Clinical trial NCT00919854: A Safety Study to Evaluate the Antiviral Activity of Darunavir in Combination With Ritonavir in HIV 1 Infected Children
Official title: A Phase II, Open Label Trial, to Evaluate Pharmacokinetics, Safety, Tolerability and Antiviral Activity of DRV in Combination With Low-Dose Ritonavir (DRV/Rtv) in Treatment-Experienced HIV-1 Infected Children From 3 Years to Below 6 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Human Immunodeficiency Virus 1
Keywords: Human immunodeficiency virus 1
HIV-1
Darunavir
Ritonavir
Norvir
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
Collaborators: name: Tibotec Pharmaceutical Limited
First posted: 2009-06-12
Enrollment: 27
Sex: ALL
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the pharmacokinetics (what the body does to the medication), safety and antiviral activity to support dose recommendations by body weight of darunavir with low-dose ritonavir (DRV/rtv), in combination with other antiretroviral drugs (ARVs), in treatment-experienced Human immunodeficiency virus 1 (HIV 1) infected children.

Detailed description: This is an open-label (all people know the identity of the intervention), study to evaluate the pharmacokinetics, safety and antiviral activity. Approximately 24 HIV-1 infected children will be enrolled in this study. The study consists of a 4-week screening period, a 48-week treatment period, and a 4-week follow-up period. Participants will receive DRV/rtv according to their body weight. Safety evaluations will include assessment of adverse events, laboratory tests, physical Examination, neurologic examination, vital signs, and electrocardiogram. The total duration of the study will be 56 weeks.

Eligibility criteria: Inclusion Criteria:

* Participants with a documented HIV 1 infection (by any of the local standard diagnostic methods, such as HIV PCR-DNA, ELISA or western blot (WB) test for HIV antibodies, etc.)
* Body weight from 10 kg to less than 20 kg at screening
* Participants currently on stable ART (anti retroviral therapy) for at least 12 weeks, who need to change their ARV regimen because it is currently failing, with a viral load of greater than 1000 copies/mL
* Screening genotype resistance test results showing less than 3 DRV resistance-associated mutations
* Parents or legal representative willing and able to give consent

Exclusion Criteria:

* Participants with presence of any currently active conditions included in the listing of WHO ( World Health Organisation) Clinical Stage 4 and participants with presence of a non-HIV encephalopathy
* Administration of any ARV (antiretroviral) or non-ARV investigational medication or investigational vaccine within 30 days prior to screening, except for those medications where dose recommendations for children are available
* Life expectancy less than 6 months, according to the judgment of the investigator
* Co-enrollment in other clinical and/or cohort trials without written permission of the Sponsor
* Participants with any active clinically significant disease (eg, tuberculosis \[TB\], cardiac dysfunction, pancreatitis, acute viral infections) or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the subject's safety or outcome of the study

Primary outcomes:
measure: Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 24 - Time to Loss of Virologic Response (TLOVR)
timeFrame: Week 24
Secondary outcomes:
measure: Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 48
timeFrame: Week 48
measure: Number of Participants With Virological Response (Viral Load Less Than 400 Copies/mL) at Week 24 and Week 48
timeFrame: Week 24 and Week 48
measure: Number of Participants With Less Than or Equal to 1 log10 Decrease in Plasma Viral Load at Week 24 and Week 48
timeFrame: Week 24 and Week 48
measure: Mean Change From Baseline to Week 24 and Week 48 in Plasma log10 Viral Load
timeFrame: Baseline, Week 24 and Week 48
measure: Mean Change From Baseline to Week 24 and Week 48 in CD4+ Percentage
timeFrame: Baseline, Week 24 and Week 48
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Rio De Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Chennai
country: India
city: Kilifi
country: Kenya
city: Durban
country: South Africa
city: Johannesburg Gauteng
country: South Africa
city: Johannesburg
country: South Africa
Study officials:
affiliation: Tibotec Pharmaceuticals, Ireland
name: Tibotec Pharmaceuticals, Ireland Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Violari A, Bologna R, Kumarasamy N, Pilotto JH, Hendrickx A, Kakuda TN, Lathouwers E, Opsomer M, Van de Casteele T, Tomaka FL. Safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients: week 48 results of the ARIEL trial. Pediatr Infect Dis J. 2015 May;34(5):e132-7. doi: 10.1097/INF.0000000000000644.