A Study of Switching to RPV Plus Other ARVs in HIV-1-infected Children (Aged 2 to <12 Years) Who Are Virologically Suppressed

A Phase 2, Open-label, Single-arm, Multicenter Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Efficacy of Switching to RPV Plus Other ARVs in HIV-1-infected Children (Aged 2 to <12 Years) Who Are Virologically Suppressed

The purpose of this study is to evaluate the steady state pharmacokinetics (PK) of rilpivirine (RPV) and determine the appropriate dose of RPV in combination with other antiretrovirals (ARVs) in participants aged greater than or equal to 2 to less than 12 years and to evaluate the safety and tolerability of RPV in combination with other ARVs in participants of same age group over a 48-week treatment period with primary endpoint at Week 24.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Rilpivirine; Drug: ARV Background Regimen

Detailed Description

Participants infected with human immunodeficiency virus type 1 (HIV-1) are routinely treated with combinations of multiple drugs which reduces HIV-1 ribonucleic acid (RNA) to undetectable levels in a substantial proportion of participants and counteracts the risk of viral resistance development. RPV is a potent non-nucleoside reverse transcriptase inhibitor (NNRTI) with in vitro activity against wild type (WT) HIV-1 and against NNRTI-resistant HIV-1 mutants. A medical need still exists for the development of age/weight appropriate formulations in children less than (<) 12 years of age. In this study, participants will switch to RPV plus other ARVs. The primary analysis will be performed at Week 24. A participant will be considered to have completed the study if he or she has completed assessments at Week 48 of the study intervention phase. The total study duration for each participant, including screening and study intervention phases, will be approximately 54 weeks. Key efficacy assessments include determination of plasma HIV-1 RNA viral load and measurement of CD4+ cell count. Key safety assessments will include the monitoring of (serious) adverse events ([S]AEs) and HIV-related events, clinical laboratory tests, cardiovascular safety monitoring (vital signs and 12 lead electrocardiogram [ECGs]), and physical examination (including growth).

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Brescia, Italy, 25123
    • Asst Spedali Civili Di Brescia
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Roma, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesu
• Portugal
  • Lisboa, Portugal, 1649 035
    • Uls Santa Maria - Hosp. Santa Maria
  • Porto, Portugal, 4200 319
    • Uls Sao Joao - Hosp. Sao Joao
• South Africa
  • Bloemfontein, South Africa, 9301
    • Josha Research
  • Tygerberg, South Africa, 7505
    • Family Clinical Research Unit FAM-CRU
• Spain
  • Esplugues De Llobregat, Spain, 08950
    • Hosp. Sant Joan de Deu
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital Mahidol University
  • Chiang Mai, Thailand, 50200
    • Research Institute For Health Sciences
  • Nonthaburi, Thailand, 11000
    • Bamrasnaradura Infectious Disease Institute
• Uganda
  • Kampala, Uganda, 10005
    • Joint Clinical Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Weighing at least 10 kilogram (kg) at screening
• Have documented chronic Human Immunodeficiency Virus (HIV-1) infection
• On a stable antiretroviral (ARV) regimen for at least 6 months prior to screening and virologically suppressed with documented evidence of at least 2 plasma viral loads less than (<) 50 HIV-1 ribonucleic acid (RNA) copies/milliliter (mL): one within 2-12 months prior to screening and one at screening
• Can switch from any ARV class
• Never been treated with a therapeutic HIV vaccine
• Historical HIV-1 genotyping result at screening for children aged >=2 to <6 years (and for children aged >=6 to <12 years if a historical HIV-1 genotyping result is available at screening) must demonstrate sensitivity to RPV and to the selected background ARVs

Exclusion Criteria:

• Have previously documented HIV-2 infection
• Have known or suspected acute (primary) HIV-1 infection
• Taken any disallowed concomitant therapies within 4 weeks before the planned first dose of study intervention
• Any current or history of adrenal disorder
• A history of virologic failure to ARVs with or without availability of an HIV-1 genotype result at the time of failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Rilpivirine (RPV) (25 mg or adjusted weight-based dose); Participants will receive rilpivirine (RPV 25 milligram [mg], adjusted weight-based dose) orally once daily in combination with an investigator selected background regimen (that is investigator-selected antiretrovirals [ARVs] such as nucleoside/nucleotide reverse transcriptase inhibitor [N{t}RTIs] and integrase inhibitors) for 48 weeks.

Drug: Rilpivirine; Rilpivirine 25 mg tablets for the 25 mg daily dose, or tablets for or a weight-adjusted dose. Administered orally once daily.; Other Names: TMC278; Drug: ARV Background Regimen; The investigator-selected ARVs, including but not limited to N(t)RTIs (example, azidothymidine [AZT], abacavir [ABC], tenofovir alafenamide [TAF], or tenofovir disoproxil fumarate [TDF] in combination with emtricitabine [FTC] or lamivudine [3TC]), whichever are approved and marketed or considered local standard of care for children aged between 2 and < 12 years in a particular country are to be administered. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) can also be administered in combination with RPV, as appropriate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 12.5 mg (for <20 kg Group)	AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing <20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the <20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 15 mg (for <20 kg Group)	AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 15 mg (for 20 to <25 mg Group)	AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 25 mg (for >=25 kg Group)	AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48	Percentage of participants with a HIV-1 RNA less than (<) 50 copies per mL and greater than or equal to (>=)50 copies/mL were assessed using Food and Drug Administration (FDA) snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within a window of time, along with study drug discontinuation status. HIV-1 RNA level <50 copies per mL, was considered as virologic success and >= 50 copies/mL was considered as virological failure as per the snapshot approach. The FDA snapshot analysis at Week 24 and Week 48 was based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48).	From Day 1 up to Weeks 24 and 48
Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48	Percentage of participants with viral load (plasma HIV-1 RNA levels) <400 copies/mL and >=400 copies/mL were assessed by the FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within a window of time, along with study drug discontinuation status. HIV-1 RNA level <400 copies per mL, was considered as virologic success and >=400 copies/mL was considered as virological failure as per the snapshot approach. The FDA snapshot analysis at Week 24 and Week 48 was based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48).	From Day 1 up to Weeks 24 and 48
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48	The immunologic change was determined by changes in CD4+ cell count using non-completer = failure imputation, that was, missing values after discontinuation were imputed with the baseline value, thus resulting in a 0 change. For intermittent missing data, last observation carried forward (LOCF) approach was applied.	From baseline (Day 1) up to Weeks 24 and 48
Predose Plasma Concentration (C[0h]) of Rilpivirine 12.5 mg (for <20 kg Group)	C(0h) was defined as the predose plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing <20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the <20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose at anytime during Day 28 to Day 32 (Week 4)
Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for <20 kg Group)	C(0h) was defined as the predose plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose at anytime during Day 28 to Day 32 (Week 4)
Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for 20 to <25 kg Group)	C(0h) was defined as the predose plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose at anytime during Day 28 to Day 32 (Week 4)
Predose Plasma Concentration (C[0h]) of Rilpivirine 25 mg (for >=25 kg Group)	C(0h) was defined as the predose plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose at anytime during Day 28 to Day 32 (Week 4)
Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 12.5 mg (for <20 kg Group)	Cmax was defined as the maximum observed plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing <20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the <20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for <20 kg Group)	Cmax was defined as the maximum observed plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for 20 to <25 mg Group)	Cmax was defined as the maximum observed plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 25 mg (for >=25 kg Group)	Cmax was defined as the maximum observed plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Percentage of Participants With Viral Genotype at the Time of Virologic Failure at Weeks 24 and 48	Percentage of participants with viral genotype at the time of virologic failure (that is, HIV 1 RNA >=50 copies/mL and >=400 copies/mL) per FDA snapshot approach were reported. Confirmed virologic failure was defined as 2 consecutive HIV-1 RNA plasma viral load measurements >=200 copies/mL and suspected virologic failure was defined as HIV-1 RNA >=200 copies/mL. No participant achieved virologic failure hence this outcome measure could not be evaluated.	Weeks 24 and 48
Percentage of Participants With Treatment Adherence >95% Based on Tablet Count up to Weeks 24 and 48	Percentage of participants with treatment adherence greater than (>) 95 percent (%) as assessed by tablet count (study intervention accountability) up to Weeks 24 and 48 of study treatment were reported. Treatment adherence was defined as having a treatment adherence of >95% by tablet count.	From Day 1 up to Weeks 24 and 48
Change From Baseline in Percentage of Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48	The immunologic change was determined by changes in CD4+ cell count using non-completer = failure imputation, that was, missing values after discontinuation were imputed with the baseline value, thus resulting in a 0 change. For intermittent missing data, last observation carried forward (LOCF) approach was applied.	From baseline (Day 1) up to Weeks 24 and 48

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2019
• Primary Completion (Actual): February 17, 2023
• Study Completion (Actual): February 23, 2023

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 9, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Rilpivirine
• Other Study ID Numbers: CR108606; 2018-004301-32 (EudraCT Number); TMC278HTX2002 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes