Clinical trial NCT01199939: A Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients
Official title: A Multicenter, Single Arm, Open-Label Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Human Immunodeficiency Virus (HIV)
Keywords: Human Immunodeficiency Virus
HIV
Etravirine
Darunavir
Prezista
Intelence
Ritonavir
INROADS
Lead sponsor: Tibotec, Inc
Sponsor class: INDUSTRY
Collaborators: name: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
First posted: 2010-09-13
Enrollment: 54
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: This study is a Phase II single arm, open-label, multicenter, study of 50 human immunodeficiency virus-1 (HIV) infected adult patients, all of whom will receive etravirine (ETR) 400mg and DRV/r 800/100mg each given orally once daily. This trial is designed to evaluate the efficacy of the aforementioned ARV regimen, as measured by the percentage of patients with HIV RNA \<50 copies/mL at 48 weeks, in early treatment-experienced HIV-infected patients. In addition to general safety parameter measurements, this trial will also assess changes in metabolic, inflammatory, immune restoration, and bone markers. Screening will occur over a 6-week period. The primary endpoint will be assessed at Week 48, and the treatment period is 48 weeks. The end of study endpoint will be met by either completing the Week 48 visit, or by early termination from the study for any reason.

Detailed description: This study is a Phase II single arm, open-label, multicenter, (all people involved know the identity of the intervention) study of 50 HIV-1 infected adult patients, all of whom will receive ETR 400mg and darunavir (DRV)/r 800/100mg each given orally once daily. This trial is designed to evaluate the efficacy of the aforementioned ARV regimen, as measured by the percentage of patients with HIV ribonucleic acid (RNA) \<50 copies/mL at 48 weeks, in early treatment-experienced HIV-infected patients. In addition to general safety parameter measurements, this trial will also assess changes in metabolic, inflammatory, immune restoration, and bone markers. Screening will occur over a 6-week period. The trial schedule includes a Baseline Visit (Day 1), Open-label Treatment Phase (Weeks 4, 8, 12, 16, 20, 24, 30, 36, 42, 48/ Early Withdrawal) and a Post-treatment Phase (4 Week Follow-Up) visit. In addition, all patients will have two pharmacokinetic (PK) samples drawn at Weeks 4 and 24, A single PK sample will be drawn at Weeks 12, 36, and 48 (or early withdrawal visit). There will also be a substudy conducting 24 hour intensive PK at week 4 for a subset of patients. For patients who consent, genotyping for CYP2C9 and CYP2C19 will be performed at Baseline. A Modified Medication Adherence Self-Report Inventory (M-MASRI) questionnaire will be collected, which is a patient-reported survey to assess adherence to medication taking. The primary endpoint will be assessed at Week 48, and the treatment period is 48 weeks. The end of study endpoint will be met by either completing the Week 48 visit, or by early termination from the study for any reason. ETR 400mg once daily for 48 weeks and DRV 800mg once daily for 48 weeks.

Eligibility criteria: Inclusion Criteria:

* Male or female patients, aged 18 years or above
* Patients with documented HIV-1 infection
* On current HAART regimen for at least 12 weeks continuous duration at screening, and with an HIV-1 plasma viral load above 500 HIV-1 RNA copies/mL by site's currently utilized viral load assay (Note: For the purposes of this study, HAART is defined as treatment with a combination of 3 or more HIV antiretroviral medications from at least 2 different classes of medications (NRTIs, NNRTIs, PIs, integrase inhibitors, CCR5 antagonists, fusion inhibitors))
* No more than 2 previous virologic failures while on PI-containing HAART regimens where virologic failure is generally defined as either a lack of suppression of the subjects' viral load to lower limit of quantification (per standard assay historically used in care) after 24 weeks of treatment or, rebound of a previously suppressed viral load (undetectable per investigator's standard of care) to detectable limits and without demonstrated re-suppression on the same regimen
* Demonstrated phenotypic sensitivity to both etravirine and darunavir based on resistance testing at Screening (FC= 2.9 for etravirine and FC = 10.0 for darunavir using the PhenoSense GT)
* The absence of all of the following Resistance Associated Mutations (RAMS) at baseline: For Darunavir: V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, L89V
* For Etravirine: L100I, E138A, I167V, V179D, V179F, Y181I, Y181V, G190S
* 7. CD4 count = 50 cells/mm3.

Exclusion Criteria:

* Primary HIV-1 infection
* Previously documented HIV-2 infection
* Use of disallowed concomitant therapy

Any condition (including but not limited to alcohol and drug use), which, in the opinion of the investigator, could compromise the patient's safety or adherence to the protocol

* Life expectancy less than 6 months according to the judgment of the investigator
* Patient has any currently active AIDS defining illness (Category C conditions according to the Center for Disease Control \[CDC\] Classification System for HIV infection 1993
* with the following exceptions, which must be discussed with the sponsor prior to enrollment: Stable cutaneous Kaposi's Sarcoma (i.e., no pulmonary or gastrointestinal involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the trial period
* Wasting syndrome due to HIV infection if, in the investigator's opinion, it is not actively progressive and its treatment does not require hospitalization or compromise the patient's safety or compliance to adhere to trial-related procedures. If the patient is on maintenance therapy (which may include Growth Hormone, appetite stimulants and anabolic steroids) for previously diagnosed wasting syndrome, he/she may be eligible for the trial. Note: An AIDS defining illness not clinically stabilized for at least 30 days will be considered clinically active. Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed in case the medication used is not part of the disallowed medications
* Any active clinically significant disease (e.g., pancreatitis, cardiac dysfunction) or findings during screening of medical history, laboratory or physical examination that, in the investigator's opinion, would compromise the patient's safety or the outcome of the trial.

Primary outcomes:
measure: Number of Participants With Confirmed Virologic Response (CVR) at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 4
timeFrame: Baseline (Day 1) and Week 4
measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 8
timeFrame: Baseline (Day 1) and Week 8
measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 16
timeFrame: Baseline (Day 1) and Week 16
measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 20
timeFrame: Baseline (Day 1) and Week 20
measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 24
timeFrame: Baseline (Day 1) and Week 24
measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 30
timeFrame: Baseline (Day 1) and Week 30
measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 36
timeFrame: Baseline (Day 1) and Week 36
measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 42
timeFrame: Baseline (Day 1) and Week 42
measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Time to Reach First Confirmed Virologic Response
timeFrame: Baseline (Day 1) to Week 48
measure: Number of Participants With Virologic Failure
timeFrame: Baseline (Day 1) to Week 48
measure: Change From Baseline in Cluster of Differentiation 4 (CD4+) and Cluster of Differentiation 8 (CD8+) Cell Counts at Week 48
timeFrame: Baseline (Day 1) and Week 48
Other outcomes:
Locations:
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Fort Pierce
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Berkley
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Hillsborough
country: United States
state: New Jersey
city: Neptune
country: United States
state: New Jersey
city: Buffalo
country: United States
state: New York
city: Manhasset
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Harlingen
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Tibotec, Inc
name: Tibotec, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Ruane PJ, Brinson C, Ramgopal M, Ryan R, Coate B, Cho M, Kakuda TN, Anderson D; INROADS study investigators. The Intelence aNd pRezista Once A Day Study (INROADS): a multicentre, single-arm, open-label study of etravirine and darunavir/ritonavir as dual therapy in HIV-1-infected early treatment-experienced subjects. HIV Med. 2015 May;16(5):288-96. doi: 10.1111/hiv.12211. Epub 2015 Jan 14.