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

HIV Infections Clinical Trial

— MIDAS  

Official title:

Maraviroc Plus Darunavir/Ritonavir Study for Treatment-Naïve Patients Infected With R5-tropic HIV-1 Based on Enhanced Sensitivity Trofile

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00993148
• Other study ID #: MIDAS
• Status: Completed
• Phase: Phase 2
• First received: October 8, 2009
• Last updated: August 26, 2014
• Start date: May 2010
• Est. completion date: April 2013

Study information

• Verified date: August 2014
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• HIV-1 Infection
• Infection

Intervention

Drug:
• maraviroc
150 mg tab by mouth once daily for 96 weeks
• darunavir
800 mg tab by mouth once daily for 96 weeks
• ritonavir
100 mg capsule by mouth once daily for 96 weeks

Locations

Country	Name	City	State
United States	CORECenter	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Miami	Miami	Florida
United States	University of Nebraska	Omaha	Nebraska
United States	Quest Clinical Research	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
Northwestern University	Pfizer, Tibotec, Inc

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Plasma HIV-1 RNA >50	Percentage of participants with confirmed plasma HIV-1 RNA > 50 copies/mL	24 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	Drug Resistance Mutations and Co-receptor Tropism Assessed by Trofile ES		At study entry and at the time of virologic failure	No
Secondary	Drug Adherence, Number of Participants With Missed Doses	Drug adherence, assessed as number of participants with missed doses over four-day recall	Week 24	No
Secondary	Trough Concentrations (Ctrough) of Maraviroc	Average trough concentration (Ctrough) of maraviroc	24 hours	No
Secondary	Median CD4 Count Change From Baseline	Median changes from baseline in peripheral CD4+ T-cell count	96 weeks	No
Secondary	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	No