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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

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ClinicalTrials.gov Identifier: NCT00799864
Recruitment Status : Completed
First Posted : December 1, 2008
Last Update Posted : August 16, 2023
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC

Tracking Information
First Submitted Date  ICMJE November 26, 2008
First Posted Date  ICMJE December 1, 2008
Last Update Posted Date August 16, 2023
Actual Study Start Date  ICMJE January 7, 2011
Actual Primary Completion Date August 16, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
  • Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration (Cmax) [ Time Frame: Up to 48 weeks ]
  • Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve (AUC24) [ Time Frame: Up to 48 weeks ]
    AUC24 is defined area under the plasma concentration time curve from 0 to 24 hours post dosing of rilpivirine.
Original Primary Outcome Measures  ICMJE
 (submitted: November 28, 2008)
To evaluate the steady-state pharmacokinetics of TMC278 25 mg once daily in patients aged = 12 to < 18 years; to evaluate short-term (2 weeks) safety, and antiviral activity of TMC278 in this age group.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
  • Number of Patients with Adverse Events [ Time Frame: Up to 244 weeks (Cohort 1 only) (including 4 week follow up visit) ]
    Safety measures include adverse events, vital signs, physical examination, hematology, biochemistry and electrocardiogram.
  • Percentage of Participants With Plasma Human Immunodeficiency Virus - 1 (HIV-1) Ribonucleic Acid (RNA) level Less Than (<) 50 Copies/mL Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm [ Time Frame: Week 48 and Week 240 (Cohort 1 only) ]
    Time to loss of virologic response algorithm (TLOVR) requires sustained HIV-1 RNA < 50 copies/mL; confirmed HIV-1 RNA more than or equal to (>=) 50 copies/mL is considered as non-response (rebound); participant is considered non-responder after permanent discontinuation.
  • Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL by FDA Snapshot Approach [ Time Frame: Week 48 and Week 240 (Cohort 1 only) ]
    FDA Snapshot Approach is based on the last observed viral load data within the Week 48 window: virologic response is defined as HIV-1 RNA <50 copies/mL (observed case); missing HIV-1 RNA is considered as non-response.
  • Evolution of viral genotype and phenotype [ Time Frame: Up to 48 Weeks and 240 Weeks (Cohort 1 only) ]
    Blood samples will be collected for the determination of HIV-1 genotype and phenotype by the Protocol Virologist based on plasma viral load.
  • Treatment adherence as measured by the Study Adherence Questionnaire [ Time Frame: Up to 48 Weeks and 240 Weeks (Cohort 1 only) ]
    This endpoint is measured by Study Adherence Questionnaire for children and teenagers. The adherence questionnaire should be completed by by the patient. Ths questionnaire includes questions about the medicine, it's color and dosage.
  • Change in Cluster of Differentiation (CD4+) cells [ Time Frame: Week 48 and Week 240 (Cohort 1 only) ]
    Change in the CD4+ cells will evaluate immunologic changes at Week 48 and Week 240 of treatment with rilpivirine.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2008)
Evaluate long-term safety and efficacy, immunologic changes and evolution of viral geno- and phenotype over 24 and 48 weeks; pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for safety and efficacy of TMC278; and treatment adherence.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1
Intervention  ICMJE
  • Drug: 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.
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
Study Arms  ICMJE Experimental: 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.
Interventions:
  • Drug: Rilpivirine
  • Drug: Zidovudine
  • Drug: Abacavir
  • Drug: Tenofovir disoproxil fumarate
  • Drug: Lamivudine
  • Drug: Emtricitabine
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 24, 2022)
54
Original Estimated Enrollment  ICMJE
 (submitted: November 28, 2008)
35
Actual Study Completion Date  ICMJE August 16, 2022
Actual Primary Completion Date August 16, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India,   Kenya,   Romania,   South Africa,   Thailand,   Uganda,   Ukraine,   United States
Removed Location Countries Spain
 
Administrative Information
NCT Number  ICMJE NCT00799864
Other Study ID Numbers  ICMJE CR002677
TMC278-TiDP38-C213 ( Other Identifier: Janssen Sciences Ireland UC )
2008-001696-30 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Janssen Sciences Ireland UC
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE Janssen Sciences Ireland UC
Original Study Sponsor  ICMJE Tibotec Pharmaceuticals, Ireland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Sciences Ireland UC Clinical Trial Janssen Sciences Ireland UC
PRS Account Janssen Sciences Ireland UC
Verification Date July 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP