Clinical trial NCT00993148: Maraviroc Plus Darunavir/Ritonavir for Treatment-Naïve Patients Infected With R5-tropic HIV-1
Official title: Maraviroc Plus Darunavir/Ritonavir Study for Treatment-Naïve Patients Infected With R5-tropic HIV-1 Based on Enhanced Sensitivity Trofile
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
HIV Infections
Keywords: Treatment naive
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Tibotec, Inc
First posted: 2009-10-12
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants With Plasma HIV-1 RNA >50
timeFrame: 24 weeks
Secondary outcomes:
measure: Percentage of Participants With Virologic Failure or Off Study Treatment Regimen
timeFrame: 24 weeks
measure: Percentage of Participants With Plasma HIV-1 RNA >50 Copies/mL
timeFrame: 48 weeks
measure: Signs/Symptoms or Laboratory Toxicities of Grade 3 or Higher
timeFrame: 96 weeks
measure: Drug Resistance Mutations and Co-receptor Tropism Assessed by Trofile ES
timeFrame: At study entry and at the time of virologic failure
measure: Drug Adherence, Number of Participants With Missed Doses
timeFrame: Week 24
measure: Trough Concentrations (Ctrough) of Maraviroc
timeFrame: 24 hours
measure: Median CD4 Count Change From Baseline
timeFrame: 96 weeks
measure: Proportion of Participants With Plasma HIV-1 RNA >50 Copies/mL
timeFrame: 96 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: CORECenter
state: Illinois
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
Study officials:
affiliation: Northwestern University
name: Babafemi Taiwo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.