Trial record 12 of 28 for:    " July 06, 2011":" August 05, 2011"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Bone, Immunologic, and Virologic Effects of a Antiretroviral Regimen

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01400412
First received: July 21, 2011
Last updated: October 17, 2013
Last verified: October 2013
  Purpose

There are now several HIV treatment options for a person with HIV infection who has not yet been treated. Most people who receive treatment and take their medications as directed have a good result. This is usually determined by measuring the amount of HIV in the blood (viral load). The best response is when HIV cannot be found (less than 50 copies/mL) in the blood. However, it has recently become clear that some people with HIV who are receiving effective HIV drugs continue to have more health problems than people without HIV infection. Sometimes, there is damage to organs in the body, including bone, kidneys, and the brain.

The main purpose of this study is to compare the effects on bones of the following two drug combinations:

  • maraviroc (MVC), emtricitabine (FTC), plus darunavir/ritonavir (DRV/r)
  • tenofovir (TDF) plus emtricitabine (FTC) plus darunavir/ritonavir (DRV/r)

Additional reasons this study is being done are the following:

  • To see how the drug combinations affect the brain and kidneys.
  • To see how well the drug combinations lower the HIV viral load.
  • To see how safe the drug combinations are, how well people are able to take the study drug combinations, and how well their immune systems respond to the study drugs.
  • To see how well the drug combinations get into the blood.

Condition Intervention Phase
HIV-1 Infection
Drug: Darunavir
Drug: Ritonavir
Drug: Tenofovir disoproxil fumarate
Drug: Emtricitabine
Drug: Placebo for Tenofovir disoproxil fumarate
Drug: Placebo for Maraviroc
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2b, Double-Blind, Placebo-Controlled, Exploratory Randomized Trial to Determine the Bone, Immunologic, Virologic, and Neurocognitive Effects of a Novel Maraviroc-Containing Antiretroviral Regimen in Treatment-Naïve Patients Infected With R5-Tropic HIV-1

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Percent change in total hip bone mineral density (BMD) [ Time Frame: At week 48 ] [ Designated as safety issue: No ]
    The baseline value is defined to be the last available measure taken before or on treatment initiation date, and the week 48 measure has to be taken between week 44 (308 days) and week 52 (364 days), inclusive, after treatment initiation.


Secondary Outcome Measures:
  • Percent change in lumbar spine bone mineral density from baseline to week 48 [ Time Frame: At week 48 ] [ Designated as safety issue: No ]
  • Change in bone mineral density of hip from baseline to week 48 [ Time Frame: At week 48 ] [ Designated as safety issue: No ]
  • Change in bone mineral density of spine from baseline to week 48 [ Time Frame: At week 48 ] [ Designated as safety issue: No ]
  • Number of bone fractures [ Time Frame: Throughout the study to week 48 ] [ Designated as safety issue: No ]
  • Percent change in expression of CD38 on CD8+ T cells from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Percent change in expression of HLA-DR on CD8+ T cells from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Percent change in expression of Ki67 on CD8+ T cells from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Percent change in expression of CD28 on CD8+ T cells from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Percent change in expression of CD57 on CD8+ T cells from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Percent change in expression of PK1 on CD8+ T cells from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Change in levels of IL-6 from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Change in level of hsCRP from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Change in levels of plasma LPS from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Change in levels of soluble CD14 from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Change in level of peripheral β7hi CD4+ T cells from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Change in levels of D-dimer from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • CD4+ T-cell change from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • CD8+ T-cell change from baseline [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Time from randomized treatment initiation to virologic failure [ Time Frame: At week 24 and 48 ] [ Designated as safety issue: No ]
  • Time from randomized treatment initiation to discontinuation of any component of randomized regimen [ Time Frame: Throughout the study to week 48 ] [ Designated as safety issue: Yes ]
  • Number of subjects who died, or experienced AIDS defining events or targeted non-AIDS defining events [ Time Frame: Throughout the study to week 48 ] [ Designated as safety issue: Yes ]
  • Number of subjects who developed grade 3 or 4 sign or symptom or laboratory toxicity [ Time Frame: Throughout the study to week 48 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 254
Study Start Date: December 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: DRV/r + MVC + FTC + TDF placebo
Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD
Drug: Darunavir
Darunavir will be administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet becomes available, it will be substituted for the two 400 mg tablet.
Drug: Ritonavir
Ritonavir will be administered orally together with darunavir as one 100 mg tablet once daily with food.
Drug: Emtricitabine
Emtricitabine will be administered orally once a day as one 200 mg capsule.
Drug: Placebo for Tenofovir disoproxil fumarate
Placebo for tenofovir disoproxil fumarate will be administered orally once a day as one tablet.
Experimental: Arm B: DRV/r + TDF + FTC + MVC placebo
Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD
Drug: Darunavir
Darunavir will be administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet becomes available, it will be substituted for the two 400 mg tablet.
Drug: Ritonavir
Ritonavir will be administered orally together with darunavir as one 100 mg tablet once daily with food.
Drug: Tenofovir disoproxil fumarate
Tenofovir disoproxil fumarate will be administered orally as one 300 mg tablet once a day.
Drug: Emtricitabine
Emtricitabine will be administered orally once a day as one 200 mg capsule.
Drug: Placebo for Maraviroc
Placebo for maraviroc will be administered orally once a day as one 150 mg tablet.

  Eligibility

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

Inclusion Criteria:

  • HIV-1 infection
  • No evidence of exclusionary resistance mutations defined as evidence of any major NRTI mutation according to the current IAS list of HIV-1 Resistance Mutations Associated with Drug Resistance, or any DRV RAMs (refer to the A5303 PSWP for a list of these mutations) on any genotype; or evidence of significant NRTI or DRV resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations are not exclusionary.
  • ARV drug-naïve, defined as </=10 days of ART at any time prior to study entry, except in the instances defined in section 4.1.3 of the protocol.
  • R5-only tropism based on Trofile testing performed within 90 days prior to study entry.
  • Screening HIV-1 RNA >1000 copies/mL obtained within 90 days prior to study entry by any FDA-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA certification or its equivalent.
  • Known hepatitis C virus (HCV) antibody status (performed at any laboratory that has a CLIA certification or its equivalent).
  • Certain laboratory values obtained within 60 days prior to study entry, as defined in section 4.1.7 of the protocol.
  • For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of ≤25 mIU/mL within 72 hours prior to study entry.
  • Female subjects of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception (as defined in section 4.1.9.1 of the protocol) while receiving the study drugs and for 6 weeks after stopping the medications.
  • Female subjects who are not of reproductive potential or whose male partner(s) has azoospermia are eligible to take study drugs without the use of contraceptives.
  • Ability and willingness of subject or legal guardian/representative to give written informed consent.
  • Willingness to undergo neuropsychological testing.
  • DXA scan performed after confirmation of the subject's eligibility by Trofile testing but no more than 4 weeks prior to randomization.

Exclusion Criteria:

  • Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
  • New use of hormonal therapies within 6 months prior to study entry. (Stable therapy for ≥6 months is permitted.)
  • New use of oral contraceptive pills (OCPs) in the past 3 months. (Stable therapy for ≥3 months is permitted.)
  • Any oral, intravenous, or inhaled steroids within 30 days prior to study entry. (Intranasal steroids and topical corticosteroids are allowed.)
  • Known allergy/sensitivity to study drugs or their formulations. (A history of sulfa allergy is not an exclusionary condition.)
  • Known hypersensitivity to soy lecithin.
  • Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry. (Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) are not exclusionary conditions.)
  • Requirement for any current medications that are prohibited with any study drugs. (Prohibited medications must be discontinued at least 30 days prior to entry. Refer to the A5303 PSWP for a list of prohibited medications.)
  • The presence of decompensated cirrhosis.
  • A history of or current, active HBV infection defined as positive hepatitis B surface antigen test (or positive HBV DNA in subjects with isolated HBcAb positivity, defined as negative HBsAg, negative HBsAb, and positive HBcAb) at screening.
  • Current or prior use of biphosphonates, teriparatide, raloxifene, or denosumab.
  • Weight >300 lbs (exceeds weight limit of DXA scanners).
  • History after 18 years of age of fracture of the spine, hip, wrist, or other site thought to be related to osteoporosis or bone fragility.
  • Currently breastfeeding.
  • Any active psychiatric illness including schizophrenia, severe depression, or severe bipolar affective disorder that, in the opinion of the investigator, could confound the analysis of the neurological examination or neuropsychological test results.
  • Active drug or alcohol abuse that, in the investigator's opinion, could prevent compliance with study procedures or confound the analysis of study endpoints.
  • Active brain infection (except for HIV-1), fungal meningitis, toxoplasmosis, central nervous system (CNS) lymphoma, brain neoplasm, or space-occupying brain lesion requiring acute or chronic therapy.
  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: NCT01400412

Locations
United States, Alabama
Alabama Therapeutics CRS (5801)
Birmingham, Alabama, United States, 35294
United States, California
UCLA CARE Center CRS (601)
Los Angeles, California, United States, 90095
Stanford CRS (501)
Palo Alto, California, United States, 94304
Ucsd, Avrc Crs (701)
San Diego, California, United States, 92103
Ucsf Aids Crs (801)
San Francisco, California, United States, 94110
Harbor-UCLA Med. Ctr. CRS (603)
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS (6101)
Aurora, Colorado, United States, 80045
United States, Illinois
Northwestern University CRS (2701)
Chicago, Illinois, United States, 60611
Rush Univ. Med. Ctr. ACTG CRS (2702)
Chicago, Illinois, United States, 60612
United States, Massachusetts
Brigham and Women's Hosp. ACTG CRS (107)
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital ACTG CRS (101)
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington U CRS (2101)
St. Louis, Missouri, United States, 63110
United States, New Jersey
New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)
Newark, New Jersey, United States, 07103
United States, New York
AIDS Care CRS (1108)
Rochester, New York, United States, 14642
Univ. of Rochester ACTG CRS (1101)
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs (3201)
Chapel Hill, North Carolina, United States, 27516
Duke Univ. Med. Ctr. Adult CRS (1601)
Durham, North Carolina, United States, 27710
Moses H. Cone Memorial Hospital CRS (3203)
Greensboro, North Carolina, United States, 27401
United States, Ohio
Univ. of Cincinnati CRS (2401)
Cincinnati, Ohio, United States, 45267
The Ohio State Univ. AIDS CRS (2301)
Columbus, Ohio, United States, 43210
United States, Tennessee
Vanderbilt Therapeutics CRS (3652)
Nashville, Tennessee, United States, 37232
United States, Texas
Houston AIDS Research Team CRS (31473)
Houston, Texas, United States, 77030
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Babafemi Taiwo, MBBS, MD Northwestern University CRS
  More Information

No publications provided

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01400412     History of Changes
Other Study ID Numbers: ACTG A5303, 1U01AI068636
Study First Received: July 21, 2011
Last Updated: October 17, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
Darunavir
Tenofovir
Tenofovir disoproxil
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014