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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
HIV-1 Infection; HIV Infections	Drug: maraviroc; Drug: darunavir; Drug: ritonavir	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	25 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Maraviroc Plus Darunavir/Ritonavir Study for Treatment-Naïve Patients Infected With R5-tropic HIV-1 Based on Enhanced Sensitivity Trofile
Study Start Date :	May 2010
Actual Primary Completion Date :	April 2013
Actual Study Completion Date :	April 2013

Arms and Interventions

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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 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

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants With Plasma HIV-1 RNA >50 [ Time Frame: 24 weeks ]
   Percentage of participants with confirmed plasma HIV-1 RNA > 50 copies/mL

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

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

Sponsors and Collaborators

Northwestern University

Pfizer

Tibotec, Inc

Investigators

Principal Investigator:	Babafemi Taiwo, MD	Northwestern University

More Information

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Publications of Results:

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.

Responsible Party:	Babafemi Taiwo, Associate Professor, Northwestern University
ClinicalTrials.gov Identifier:	NCT00993148 History of Changes
Other Study ID Numbers:	MIDAS
First Posted:	October 12, 2009
Results First Posted:	August 19, 2014
Last Update Posted:	September 5, 2014
Last Verified:	August 2014

Keywords provided by Babafemi Taiwo, Northwestern University:

Treatment naive

Additional relevant MeSH terms:

Infection; Communicable Diseases; 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	Maraviroc; HIV Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; CCR5 Receptor Antagonists