Tocilizumab in Cardiac Transplantation

• Status: Recruiting
• Trial end date: 2023-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: PPD
• Treatments: Calcineurin Inhibitors; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Mycophenolic Acid; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone; Tacrolimus

Criteria

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 <7.0gm/dL (last measurement within 7 days prior to transplant);

24. Subjects with a platelet count of less than 100,000/mm^3 (last measurement within 7 days prior to transplant);

25. Subjects with an absolute neutrophil count (ANC) of less than 2,000/mm^3 (last measurement within 7 days prior to transplant);

26. Subjects with Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) levels >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 <7.0gm/dL within 7 days prior to randomization;

25. Subjects with a platelet count of less than 100,000/mm^3 within 7 days prior to randomization;

26. Subjects with an absolute neutrophil count (ANC) of less than 2,000/mm^3 within 7 days prior to randomization;

27. Subjects with AST or ALT levels >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).