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

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

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.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus (HIV)
• Intervention / Treatment: Drug: Etravirine; Drug: Ritonavir; Drug: Darunavir

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico
• United States
  • California
    • Long Beach, California, United States
    • Los Angeles, California, United States
    • San Francisco, California, United States
  • Colorado
    • Denver, Colorado, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Fort Pierce, Florida, United States
    • Miami, Florida, United States
    • Orlando, Florida, United States
  • Georgia
    • Decatur, Georgia, United States
    • Macon, Georgia, United States
  • Michigan
    • Berkley, Michigan, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • New Jersey
    • Hillsborough, New Jersey, United States
    • Neptune, New Jersey, United States
  • New York
    • Buffalo, New York, United States
    • Manhasset, New York, United States
  • North Carolina
    • Charlotte, North Carolina, United States
  • Texas
    • Austin, Texas, United States
    • Dallas, Texas, United States
    • Harlingen, Texas, United States
    • Houston, Texas, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Etravirine; 400mg once daily orally for 48 weeks; Drug: Ritonavir; 100mg once daily orally for 48 weeks; Drug: Darunavir; 800mg once daily orally for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Confirmed Virologic Response (CVR) at Week 48	CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 4		Baseline (Day 1) and Week 4
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 8		Baseline (Day 1) and Week 8
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 12		Baseline (Day 1) and Week 12
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 16		Baseline (Day 1) and Week 16
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 20		Baseline (Day 1) and Week 20
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 24		Baseline (Day 1) and Week 24
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 30		Baseline (Day 1) and Week 30
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 36		Baseline (Day 1) and Week 36
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 42		Baseline (Day 1) and Week 42
Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 48		Baseline (Day 1) and Week 48
Time to Reach First Confirmed Virologic Response	CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.	Baseline (Day 1) to Week 48
Number of Participants With Virologic Failure	Virologic Failure is defined as participant who is a rebounder or a non-responder. Rebounder participant is defined as a participant who is still in the study at Week 12 and first achieves 2 consecutive virologic responses (<50 copies/mL) followed by 2 consecutive non-responses or a discontinued participant (any reason) for which the last observed time point shows a non-response. Non responder participant is defined as a participant who is still in the study at Week 12 and never achieves 2 consecutive responses.	Baseline (Day 1) to Week 48
Change From Baseline in Cluster of Differentiation 4 (CD4+) and Cluster of Differentiation 8 (CD8+) Cell Counts at Week 48		Baseline (Day 1) and Week 48

Collaborators and Investigators

• Sponsor: Tibotec, Inc
• Collaborators: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
• Investigators: Study Director: Tibotec, Inc. Clinical Trial, Tibotec, Inc

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: September 9, 2010
• First Submitted That Met QC Criteria: September 9, 2010
• First Posted (Estimate): September 13, 2010

Study Record Updates

• Last Update Posted (Estimate): December 4, 2013
• Last Update Submitted That Met QC Criteria: October 4, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: HIV; Human Immunodeficiency Virus; Ritonavir; Etravirine; Darunavir; Prezista; Intelence; INROADS
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Darunavir; Etravirine
• Other Study ID Numbers: CR017149; TMC125HIV4007 (Other Identifier: Tibotec, Inc.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No