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

This study has been completed.
Sponsor:
Collaborator:
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by (Responsible Party):
Tibotec, Inc
ClinicalTrials.gov Identifier:
NCT01199939
First received: September 9, 2010
Last updated: October 4, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Human Immunodeficiency Virus (HIV)
Drug: Etravirine
Drug: Ritonavir
Drug: Darunavir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Tibotec, Inc:

Primary Outcome Measures:
  • Number of Participants With Confirmed Virologic Response (CVR) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.


Secondary Outcome Measures:
  • Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 4 [ Time Frame: Baseline (Day 1) and Week 4 ] [ Designated as safety issue: No ]
  • Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 8 [ Time Frame: Baseline (Day 1) and Week 8 ] [ Designated as safety issue: No ]
  • Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 12 [ Time Frame: Baseline (Day 1) and Week 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 16 [ Time Frame: Baseline (Day 1) and Week 16 ] [ Designated as safety issue: No ]
  • Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 20 [ Time Frame: Baseline (Day 1) and Week 20 ] [ Designated as safety issue: No ]
  • Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 24 [ Time Frame: Baseline (Day 1) and Week 24 ] [ Designated as safety issue: No ]
  • Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 30 [ Time Frame: Baseline (Day 1) and Week 30 ] [ Designated as safety issue: No ]
  • Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 36 [ Time Frame: Baseline (Day 1) and Week 36 ] [ Designated as safety issue: No ]
  • Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 42 [ Time Frame: Baseline (Day 1) and Week 42 ] [ Designated as safety issue: No ]
  • Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ] [ Designated as safety issue: No ]
  • Time to Reach First Confirmed Virologic Response [ Time Frame: Baseline (Day 1) to Week 48 ] [ Designated as safety issue: No ]
    CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.

  • Number of Participants With Virologic Failure [ Time Frame: Baseline (Day 1) to Week 48 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Cluster of Differentiation 4 (CD4+) and Cluster of Differentiation 8 (CD8+) Cell Counts at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: May 2010
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01199939

Locations
United States, California
Long Beach, California, United States
Los Angeles, California, United States
San Francisco, California, United States
United States, Colorado
Denver, Colorado, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Fort Pierce, Florida, United States
Miami, Florida, United States
Orlando, Florida, United States
United States, Georgia
Decatur, Georgia, United States
Macon, Georgia, United States
United States, Michigan
Berkley, Michigan, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, New Jersey
Hillsborough, New Jersey, United States
Neptune, New Jersey, United States
United States, New York
Buffalo, New York, United States
Manhasset, New York, United States
United States, North Carolina
Charlotte, North Carolina, United States
United States, Texas
Austin, Texas, United States
Dallas, Texas, United States
Harlingen, Texas, United States
Houston, Texas, United States
United States, Washington
Seattle, Washington, United States
Puerto Rico
San Juan, Puerto Rico
Sponsors and Collaborators
Tibotec, Inc
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Investigators
Study Director: Tibotec, Inc. Clinical Trial Tibotec, Inc
  More Information

No publications provided

Responsible Party: Tibotec, Inc
ClinicalTrials.gov Identifier: NCT01199939     History of Changes
Other Study ID Numbers: CR017149, TMC125HIV4007
Study First Received: September 9, 2010
Results First Received: October 4, 2013
Last Updated: October 4, 2013
Health Authority: United States: Food and Drug Administration
Puerto Rico: Food and Drug Administration

Keywords provided by Tibotec, Inc:
Human Immunodeficiency Virus
HIV
Etravirine
Darunavir
Prezista
Intelence
Ritonavir
INROADS

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Ritonavir
Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 14, 2014