Pharmacokinetics, Safety, Tolerability of Dolutegravir/Rilpivirine in Pediatrics

Phase 1/2 Study of Switching to Fixed Dose Combination Dolutegravir/Rilpivirine Among Virologically Suppressed Children, 6 to Less Than 12 Years of Age, Living With HIV-1

The purpose of this study is to provide data on the pharmacokinetic (PK), safety, tolerability, efficacy and acceptability of this fixed dose combination (FDC) single tablet 2-drug regimen for virologically suppressed (HIV-1 RNA [Ribonucleic Acid] < 50 [cells per milliliter] c/mL) children 6 to less than 12 years of age, weighing at least 25 kilogram (kg).

Study Overview

• Status: Recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Dolutegravir/Rilpivirine FDC

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Not yet recruiting
      • GSK Investigational Site
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
      • Principal Investigator: Jagmohan Batra
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • GSK Investigational Site
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
      • Principal Investigator: Natella Rahkmanina
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Lisa Gay Robinson
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
    • Miami, Florida, United States, 33136
      • Recruiting
      • GSK Investigational Site
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
      • Principal Investigator: Charles Mitchell
    • Tampa, Florida, United States, 33606
      • Not yet recruiting
      • GSK Investigational Site
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
      • Principal Investigator: Carina Rodriguez
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • GSK Investigational Site
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
      • Principal Investigator: Andres Camacho-Gonzalez
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • GSK Investigational Site
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
      • Principal Investigator: Susan Gillespie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Human immuno virus Type-1 (HIV-1) infected child 6 years to less than 12 years of age at the time of signing the informed consent form .
• Body weight greater than or equal to 25 kilogram (kg) at entry.
• Confirmed HIV-1-infection
• Participant has taken the same Antiretroviral therapy (ART) regimen in the 6 months (180 days) prior to Screening, as determined by the site investigator based on participant/parent/guardian report and available medical records.
• Has a plasma HIV-1 Ribonucleic Acid (RNA) result less than 50 copies/mL at Screening
• Has at least one documented plasma HIV-1 RNA result less than the lower limit of detection of the assay from a specimen collected in the 6-12 months (180-365 days) prior to Screening OR Has at least one documented plasma HIV-1 RNA result less than the lower limit of detection of the assay from a specimen collected less than 6 months (within 179 days) prior to entry and at least one documented plasma HIV-1 RNA result less than the lower limit of detection of the assay from a specimen collected in the 12-18 months (365-545 days) prior to Screening
• For participants of reproductive potential (defined as having reached menarche), not pregnant based on testing performed at Screening (i.e., from a specimen collected within 30 days prior to entry) and at Baseline/Day 1.
• For participants of reproductive potential who are engaging in sexual activity that could lead to pregnancy, willing to use two methods of contraception while receiving study drug and for approximately one month after permanently discontinuing study drug, based on participant/parent/guardian report at entry.
• For participants of reproductive potential, not breastfeeding based on participant/parent/ guardian report at Baseline/Day 1.

Exclusion Criteria:

• Documented resistance (ever) to Non-nucleoside reverse transcriptase inhibitors (NNRTIs) or integrase inhibitors
• Documented HIV-1 RNA result greater than or equal to the lower limit of detection of the assay based on a specimen collected in the 12 months (365 days) prior to Screening
• Any change (ever) of any Antiretroviral (ARV) agent due to virologic failure, as determined by the site investigator based on participant/parent/guardian report and available medical records
• Has a history (ever) of allergy to DTG, RPV, or any other component of JULUCA as determined by the site investigator based on participant/parent/guardian report and available medical records.
• Has a history (ever) of congestive heart failure, symptomatic arrhythmia, or any clinically significant cardiac disease as determined by the site investigator based on participant/ parent/guardian report and available medical records
• Has a history (ever) of unstable liver disease (defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) as determined by the site investigator based on participant/parent/guardian report and available medical records
• Has any of the following as determined by the site investigator based on participant/ parent/guardian report and available medical records: Current clinical evidence of pancreatitis; Currently active AIDS-defining (WHO Clinical Stage 4) opportunistic infection; Currently active TB and/or current rifamycin-containing TB treatment.
• Has an anticipated need for any HCV therapy during the first 24 weeks of study and for HCV therapy based on interferon or any drugs that have a potential for adverse drug: drug interactions with study treatment throughout the entire study period.
• Receipt of the following as determined by the site investigator based on participant/ parent/guardian report and available medical records: Any investigational agent within 90 days prior to entry; Any prohibited medication within 30 days prior to entry; Any medication with a known risk of Torsades de Pointes within seven days prior to entry
• Receipt (ever) of an ART regimen that included both DTG and RPV, as determined by the site investigator based on participant/parent/guardian report and available medical records
• Any ≥ grade 3 result for the following based on grading per the Division of Acquired Immunodeficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events: Haemoglobin (<8.5 gram per deciliter [g/dL] or <5.25 millimoles per liter [mmol/L]); Absolute neutrophil count (<600 cells/mm^3 or <0.600 x 109 cells/L); Platelet count (<50,000cells/mm^3 or <50.00 x 109 cells/L); Estimated glomerular filtration rate (eGFR: <60ml/min/1.73m^2); ALT (≥5.0 x Upper limit of Normal [ULN]); Aspartate Aminotransferase (AST) (≥5.0 x ULN)
• Has the following combination of laboratory test results at screening: Alanine transaminase [ALT] greater than or equal to 3 x ULN and total bilirubin greater than or equal to 1.5 x ULN and direct bilirubin greater than 35% of total bilirubin
• Evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening.
• QTc >450 milliseconds (msec) at Screening
• Severe acute malnutrition (Body Mass Index [BMI] for age <-3 or nutritional oedema)
• Has any documented or suspected clinically significant medical or psychiatric condition or any other condition that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.
• The child is a ward of State or government.

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: Dolutegravir(DTG)/Rilpivirine (RPV)	Drug: Dolutegravir/Rilpivirine FDC; Dolutegravir/Rilpivirine will be administered.; Other Names: JULUCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the curve (AUC0-24h) of DTG	Up to Week 24
Area under the curve (AUC0-24h) of RPV	Up to Week 24
Number of Participants with Adverse Events (AEs) at Week 24	At Week 24
Number of Participants with Grade 3 or higher AEs at Week 24	At Week 24
Number of Participants with Grade 3 or higher AEs assessed as related to study drug at Week 24	At Week 24
Number of Participants with Fatal AEs assessed as related to study drug at Week 24	At Week 24
Number of Participants with Serious Adverse Events (SAEs) assessed as related to study drug at Week 24	At Week 24
Number of Participants with AEs assessed as related to study drug that led to permanent discontinuation of study drug at Week 24	At Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants with HIV-1 RNA less than 50 copies per milliliter (c/mL)	At Week 24 and 48
Cluster of differentiation 4 (CD4+) Cell Count	At Week 24 and 48
Percentage of CD4+ Cell Count	At Week 24 and 48
Number of Participants with Adverse Events (AEs) at Week 48	At Week 48
Number of Participants with Grade 3 or higher AEs at Week 48	At Week 48
Number of Participants with Grade 3 or higher AEs assessed as related to study drug at Week 48	At Week 48
Number of Participants with Fatal AEs assessed as related to study drug at Week 48	At Week 48
Number of Participants with Serious Adverse Events (SAEs) assessed as related to study drug at Week 48	At Week 48
Number of Participants with AEs assessed as related to study drug that led to permanent discontinuation of study drug at Week 48	At Week 48
Minimum drug concentration (Cmin) of DTG	Up to Week 24
Cmin of RPV	Up to Week 24
Cmin of DTG at Week 4 Visit	Pre-dose, 1, 2, 4, 5, 6, 10 and 24 hours (h) post-dose at Week 4
Cmin of RPV at Week 4 Visit	Pre-dose, 1, 2, 4, 5, 6, 10 and 24 hours (h) post-dose at Week 4
Concentration of HIV-1 RNA	Baseline (Day 1), Week 4, 8, 12, 16, 20, 24, 36 and 48
Number of Participants with HIV-1 Genotype at the time of Virologic failure (HIV-1 RNA greater than or equal to 200 copies/mL)	Baseline (Day 1) and up to Week 48
Number of Participants with HIV-1 Phenotype at the time of Virologic failure (HIV-1 RNA greater than or equal to 200 copies/mL)	Up to Week 48
Number of Participants with HIV-1 genotypes at Baseline, Week 24 and 48	Baseline (Day 1), Week 24 and 48
Number of Participants with Acceptability to JULUCA	At Week 4, 24 and 48
Number of Participants with Adherence to JULUCA	At Week 4, 24 and 48

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: Janssen Research & Development, LLC
• Investigators: Study Director: GSK Clinical Trials, ViiV Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Estimated): July 22, 2025
• Study Completion (Estimated): June 8, 2027

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: January 5, 2023
• First Posted (Actual): January 6, 2023

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Dolutegravir; Rilpivirine; JULUCA
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; 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; HIV Integrase Inhibitors; Integrase Inhibitors; Dolutegravir; Rilpivirine; Dolutegravir, rilpivirine drug combination
• Other Study ID Numbers: 205868; 2022-000829-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No