Maraviroc Plus Darunavir/Ritonavir for Treatment-Naïve Patients Infected With R5-tropic HIV-1 - Full Text View

Sponsor:	Northwestern University
Collaborators:	Pfizer Tibotec, Inc
Information provided by:	Northwestern University
ClinicalTrials.gov Identifier:	NCT00993148

Purpose

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	Intervention	Phase
HIV-1 Infection HIV Infections	Drug: maraviroc Drug: darunavir Drug: ritonavir	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Maraviroc Plus Darunavir/Ritonavir Study for Treatment-Naïve Patients Infected With R5-tropic HIV-1 Based on Enhanced Sensitivity Trofile

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir Darunavir Maraviroc Darunavir ethanolate

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

Proportion of subjects with confirmed plasma HIV-1 RNA > 50 copies/mL [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	25
Study Start Date:	December 2009
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Intervention Details:

150 mg tab by mouth once daily for 48 weeks

800 mg tab by mouth once daily for 48 weeks

100 mg capsule by mouth once daily for 48 weeks

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00993148

Contacts

Contact: Baiba Berzins, MPH

(312) 695-5012

baiba@northwestern.edu

Locations

United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

Pfizer

Tibotec, Inc

Investigators

Principal Investigator:

Babafemi Taiwo, MD

Northwestern University

More Information

No publications provided

Responsible Party:	Northwestern University ( Babafemi Taiwo, MD )
Study ID Numbers:	MIDAS
Study First Received:	October 8, 2009
Last Updated:	November 6, 2009
ClinicalTrials.gov Identifier:	NCT00993148 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Northwestern University:

Treatment naive

Additional relevant MeSH terms:

Communicable Diseases
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Darunavir
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
RNA Virus Infections
HIV Protease Inhibitors
Anti-HIV Agents

Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on November 30, 2009