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

HIV-1 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00799864
• Other study ID #: CR002677
• Secondary ID: TMC278-TiDP38-C2
• Status: Completed
• Phase: Phase 2
• Start date: January 7, 2011
• Est. completion date: August 16, 2022

Study information

• Verified date: July 2023
• Source: Janssen Sciences Ireland UC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: August 16, 2022
• Est. primary completion date: August 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV-1

Intervention

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.
• 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).
• 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).
• 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).
• 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).
• 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).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Sciences Ireland UC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration (Cmax)		Up to 48 weeks
Primary	Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve (AUC24)	AUC24 is defined area under the plasma concentration time curve from 0 to 24 hours post dosing of rilpivirine.	Up to 48 weeks
Secondary	Number of Patients with Adverse Events	Safety measures include adverse events, vital signs, physical examination, hematology, biochemistry and electrocardiogram.	Up to 244 weeks (Cohort 1 only) (including 4 week follow up visit)
Secondary	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 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.	Week 48 and Week 240 (Cohort 1 only)
Secondary	Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL by FDA Snapshot Approach	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.	Week 48 and Week 240 (Cohort 1 only)
Secondary	Evolution of viral genotype and phenotype	Blood samples will be collected for the determination of HIV-1 genotype and phenotype by the Protocol Virologist based on plasma viral load.	Up to 48 Weeks and 240 Weeks (Cohort 1 only)
Secondary	Treatment adherence as measured by the Study Adherence Questionnaire	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.	Up to 48 Weeks and 240 Weeks (Cohort 1 only)
Secondary	Change in Cluster of Differentiation (CD4+) cells	Change in the CD4+ cells will evaluate immunologic changes at Week 48 and Week 240 of treatment with rilpivirine.	Week 48 and Week 240 (Cohort 1 only)