Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients

Official Title:

Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients

Basic Trial Information

Phase Type Age Sponsor Protocol IDs Status
Phase 2 Interventional 18 Years and older National Institute of Allergy and Infectious Diseases (NIAID) HIVTR-CCR5
20730
NCT02741323
Enrolling patients

Study Design:


Principal Investigator

Professor of Surgery
Surgical Director, Kidney and Pancreas Transplant Program
Surgical Director, Pediatric Renal Transplant Program
Co-Director, Pancreatic Islet Cell Transplant Program
Chair, Department of Surgery Research Committee
Program, Director, T32 Training Program in Transplant Surgery

Clinical Research Coordinator

UCSF Medical Center at Parnassus
415-476-2575 Phone

Trial Summary

Maraviroc (MVC) is a type of HIV medicine called a CCR5 inhibitor. This study will evaluate the safety and tolerability of MVC in HIV-infected adults receiving a kidney transplant.

Eligibility

Inclusion Criteria:
  • Participant is able to understand and provide informed consent.
  • Documented HIV infection (by any licensed enzyme-linked immunosorbent assay [ELISA]
    and confirmation by Western Blot, positive HIV antibody (ab) indirect fluorescent
    antibody (IFA), or documented history of detectable HIV-1 RNA).
  • Participant is 18 years of age or older.
  • CD4+ T-cell count greater than or equal to 200/µL at any time in the 16 weeks prior
    to enrollment.
  • Most recent HIV-1 RNA less than 50 copies RNA/mL. Eligibility at the time of
    enrollment will be determined based on the most recent HIV-1 RNA, not more than 16
    weeks prior to enrollment. Subjects who require a switch in combination
    antiretroviral therapy (cART) regimen to become study eligible must also have an
    eligible HIV-1 RNA result at least 4 weeks post change in cART.
  • Participant meets standard listing criteria for placement on transplant waiting list.
  • For participants with an HIV+ deceased donor:
        - No active opportunistic infections.
        - Concurrence by the study team that based on medical history and ART, viral
           suppression can be achieved in the recipient post-transplant.
        - Must be enrolled in an Institutional Review Board (IRB) approved research
           protocol that fulfills the requirements of the DHHA Hope Act Policy (see the
           protocol for more information).
        - HIV+ deceased donor must have no evidence of invasive opportunistic
           complications of HIV infection, and must have a pre-implant biopsy.
  • Antiretroviral (ARV) Use: Participant is on stable cART regimen for at least 3 months
    prior to enrollment (unless changes are made due to toxicity, drug interactions,
    convenience or to an eligible integrase inhibitor-based regimen). Switch should not
    be due to virologic failure.
        - If on a non-integrase inhibitor based regimen, participant must be switched to
           an integrase inhibitor-based regimen based on lack of any prior drug resistance
           or antiretroviral-treatment failure, and be willing to remain on indefinitely
           unless a change is medically necessary. Participants who need to be switched
           must have been on a stable cART regimen for at least 3 months prior, and must be
           on the new integrase inhibitor-based regimen for at least 4 weeks prior to
           entry. Subjects who require a switch in cART regimen to become study eligible
           must also have an eligible HIV-1 RNA result at least 4 weeks post change in cART
           (and not more than 16 weeks prior to transplant).
        - If already on a stable regimen of 2 nucleoside reverse transcriptase inhibitors
           (NRTIs) and an integrase inhibitor, participant is willing to remain on this
           regimen indefinitely unless a change in regimen is medically indicated.
        - If untreated, must initiate and be willing to remain on indefinitely an
           antiretroviral regimen of two nucleoside reverse transcriptase inhibitors
           (NRTIs) and an integrase inhibitor unless a change is medically necessary.
  • No known allergy or intolerance to components of maraviroc (MVC) or its formulation.
  • No known contraindication to MCV.
  • Female participants of child-bearing potential must have a negative serum beta-human
    chorionic gonadotropin (HCG) pregnancy test within 30 days of randomization.
Exclusion Criteria:
  • Participant is currently on MVC.
  • Participant needs multi-organ transplant.
  • Participant has a live donor who is HIV+.
  • Participant is unable to switch to an integrase inhibitor-based cART regimen.
  • Participant has received immunosuppressant medication in the 6 months prior to
    enrollment. Note: Low dose maintenance steroids (less than or equal to 10 mg per day
    of prednisone, or equivalent strength steroid) will not be considered
    immunosuppression.
  • Opportunistic Complication History: Any history of progressive multifocal
    leukoencephalopathy (PML), chronic intestinal cryptosporidiosis of greater than 1
    month duration, or primary central nervous system (CNS) lymphoma. Note: History of
    pulmonary coccidiodomycosis will be treated per local site policy regarding this
    infection in HIV negative transplant candidates, generally requiring a 5-year
    disease-free interval.
  • Participant has a history of any neoplasm except for the following: resolved kaposi's
    sarcoma, in situ anogenital carcinoma, adequately treated basal or squamous cell
    carcinoma of the skin, solid tumors (except primary CNS lymphoma) treated with
    curative therapy and disease free for more than 5 years. History of renal cell
    carcinoma requires disease-free state for 2 years. History of leukemia and
    disease-free duration will be per site policy.
  • Substance use that in the opinion of the investigator would interfere with compliance
    with the study requirements.
  • Participant is pregnant or breastfeeding. Note: Participants who become pregnant
    post-transplant will continue to be followed in the study and will be managed per
    local site practice. Women that become pregnant should not breastfeed.
  • Participant has used interleukin-2 (IL-2) or granulocyte-macrophage
    colony-stimulating factor (GM-CSF) in the prior six months.
  • Participant has received interferon-alpha therapy in the prior 12 weeks.
  • Use of investigational drugs within 4 weeks of enrollment.
  • Past or current medical problems or findings from medical history, 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.

Detailed Description

MVC is a CCR5 inhibitor that may have a positive role in modulating the immune response
following transplantation. The purpose of this study is to evaluate the safety and
tolerability of MVC in HIV-infected adults in need of a kidney transplant. The study will
also evaluate whether using both immunosuppressant drugs and MVC will improve kidney
function after a kidney transplant.
This study will enroll HIV-infected adults on combination antiretroviral therapy (cART) who
need a kidney transplant. At the time of their kidney transplant, study participants will be
randomly assigned to receive either MVC or placebo as an addition to their cART regimen.
(MVC or placebo will be provided by the study. However, the HIV medicines in their cART
regimens will not be provided by the study.) Participants will receive MVC or placebo
throughout their participation in the study, which will be 1 to 3 years depending on when
they enroll in the study.
Study visits will occur at enrollment (Day 0) and post-transplant Weeks 1, 2, 4, 8, 13, 26,
39, 52, 78, 104, 130, and 156. Study visits may include a physical examination, blood
collection, lymph node collection, urine sample collection, and a kidney biopsy. During the
study, participants will also be monitored closely for evidence of drug toxicities, HIV
treatment failure and rejection.

Important

Final eligibility is determined by the health professionals conducting the trial and the protocol approved by the Committee on Human Resources (CHR) at the University of California, San Francisco (UCSF). The Patient Consent Form for this trial is available upon request. For more information about this trial, please see the full posting at ClinicalTrials.gov.

Information about this trial was obtained from the NIH Clinical Trials website, http://clinicaltrials.gov on 6/15/2017. UCSF specific information including the PI (Principal Investigator), trial enrollment status, and UCSF Study ID, supplement the ClinicalTrials.gov study posting.
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