Maraviroc Plus Darunavir/Ritonavir for Treatment-Naïve Patients Infected With R5-tropic HIV-1 (MIDAS)

This study has been completed.
Sponsor:
Collaborators:
Pfizer
Tibotec, Inc
Information provided by (Responsible Party):
Babafemi Taiwo, Northwestern University
ClinicalTrials.gov Identifier:
NCT00993148
First received: October 8, 2009
Last updated: August 26, 2014
Last verified: August 2014

October 8, 2009
August 26, 2014
May 2010
April 2013   (final data collection date for primary outcome measure)
Percentage of Participants With Plasma HIV-1 RNA >50 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Percentage of participants with confirmed plasma HIV-1 RNA > 50 copies/mL
Proportion of subjects with confirmed plasma HIV-1 RNA > 50 copies/mL [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00993148 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Virologic Failure or Off Study Treatment Regimen [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Percentage of participants with virologic failure (confirmed plasma HIV-1 RNA > 50 copies/mL) or off study treatment regimen (composite end point)
  • Percentage of Participants With Plasma HIV-1 RNA >50 Copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Percentage of participants with confirmed plasma HIV-1 RNA level >50 copies/mL
  • Signs/Symptoms or Laboratory Toxicities of Grade 3 or Higher [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
    Signs/symptoms or laboratory toxicities of Grade 3 or higher, or of any grade which led to a permanent change or discontinuation of study treatment regimen
  • Drug Resistance Mutations and Co-receptor Tropism Assessed by Trofile ES [ Time Frame: At study entry and at the time of virologic failure ] [ Designated as safety issue: No ]
  • Drug Adherence, Number of Participants With Missed Doses [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Drug adherence, assessed as number of participants with missed doses over four-day recall
  • Trough Concentrations (Ctrough) of Maraviroc [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Average trough concentration (Ctrough) of maraviroc
  • Median CD4 Count Change From Baseline [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    Median changes from baseline in peripheral CD4+ T-cell count
  • Proportion of Participants With Plasma HIV-1 RNA >50 Copies/mL [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
    Proportion of participants with confirmed plasma HIV-1 RNA level >50 copies/mL
  • Proportion of subjects with virologic failure or off study treatment regimen (composite end point) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Dynamics of plasma HIV RNA decay measured on Days 7 and 14 in all subjects and additional sampling on days 2, 4, and 10 in a subset of 15 subjects [ Time Frame: Days 2,4,7,10,14 ] [ Designated as safety issue: No ]
  • Proportion of subjects with confirmed plasma HIV-1 RNA > 1000 copies/mL [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Proportion of subjects with confirmed plasma HIV-1 RNA level confirmed >400 copies/mL [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Proportion of subjects with confirmed plasma HIV-1 RNA level confirmed >400 copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Proportion of subjects with confirmed plasma HIV-1 RNA level >50 copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Signs/symptoms or laboratory toxicities of Grade 3 or higher, or of any grade which led to a permanent change or discontinuation of study treatment regimen [ Time Frame: Through 48 weeks ] [ Designated as safety issue: Yes ]
  • Drug resistance mutations and co-receptor tropism assessed by Trofile ES [ Time Frame: At study entry and at the time of virologic failure ] [ Designated as safety issue: No ]
  • Evolution of CXCR4 and dual/mixed HIV during the early phase of viral decay [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Drug adherence, assessed as number of missed doses over four-day recall [ Time Frame: Day 14 and weeks 4, 12, 24, and 48 ] [ Designated as safety issue: No ]
  • Trough concentrations (Cmin) of maraviroc and darunavir and associations of these PK parameters with efficacy outcome measures and adherence assessments [ Time Frame: Day 14 and weeks 4, 12, 24, and 48 and at virologic failure ] [ Designated as safety issue: No ]
  • Change in fasting lipids [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Subject-specific changes from baseline (average of pre-entry and entry) in peripheral CD4+ T-cell count [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Subject-specific changes from baseline (average of pre-entry and entry) in CD4+ and CD8+ T-cell subsets [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change in markers of inflammation, immune activation and coagulation [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Maraviroc Plus Darunavir/Ritonavir for Treatment-Naïve Patients Infected With R5-tropic HIV-1
Maraviroc Plus Darunavir/Ritonavir Study for Treatment-Naïve Patients Infected With R5-tropic HIV-1 Based on Enhanced Sensitivity Trofile

The objective of this study is to evaluate the safety and efficacy of a novel combination antiretroviral therapy regimen consisting of maraviroc plus darunavir/ritonavir in treatment-naive patients infected with R5-tropic HIV-1. The hypothesis is that in treatment-naive subjects infected with R5-tropic HIV-1, combination antiretroviral therapy with maraviroc plus darunavir/ritonavir is well tolerated and efficacious.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV-1 Infection
  • HIV Infections
  • Drug: maraviroc
    150 mg tab by mouth once daily for 96 weeks
    Other Name: Selzentry
  • Drug: darunavir
    800 mg tab by mouth once daily for 96 weeks
    Other Name: Prezista
  • Drug: ritonavir
    100 mg capsule by mouth once daily for 96 weeks
    Other Name: norvir
Experimental: Maraviroc plus darunavir/ritonavir
Single arm open label trial of maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily for 96 weeks
Interventions:
  • Drug: maraviroc
  • Drug: darunavir
  • Drug: ritonavir
Taiwo B, Acosta EP, Ryscavage P, Berzins B, Lu D, Lalezari J, Castro J, Adeyemi O, Kuritzkes DR, Eron JJ, Tsibris A, Swindells S. Virologic response, early HIV-1 decay, and maraviroc pharmacokinetics with the nucleos(t)ide-free regimen of maraviroc plus darunavir/ritonavir in a pilot study. J Acquir Immune Defic Syndr. 2013 Oct 1;64(2):167-73. doi: 10.1097/QAI.0b013e3182a03d95.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
April 2013
April 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV-1 infection, as documented by any licensed HIV test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA any time prior to study entry
  • Plasma HIV-1 RNA 5, 000 to 500,000 copies/mL obtained within 90 days prior to study entry
  • Exclusive R5 tropism based on enhanced sensitivity Trofile assay done within 90 days prior to entry
  • CD4 cell count > 100 cells/mm3 within 90 days prior to study entry
  • HIV genotype (for RT and protease) performed at any time before study entry (Subjects with single or combination NNRTI or NRTI RAM(s) at screening are permitted)
  • ARV drug-naïve, defined as no previous ARV treatment at any time prior to study entry
  • Negative result from a hepatitis B surface antigen test performed within 90 days prior to study entry
  • Negative result from a hepatitis C antibody test performed within 90 days prior to study entry
  • Laboratory values obtained within 30 days prior to study entry:

    • ANC >=750/mm3
    • Hemoglobin >=10 g/dL
    • Platelets >=50,000/mm3
    • AST (SGOT), ALT (SGPT), and alkaline phosphatase <=5 x ULN
    • Calculated creatinine clearance (CrCl) >=30 mL/min, as estimated by the Cockcroft-Gault equation*
  • Negative serum or urine pregnancy test within 48 hours prior to study entry for women with reproductive potential
  • If participating in sexual activity that could lead to pregnancy, the study subjects with reproductive potential must use one form of contraceptive while receiving protocol-specified medications and for 60 days after stopping the medications.
  • Men and women age >=18 years
  • Ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria:

  • Serious illness requiring systemic treatment and/or hospitalization until candidate 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
  • Screening HIV genotype obtained any time prior to study entry with any DRV RAM (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, and L89V)
  • Treatment within 30 days prior to study entry with immune modulators such as systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF), erythropoietin, or any investigational therapy. NOTE: Subjects receiving stable physiologic glucocorticoid doses (defined as prednisone ≤10 mg/day [or equivalent] as a stable or tapering dose) are permitted. Subjects receiving corticosteroids for acute therapy for PCP or asthma exacerbation, or receiving a short course (defined as ≤2 weeks of pharmacologic glucocorticoid therapy) are permitted
  • Breast-feeding
  • Requirement for any medication that is prohibited with a study medication
  • Known allergy/sensitivity to study drugs or their formulations. A history of sulfa allergy is not an exclusion
  • Active drug or alcohol use or dependence that could interfere with adherence to study requirements
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00993148
MIDAS
Yes
Babafemi Taiwo, Northwestern University
Northwestern University
  • Pfizer
  • Tibotec, Inc
Principal Investigator: Babafemi Taiwo, MD Northwestern University
Northwestern University
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP