FTC/RPV/TDF on T-Cell Activation, CD4 Cell Count, Inflammatory Biomarkers and Viral Reservoir

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by AIDS Clinical Trials Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01777997
First received: January 10, 2013
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

This study is being done with people who are infected with HIV, but do not show any signs of having HIV. They are also feeling well without taking HIV medication and have low or undetectable levels of the virus in the blood. The purpose of this study is to see if taking HIV medication (antiretroviral therapy [ART]) will reduce immune activation (a signal that the body is fighting an infection) in people who have HIV, but do not show symptoms. Also this study will help determine how safe the drug is and how well people react to the drug.

For this study, the following antiretroviral therapy (ART) will be provided in the form of a single tablet that contains three different drugs: emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF). These drugs are combined as one tablet which is approved by the Food and Drug Administration (FDA) as a single pill to treat HIV infection. The HIV medication provided is one of the recommended treatments for HIV, including people with low viral loads (how much HIV you have in your body) who are taking HIV drugs for the first time. The risks seen with this HIV medication are the same that one would encounter when taking these drugs outside of the study.


Condition Intervention Phase
HIV-1 Infection
Drug: Emtricitabine/rilpivirine/tenofovir disoproxil fumarate
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Single-Arm, Open-Label Study to Evaluate the Effect of Fixed-Dose Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate on T-Cell Activation, Absolute CD4+ T-Cell Count, Inflammatory Biomarkers and Viral Reservoir in Treatment-Naïve HIV-1 Controllers

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Change in levels of CD8+ T-cell activation (defined as the percentage HLA-DR+/CD38+) from baseline to weeks 24 and 48 on ART [ Time Frame: From baseline to week 48 on ART ] [ Designated as safety issue: No ]
    Change from baseline (average of study entry and study week 12), estimated with a repeated measures analysis (weeks 24 and 48 on ART) using generalized estimating equations (GEE)


Secondary Outcome Measures:
  • Plasma HIV-1 RNA level measured by Single Copy Assay (SCA) as above versus below the limit of the assay [ Time Frame: At baseline and weeks 4, 12, 24, 36 and 48 on ART ] [ Designated as safety issue: No ]
    At a specific week, the proportion of subjects with HIV-1 RNA by SCA < assay limit

  • Change in CD4+ T-cell count [ Time Frame: From baseline to weeks 12, 24, 36 and 48 on ART ] [ Designated as safety issue: No ]
    Change equals each specific week CD4+ T-cell count, respectively, minus the baseline CD4+ T-cell count (average of study entry and study week 12)

  • Change in levels of CD8+ T-cell activation [ Time Frame: From baseline to weeks 4, 24 and 48 on ART ] [ Designated as safety issue: No ]
    Change equals each specific week percentage, respectively, minus the baseline percentage (average of study entry and study week 12)

  • Change in levels of CD4+ T-cell activation (defined as the percentage HLA-DR+/CD38+) [ Time Frame: From baseline to weeks 4, 24 and 48 on ART ] [ Designated as safety issue: No ]
    Change equals each specific week percentage, respectively, minus the baseline percentage (average of study entry and study week 12)

  • Change in levels of Interleukin (IL)-6 [ Time Frame: From baseline to weeks 4, 24 and 48 on ART ] [ Designated as safety issue: No ]
    Change equals each specific week result, respectively, minus the baseline result (average of study entry and study week 12)

  • Change in levels of 2D-dimer [ Time Frame: From baseline to weeks 4, 24 and 48 on ART ] [ Designated as safety issue: No ]
    Change equals each specific week result, respectively, minus the baseline result (average of study entry and study week 12)

  • Change in quality of life (QoL) index [ Time Frame: From baseline to weeks 4, 24 and 48 on ART ] [ Designated as safety issue: No ]
    The QoL index is obtained by averaging the five responses on the Euro-Quality of Life questionnaire (EQ-5D). Change equals each specific week index, respectively, minus the baseline index (average of study entry and study week 12)

  • Number of subjects who experience Grade 3 or 4 signs and symptoms or laboratory abnormalities, diagnoses, or other serious adverse events (SAEs) [ Time Frame: From baseline through week 48 on ART ] [ Designated as safety issue: Yes ]
    Grading uses the Division of AIDS (DAIDS) 2004 (clarification 2009) Severity of Adverse Events Table, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life-threatening.


Estimated Enrollment: 57
Study Start Date: February 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fixed dose combination FTC/RPV/TDF for 48 or 96 weeks

Step 1 From entry through week 12 the participants will receive no study treatment. From week 12 through week 60, the participants will receive one FTC/RPV/TDF (200mg/25mg/300mg) tablet orally once daily with a meal.

Step 2 (Optional) From week 60 through Week 108, the participants will either receive one FTC/RPV/TDF (200mg/25mg/300mg)table orally once daily with a meal or no study treatment.

Drug: Emtricitabine/rilpivirine/tenofovir disoproxil fumarate
Other Names:
  • FTC/RPV/TDF
  • Complera

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Step 1

  • HIV-1 infection
  • ART-naïve defined as ≤7 days of ARV treatment at any time prior to entry Documentation of HIV-1 RNA <500 copies/mL verified by at least two measurements prior to the screening RNA specimen
  • Screening HIV-1 RNA <500 copies/mL using an US FDA-approved assay obtained within 60 days prior to study entry by any laboratory that has a CLIA certification or its equivalent
  • Laboratory values obtained within 60 days prior to entry by any laboratory that has a CLIA certification or its equivalent:

    • Absolute neutrophil count (ANC) >=500/mm3
    • Hemoglobin >=8.0 g/dL
    • Platelet count >=40,000/mm3
    • Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and alkaline phosphatase <=5 X Upper Limit of Normal (ULN)
    • Total bilirubin <=2.5 X ULN
    • Calculated creatinine clearance (CrCl) >=60 mL/min
  • For females of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to study entry by any laboratory that has a CLIA certification or its equivalent. Female subjects of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable form of contraceptive (ie, condoms (male or female) with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an IUD; or hormone-based contraceptive) while receiving the protocol-specified treatment and for 6 weeks after stopping the medications.
  • No evidence of any exclusionary resistance mutations based on results from any genotype assay from any laboratory that has a CLIA certification or its equivalent

Step 2

  • Completion of Step 1.
  • Ability and willingness of subject to choose to receive either open-label ART FDC (FTC/RPV/TDF) or no study treatment for an additional 48 weeks.
  • For females of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to the week 60 visit by any laboratory that has a CLIA certification or its equivalent.

Exclusion Criteria:

Step 1

  • Chronic hepatitis B virus (HBV) infection (documented by hepatitis B surface antigen (HBsAg) seropositivity)
  • Breastfeeding
  • Use of immunomodulators (eg, interleukins, interferons, cyclosporine), topical imiquimod, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry or plans to start immunomodulators, topical imiquimod, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy during the study
  • Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry
  • Symptomatic HIV disease and/or AIDS-defining illness.
  • Vaccinations within 7 days prior to study entry
  • Plans to initiate hepatitis C treatment during the study
  • Perinatally-acquired HIV
  • Use of any of the following medications within 7 days prior to study entry:

    • St. John's wort (Hypercium perforatum)
    • Anticonvulsants (eg, oxacarbazepine, phenobarbital, phenytoin)
    • Anti-infectives (eg, rifabutin, rifampin, rifapentine)
    • Corticosteroids (eg, dexamethasone (more than 1 dose))
    • Proton pump inhibitors (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)

Step 2

  • Plans to start immunomodulators, topical imiquimod, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy during Step 2 of the study.
  • Plans to initiate hepatitis C treatment during Step 2 of the study. NOTE: Please refer to the protocol for detailed eligibility criteria.
  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: NCT01777997

  Hide Study Locations
Locations
United States, Alabama
Alabama Therapeutics CRS (5801) Recruiting
Birmingham, Alabama, United States, 35294
Contact: Karen Savage, BSN    205-975-7925    kgsavage@uab.edu   
Principal Investigator: Victoria Johnson, MD         
United States, California
UCLA CARE Center CRS (601) Recruiting
Los Angeles, California, United States, 90035
Contact: Maricela Gonzalez    310-557-3798    mmgonzalez@mednet.ucla.edu   
Principal Investigator: Judith S. Currier, MD, MSc         
Ucsd, Avrc Crs (701) Recruiting
San Diego, California, United States, 92103
Contact: Jill Kunkel    619-543-3094    jkunkel@ucsd.edu   
Principal Investigator: Constance A. Benson, MD         
United States, Colorado
University of Colorado Hospital CRS (6101) Recruiting
Aurora, Colorado, United States, 80045
Contact: Mary G Ray, RN, MSN    303-724-0712    graham.ray@uchsc.edu   
Principal Investigator: Thomas B Campbell, MD         
United States, District of Columbia
Georgetown University CRS (GU CRS) (1008) Recruiting
Washington, District of Columbia, United States, 20007
Contact: Abimael Lopez    202-687-7387    al374@georgetown.edu   
Principal Investigator: Princy N. Kumar, MD         
United States, Georgia
The Ponce de Leon Ctr. CRS (5802) Recruiting
Atlanta, Georgia, United States, 30308
Contact: Ericka Patrick    404-616-6313    erpatri@emory.edu   
Principal Investigator: Carlos del Rio, MD         
United States, Illinois
Northwestern University CRS (2701) Recruiting
Chicago, Illinois, United States, 60611
Contact: Baiba Berzins, MPH    312-695-5012    baiba@northwestern.edu   
Principal Investigator: Babafemi Taiwo, MBBS, MD         
United States, Maryland
IHV Baltimore Treatment CRS (4651) Recruiting
Baltimore, Maryland, United States, 21201
Contact: Gregory Brogden, BS    410-706-1660    gbrogden@ihv.umaryland.edu   
Principal Investigator: Charles Davis, MD         
Beth Israel Deaconess Medical Center ACTG CRS (103) Recruiting
Boston, Maryland, United States, 02215
Contact: Andrea Kershaw, ANP    617-632-7627    akersha1@bidmc.harvard.edu   
Principal Investigator: Mary Albrecht, MD         
United States, Massachusetts
Bmc Actg Crs (104) Recruiting
Boston, Massachusetts, United States, 02118
Contact: Betsy Adams, RN    617-414-7082    betsy.adams@bmc.org   
Principal Investigator: Paul Skolnik, MD         
Brigham and Women's Hosp. ACTG CRS (107) Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jon Gothing, RN    617-732-5635    jgothing@partners.org   
Principal Investigator: Paul E. Sax, MD         
Massachusetts General Hospital ACTG CRS (101) Recruiting
Boston, Massachusetts, United States, 02114
Contact: Teri Flynn, RN, ANP, MSN    617-724-0072    tflynn@partners.org   
Principal Investigator: Rajesh Gandhi, MD         
United States, Missouri
Washington University CRS (2101) Recruiting
St. Louis, Missouri, United States, 63110
Contact: Michael Klebert, RNC, PhD, ANP    1-314-747-1098    mklebert@im.wustl.edu   
Principal Investigator: Edgar T. Overton, MD         
United States, New York
Bronx-Lebanon Hosp. Ctr. CRS (31469) Recruiting
Bronx, New York, United States, 10457
Contact: Megan A Tuohy, MPH    718-901-6346    mtuohy@bronxleb.org   
Principal Investigator: Edward Telzak, MD         
HIV Prevention & Treatment CRS (30329) Recruiting
New York, New York, United States, 10032
Contact: Steven Chang    212-305-1570    sc1286@columbia.edu   
Principal Investigator: Scott M. Hammer, MD         
Univ. of Rochester ACTG CRS (1101) Recruiting
Rochester, New York, United States, 14642
Contact: Carol Greisberger, RN, BS    585-275-2740    carol_greisberger@urmc.rochester.edu   
Principal Investigator: Amneris Luque, MD         
AIDS Community Health Ctr. ACTG CRS (1108) Recruiting
Rochester, New York, United States, 14604
Contact: Carol Greisberger, RN, CCRC    585-275-2740    Carol_Greisberger@urmc.rochester.edu   
Principal Investigator: Roberto Corales, DO         
United States, North Carolina
Unc Aids Crs (3201) Recruiting
Chapel Hill, North Carolina, United States, 27516
Contact: Cheryl Marcus, RN, BSN    919-843-8761    cjm@med.unc.edu   
Principal Investigator: David Wohl, MD         
Moses H. Cone Memorial Hospital CRS (3203) Recruiting
Greensboro, North Carolina, United States, 27401
Contact: Kim Epperson, RN    336-832-7888    kim.epperson@mosecone.com   
Principal Investigator: Timothy Lane         
Regional Center for Infectious Disease, Wendover Medical Center CRS (3203) Recruiting
Greensboro, North Carolina, United States, 27401
Contact: Kim Epperson, R.N., BSN., CCRC    (336) 832-3262      
United States, Ohio
University of Cincinnati CRS (2401) Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Tammy Mansfield, RN, ACRN    513-584-6040    mansfitl@ucmail.uc.edu   
Principal Investigator: Judith Feinberg, MD         
Case CRS (2501) Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jane Baum, RN    216-844-2546    baum.jane@clevelandactu.org   
Principal Investigator: Michael M. Lederman, MD         
Metro Health CRS (2503) Recruiting
Cleveland, Ohio, United States, 44109
Contact: Julie Ziegler    216-778-7847    jziegler@metrohealth.org   
Principal Investigator: Robert C. Kalayjian, MD         
The Ohio State Univ. AIDS CRS (2301) Recruiting
Columbus, Ohio, United States, 43210
Contact: Todd Lusch, BA    614-293-8112    todd.lusch@osumc.edu   
Principal Investigator: Susan Koletar, MD         
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS (6201) Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joseph Quinn, RN    215-349-8091    joseph.quinn@uphs.upenn.edu   
Principal Investigator: Pablo Tebas, MD         
Pitt CRS (1001) Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Christine A. Tripoli, BSN, RN    412-647-0771    tripolica@upmc.edu   
Principal Investigator: Sharon A. Riddler, MD, MPH         
United States, Rhode Island
The Miriam Hosp. ACTG CRS (2951) Recruiting
Providence, Rhode Island, United States, 02906
Contact: Pamela Poethke, RN    401-793-4971    ppoethke@lifespan.org   
Principal Investigator: Karen T. Tashim, MD         
United States, Texas
Houston AIDS Research Team CRS (31473) Recruiting
Houston, Texas, United States, 77030
Contact: Hilda Cuervo    713-500-6751    Hilda.cuervo@uth.tmc.edu   
Principal Investigator: Roberto C. Arduino, MD         
United States, Washington
University of Washington AIDS CRS (1401) Recruiting
Seattle, Washington, United States, 98104
Contact: Christine Jonsson    206-744-8886    cjonsson@uw.edu   
Principal Investigator: Ann Collier, MD         
Sponsors and Collaborators
AIDS Clinical Trials Group
  More Information

No publications provided

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01777997     History of Changes
Other Study ID Numbers: ACTG A5308, 1U01AI068636
Study First Received: January 10, 2013
Last Updated: June 5, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Emtricitabine
Tenofovir
Tenofovir disoproxil
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 22, 2014