Overview

Treg Modulation With CD28 and IL-6 Receptor Antagonists

Status:
Recruiting
Trial end date:
2022-12-01
Target enrollment:
0
Participant gender:
All
Summary
The purpose of this study is to evaluate the safety of using lulizumab pegol with tocilizumab, belatacept, and everolimus in kidney transplant recipients.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators:
Bristol-Myers Squibb
Clinical Trials in Organ Transplantation
Treatments:
Abatacept
Antilymphocyte Serum
Everolimus
Methylprednisolone
Methylprednisolone Hemisuccinate
Mycophenolic Acid
Prednisone
Sirolimus
Thymoglobulin
Criteria
Inclusion Criteria:

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

1. Able to understand and provide informed consent

2. Agreement to use highly effective (<1% failure rate) methods of contraception: Women
of Childbearing Potential (WOCBP)-

- Progestogen only hormonal contraception associated with inhibition of ovulation,

- Hormonal methods of contraception including oral contraceptive pills containing a
combination of estrogen + progesterone, vagina ring, injectables, implants and
intrauterine devices (IUDs),

- Non-hormonal IUDs,

- Bilateral tubal occlusion,

- Vasectomized partner,

- Intrauterine hormone-releasing system (IUS), or

- Complete abstinence.

Note: Female participants of childbearing potential must consult with their physician
and determine the most suitable method(s) from this list to be used for 12 months
while on study drug regimen.

Male Participants-

--Must use a latex or other synthetic condom during any sexual activity with WOCBP
until one month after the last dose of lulizumab (e.g., up to 3.5 months in duration).

3. Recipient of primary, nonhuman leukocyte antigen identical living donor kidney
transplant

4. No donor specific antibodies prior to transplant that are considered to be of clinical
significance by the site investigator

5. Epstein-Barr virus (EBV) positive serology

6. Cytomegalovirus (CMV) positive serology, unless donor-recipient pair are both CMV
negative

7. Negative testing for latent Tuberculosis (TB) infection within 3 months prior to
transplant

- Testing should be conducted using either a purified protein derivative (PPD) or
an interferon-gamma release assay blood test for TB (i.e. QuantiFERON®-TB Gold
in-Tube test or T-SPOT® TB test)

- Subjects with a positive test for latent TB infection must complete appropriate
therapy for Latent tuberculosis infection (LTBI). ---A subject is considered
eligible only if they have a negative test for LTBI within 3 months prior to
transplant or, they have appropriately completed LTBI therapy prior to
transplant.

Note: Latent TB infection treatment regimens should be among those endorsed by the CDC
(Division of TB Elimination, 2016).

8. In the absence of contraindication, vaccinations must be up to date for hepatitis B,
influenza, pneumococcal, varicella and herpes zoster, and measles, mumps, and rubella
(MMR)

9. Hepatitis C Virus (HCV) antibody positive subjects with negative HCV by PCR testing
are eligible if they:

- have spontaneously cleared infection, or

- are in sustained virologic remission for at least 12 weeks after treatment for
HCV.

10. Negative SARS-CoV-2 PCR test result performed within 2 weeks of transplant (SARS-CoV-2
is the virus that causes COVID-19)

Exclusion Criteria:

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

1. Prisoners or subjects who are compulsorily detained

2. Inability or unwillingness of a participant to give written informed consent or comply
with study protocol

3. Candidate for a multiple solid organ or tissue transplants

4. Prior history of organ or cellular transplantation

5. Known to have idiopathic focal segmental glomerulosclerosis (FSGS) as the underlying
cause of kidney failure (ESRD)

6. Requirement for uninterrupted anticoagulation therapy, including Plavix.

7. Known hypersensitivity to mechanistic target of rapamycin (mTOR) inhibitors or
contraindication to everolimus (including history of wound healing complications)

8. History of severe allergic and/or anaphylactic reactions to humanized or murine
monoclonal antibodies

9. Hypersensitivity to rabbit proteins or rabbit anti-thymocyte Globulin (ATG)

10. Known hypersensitivity to ACTEMRA® (tocilizumab) or lulizumab pegol (BMS-931699)

11. The human immunodeficiency virus (HIV) infected subjects, including those who are well
controlled on antiretrovirals

12. Positive hepatitis B surface antigen (HBSAg), or hepatitis B core antibody (HBcAB)
serology

13. Hepatitis C virus antibody positive (HCV Ab+) subjects who have failed to demonstrate
sustained viral remission for more than 12 weeks after anti-viral treatment

14. Subjects with a previous history of active Tuberculosis (TB)

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)

16. Donor or recipient residing in areas where the annual incidence ≥ 21 cases per
100,000) for coccidioidomycosis according to current CDC map:
(https://www.cdc.gov/fungal/diseases/coccidioidomycosis/causes.html)

- Donors or recipients residing in low risk zones (annual <21 cases per 100,000)
will not require additional screening

17. History of malignancy except treated basal cell cancer of the skin

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 or
diverticulitis

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

22. Receipt of a live vaccine within 30 days prior to transplantation.

23. 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

24. Severe hyperlipidemia (defined by total cholesterol >350 mg/dL, LDL >190 mg/dL, or
triglycerides >500 mg/dL)

25. Transaminase levels elevated more than 1.5 times the upper limit of normal (ULN)
within 7 days prior to enrollment

26. The absolute neutrophil count (ANC) < 2,000 per mm^3 within 7 days prior to enrollment

27. Platelet count less than 100,000 per mm^3 within 7 days prior to enrollment

28. More than 50% CD8+/ CD28- T-cells in peripheral blood

29. A calculated panel reactive antibody (cPRA) ≥20%, as determined by each participating
site's laboratory

30. Positive pregnancy test in women of child bearing potential, currently breastfeeding,
or planning to become pregnant during the timeframe of the study or follow-up period

31. Participation in any other studies with investigational drugs or regimens in the
preceding year

32. A history of a positive SARS-CoV-2 PCR test result (SARS-CoV-2 is the virus that
causes COVID-19)