A Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients

NCT ID: NCT01199939

Last Updated: 2013-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2012-10-31

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.

Conditions

Human Immunodeficiency Virus (HIV)

Keywords

Human Immunodeficiency Virus; HIV; Etravirine; Darunavir; Prezista; Intelence; Ritonavir; INROADS

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ETR + DRV/rtv

Darunavir 800mg once daily orally for 48 weeks,Etravirine 400mg once daily orally for 48 weeks,Ritonavir 100mg once daily orally for 48 weeks

Group Type: EXPERIMENTAL

Etravirine

Intervention Type: DRUG

400mg once daily orally for 48 weeks

Ritonavir

Intervention Type: DRUG

100mg once daily orally for 48 weeks

Darunavir

Intervention Type: DRUG

800mg once daily orally for 48 weeks

Interventions

Etravirine

400mg once daily orally for 48 weeks

Intervention Type: DRUG

Ritonavir

100mg once daily orally for 48 weeks

Intervention Type: DRUG

Darunavir

800mg once daily orally for 48 weeks

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

INDUSTRY

Sponsor Role: collaborator

Tibotec, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tibotec, Inc. Clinical Trial

Role: STUDY_DIRECTOR

Tibotec, Inc

Locations

Long Beach, California, United States

Los Angeles, California, United States

San Francisco, California, United States

Denver, Colorado, United States

Washington D.C., District of Columbia, United States

Ft. Pierce, Florida, United States

Miami, Florida, United States

Orlando, Florida, United States

Decatur, Georgia, United States

Macon, Georgia, United States

Berkley, Michigan, United States

St Louis, Missouri, United States

Hillsborough, New Jersey, United States

Neptune City, New Jersey, United States

Buffalo, New York, United States

Manhasset, New York, United States

Charlotte, North Carolina, United States

Austin, Texas, United States

Dallas, Texas, United States

Harlingen, Texas, United States

Houston, Texas, United States

Seattle, Washington, United States

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

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.

Reference Type: DERIVED

PMID: 25585528 (View on PubMed)

Other Identifiers

TMC125HIV4007

Identifier Type: OTHER

Identifier Source: secondary_id

CR017149

Identifier Type: -

Identifier Source: org_study_id