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

NCT00799864 | Completed Phase 2 Results DMC

• 3 other identifiers: CR002677TMC278-TiDP38-C2132008-001696-30
• Study Type: interventional
• Target: 54
• Locations: 8 countries
• Sites: 17

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.

Conditions

HIV-1

Keywords

HIV Infection; Antiretroviral; HIV-1; AIDS; Children; Rilpivirine (TMC278); Pediatric

Outcome Measures

Primary Outcomes (4)

• Cohorts 1 and 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Observed Plasma Concentration at Steady State (Cmax,ss)

  Cmax,ss was the maximum observed plasma concentration of rilpivirine at steady state (steady state starting from Day 14).

  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)

• Cohort 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration at Steady State (Cmax,ss)

  Cmax,ss was the maximum plasma concentration of rilpivirine at steady state (steady state starting from Day 14). In the below data table, the measure type "Number" corresponds to Cmax,ss concentration.

  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)

• Cohorts 1 and 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss)

  AUC24,ss was defined as the area under the plasma concentration versus time curve from time 0 to 24 hours post dosing of rilpivirine at steady state (steady state starting from Day 14).

  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)

• Cohort 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss)

  AUC24,ss was defined as the area under the plasma concentration versus time curve from time 0 to 24 hours post dosing of rilpivirine at steady state (steady state starting from Day 14). In the below data table, the measure type "Number" corresponds to AUC24, ss concentration.

  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 (6)

• Cohorts 1 and 2: Number of Participants With Adverse Events (AEs)

  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)

• 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

  At Week 48 (for Cohorts 1 and 2) and at Week 240 (for Cohort 1 only)

• Cohorts 1 and 2: Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL by Food and Drug Administration (FDA) Snapshot Approach

  At Week 48 (for Cohorts 1 and 2) and at Week 240 (for Cohort 1 only)

• Cohorts 1 and 2: Number of Participants With Post Baseline Genotype Data

  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)

• Cohorts 1 and 2: Percentage of Participants With Treatment Adherence >95% Based on Drug Accountability

  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)

Study Arms (1)

Rilpivirine (TMC278)

EXPERIMENTAL

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.

Drug: Rilpivirine; Drug: Zidovudine; Drug: Abacavir; Drug: Tenofovir disoproxil fumarate; Drug: Lamivudine; Drug: Emtricitabine

Interventions

Rilpivirine 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.

Rilpivirine (TMC278)

Zidovudine 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).

Rilpivirine (TMC278)

Abacavir 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).

Rilpivirine (TMC278)

Tenofovir disoproxil fumarate 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).

Rilpivirine (TMC278)

Lamivudine 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).

Rilpivirine (TMC278)

Emtricitabine 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).

Rilpivirine (TMC278)

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Sciences Ireland UC: lead

Study Sites (17)

Unknown Facility

Syracuse, New York, United States

Location

Unknown Facility

Memphis, Tennessee, United States

Location

Unknown Facility

Chennai, India

Location

Unknown Facility

Mangalore, India

Location

Unknown Facility

Nairobi, Kenya

Location

Unknown Facility

Bucharest, Romania

Location

Unknown Facility

Bloemfontein, South Africa

Location

Unknown Facility

Dundee, South Africa

Location

Unknown Facility

Middelburg, South Africa

Location

Unknown Facility

Pretoria, South Africa

Location

Unknown Facility

Thabazimbi, South Africa

Location

Unknown Facility

Vosloorus, South Africa

Location

Unknown Facility

Bangkok, Thailand

Location

Unknown Facility

Nonthaburi, Thailand

Location

Unknown Facility

Entebbe, Uganda

Location

Unknown Facility

Kampala, Uganda

Location

Unknown Facility

Kiev, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 34871089 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Rilpivirine; Zidovudine; abacavir; Tenofovir; Lamivudine; Emtricitabine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Zalcitabine; Deoxycytidine; Cytidine

Results Point of Contact

• Title: Director 1 Clinical Leader
• Organization: Janssen R&D BE

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Sciences Ireland UC Clinical Trial

  Janssen Sciences Ireland UC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2008
• First Posted: December 1, 2008
• Study Start: January 1, 2011
• Primary Completion: August 1, 2022
• Study Completion: August 1, 2022
• Last Updated: June 25, 2024
• Results First Posted: June 25, 2024

Record last verified: 2024-05

Locations

KE (1); ZA (6); RO (1); TH (2); UG (2); IN (2); UA (1); US (2)