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Pharmacokinetics, Safety, Tolerability of Dolutegravir/Rilpivirine in Pediatrics

Primary Purpose

HIV Infections

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Dolutegravir/Rilpivirine FDC
Sponsored by
ViiV Healthcare
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Dolutegravir, Rilpivirine, JULUCA

Eligibility Criteria

6 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Dolutegravir(DTG)/Rilpivirine (RPV)

    Arm Description

    Outcomes

    Primary Outcome Measures

    Area under the curve (AUC0-24h) of DTG
    Area under the curve (AUC0-24h) of RPV
    Number of Participants with Adverse Events (AEs) at Week 24
    Number of Participants with Grade 3 or higher AEs at Week 24
    Number of Participants with Grade 3 or higher AEs assessed as related to study drug at Week 24
    Number of Participants with Fatal AEs assessed as related to study drug at Week 24
    Number of Participants with Serious Adverse Events (SAEs) assessed as related to study drug 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

    Secondary Outcome Measures

    Proportion of Participants with HIV-1 RNA less than 50 copies per milliliter (c/mL)
    Cluster of differentiation 4 (CD4+) Cell Count
    Percentage of CD4+ Cell Count
    Number of Participants with Adverse Events (AEs) at Week 48
    Number of Participants with Grade 3 or higher AEs at Week 48
    Number of Participants with Grade 3 or higher AEs assessed as related to study drug at Week 48
    Number of Participants with Fatal AEs assessed as related to study drug at Week 48
    Number of Participants with Serious Adverse Events (SAEs) assessed as related to study drug 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
    Minimum drug concentration (Cmin) of DTG
    Cmin of RPV
    Cmin of DTG at Week 4 Visit
    Cmin of RPV at Week 4 Visit
    Concentration of HIV-1 RNA
    Number of Participants with HIV-1 Genotype at the time of Virologic failure (HIV-1 RNA greater than or equal to 200 copies/mL)
    Number of Participants with HIV-1 Phenotype at the time of Virologic failure (HIV-1 RNA greater than or equal to 200 copies/mL)
    Number of Participants with HIV-1 genotypes at Baseline, Week 24 and 48
    Number of Participants with Acceptability to JULUCA
    Number of Participants with Adherence to JULUCA

    Full Information

    First Posted
    December 7, 2022
    Last Updated
    May 9, 2023
    Sponsor
    ViiV Healthcare
    Collaborators
    Janssen Research & Development, LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05674656
    Brief Title
    Pharmacokinetics, Safety, Tolerability of Dolutegravir/Rilpivirine in Pediatrics
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 1, 2023 (Anticipated)
    Primary Completion Date
    February 26, 2025 (Anticipated)
    Study Completion Date
    January 13, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    ViiV Healthcare
    Collaborators
    Janssen Research & Development, LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HIV Infections
    Keywords
    Dolutegravir, Rilpivirine, JULUCA

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Dolutegravir(DTG)/Rilpivirine (RPV)
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Dolutegravir/Rilpivirine FDC
    Other Intervention Name(s)
    JULUCA
    Intervention Description
    Dolutegravir/Rilpivirine will be administered.
    Primary Outcome Measure Information:
    Title
    Area under the curve (AUC0-24h) of DTG
    Time Frame
    Up to Week 24
    Title
    Area under the curve (AUC0-24h) of RPV
    Time Frame
    Up to Week 24
    Title
    Number of Participants with Adverse Events (AEs) at Week 24
    Time Frame
    At Week 24
    Title
    Number of Participants with Grade 3 or higher AEs at Week 24
    Time Frame
    At Week 24
    Title
    Number of Participants with Grade 3 or higher AEs assessed as related to study drug at Week 24
    Time Frame
    At Week 24
    Title
    Number of Participants with Fatal AEs assessed as related to study drug at Week 24
    Time Frame
    At Week 24
    Title
    Number of Participants with Serious Adverse Events (SAEs) assessed as related to study drug at Week 24
    Time Frame
    At Week 24
    Title
    Number of Participants with AEs assessed as related to study drug that led to permanent discontinuation of study drug at Week 24
    Time Frame
    At Week 24
    Secondary Outcome Measure Information:
    Title
    Proportion of Participants with HIV-1 RNA less than 50 copies per milliliter (c/mL)
    Time Frame
    At Week 24 and 48
    Title
    Cluster of differentiation 4 (CD4+) Cell Count
    Time Frame
    At Week 24 and 48
    Title
    Percentage of CD4+ Cell Count
    Time Frame
    At Week 24 and 48
    Title
    Number of Participants with Adverse Events (AEs) at Week 48
    Time Frame
    At Week 48
    Title
    Number of Participants with Grade 3 or higher AEs at Week 48
    Time Frame
    At Week 48
    Title
    Number of Participants with Grade 3 or higher AEs assessed as related to study drug at Week 48
    Time Frame
    At Week 48
    Title
    Number of Participants with Fatal AEs assessed as related to study drug at Week 48
    Time Frame
    At Week 48
    Title
    Number of Participants with Serious Adverse Events (SAEs) assessed as related to study drug at Week 48
    Time Frame
    At Week 48
    Title
    Number of Participants with AEs assessed as related to study drug that led to permanent discontinuation of study drug at Week 48
    Time Frame
    At Week 48
    Title
    Minimum drug concentration (Cmin) of DTG
    Time Frame
    Up to Week 24
    Title
    Cmin of RPV
    Time Frame
    Up to Week 24
    Title
    Cmin of DTG at Week 4 Visit
    Time Frame
    Pre-dose, 1, 2, 4, 5, 6, 10 and 24 hours (h) post-dose at Week 4
    Title
    Cmin of RPV at Week 4 Visit
    Time Frame
    Pre-dose, 1, 2, 4, 5, 6, 10 and 24 hours (h) post-dose at Week 4
    Title
    Concentration of HIV-1 RNA
    Time Frame
    Baseline (Day 1), Week 4, 8, 12, 16, 20, 24, 36 and 48
    Title
    Number of Participants with HIV-1 Genotype at the time of Virologic failure (HIV-1 RNA greater than or equal to 200 copies/mL)
    Time Frame
    Baseline (Day 1) and up to Week 48
    Title
    Number of Participants with HIV-1 Phenotype at the time of Virologic failure (HIV-1 RNA greater than or equal to 200 copies/mL)
    Time Frame
    Up to Week 48
    Title
    Number of Participants with HIV-1 genotypes at Baseline, Week 24 and 48
    Time Frame
    Baseline (Day 1), Week 24 and 48
    Title
    Number of Participants with Acceptability to JULUCA
    Time Frame
    At Week 4, 24 and 48
    Title
    Number of Participants with Adherence to JULUCA
    Time Frame
    At Week 4, 24 and 48

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    6 Years
    Maximum Age & Unit of Time
    12 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    US GSK Clinical Trials Call Center
    Phone
    877-379-3718
    Email
    GSKClinicalSupportHD@gsk.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    EU GSK Clinical Trials Call Center
    Phone
    +44 (0) 20 89904466
    Email
    GSKClinicalSupportHD@gsk.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    GSK Clinical Trials
    Organizational Affiliation
    ViiV Healthcare
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing 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.

    Learn more about this trial

    Pharmacokinetics, Safety, Tolerability of Dolutegravir/Rilpivirine in Pediatrics

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