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 Gesù
• Portugal
  • Lisboa, Portugal, 1649-035
    • Chln - Hosp. Santa Maria
  • Porto, Portugal, 4200-319
    • Chsj - 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 11 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[24h]) of Rilpivirine (RPV)	AUC(24h) is area under the plasma concentration-time curve from time of administration to 24 hours postdose, calculated by linear-linear trapezoidal summation or population pharmacokinetic (PK) analysis.	Up to 24 hours postdose
Percentage of Participants with Grade 3 and 4 Adverse Events (AEs) and Serious Adverse Events (SAEs) Through Week 24	Percentage of participants with Grade 3 and 4 AEs will be assessed on Division of AIDS (DAIDS) grading table where Grade 3: Severe and Grade 4: Potentially Life-threatening. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is an AE deemed medically important, or is a suspected transmission of any infectious agent via a medicinal product, or is an AE resulting in any of the following outcomes: death, is life-threatening.	Up to Week 24
Percentage of Participants with Human Immunodeficiency Virus (HIV)-Related Events	Percentage of participants with HIV-related events HIV-related events (including acquired immune deficiency syndrome [AIDS]-defining illnesses and Stage-3-defining Opportunistic Illnesses in HIV Infection) through 24 weeks of study treatment will be reported.	Up to Week 24
Percentage of Participants Experiencing Premature Discontinuation due to AEs Through Week 24	Percentage of participants who prematurely discontinued study due to AEs will be reported.	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with AEs/Human Immunodeficiency Virus (HIV)-related Events Through 24 and 48 Weeks	Percentage of participants with AEs/HIV-related events through 24 and 48 weeks of study treatment will be reported.	Up to 24 and 48 weeks
Severity of AEs/HIV-related Events Through 24 and 48 Weeks of Study Treatment	Severity of AEs/HIV-related events will be assessed based on DAIDS grading table where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Potentially Life-threatening.	Up to 24 and 48 weeks
Percentage of Participants with Abnormalities in Clinically Laboratory Parameters	Percentage of participants with abnormalities in Clinically Laboratory results will be reported.	Up to 24 and 48 weeks
Percentage of Participants with Abnormalities in Electrocardiogram (ECG)	Percentage of participants with abnormalities in ECG will be reported.	Up to 24 and 48 weeks
Percentage of Participants with Abnormalities in Vital Signs	Percentage of participants with abnormalities in vital signs will be reported.	Up to 24 and 48 weeks
Percentage of Participants with Abnormalitie in Physical Examination	Percentage of participants with abnormalitie in physical examination will be reported.	Up to 24 and 48 weeks
Percentage of Participants with HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through 24 and 48 Weeks	Percentage of participants having viral load (plasma HIV-1 RNA levels) less than (<) 50 copies/milliliter (mL) and >=50 copies/mL measured by the Food and Drug Administration (FDA) snapshot algorithm will be reported. The FDA snapshot analysis is based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48).	Up to 24 and 48 weeks
Percentage of Participants with HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through 24 and 48 Weeks	Percentage of participants having viral load (plasma HIV-1 RNA levels) less than (<) 400 copies/milliliter (mL) and >=400 copies/mL measured by the Food and Drug Administration (FDA) snapshot algorithm will be reported. The FDA snapshot analysis is based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48).	Up to 24 and 48 weeks
Cluster Differentiation 4 (CD4+) Cell Count Through 24 and 48 Weeks	CD4+ cell count for immunologic changes will be determined through Weeks 24 and 48.	Up to 24 and 48 weeks
Predose Plasma Concentration (C0h) of RPV	C0h is defined as the predose plasma concentration or concentration just prior to study drug administration (observed and through population PK analysis).	Predose
Maximum Observed Plasma Concentration (Cmax) of RPV	Cmax is the maximum observed plasma concentration.	Predose, 2, 4, 5, 6, 9, 12, 24 hours postdose
Percentage of Participants with Virologic Failure	Percentage of participants with virologic failure (that is, HIV 1 RNA >=50 and >=400 copies/mL) per Snapshot approach will be reported.	Up to 24 and 48 weeks
Percentage of Participants with Treatment Adherence Based on Tablet Count Through 24 and 48 Weeks	Percentage of participants with treatment adherence as assessed by tablet count (study intervention accountability) through 24 and 48 weeks of study treatment will be reported.	Up to 24 and 48 weeks
Percentage of Participants with Treatment Adherence as Assessed by PENTA Adherence Questionnaire Through 24 and 48 Weeks	Percentage of participants with treatment adherence as assessed by the Pediatric European Network for the Treatment of AIDS (PENTA) adherence questionnaire through 24 and 48 weeks of study treatment will be reported. The responses to the PENTA adherence questionnaire will be tabulated at each time point. Treatment adherence will be further summarized per time point based on a "worst case" combination of results for a number of sponsor-selected questions, categorizing participants into "treatment adherent" and "treatment non-adherent".	Up to 24 and 48 weeks

Collaborators and Investigators

• Sponsor: 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): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme 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