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

NCT ID: NCT00799864

Last Updated: 2024-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2022-08-31

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.

Conditions

HIV-1

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rilpivirine (TMC278)

The patients received rilpivirine with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) as a background regimen in cohort 1 \[aged greater than or equal to (\> =) 12 to less than (\<) 18 years\] for up to 240 weeks which is already completed and recruitment closed and will receive this treatment in cohort 2 (children aged \> = 6 to \< 12 years) for up to 48 weeks. The NRTIs include zidovudine, abacavir, or tenofovir disoproxil fumarate in combination with lamivudine or emtricitabine.

Group Type: EXPERIMENTAL

Rilpivirine

Intervention Type: DRUG

Patients will receive rilpivirine (RPV) tablet 25 milligram dose or an adjusted dose orally once daily in Cohort 1 (adolescents aged \>=12 to \<18 years) up to 240 weeks. Patients will receive RPV weight-adjusted dose orally once daily in Cohort 2 (children aged \>=6 to \<12 years) or 25 mg once daily for up to 48 weeks.

Zidovudine

Intervention Type: DRUG

Type=exact, form= appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).

Abacavir

Intervention Type: DRUG

Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).

Tenofovir disoproxil fumarate

Intervention Type: DRUG

Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for 240 weeks (Cohort 1).

Lamivudine

Intervention Type: DRUG

Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).

Emtricitabine

Intervention Type: DRUG

Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).

Interventions

Rilpivirine

Patients will receive rilpivirine (RPV) tablet 25 milligram dose or an adjusted dose orally once daily in Cohort 1 (adolescents aged \>=12 to \<18 years) up to 240 weeks. Patients will receive RPV weight-adjusted dose orally once daily in Cohort 2 (children aged \>=6 to \<12 years) or 25 mg once daily for up to 48 weeks.

Intervention Type: DRUG

Zidovudine

Type=exact, form= appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).

Intervention Type: DRUG

Abacavir

Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).

Intervention Type: DRUG

Tenofovir disoproxil fumarate

Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for 240 weeks (Cohort 1).

Intervention Type: DRUG

Lamivudine

Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).

Intervention Type: DRUG

Emtricitabine

Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).

Intervention Type: DRUG

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Sciences Ireland UC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Sciences Ireland UC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Sciences Ireland UC

Locations

Syracuse, New York, United States

Memphis, Tennessee, United States

Chennai, , India

Mangalore, , India

Nairobi, , Kenya

Bucharest, , Romania

Bloemfontein, , South Africa

Dundee, , South Africa

Middelburg, , South Africa

Pretoria, , South Africa

Thabazimbi, , South Africa

Vosloorus, , South Africa

Bangkok, , Thailand

Nonthaburi, , Thailand

Entebbe, , Uganda

Kampala, , Uganda

Kiev, , Ukraine

Countries

United States; India; Kenya; Romania; South Africa; Thailand; Uganda; Ukraine

References

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.

Reference Type: DERIVED

PMID: 34871089 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TMC278-TiDP38-C213

Identifier Type: OTHER

Identifier Source: secondary_id

2008-001696-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR002677

Identifier Type: -

Identifier Source: org_study_id