A Study to Evaluate Antiviral Activity of Darunavir + Ritonavir in HIV-1 Infected Adolescents

Study Overview
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Brief Summary
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The purpose of this study is to evaluate pharmacokinetics (what body does to medication), safety, tolerability, and efficacy (effectiveness) of darunavir with low-dose ritonavir (DRV/rtv) administered once daily, in combination with an investigator-selected background regimen consisting of other antiretrovirals (ARVs) ie, 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), in treatment-naive (never treated before) HIV-1 infected adolescents aged from 12 to <18 years and weighing at least 40 kg.

Detailed Description
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This is an open-label (all people know the identity of the intervention), single-arm, Phase II study to evaluate the pharmacokinetics, safety, tolerability, and efficacy of darunavir/ritonavir (DRV/rtv) administered once daily, in combination an investigator-selected background regimen (2 NRTIs), in treatment-naive HIV-1 infected adolescents over 48 weeks. A total of 12 patients will be enrolled in this study. Patients will be considered treatment-naive if they have never received treatment with an ARV medication, including both investigational as well as commercially available ARVs indicated for the treatment of HIV-infection and ARVs for the treatment of hepatitis B infection with anti-HIV activity. The investigator-selected background regimen will consist of 2 NRTIs, either zidovudine/lamivudine or abacavir/lamivudine, whichever is approved and marketed or considered local standard of care for adolescents aged from 12 to <18 years in a particular country. The study will consist of a 4-week screening period, a 48-week treatment period, and a 4-week follow-up period. Safety, efficacy, resistance (reduction in effectiveness of a medication), pharmacokinetic analyses, and pharmacodynamic (what medication does to body) analyses will be performed at Week 24 (primary analysis) and Week 48 (final analysis). Patients who will complete the 48 weeks of treatment with DRV/rtv and who will continue to benefit from this treatment, will have the opportunity to continue this treatment until they no longer benefit from the medication, until DRV is commercially available or can be accessed from another source (eg, access program, government program) or until the development program is discontinued.

Official Title
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A Phase II, Open-Label Trial, to Evaluate Pharmacokinetics, Safety, Tolerability and Antiviral Activity of Drv/Rtv Once Daily in Treatment-Naive HIV-1 Infected Adolescents Aged Between 12 and < 18 Years

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: darunavir
* Drug: ritonavir
* Drug: zidovudine
* Drug: lamivudine
* Drug: abacavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a documented HIV-1 infection Body weight from at least 40 kg at screening Screening plasma HIV-1 RNA >= 1000 copies/mL Parents or legal representative and trial patients (where appropriate, depending on age and local regulation) willing and able to give consent and assent General medical condition, in the investigator's opinion, does not interfere with the assessments and the completion of the trial Able to swallow darunavir tablets (400 mg) and ritonavir capsules (100 mg) Exclusion Criteria: Patients with presence of any currently active conditions included in the listing of World Health Organisation (WHO) Clinical Stage 4 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 trial protocol Previous or current use of antiretrovirals (ARVs) Primary or acute HIV infection Use of any investigational agents within 30 days prior to screening Use of disallowed concomitant therapy Pregnant or breast-feeding Female patient of childbearing potential without use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period Patients with clinical or laboratory evidence of significantly decreased hepatic function or decompensation (ie, liver insufficiency), irrespective of liver enzyme levels Any active clinically significant disease (eg, cardiac dysfunction, pancreatitis, acute viral infection) or findings during screening of medical history or physical examination that are expected to compromise the patient's safety or outcome in the trial

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DRV/rtv (darunavir/ritonavir)<br>Patients will receive darunavir tablets 2 x 400 mg in combination with ritonavir capsule 100 mg once daily for 48 weeks along with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) ie, either zidovudine/lamivudine or abacavir/lamivudine | Drug: darunavir<br>* Type=exact number, unit=mg, number=400, formulation=tablet, route=oral. 2 tablets of darunavir administered once daily for 48 weeks<br>* Other names: DRV;Drug: ritonavir<br>* Type=exact number, unit=mg, number=100, formulation=capsule, route=oral. 1 capsule of ritonavir administered once daily for 48 weeks<br>* Other names: rtv;Drug: zidovudine<br>* NRTI (zidovudine) administered as per approved, marketed, or considered local standard of care for patients aged between 12 and < 18 years in a particular country<br>Drug: lamivudine<br>* NRTI (lamivudine) administered as per approved, marketed, or considered local standard of care for patients aged between 12 and < 18 years in a particular country<br>Drug: abacavir<br>* NRTI (abacavir) administered as per approved, marketed, or considered local standard of care for patients aged between 12 and < 18 years in a particular country<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological Response[Viral Load <50 Copies/mL, TLOVR] | The analysis is based on virologic response defined as percentage of patients with confirmed plasma viral load <50 HIV-1 RNA copies/mL at Week 24 calculated according to the Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) algorithm. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological Response [Viral Load <50 Copies/mL, FDA-SNAPSHOT] | The analysis is based on the last observed viral load (VL) data within the Week 24 window. Virologic response is defined as a VL<50 copies/mL (observed case). Virologic Failure includes a) patients who had >=50 copies/mL in the Week-24 window, b) patients who discontinued prior to Week 24 for lack or loss of efficacy, c) patients who had a switch in their background regimen that was not permitted by the protocol, and d) patients who discontinued for reasons other than adverse events (AEs)/death, and lack or loss of efficacy (provided their last available viral load was detectable). | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMC114, HIV Infections, TMC114-TiDP29-C230, TMC114-C230, HIV-1, Darunavir, Ritonavir, NRTI, Treatment Naive