Clinical trial NCT00799864: A Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Antiviral Activity of Rilpivirine (TMC278) in Human Immunodeficiency Virus Infected Adolescents and Children Aged Greater Than or Equal to 6 Years
Official title: A Phase II, Open Label, Single Arm Trial to Evaluate the Pharmacokinetics,Safety, Tolerability, and Antiviral Activity of Rilpivirine (TMC278) in Antiretroviral Naive HIV-1 Infected Adolescents and Children Aged >= 6 to <18 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1
Keywords: HIV Infection
Antiretroviral
HIV-1
AIDS
Children
Rilpivirine (TMC278)
Pediatric
Lead sponsor: Janssen Sciences Ireland UC
Sponsor class: INDUSTRY
First posted: 2008-12-01
Enrollment: 54
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
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, safety and antiviral activity of rilpivirine (TMC278) 25 milligram (mg) or adjusted dose once daily in combination with an investigator-selected background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors (N\[t\]RTIs) (zidovudine \[AZT\], abacavir \[ABC\], or tenofovir disoproxil fumarate \[TDF\] in combination with lamivudine \[3TC\] or emtricitabine \[FTC\] in antiretroviral (ARV) treatment-naïve adolescents and children aged greater than or equal to (\>=) 6 to less than (\<) 18 years.

Detailed description: This is a Phase II, open-label (all people involved know the identity of the assigned drug) and single arm study. The study will consist of a screening period of maximum 8 weeks, an initial treatment period of 48 weeks, a post week 48 treatment extension period of 4 years (Cohort 1 only), and a 4 week follow-up (cohort 2 only) period. Participants who withdraw from the trial on or before the Week 48 visit or subjects with ongoing (serious) adverse events (\[S\]AEs), laboratory abnormalities, or viral load increase at the last on-treatment visit in the extension, will be seen for a follow-up visit 4 weeks later. The initial 48-week treatment period will be structured into 2 age Cohorts; Cohort 1 (Aged greater than or equal to \[\>=\] 12 to less than \[\<\] 18 years) and Cohort 2 (Children Aged \>= 6 to \< 12 years). The trial is designed to evaluate the steady-state pharmacokinetic (PK) profile (based on intensive PK analysis) and the short-term safety and antiviral activity of rilpivirine (RPV). Participants will receive RPV 25 milligram (mg), or weight-adjusted dose orally once daily for 240 weeks when administered in combination with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). The trial will also evaluate long-term (48 weeks and 240 weeks \[Cohort 1\]) safety, efficacy, and pharmacokinetics of rilpivirine in combination with the background regimen of 2 NRTIs. Patients safety will be monitored throughout the study and during the follow up visits.

Eligibility criteria: Inclusion Criteria:

* Has documented human immuno deficiency virus (HIV-1) infection
* Patients who meet the following criteria; a) Cohort 1: Patients Aged greater than or equal to (\>=) 12 to less than (\<) 18 years, weight is \>= 32 kilogram (kg), b) Cohort 2; Aged \>= 6 to \< 12 years, weight is \>= 17 kg
* Must have HIV-1 plasma viral load at screening greater than equal to 500 HIV-1 ribonucleic acid (RNA) copies/mL
* Have not received treatment with a therapeutic HIV vaccine or an HIV drug with the exception of a single dose of nevirapine (NVP) (Cohort 1 and Cohort 2) or up to 6 weeks of zidovudine (AZT) use (Cohort 2 only) prior to screening to prevent mother-to-child transmission (MTCT)
* In the judgment of the investigator, it is appropriate to initiate antiretroviral therapy (ARV) therapy based on a patient's medical condition and taking into account guidelines for the treatment of HIV-1 infection in children of this age group

Exclusion Criteria:

* Any previous use of ARVs with the exception of single dose NVP (Cohort 1 and Cohort 2) or up to 6 weeks of AZT (Cohort 2 only) to prevent MTCT
* Plasma viral load at screening greater than 100,000 HIV-1 RNA copies/mL
* Documented genotypic evidence of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance at screening or from historical data available in the source documents
* Use of disallowed concomitant therapy from 4 weeks prior to the baseline visit
* Patient has any currently active Acquired Immunodeficiency Syndrome (AIDS) defining illness
* Patient has active tuberculosis and/or is being treated for tuberculosis at screening
* Personal history of cardiac disease (including congenital heart disease), or symptomatic arrhythmias, with the exception of sinus arrhythmia; personal history of asymptomatic arrhythmias is excluded if the asymptomatic arrhythmia is clinically significant in the opinion of the investigator

Primary outcomes:
measure: Cohorts 1 and 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
timeFrame: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
measure: Cohort 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration at Steady State (Cmax,ss)
timeFrame: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
measure: Cohorts 1 and 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss)
timeFrame: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
measure: Cohort 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss)
timeFrame: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
Secondary outcomes:
measure: Cohorts 1 and 2: Number of Participants With Adverse Events (AEs)
timeFrame: Cohort 1: From baseline (Day 1) up to Week 240; Cohort 2: From Baseline (Day 1) up to 240 weeks (for participants recruited up to protocol amendment 9); up to 48 weeks (for participants recruited after implementation of protocol amendment 10)
measure: Cohorts 1 and 2: Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) Level Less Than (<) 50 Copies/mL by Time to Loss of Virologic Response (TLOVR) Method
timeFrame: At Week 48 (for Cohorts 1 and 2) and at Week 240 (for Cohort 1 only)
measure: Cohorts 1 and 2: Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL by Food and Drug Administration (FDA) Snapshot Approach
timeFrame: At Week 48 (for Cohorts 1 and 2) and at Week 240 (for Cohort 1 only)
measure: Cohorts 1 and 2: Number of Participants With Post Baseline Genotype Data
timeFrame: Cohort 1: From baseline (Day 1) up to Week 240; Cohort 2: From baseline (Day 1) up to 240 weeks (for participants recruited up to protocol amendment 9); up to 48 weeks (for participants recruited after implementation of protocol amendment 10)
measure: Cohorts 1 and 2: Percentage of Participants With Treatment Adherence >95% Based on Drug Accountability
timeFrame: Cohort 1: From baseline (Day 1) up to Week 240; Cohort 2: From baseline (Day 1) up to 240 weeks (for participants recruited up to protocol amendment 9); up to 48 weeks (for participants recruited after implementation of protocol amendment 10)
measure: Cohorts 1 and 2: Change From Baseline in Cluster of Differentiation (CD4+) Cells
timeFrame: Baseline (Day 1) and Week 48 for Cohorts 1 and 2; Week 240 for Cohort 1 alone
Other outcomes:
Locations:
city: Syracuse
country: United States
state: New York
city: Memphis
country: United States
state: Tennessee
city: Chennai
country: India
city: Mangalore
country: India
city: Nairobi
country: Kenya
city: Bucuresti
country: Romania
city: Bloemfontein
country: South Africa
city: Dundee
country: South Africa
city: Middelburg
country: South Africa
city: Pretoria
country: South Africa
city: Thabazimbi
country: South Africa
city: Vosloorus
country: South Africa
city: Bangkok
country: Thailand
city: Nonthaburi
country: Thailand
city: Entebbe
country: Uganda
city: Kampala
country: Uganda
city: Kiev
country: Ukraine
Study officials:
affiliation: Janssen Sciences Ireland UC
name: Janssen Sciences Ireland UC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Lombaard J, Ssali F, Thanyawee P, Fourie J, Vanveggel S, Linthicum C, Van Eygen V, Van Solingen-Ristea R. Phase 2 Open-Label Study of Long-Term Safety, Tolerability, and Antiviral Activity of Rilpivirine in Antiretroviral-Naive Adolescents Living with HIV-1. Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0091621. doi: 10.1128/AAC.00916-21. Epub 2021 Dec 6.