Clinical Trials

MainTitle

Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients

This study is currently recruiting participants. (see Contacts and Locations)

Verified November 2017 by National Institute of Allergy and Infectious Diseases (NIAID)

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)


Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT02741323

First received: April 13, 2016
Last updated: November 20, 2017
Last Verified: November 2017
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Infections
Kidney Diseases

Drug : Maraviroc
Drug : Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Measured glomerular filtration rate by iohexol clearance [ Time Frame: Measured at Week 52 ]
  • Number of participants with graft loss, Grade 3 or greater toxicities, and/or permanent treatment discontinuations [ Time Frame: Measured through Week 52 ]
Secondary Outcome Measures:
  • Proportion of participants with estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m^2 [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
    Measured by chronic kidney disease epidemiology collaboration equation (CKD-EPI), cystatin C, and chronic kidney disease (CKD)-cystatin C
  • Proportion of participants with defined CKD stage 4 or 5 [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Mean eGFR [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
    Calculated by CKD-EPI, cystatin C, and CKD-cystatin C
  • Measurement of the slope of eGFR [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
    Calculated by CKD-EPI, cystatin C, and CKD-cystatin C variable models over time based on serum creatinine
  • HIV reactivation (frequency of CD4+ T cells producing HIV multiply spliced RNAs upon T-cell receptor stimulation [TCR] stimulation) [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • HIV DNA in peripheral blood CD4+ T cells [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • HIV RNA in peripheral blood CD4+ T cells [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Plasma HIV RNA levels (single copy assay) [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Incidence of clinically suspected and biopsy proven acute rejection [ Time Frame: Measured through Week 156 ]
    Defined by histologic evidence of rejection and graft dysfunction as identified on central read of biopsy slides
  • Incidence of acute cellular rejection grade equal to or greater than IA [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
    Measured by the Banff 2007 criteria as identified on central read of biopsy slides
  • The severity of first and highest grade of acute cellular rejection [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Incidence of antibody mediated rejection [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Prevalence of de novo anti-donor human leukocyte antigen (HLA) antibodies [ Time Frame: Measured at Week 52 ]
  • Histology/in situ hybridization to assess HIV infection in the renal allograft [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Incidence of death [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Incidence of graft loss [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Incidence of all adverse events (AEs) greater than or equal to Grade 3 [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Incidence of serious adverse events (SAEs) greater than or equal to Grade 3 [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Incidence of opportunistic infections or neoplasms [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Incidence of non-opportunistic infections requiring hospitalization or systemic therapy [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Calcineurin inhibitor trough levels for participants on maraviroc versus placebo [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Calcineurin inhibitor AUC for participants on maraviroc versus placebo [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • AUC of CCR5 blockade (maraviroc) [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]
  • Trough levels of CCR5 blockade (maraviroc) [ Time Frame: Measured through participants' last study visit, which will be during Years 1 to 3, depending on when they enroll in the study ]

Estimated Enrollment: 130
Study Start Date: January 1, 2017
Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Arm 1: Maraviroc (MVC)
Participants will receive MVC at the time of admission for transplantation and prior to transplant. Participants will receive MVC throughout their participation in the study, which will be 1 to 3 years depending on when they enroll.
Drug: Maraviroc

Initial dose of 300 mg twice daily (150mg twice daily if co-prescribed with a potent CYP3A inhibitor or 600mg twice daily if co-prescribed with a potent CYP3A inducer). Will be modified if GFR < 30, if co-prescribed with a potent CYP3A inhibitor or inducer, or if the calcineurin inhibitor used for maintenance immunosuppression is changed to cyclosporine (which is only allowed for tacrolimus toxicity).

Other Name: MVC
Placebo Comparator: Arm 2: Placebo
Participants will receive placebo at the time of admission for transplantation and prior to transplant. Participants will receive placebo throughout their participation in the study, which will be 1 to 3 years depending on when they enroll.
Drug: Placebo

Initial dose of 300 mg twice daily (150mg twice daily if co-prescribed with a potent CYP3A inhibitor or 600mg twice daily if co-prescribed with a potent CYP3A inducer). Will be modified if GFR < 30, if co-prescribed with a potent CYP3A inhibitor or inducer, or if the calcineurin inhibitor used for maintenance immunosuppression is changed to cyclosporine (which is only allowed for tacrolimus toxicity).

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

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 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 a 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 non-protease inhibitor-based regimen). Switch should not be due to virologic failure. A regimen consisting of 2 NTRTIs and an integrase inhibitor is preferred due to minimal drug interaction but any non-protease inhibitor regimen may be used.
    • If on a protease inhibitor based regimen, participant must be switched to a non-protease 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 have an eligible HIV-1 RNA result post change in cART.
    • If already on a stable non-protease inhibitor-based regimen, 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 a non-protease inhibitor-based antiretroviral regimen unless a change is medically necessary.
  • No known allergy or intolerance to components of maraviroc (MVC) or its formulation.
  • No known contraindication to MVC.
  • 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 a non-protease 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.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02741323

Locations

United States, Alabama
UAB HIVTR-CCR5 Non-Network CRS Recruiting
Birmingham, Alabama, United States, 35233-2060
Contact: Tina W. Ayer, B.S., CCRP    205-996-2577    tayer@uabmc.edu
United States, California
UCLA HIVTR-CCR5 Non-Network CRS Recruiting
Los Angeles, California, United States, 90024
Contact: Janette Gadzhyan    310-794-8516    jgadzhyan@mednet.ucla.edu
UCSF HIVTR-CCR5 Non-network CRS Recruiting
San Francisco, California, United States, 94118
Contact: Rodney Rogers    415-514-6454    Rodney.Rogers@ucsf.edu
United States, District of Columbia
Georgetown HIVTR-CCR5 Non-Network CRS Recruiting
Washington, District of Columbia, United States, 20007
Contact: Takada Harris    202-444-6395    Takada.M.Harris@gunet.georgetown.edu
United States, Georgia
Emory HIVTR-CCR5 Non-Network CRS Recruiting
Atlanta, Georgia, United States, 30322
Contact: Susan Mead    404-712-1816    smead@emory.edu
United States, Illinois
Northwestern HIVTR-CCR5 Non-Network CRS Recruiting
Chicago, Illinois, United States, 60611-2927
Contact: Jane Charette, R.N., B.S.N., C.C.R.C.    312-694-0238    jane-charette@northwestern.edu
United States, Maryland
Univ. of Maryland HIVTR-CCR5 Non-Network CRS Recruiting
Baltimore, Maryland, United States, 21201
Contact: Amy Nelson, R.N., CCRP    410-706-3243    ANelson@IHV.umaryland.edu
JHU HIVTR-CCR5 Non-Network CRS Recruiting
Baltimore, Maryland, United States, 21287
Contact: Darin Ostrander, Ph.D.    443-742-0256    dostran1@jhmi.edu
United States, New York
Mt. Sinai Med. Ctr. HIVTR-CCR5 Non-Network CRS Recruiting
New York, New York, United States, 10029
Contact: Brandy Haydel    212-241-0255    brandy.haydel@mountsinai.org
United States, Pennsylvania
Univ. of Penn HIVTR-CCR5 Non-network CRS Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Maryann Najdzinowicz    215-662-4007    maryann.najdzinowicz@uphs.upenn.edu

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator: Peter Stock, MD, PhD University of California, San Francisco
More Information

More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT02741323   History of Changes  
Other Study ID Numbers: HIVTR-CCR5  
  20730  
Study First Received: April 13, 2016  
Last Updated: November 20, 2017  

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

HIV-infected with end-stage kidney disease

Additional relevant MeSH terms:
HIV Infections
Kidney Diseases
Maraviroc
Calcineurin Inhibitors

ClinicalTrials.gov processed this data on December 18, 2017
This information is provided by ClinicalTrials.gov.