Clinical trial NCT04012931: A Study of Switching to RPV Plus Other ARVs in HIV-1-infected Children (Aged 2 to <12 Years) Who Are Virologically Suppressed
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-07-09
Enrollment: 26
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
measure: 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)
timeFrame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
measure: 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)
timeFrame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
measure: 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)
timeFrame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Secondary outcomes:
measure: Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48
timeFrame: From Day 1 up to Weeks 24 and 48
measure: Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48
timeFrame: From Day 1 up to Weeks 24 and 48
measure: Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48
timeFrame: From baseline (Day 1) up to Weeks 24 and 48
measure: Predose Plasma Concentration (C[0h]) of Rilpivirine 12.5 mg (for <20 kg Group)
timeFrame: Predose at anytime during Day 28 to Day 32 (Week 4)
measure: Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for <20 kg Group)
timeFrame: Predose at anytime during Day 28 to Day 32 (Week 4)
measure: Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for 20 to <25 kg Group)
timeFrame: Predose at anytime during Day 28 to Day 32 (Week 4)
measure: Predose Plasma Concentration (C[0h]) of Rilpivirine 25 mg (for >=25 kg Group)
timeFrame: Predose at anytime during Day 28 to Day 32 (Week 4)
measure: Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 12.5 mg (for <20 kg Group)
timeFrame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
measure: Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for <20 kg Group)
timeFrame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
measure: Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for 20 to <25 mg Group)
timeFrame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
measure: Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 25 mg (for >=25 kg Group)
timeFrame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
measure: Percentage of Participants With Viral Genotype at the Time of Virologic Failure at Weeks 24 and 48
timeFrame: Weeks 24 and 48
measure: Percentage of Participants With Treatment Adherence >95% Based on Tablet Count up to Weeks 24 and 48
timeFrame: From Day 1 up to Weeks 24 and 48
measure: Change From Baseline in Percentage of Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48
timeFrame: From baseline (Day 1) up to Weeks 24 and 48
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu
city: Lisboa
country: Portugal
facility: Uls Santa Maria - Hosp. Santa Maria
city: Porto
country: Portugal
facility: Uls Sao Joao - Hosp. Sao Joao
city: Bloemfontein
country: South Africa
facility: Josha Research
city: Tygerberg
country: South Africa
facility: Family Clinical Research Unit FAM-CRU
city: Esplugues De Llobregat
country: Spain
facility: Hosp. Sant Joan de Deu
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Bangkok
country: Thailand
facility: Siriraj Hospital Mahidol University
city: Chiang Mai
country: Thailand
facility: Research Institute for Health Sciences
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Infectious Disease Institute
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: