindication, vaccinations should must be up to date per the DAIT Guidance for Patients in Transplant Trials (Refer to the Manual of Procedures);

8. Subjects living in areas of endemic coccidioidomycosis or who have antibody to coccidioidomycosis are eligible for inclusion but must be treated prophylactically with fluconazole or itraconazole.

 

4.3 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;

  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 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.

  6. Negative SARS-COV2 PCR testing prior to transplant as per institution policy.

Exclusion Criteria

4.2 Exclusion Criteria – Study Entry

Individuals who meet any of these criteria are not eligible for enrollment as study participants:

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 Actemra® (tocilizumab);

7. Previous treatment with Actemra® (tocilizumab);

8. HIV positive patients;

9. Hepatitis B surface antigen positive patients;

10. Hepatitis B core antibody positive patients;

11. Hepatitis C virus antibody 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;

12. Subjects must be tested for latent TB infection (LTBI) within a year prior to transplant. Testing should be conducted using either a PPD or Interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB). Patients with a positive test for latent TB infection (LTBI) must complete appropriate therapy for LTBI (https://www.cdc.gov/tb/topic/treatment/ltbi.htm). 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;

13. Patients with a previous history of active Tuberculosis (TB);

14. Known active current viral, fungal, mycobacterial or other infections (including, but not limited to atypical mycobacterial disease, blastomycosis, cryptococcus, and herpes zoster), not including drive line infections;

15. Patients with a history of splenectomy;

16. 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;

17. History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura;

18. History of demyelinating disorders (e.g., multiple sclerosis, chronic inflammation demyelinating polyneuropathy);

19. History of gastrointestinal perforations; active peptic ulcer disease, active GI bleed, active inflammatory bowel disease or diverticulitis (diverticulosis is not an exclusion). GI Bleeding that occurs only in the setting of an implanted VAD, and which is well controlled, is not a contraindication to enrollment in this study;;

20. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation;

21. Radiation therapy within 3 weeks before enrollment. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy;

22. Patients with a hemoglobin <7.0gm/dL (last measurement within 7 days prior to transplant);

23. Patients with a platelet count of less than 100,000/mm (last measurement within 7 days prior to transplant);

24. Patients with an absolute neutrophil count (ANC) of less than 2,000/mm3 (last measurement within 7 days prior to transplant);

25. Patients with AST or ALT levels >3 x ULN;

26. Patients who are administered or intended to be administered cytolytic (such as anti-thymocyte globulin) or anti-CD25 monoclonal antibody agents as induction therapy in the immediate post-transplant period;

27. Intent to give the recipient a live vaccine within 30 days prior to randomization;

28. 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.

29. History of Chagas disease and/or previous positive laboratory testing for Chagas Disease (see https://www.cdc.gov/dpdx/trypanosomiasisAmerican/index.html).Testing is indicated only for people who have lived in endemic areas and/or when there is clinical suspicion of Chagas Disease.

30. History of AL amyloidosis (TTR amyloids are permitted).

 

4.2 Exclusion Criteria – Randomization

  1. Recipient of multiple solid organ or tissue transplants;

  2. Recipients 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 Actemra® (tocilizumab);

  6. Previous treatment with Actemra® (tocilizumab);

  7. HIV positive;

  8. Hepatitis B surface antigen positive;

  9. Hepatitis B core antibody positive;

  10. HepatitisBnegativetransplantrecipientthatreceivedatransplantfromaHepatitisBcore

    antibody positive donor;

  11. Recipient of a Hepatitis C virus nucleic acid test (NAT) positive donor organ;

  12. SARS-CoV-2 PCR positive test on the donor;

  13. Patients with a previous history of active Tuberculosis (TB);

  14. Subjects must be tested for latent TB infection (LTBI) within a year prior to transplant. Testing

    should be conducted using either a PPD or Interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB). Patients with a positive test for latent TB infection (LTBI) must complete appropriate therapy for LTBI. (https://www.cdc.gov/tb/topic/treatment/ltbi.htm). 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;

  15. Known active current viral, fungal, mycobacterial or other infections (including, but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster), not including drive line infections;

  16. Patients with a history of splenectomy;

  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 (e.g.,multiple sclerosis, chronic inflammation

    demyelinating polyneuropathy);

  20. History of gastrointestinal perforations; active inflammatory bowel disease, active peptic ulcer disease, active GI bleed, or diverticulitis (diverticulosis is not an exclusion);

  21. Any previous treatment with alkylating agents such as chlorambucil or with total lymphoid

    irradiation;

  22. Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require

    concurrent radiotherapy (which must be localized in its field size) should be deferred until the

    radiotherapy is completed and 3 weeks have elapsed since the last date of therapy;

  23. Patients with a hemoglobin<7.0gm/dL(last measurement within 7 days prior to transplant);

  24. Patients with a platelet count of less than 100,000/mm3 (last measurement within 7 days prior

    to transplant);

  25. Patients with an absolute neutrophil count (ANC) of less than 2,000/mm3 (last measurement

    within 7 days prior to transplant);

  26. Patients with AST or ALT levels >3xULN;

  27. Patients who are administered or intended to be administered cytolytic (such as

    anti-thymocyte globulin) or anti-CD25 monoclonal antibody agents as induction therapy in the immediate post-transplant period;

  28. Receipt of a live vaccine within 30 days prior to randomization;

  29. Use of investigational drugs after transplantation;

  30. Past or current medicalproblemsorfindingsfromphysicalexaminationorlaboratorytesting

    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;

  31. Patients with known donor-specific antibody at the time of evaluation of antibodies for heart transplant surgery (within 6 months).

  32. History of Chagas disease and/or previous positive laboratory testing for Chagas Disease (see https://www.cdc.gov/dpdx/trypanosomiasisAmerican/index.html).Testing is indicated only for people who have lived in endemic areasand/or when there is clinical suspicion of Chagas Disease.

  33. History of AL amyloidosis (TTR amyloids are permitted).

Participant Reimbursement

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 Actemra® (tocilizumab);7. Previous treatment with Actemra® (tocilizumab);8. HIV positive patients;9. Hepatitis B surface antigen positive patients;10. Hepatitis B core antibody positive patients;11. Hepatitis C virus positive (HCV+) patients who have failed to demonstrate sustained viral remission for more than 12 months (after anti-viral treatment);12. Subjects must be tested for latent TB infection (LTBI) within a year prior to transplant. Testing should be conducted using either a PPD or Interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB). Patients with a positive test for latent TB infection (LTBI) must complete appropriate therapy for LTBI. (https://www.cdc.gov/tb/topic/treatment/lbti.htm) 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;13. Patients with a previous history of active Tuberculosis (TB);14. Known active current viral, fungal, mycobacterial or other infections (including, but not limited to atypical mycobacterial disease, blastomycosis, cryptococcus, and herpes zoster), not including drive line infections;15. 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;16. History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura;17. History of demyelinating disorders (e.g., multiple sclerosis, chronic inflammation demyelinating polyneuropathy);18. History of gastrointestinal perforations, active peptic ulcer disease, active GI bleed, active inflammatory bowel disease, or diverticulitis;19. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation;20. Radiation therapy within 3 weeks before enrollment. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy;21. Patients with a hemoglobin <7.0gm/dL (last measurement within 7 days prior to enrollment);22. Patients with a platelet count of less than 100,000/mm3 (last measurement within 7 days prior to enrollment);23. Patients with an absolute neutrophil count (ANC) of less than 2,000/mm3 (last measurement within 7 days prior to enrollment);24. Patients with AST or ALT levels >3 x ULN;25. Patients who are administered or intended to be administered cytolytic (such as anti-thymocyte globulin) or anti-CD25 monoclonal antibody agents as induction therapy in the immediate post-transplant period;26. Receipt of a live vaccine within 30 days prior to randomization;27. 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.