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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

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ClinicalTrials.gov Identifier: NCT00799864
Recruitment Status : Recruiting
First Posted : December 1, 2008
Last Update Posted : November 8, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease Intervention/treatment Phase
Human Immuno Deficiency (HIV) Infection Drug: Rilpivirine Drug: Zidovudine Drug: Abacavir Drug: Tenofovir disoproxil fumarate Drug: Lamivudine Drug: Emtricitabine Phase 2

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 and 240 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 25 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.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : January 7, 2011
Estimated Primary Completion Date : January 10, 2020
Estimated Study Completion Date : June 27, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Rilpivirine
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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= appropriate pediatric formulation, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 240 weeks.
Drug: Abacavir
Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 240 weeks.
Drug: Tenofovir disoproxil fumarate
Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 240 weeks.
Drug: Lamivudine
Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 240 weeks.
Drug: Emtricitabine
Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients will receive this selected NRTI once daily for 240 weeks.


Outcome Measures

Primary Outcome Measures :
  1. Pharmacokinetics of Rilpivirine (TMC278) as measured by maximum plasma concentration (Cmax) [ Time Frame: Up to 48 weeks ]
  2. 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.

  3. Pharmacokinetics of Rilpivirine as measured by time to reach the maximum plasma concentration (tmax) [ Time Frame: Up to 48 weeks ]

Secondary Outcome Measures :
  1. Number of Patients with Adverse Events [ Time Frame: Up to 244 weeks (including 4 week follow up visit) ]
    Safety measures include adverse events, vital signs, physical examination, hematology, biochemistry and electrocardiogram

  2. 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 ]
    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.

  3. Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL by FDA Snapshot Approach [ Time Frame: Week 48 ]
    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.

  4. Evolution of viral genotype and phenotype [ Time Frame: Up to 48 weeks ]
    This endpoint is measured at week 48 of treatment with rilpivirine.

  5. Treatment adherence as measured by the Study Adherence Questionnaire [ Time Frame: Up to 48 weeks ]
    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.

  6. Change in Cluster of Differentiation (CD4+) cells [ Time Frame: Week 48 ]
    Change in the CD4+ cells will evaluate immunologic changes at week 48 of treatment with rilpivirine.

  7. Assessment of Pharmacokinetic-Pharmacodynamic Relationships [ Time Frame: Up to 48 weeks ]
    This endpoint evaluates pharmacokinetic-pharmacodynamic relationships for safety and efficacy of rilpivirine.


Eligibility Criteria

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Has diagnosed with 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Locations
United States, New York
SUNY Upstate Medical University Recruiting
Syracuse, New York, United States, 13210
United States, Tennessee
St Jude Children's Research Hospital Completed
Memphis, Tennessee, United States, 38105
United States, Virginia
Children'S Hospital of the King'S Daughters Withdrawn
Norfolk, Virginia, United States, 23507
India
Yr Gaitonde Center For Aids Research and Education Completed
Chennai, India, 600113
Kasturba Medical College Hospital Completed
Mangalore, India, 575001
Kenya
Kenya Medical Research Institute/Walter Reed Project Not yet recruiting
Kericho, Kenya, 20200
KAVI Institute of Clinical Research Not yet recruiting
Nairobi, Kenya, 254
South Africa
Boanerges Clinical Research Completed
Bloemfontein, South Africa, 9301
Josha Research Recruiting
Bloemfontein, South Africa, 9301
Quinta-Med Withdrawn
Bloemfontein, South Africa, 9301
Jan Fourie Medical Practice Completed
Dundee, South Africa, 3000
University of KwaZulu-Natal Withdrawn
Durban, South Africa, 4001
Harriet Shezi Childrens Clinic, Paediatric Department Withdrawn
Johannesburg Gauteng, South Africa, 2013
Mzansi Ethical Research Centre Recruiting
Middelburg, South Africa, 1055
Triple M Research Withdrawn
Port Elizabeth, South Africa, 6070
Synexuss Sastanza Completed
Pretoria, South Africa, 0122
Chris Hani Baragwanath Hospital Withdrawn
Soweto, South Africa
Limpopo Clinical Research Initiative Not yet recruiting
Thabazimbi, South Africa, 380
East Rand Urology Research Unit Not yet recruiting
Vosloorus, South Africa, 1475
Thailand
Thai Red Cross Aids Research Centre Recruiting
Bangkok, Thailand, 10330
Queen Sirikit National Institute of Child Health Withdrawn
Bangkok, Thailand, 10400
Bamrasnaradura Infectious Disease Institute Recruiting
Nonthaburi, Thailand, 11000
Uganda
Mrc/ Uvri Uganda Research Unit on Aids Not yet recruiting
Entebbe, Uganda
Joint Clinical Research Centre Recruiting
Kampala, Uganda, 10005
Makerere University Medical School Withdrawn
Kampala, Uganda
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 ( Other Identifier: Janssen Sciences Ireland UC )
2008-001696-30 ( EudraCT Number )
First Posted: December 1, 2008    Key Record Dates
Last Update Posted: November 8, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Device Product: No

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
Lamivudine
Antiviral Agents
Emtricitabine
Zidovudine
Abacavir
Rilpivirine
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Antimetabolites