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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; HIV-1 Infection
• Intervention / Treatment: Drug: maraviroc; Drug: darunavir; Drug: ritonavir

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States
      • Quest Clinical Research
  • Florida
    • Miami, Florida, United States
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • CORECenter
  • Nebraska
    • Omaha, Nebraska, United States
      • University of Nebraska

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: maraviroc; 150 mg tab by mouth once daily for 96 weeks; Other Names: Selzentry; Drug: darunavir; 800 mg tab by mouth once daily for 96 weeks; Other Names: Prezista; Drug: ritonavir; 100 mg capsule by mouth once daily for 96 weeks; Other Names: norvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Plasma HIV-1 RNA >50	Percentage of participants with confirmed plasma HIV-1 RNA > 50 copies/mL	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Virologic Failure or Off Study Treatment Regimen	Percentage of participants with virologic failure (confirmed plasma HIV-1 RNA > 50 copies/mL) or off study treatment regimen (composite end point)	24 weeks
Percentage of Participants With Plasma HIV-1 RNA >50 Copies/mL	Percentage of participants with confirmed plasma HIV-1 RNA level >50 copies/mL	48 weeks
Signs/Symptoms or Laboratory Toxicities of Grade 3 or Higher	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	96 weeks
Drug Resistance Mutations and Co-receptor Tropism Assessed by Trofile ES		At study entry and at the time of virologic failure
Drug Adherence, Number of Participants With Missed Doses	Drug adherence, assessed as number of participants with missed doses over four-day recall	Week 24
Trough Concentrations (Ctrough) of Maraviroc	Average trough concentration (Ctrough) of maraviroc	24 hours
Median CD4 Count Change From Baseline	Median changes from baseline in peripheral CD4+ T-cell count	96 weeks
Proportion of Participants With Plasma HIV-1 RNA >50 Copies/mL	Proportion of participants with confirmed plasma HIV-1 RNA level >50 copies/mL	96 weeks

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: Pfizer; Tibotec, Inc
• Investigators: Principal Investigator: Babafemi Taiwo, MD, Northwestern University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: October 8, 2009
• First Submitted That Met QC Criteria: October 9, 2009
• First Posted (Estimate): October 12, 2009

Study Record Updates

• Last Update Posted (Estimate): September 5, 2014
• Last Update Submitted That Met QC Criteria: August 26, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Treatment naive
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Ritonavir; Maraviroc; Darunavir
• Other Study ID Numbers: MIDAS