A Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Antiviral Efficacy of Rilpivirine (TMC278) in Human Immunodeficiency Virus Infected Adolescents and Children Aged Greater Than or Equal to 6 Years

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Janssen Sciences Ireland UC
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier:
NCT00799864
First received: November 26, 2008
Last updated: June 22, 2016
Last verified: June 2016
  Purpose
The purpose of this study is to evaluate the pharmacokinetics (what the body does to the drug), safety and effectiveness of rilpivirine (TMC278) 25 milligram (mg) or adjusted dose once daily in combination with an investigator-selected background regimen containing 2 nucleoside reverse transcriptase inhibitors (NRTIs) (zidovudine [AZT]/lamivudine [3TC] or abacavir [ABC]/3TC) in antiretroviral (ARV) treatment.

Condition Intervention Phase
Human Immuno Deficiency (HIV) Infection
Drug: Rilpivirine
Drug: Zidovudine
Drug: Abacavir
Drug: Tenofovir disoproxil fumarate
Drug: Lamivudine
Drug: Emtricitabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Janssen Sciences Ireland UC:

Primary Outcome Measures:
  • Pharmacokinetics of Rilpivirine (TMC278) as measured by maximum plasma concentration (Cmax) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics of Rilpivirine as measured by area under the plasma concentration curve (AUC24) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    AUC24 is defined area under the plasma concentration time curve from 0 to 24 hours post dosing of rilpivirine.

  • Pharmacokinetics of Rilpivirine as measured by time to reach the maximum plasma concentration (tmax) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Patients with Adverse Events [ Time Frame: Up to 244 weeks (including 4 week follow up visit) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    This endpoint is measured at week 48 of treatment with rilpivirine.

  • Treatment adherence as measured by the Study Adherence Questionnaire [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Change in the CD4+ cells will evaluate immunologic changes at week 48 of treatment with rilpivirine.

  • Assessment of Pharmacokinetic-Pharmacodynamic Relationships [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    This endpoint evaluates pharmacokinetic-pharmacodynamic relationships for safety and efficacy of rilpivirine.


Estimated Enrollment: 56
Study Start Date: January 2011
Estimated Study Completion Date: October 2023
Estimated Primary Completion Date: October 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rilpivirine (TMC278)
The patients will receive 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] and Cohort 2 (children aged > = 6 to < 12 years). The NRTIs includes zidovudine, abacavir, or tenofovir disoproxil fumarate in combination with lamivudine or emtricitabine.
Drug: Rilpivirine
Patients will receive rilpivirine tablet 25 milligram or adjusted dose orally once daily for 240 weeks.
Drug: Zidovudine
Type=exact, form=tablet, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 240 weeks.
Drug: Abacavir
Type=exact, form=tablet, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 240 weeks.
Drug: Tenofovir disoproxil fumarate
Type=exact, form=tablet, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 240 weeks.
Drug: Lamivudine
Type=exact, form=tablet, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 240 weeks.
Drug: Emtricitabine
Type=exact, form=tablet, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 240 weeks.

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, and a 4 week follow-up period taking place regardless of the presence of serious adverse events (SAEs) if patients withdraw early (ie, before Week 48) or if patients do not participate in the extension after Week 48; after Week 48, a 4-week follow-up visit is only required in case of ongoing (S)AEs at the final on treatment visit. 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) and each Cohort will have 2 parts. The first part of the trial (Part 1) is designed to evaluate the steady-state pharmacokinetic (PK) profile and the short-term safety and antiviral activity of rilpivirine 25 mg or adjusted dose once daily when administered in combination with 2 NRTIs. At Week 2/4, intensive PK will be done and an analysis together with short-term safety and antiviral activity will be reviewed by a data monitoring committee (DMC). For adolescents (Cohort 1) if the mean steady-state exposure in this first group of patients is comparable to that of the adult population (ie, is within 80-125 percentage of the mean exposure of the 25 mg once daily dose group in study, TMC278-C204), and the Week 2/4 safety and antiviral activity results have been reviewed and deemed satisfactory by the DMC, the second part of the trial will start. The second part of the trial will evaluate long-term (48 weeks) safety, efficacy, and pharmacokinetics of rilpivirine in combination with the background regimen of 2 NRTIs with a primary analysis time point at 24 weeks. For patients aged greater than or equal to (> =) 6 to less than (<) 12 years (Cohort 2), after being treated for at least 4 weeks and the Week 2 intensive PK and Week 4 safety and antiviral activity have been reviewed and results are satisfactory, recruitment in Part 1 will resume and additional subjects will be enrolled to have at least 10 subjects in Part 1. Once an appropriate RPV dose has been selected, Part 1 of Cohort 2 will be considered complete and Part 2 will start. All patients from Part 1 will roll over in Part 2 and additional patients will be recruited in Part 2 to have at least 20 subjects (including those from Part 1) overall. In both cohorts of the trial, the ART will consist of rilpivirine 25 mg or adjusted dose once daily and an investigator-selected background regimen containing 2 NRTIs. Patients safety will be monitored throughout the study and during the follow up visits.
  Eligibility

Ages Eligible for Study:   6 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has diagnosed with documented chronic 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 5,000 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) or up to 6 weeks of zidovudine (AZT) use (Cohort 2) prior to screening to prevent mother-to-child transmission
  • In the judgment of the investigator, it is appropriate to initiate anti retroviral therapy (ARV) therapy based on the patients 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) or up to 6 weeks of AZT (Cohort 2)
  • Plasma viral load at screening greater than 100,000 HIV-1 ribonucleic acid (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00799864

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 32 Study Locations
Sponsors and Collaborators
Janssen Sciences Ireland UC
Investigators
Study Director: Janssen Sciences Ireland UC Clinical Trial Janssen Sciences Ireland UC
  More Information

Additional Information:
Responsible Party: Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier: NCT00799864     History of Changes
Other Study ID Numbers: CR002677  TMC278-TiDP38-C213  2008-001696-30 
Study First Received: November 26, 2008
Last Updated: June 22, 2016
Health Authority: Europe: European Medicines Agency
India: Drugs Controller General of India
South Africa: Medicines Control Council
Thailand: Food and Drug Administration, Ministry of Public Health
Uganda: National Drug Authority
United States: Food and Drug Administration

Keywords provided by Janssen Sciences Ireland UC:
HIV Infection
Antiretroviral
HIV-1
AIDS
Children
Rilpivirine (TMC278)
Pediatric

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Rilpivirine
Abacavir
Lamivudine
Zidovudine
Antiviral Agents
Emtricitabine
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Antimetabolites

ClinicalTrials.gov processed this record on July 27, 2016