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

NCT01199939 | Completed Phase 2 Results

• 2 other identifiers: CR017149TMC125HIV4007
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 23

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.

Conditions

Human Immunodeficiency Virus (HIV)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• 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

Study Arms (1)

ETR + DRV/rtv

EXPERIMENTAL

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; Drug: Ritonavir; Drug: Darunavir

Interventions

Etravirine DRUG

400mg once daily orally for 48 weeks

ETR + DRV/rtv

Ritonavir DRUG

100mg once daily orally for 48 weeks

ETR + DRV/rtv

Darunavir DRUG

800mg once daily orally for 48 weeks

ETR + DRV/rtv

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• \. CD4 count = 50 cells/mm3.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tibotec, Inc: lead
• Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA: collaborator

Study Sites (23)

Unknown Facility

Long Beach, California, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Denver, Colorado, United States

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

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Ft. Pierce, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Decatur, Georgia, United States

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Macon, Georgia, United States

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Berkley, Michigan, United States

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St Louis, Missouri, United States

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Hillsborough, New Jersey, United States

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Neptune City, New Jersey, United States

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Buffalo, New York, United States

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Manhasset, New York, United States

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Charlotte, North Carolina, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Harlingen, Texas, United States

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Houston, Texas, United States

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Seattle, Washington, United States

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San Juan, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 25585528 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

etravirine; Ritonavir; Darunavir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Furans

Results Point of Contact

• Title: SENIOR MEDICAL DIRECTOR
• Organization: Janssen Pharmaceuticals

1 609 730-2931

Study Officials

• Tibotec, Inc. Clinical Trial

  Tibotec, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2010
• First Posted: September 13, 2010
• Study Start: May 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: December 4, 2013
• Results First Posted: December 4, 2013

Record last verified: 2013-10

Locations

US (22); PR (1)