A Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients
Condition: Human Immunodeficiency Virus (HIV)
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes
Intervention: Etravirine; Ritonavir; Darunavir
Intervention description: 400mg once daily orally for 48 weeks; 100mg once daily orally for 48 weeks; 800mg once daily orally for 48 weeks
Intervention MeSH terms: Ritonavir; Darunavir; Etravirine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Human Immunodeficiency Virus; HIV; Etravirine; Darunavir; Prezista; Intelence; Ritonavir; INROADS

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.
    

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.