HIV InfectionsPhase 1/2NCT03760458
The Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age
A Phase 1/2 study testing Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Dispersible Tablets and Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Immediate Release Tablets (Immediate release) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 14 sites in 4 countries.
Trial summary
The purpose of this study was to examine the pharmacokinetics, safety, and tolerability of abacavir/dolutegravir/lamivudine dispersible and immediate release tablets in children living with HIV less than 12 years of age. Read more about this study
- Who is it for?
- Ages Up to 11 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Dispersible Tablets and Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Immediate Release Tablets (Immediate release)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 14 sitesin 4 countries
- Study dates
- 9 Sep 2020to 31 May 2022
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Weight 6 kg to less than 40 kg at entry
- Antiretroviral therapy (ART)-naïve at entry or has been taking a stable ART regimen for at least six consecutive months at entry
- Note: For ART-naïve children, receipt of antiretroviral (ARV) prophylaxis prior to diagnosis of HIV infection is permitted. For these children, ascertainment of this criterion may be based on parent or guardian report only, but available medical records should also be reviewed in relation to this criterion.
- Note: For ART-experienced children (on a stable ART regimen), dose and formulation changes (e.g., for growth) within the six months prior to entry are permitted. For these children, ascertainment of this criterion must be based on medical records.
- For ART-experienced children (on a stable ART regimen), has had a suppressed HIV viral load (HIV-1 RNA less than 200 copies/mL) for at least six consecutive months prior to entry
- Note: To fulfill this criterion, at least two documented HIV-1 RNA results less than 200 copies/mL must be available, one based on a specimen collected at least six months prior to entry and one based on a specimen collected within 30 days prior to entry.
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- Note: Any documented HIV-1 RNA result greater than or equal to 200 copies/mL based on a specimen collected within six months prior to entry is exclusionary (see exclusion criterion below).
- At screening, has normal, Grade 1, or Grade 2 laboratory test results for all of the following, based on testing of specimens collected within 30 days prior to entry and grading per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (refer to the study protocol for guidance on severity grading):
- Hemoglobin (greater than or equal to 8.5 g/dL or greater than or equal to 5.25 mmol/L)
- Absolute neutrophil count (greater than or equal to 600 cells/mm^3 or greater than or equal to 0.600 x 10^9 cells/L)
- Platelet count (greater than or equal to 50,000 cells/mm^3 or greater than or equal to 50.00 x 10^9 cells/L)
- Estimated glomerular filtration rate (eGFR; bedside Schwartz formula; greater than or equal to 60 ml/min/1.73 m^2)
- Alanine transaminase (ALT) (less than 5.0 x ULN)
- Aspartate aminotransferase (AST) (less than 5.0 x ULN)
- Total bilirubin (less than 2.6 x ULN)
- Direct bilirubin (less than or equal to ULN)
- Note: Laboratory tests may be repeated during the screening period (i.e., within 30 days prior to entry), with the latest results used for eligibility determination.
- Note: For treatment-experienced children on an atazanavir-containing ART regimen, Grade 3 or higher total bilirubin is permitted.
- At screening, has a negative test result for hepatitis B surface antigen based on testing of a specimen collected within 30 days prior to entry
- Confirmed HIV-1-infection based on documented testing of two samples collected at different time points:
- Sample #1 may be tested using any of the following:
- Two rapid antibody tests from different manufacturers or based on different principles and epitopes
- One enzyme immunoassay OR Western Blot OR immunofluorescence assay OR chemiluminescence assay
- One HIV DNA polymerase chain reaction (PCR)*
- One quantitative HIV RNA PCR (above the limit of detection of the assay)*
- One qualitative HIV RNA PCR*
- One HIV total nucleic acid test*
- Sample #2 may be tested using any of the following:
- Rapid antibody test. If this option is used in combination with two rapid tests for Sample #1, at least one of the three rapid tests must be United States Food and Drug Administration (FDA)-approved, and the third rapid test must be from a third manufacturer or based on a third principle or epitope.
- One enzyme immunoassay OR Western Blot OR immunofluorescence assay OR chemiluminescence assay
- One HIV DNA PCR*
- One quantitative HIV RNA PCR (above the limit of detection of the assay)*
- One qualitative HIV RNA PCR*
- One HIV total nucleic acid test*
- For participants who are less than two years of age, or who are two years of age and older with any exposure to breast milk in the past 28 days, HIV-1 infection must be confirmed using the tests indicated above with an asterisk (*) for Sample #1 and Sample #2.
- Whole blood, plasma, or serum samples must be tested. If both samples are tested using antibody tests, at least one of the samples must be tested in a laboratory that operates according to Good Clinical Laboratory Practice guidelines and participates in an appropriate external quality assurance program. If nucleic acid testing is used, at least one test must be performed in a Clinical Laboratory Improvement Amendments (CLIA) certified (for US sites) or Virology Quality Assurance (VQA) certified (for non-US sites) laboratory. For tests performed in other settings, adequate source documentation including the date of specimen collection, date of testing, test performed, and test result must be available. FDA approved testing methods should be used when possible.
- HLA-B*5701-negative based on documented testing at any time prior to entry
- Note: Documented testing is required even if the potential participant has received ABC prior to study entry.
- For females of reproductive potential (defined as having experienced menarche), not pregnant based on testing performed at screening
- For females 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, based on participant and parent or guardian report at entry
- One of the two methods must be highly effective; highly effective methods include surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy) and the following:
- Contraceptive intrauterine device or intrauterine system
- Subdermal contraceptive implant
- Progestogen injections
- Combined estrogen and progestogen oral contraceptive pills
- Percutaneous contraceptive patch
- Contraceptive vaginal ring
- The highly effective method must be initiated prior to study entry. The second method should ideally be a barrier method. Male or female condom use is recommended with all other methods of contraception for dual protection against pregnancy and to avoid transmission of HIV and other sexually transmitted infections.
- Based on parent or guardian report at entry, child is expected to be available for 48 weeks of follow-up
- Parent or legal guardian is willing and able to provide written informed consent for child's study participation and, when applicable per local institutional review board/ethics committee (IRB/EC) policies and procedures, child is willing and able to provide written informed assent for study participation
Who cannot join
- Documented resistance to ABC, DTG, or 3TC
- Note: Testing to rule out resistance is not required, and the M184V resistance mutation is not exclusionary.
- For ART-experienced children (on a stable ART regimen), documented HIV-1 RNA result greater than or equal to 200 copies/mL based on a specimen collected within six months prior to entry
- History of any of the following as determined by the site investigator based on participant/parent/guardian report and available medical records:
- Malignancy (ever)
- Hypersensitivity reaction to ABC (ever)
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- Receipt of any prohibited medication (refer to the study protocol for more information) within 30 days prior to study entry
- Receipt of systemic interferon or any chronic systemic immunosuppressant medication within 30 days prior to study entry
- Note: Systemic corticosteroids (e.g., prednisone or equivalent up to 2 mg/kg) taken for replacement or short course therapy are permitted. Intranasal or inhaled steroid use is also permitted.
- 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 tuberculosis (TB) and/or currently receiving rifampicin-containing TB treatment
- Currently-active AIDS-defining (WHO Clinical Stage 4) opportunistic infection
- Has any documented or suspected clinically significant medical 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 the study objectives
Trial locations and contacts
14 sites in 4 countries.
14 sites in 4 countries
United States5 sites
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, 80045
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, 60612
Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, 60614-3393
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, 90095-1752
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, 38105-3678
South Africa4 sites
Soweto IMPAACT CRS
Johannesburg, Gauteng, 1862
Wits RHI Shandukani Research Centre CRS
Johannesburg, Gauteng, 2001
Famcru Crs
Tygerberg, Western Cape, 7505
Umlazi CRS
Umlazi, KwaZulu-Natal, 4066
Thailand3 sites
Siriraj Hospital, Mahidol University NICHD CRS
Bangkok, Bangkoknoi, 10700
Chiangrai Prachanukroh Hospital NICHD CRS
Changklan, Muang, Chiang Mai, 50100
Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
Chiang Mai, 50200
About this study
Official title: Phase I/II Study of the Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age
The purpose of this study was to examine the pharmacokinetics, safety, and tolerability of abacavir/dolutegravir/lamivudine dispersible and immediate release tablets in children living with HIV less than 12 years of age.
Read the detailed description
This study examined the pharmacokinetics (PK), safety, and tolerability of fixed-dose combination abacavir (ABC)/dolutegravir (DTG)/lamivudine (3TC) dispersible and immediate release tablets in children living with HIV less than 12 years of age.
Children were enrolled into one of five ABC/DTG/3TC dosing groups based on their weight. The first 5-7 children within each weight-band underwent intensive PK assessments 5-10 days after starting ABC/DTG/3TC to confirm dose selection. Children remained on their initial dose of ABC/DTG/3TC through Week 4. After Week 4, ABC/DTG/3TC dosing was adjusted based on PK results at the individual or weight-band level, and/or an individual child's growth and weight gain over time.
Follow-up study visits for all participants occurred at Weeks 1, 4, 12, 24, 36, and 48. If participants had a known M184 resistance mutation, they had additional study visits at Weeks 8, 16, and 20. Study visits included physical examination, study drug adherence and tolerability questionnaires, blood collection, and intensive PK sampling. Following the Week 48 study visit, some children were allowed to continue follow-up through up to 144 weeks if alternative post-study drug supply was not yet available.
- Conditions
- HIV Infections
- Being tested
- Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Dispersible Tablets, Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Immediate Release Tablets (Immediate release)
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Dispersible TabletsDrug
Fixed-dose combination dispersible tablets containing 60 mg ABC, 5 mg DTG, and 30 mg 3TC; administered orally once daily with or without food
Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Immediate Release Tablets (Immediate release)Drug
Also called Triumeq
Fixed-dose combination immediate release tablets containing 600 mg ABC, 50 mg DTG, and 300 mg 3TC; administered orally once daily with or without food
| Study group | Role | What they receive |
|---|---|---|
| Weight Band #1 (6 to less than 10 kg at study entry) | Experimental | Children weighing 6 to less than 10 kg at study entry. These children received 3 dispersible tablets of ABC/DTG/3TC daily while weighing 6-<10 kg; as their weight increased, they received higher doses consistent with their new weight band. Receives: Drug: Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Dispersible Tablets |
| Weight Band #2 (10 to less than 14 kg at study entry) | Experimental | Children weighing 10 to less than 14 kg at study entry. These children received 4 dispersible tablets of ABC/DTG/3TC daily while weighing 10-<14 kg; as their weight increased, they received higher doses consistent with their new weight band. Receives: Drug: Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Dispersible Tablets |
| Weight Band #3 (14 to less than 20 kg at study entry) | Experimental | Children weighing 14 to less than 20 kg at study entry. These children received 5 dispersible tablets of ABC/DTG/3TC daily while weighing 14-<20 kg; as their weight increased, they received higher doses consistent with their new weight band. Receives: Drug: Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Dispersible Tablets |
| Weight Band #4 (20 to less than 25 kg at study entry) | Experimental | Children weighing 20 to less than 25 kg at study entry. These children received 6 dispersible tablets of ABC/DTG/3TC daily while weighing 20-<25 kg; as their weight increased, they received higher doses consistent with their new weight band. Receives: Drug: Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Dispersible Tablets |
| Weight Band #5 (25 kg or greater at study entry) | Experimental | Children weighing 25 kg or greater at study entry. These children received 1 immediate release tablet of ABC/DTG/3TC daily. Receives: Drug: Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Immediate Release Tablets (Immediate release) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric Mean Area Under the Plasma Concentration-time Curve Over 24 Hours (AUC0-24h) for ABC, DTG, and 3TC
Based on analysis of intensive pharmacokinetic (PK) samples. The geometric mean AUC0-24h for each Weight Band was compared to the lower and upper reference values (in ug*h/mL) for DTG (35.1, 134), ABC (6.3, 50.4), and 3TC (6.3, 26.5). Steady state was measured at Week 1, but was re-collected later for two participants due to a specimen handling error for the Week 1 specimens.
Measured: Week 1; Blood samples were drawn at pre-dose and 1, 2, 3, 4, 6, 8, and 24 hours post dosing.
Geometric Mean Maximum Plasma Concentration (Cmax) for ABC, DTG, and 3TC
Based on analysis of intensive PK samples. Steady state was measured at Week 1, but was re-collected later for two participants due to a specimen handling error for the Week 1 specimens.
Measured: Week 1; Blood samples were drawn at pre-dose and 1, 2, 3, 4, 6, 8, and 24 hours post dosing.
Geometric Mean Concentration at 24 Hours Post-dose (C24h) for ABC, DTG, and 3TC
Based on analysis of intensive PK samples. The geometric mean C24h for each Weight Band was compared to the lower and upper reference values (in ug/mL) for DTG (0.67, 2.97). Steady state was measured at Week 1, but was re-collected later for two participants due to a specimen handling error for the Week 1 specimens.
Measured: Week 1; Blood samples were drawn at pre-dose and 1, 2, 3, 4, 6, 8, and 24 hours post dosing.
Percentage of Participants Who Had at Least One Adverse Event Through Week 24
Adverse event (AE) grading was based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. AEs of any grade were reported.
Measured: Measured from treatment initiation through Week 24
Percentage of Participants Who Had at Least One Grade 3 or Grade 4 Adverse Event Assessed as Related to Study Drug Through Week 24
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator.
Measured: Measured from treatment initiation through Week 24
Percentage of Participants Who Had a Grade 5 Adverse Event Assessed as Related to Study Drug Through Week 24
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator.
Measured: Measured from treatment initiation through Week 24
Percentage of Participants Who Had at Least One Life-threatening Adverse Event Assessed as Related to Study Drug Through Week 24
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator. Life-threatening was defined according to Version 2.0 of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual).
Measured: Measured from treatment initiation through Week 24
Percentage of Participants Who Had at Least One Serious Adverse Event Assessed as Related to Study Drug Through Week 24
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator. Seriousness was defined according to Version 2.0 of the DAIDS EAE Manual.
Measured: Measured from treatment initiation through Week 24
Percentage of Participants Who Had at Least One Adverse Event Assessed as Related to Study Drug That Led to Permanent Discontinuation of Study Drug Through Week 24
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator.
Measured: Measured from treatment initiation through Week 24
Secondary outcomes (41)
Population PK: Geometric Mean AUC0-24h for ABC, DTG, and 3TC
Population PK: Geometric Mean Area Under the Plasma Concentration-time Curve for ABC, DTG, and 3TC derived from population PK model. Population apparent oral clearance and apparent volume of distribution were determined with non-linear mixed effects modeling. DTG and 3TC were fit to a 1-compartment model and ABC was fit to 2-compartment model. Weight was a covariate on clearance and volume for all drugs and enzyme maturation as a covariate on apparent oral clearance for DTG. The posthoc parameter of AUC0-24 was estimated using non-compartmental analysis of simulated steady-state concentration-time profiles and stratified by weight band.
Measured: Measured from Week 1 through Week 48 over 24 hours post-dose
Population PK: Geometric Mean Concentration at Time 0 (Pre-dose) (C0h) for ABC, DTG, and 3TC
Population PK: Geometric Mean Area Under the Plasma Concentration-time Curve for ABC, DTG, and 3TC derived from population PK model. Population apparent oral clearance and apparent volume of distribution were determined with non-linear mixed effects modeling. DTG and 3TC were fit to a 1-compartment model and ABC was fit to 2-compartment model. Weight was a covariate on clearance and volume for all drugs and enzyme maturation as a covariate on apparent oral clearance for DTG. The posthoc parameter of AUC0-24 was estimated using non-compartmental analysis of simulated steady-state concentration-time profiles and stratified by weight band.
Measured: Measured from Week 1 through Week 48 over 24 hours post-dose
Population PK: Geometric Mean Concentration at 24 Hours Post-dose (C24h) for ABC, DTG, and 3TC
Population PK: Geometric Mean Area Under the Plasma Concentration-time Curve for ABC, DTG, and 3TC derived from population PK model. Population apparent oral clearance and apparent volume of distribution were determined with non-linear mixed effects modeling. DTG and 3TC were fit to a 1-compartment model and ABC was fit to 2-compartment model. Weight was a covariate on clearance and volume for all drugs and enzyme maturation as a covariate on apparent oral clearance for DTG. The posthoc parameter of AUC0-24 was estimated using non-compartmental analysis of simulated steady-state concentration-time profiles and stratified by weight band.
Measured: Measured from Week 1 through Week 48 over 24 hours post-dose
Population PK: Geometric Mean Maximum Plasma Concentration (Cmax) for ABC, DTG, and 3TC
Population PK: Geometric Mean Area Under the Plasma Concentration-time Curve for ABC, DTG, and 3TC derived from population PK model. Population apparent oral clearance and apparent volume of distribution were determined with non-linear mixed effects modeling. DTG and 3TC were fit to a 1-compartment model and ABC was fit to 2-compartment model. Weight was a covariate on clearance and volume for all drugs and enzyme maturation as a covariate on apparent oral clearance for DTG. The posthoc parameter of AUC0-24 was estimated using non-compartmental analysis of simulated steady-state concentration-time profiles and stratified by weight band.
Measured: Measured from Week 1 through Week 48 over 24 hours post-dose
Population PK: Geometric Mean Time to Maximum Concentration (Tmax) for ABC, DTG, and 3TC
Population PK: Geometric Mean Area Under the Plasma Concentration-time Curve for ABC, DTG, and 3TC derived from population PK model. Population apparent oral clearance and apparent volume of distribution were determined with non-linear mixed effects modeling. DTG and 3TC were fit to a 1-compartment model and ABC was fit to 2-compartment model. Weight was a covariate on clearance and volume for all drugs and enzyme maturation as a covariate on apparent oral clearance for DTG. The posthoc parameter of AUC0-24 was estimated using non-compartmental analysis of simulated steady-state concentration-time profiles and stratified by weight band.
Measured: Measured from Week 1 through Week 48 over 24 hours post-dose
Population PK: Geometric Mean Apparent Oral Clearance (CL/F) for ABC, DTG, and 3TC
Population PK: Geometric Mean Area Under the Plasma Concentration-time Curve for ABC, DTG, and 3TC derived from population PK model. Population apparent oral clearance and apparent volume of distribution were determined with non-linear mixed effects modeling. DTG and 3TC were fit to a 1-compartment model and ABC was fit to 2-compartment model. Weight was a covariate on clearance and volume for all drugs and enzyme maturation as a covariate on apparent oral clearance for DTG. The posthoc parameter of AUC0-24 was estimated using non-compartmental analysis of simulated steady-state concentration-time profiles and stratified by weight band.
Measured: Measured from Week 1 through Week 48 over 24 hours post-dose
Population PK: Geometric Mean Half-life (t1/2) for ABC, DTG, and 3TC
Population PK: Geometric Mean Area Under the Plasma Concentration-time Curve for ABC, DTG, and 3TC derived from population PK model. Population apparent oral clearance and apparent volume of distribution were determined with non-linear mixed effects modeling. DTG and 3TC were fit to a 1-compartment model and ABC was fit to 2-compartment model. Weight was a covariate on clearance and volume for all drugs and enzyme maturation as a covariate on apparent oral clearance for DTG. The posthoc parameter of AUC0-24 was estimated using non-compartmental analysis of simulated steady-state concentration-time profiles and stratified by weight band.
Measured: Measured from Week 1 through Week 48 over 24 hours post-dose
Percentage of Participants With at Least One Adverse Event Through Week 48
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported.
Measured: Measured from treatment initiation through Week 48
Percentage of Participants Who Had at Least One Grade 3 or Grade 4 Adverse Event Assessed as Related to Study Drug Through Week 48
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator.
Measured: Measured from treatment initiation through Week 48
Percentage of Participants Who Had a Grade 5 Adverse Event Assessed as Related to Study Drug Through Week 48
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator.
Measured: Measured from treatment initiation through Week 48
Percentage of Participants Who Had at Least One Life-threatening Adverse Event Assessed as Related to Study Drug Through Week 48
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator. Life-threatening was defined according to Version 2.0 of the DAIDS EAE Manual.
Measured: Measured from treatment initiation through Week 48
Percentage of Participants Who Had at Least One Serious Adverse Event Assessed as Related to Study Drug Through Week 48
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator. Seriousness was defined according to Version 2.0 of the DAIDS EAE Manual.
Measured: Measured from treatment initiation through Week 48
Percentage of Participants Who Had at Least One Adverse Event Assessed as Related to Study Drug That Led to Permanent Discontinuation of Study Drug Through Week 48
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator.
Measured: Measured from treatment initiation through Week 48
Percentage of Participants Who Had at Least One Adverse Event Through Week 60
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported.
Measured: Measured from treatment initiation through Week 60
Percentage of Participants Who Had at Least One Grade 3 or Grade 4 Adverse Event Assessed as Related to Study Drug Through Week 60
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator.
Measured: Measured from treatment initiation through Week 60
Percentage of Participants Who Had a Grade 5 Adverse Event Assessed as Related to Study Drug Through Week 60
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator.
Measured: Measured from treatment initiation through Week 60
Percentage of Participants Who Had at Least One Life-threatening Adverse Event Assessed as Related to Study Drug Through Week 60
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator. Life-threatening was defined according to Version 2.0 of the DAIDS EAE Manual.
Measured: Measured from treatment initiation through Week 60
Percentage of Participants Who Had at Least One Serious Adverse Event Assessed as Related to Study Drug Through Week 60
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator. Seriousness was defined according to Version 2.0 of the DAIDS EAE Manual.
Measured: Measured from treatment initiation through Week 60
Percentage of Participants Who Had at Least One Adverse Event Assessed as Related to Study Drug That Led to Permanent Discontinuation of Study Drug Through Week 60
AE grading was based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017. AEs of any grade were reported. The relationship to study drug was assessed by the site investigator.
Measured: Measured from treatment initiation through Week 60
Percentage of Participants Who Experienced Virologic Failure Through Week 48
Percentage of participants who experienced virologic failure based on the following definition: ART-experienced participants who had two subsequent viral loads greater or equal to 200 copies/mL at any time, or for ART-naive participants, two subsequent viral loads greater to or equal to 200 copies/mL at 24 weeks or after. The results are presented by ART experienced, ART naïve, and overall.
Measured: Measured from treatment initiation through Week 48
Percentage of Participants Who Experienced Virologic Failure Through Week 60
Percentage of participants who experienced virologic failure based on the following definition: ART-experienced participants who had two subsequent viral loads greater or equal to 200 copies/mL at any time, or for ART-naive participants, two subsequent viral loads greater to or equal to 200 copies/mL at 24 weeks or after. The results are presented by ART experienced, ART naïve, and overall.
Measured: Measured from treatment initiation through Week 60
Percentage of Participants With HIV-1 RNA Less Than 200 Copies/mL
Viral loads less than the lower limit of quantification were imputed as one less than the lower limit.
Measured: Weeks 4, 24, and 48
Percentage of Participants With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL Using FDA Snapshot Algorithm
Percentage of participants with virologic success of HIV-1 RNA less than 200 copies/mL using FDA snapshot algorithm at Weeks 4, 24, and 48. Viral loads less than the lower limit of quantification were imputed as one less than the lower limit.
Measured: Weeks 4, 24, and 48
Percentage of Participants With Virologic Success of HIV-1 RNA Less Than 50 Copies/mL Using FDA Snapshot Algorithm
Percentage of participants with virologic success of HIV-1 RNA less than 50 copies/mL using FDA snapshot algorithm at Weeks 4, 24, and 48. Viral loads less than the lower limit of quantification were imputed as one less than the lower limit.
Measured: Weeks 4, 24, and 48
Median (Q1, Q3) CD4+ Cell Count
Per protocol, CD4 + cell counts were not required at Week 60. CD4 results were therefore analyzed through Week 48. For participants who discontinued study drug prior to the other timepoints due to safety or virologic failure, results imputed using the baseline value.
Measured: Weeks 4, 24, and 48
Median (Q1, Q3) CD4+ Percentage
Per protocol, CD4+ cell count percentages were not required at Week 60. CD4 results were therefore analyzed through Week 48. For participants who discontinued study drug prior to the other timepoints due to safety or virologic failure, results imputed using the baseline value.
Measured: Weeks 4, 24, and 48
Median (Q1,Q3) Change From Baseline in Total Cholesterol
Baseline is defined as the latest pre-dose assessment with a non-missing value. Where time was not collected, assessments on the day of treatment initiation are assumed to be taken prior to first dose. Missing results for participants who discontinued study treatment prior to the specified timepoint due to safety or virologic failure were imputed using the baseline value. Per protocol, there was no expectation of evaluating lipids in a fasting state for this study. A relative few participants were identified as having been in a fasted state at a given study visit, but the majority did not fast for this evaluation.
Measured: Baseline, Weeks 24 and 48
Median (Q1,Q3) Change From Baseline in HDL
Baseline is defined as the latest pre-dose assessment with a non-missing value. Where time was not collected, assessments on the day of treatment initiation are assumed to be taken prior to first dose. Missing results for participants who discontinued study treatment prior to the specified timepoint due to safety or virologic failure were imputed using the baseline value. Per protocol, there was no expectation of evaluating lipids in a fasting state for this study. A relative few participants were identified as having been in a fasted state at a given study visit, but the majority did not fast for this evaluation.
Measured: Baseline, Weeks 24 and 48
Median (Q1,Q3) Change From Baseline in LDL
Baseline is defined as the latest pre-dose assessment with a non-missing value. Where time was not collected, assessments on the day of treatment initiation are assumed to be taken prior to first dose. Missing results for participants who discontinued study treatment prior to the specified timepoint due to safety or virologic failure were imputed using the baseline value. Per protocol, there was no expectation of evaluating lipids in a fasting state for this study. A relative few participants were identified as having been in a fasted state at a given study visit, but the majority did not fast for this evaluation.
Measured: Baseline, Weeks 24 and 48
Median (Q1,Q3) Change From Baseline in Triglycerides
Baseline is defined as the latest pre-dose assessment with a non-missing value. Where time was not collected, assessments on the day of treatment initiation are assumed to be taken prior to first dose. Missing results for participants who discontinued study treatment prior to the specified timepoint due to safety or virologic failure were imputed using the baseline value. Per protocol, there was no expectation of evaluating lipids in a fasting state for this study. A relative few participants were identified as having been in a fasted state at a given study visit, but the majority did not fast for this evaluation.
Measured: Baseline, Weeks 24 and 48
Parent/Guardian-reported Percent Adherence to Study Drug
Parent/guardian-reported percent adherence to study drug in the 30 days prior to the study visit according to adherence questionnaire responses.
Measured: Weeks 4, 24, and 48
Parent/Guardian-reported Number of Missed Doses of Study Drug
Parent/guardian-reported number of missed doses of study drug in the 30 days prior to the study visit according to adherence questionnaire responses.
Measured: Weeks 4, 24, and 48
Parent/Guardian-reported Reason for Missed Doses of Study Drug
Parent/guardian-reported reason for missed doses of study drug in the 30 days prior to the study visit according to adherence questionnaire responses.
Measured: Weeks 4, 24, and 48
Parent/Guardian-reported Response of How Well the Person Usually Responsible Administered the Study Drug in the Way They Were Supposed to
Parent/guardian-reported response of how well the person usually responsible administered the study drug in the way they were supposed to in the 30 days prior to the study visit according to adherence questionnaire responses.
Measured: Weeks 4, 24, and 48
Parent/Guardian-reported Response of How Often the Child Received the Study Drug in the Way They Were Supposed to
Parent/guardian-reported response of how often the child received the study drug in the way they were supposed to in the 30 days prior to the study visit according to adherence questionnaire responses.
Measured: Weeks 4, 24, and 48
Parent/Guardian-reported Ease of Giving Study Drug
Parent/guardian-reported ease of giving study drug according to palatability questionnaire responses.
Measured: Weeks 4, 12, 24, and 48
Parent/Guardian-reported Response of Child's Face When Taking Study Drug
Parent/guardian-reported response of child's face when taking study drug according to palatability questionnaire responses.
Measured: Weeks 4, 12, 24, and 48
Parent/Guardian-reported Response of Child's Face When Taking Favorite Food
Parent/guardian-reported response of child's face when taking favorite food according to palatability questionnaire responses.
Measured: Weeks 4, 12, 24, and 48
Parent/Guardian-reported Time for Study Drug Tablets to Dissolve
Parent/guardian-reported time for study drug tablets to dissolve according to acceptability questionnaire responses
Measured: Weeks 4, 12, 24, and 48
Parent/Guardian-reported Satisfaction With the Number of Study Drug Tablets to Dissolve
Parent/guardian-reported satisfaction with the number of study drug tablets to dissolve according to acceptability questionnaire responses
Measured: Weeks 4, 12, 24, and 48
Antiretroviral (ARV) Resistance Mutations
ARV resistance mutations at time of virologic failure and at entry for children with virologic failure.
Measured: Entry and confirmation of virologic failure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2018
- Study start9 Sep 2020
- Primary completion14 Dec 2021
- Study completion31 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- International Maternal Pediatric Adolescent AIDS Clinical Trials Group, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH), ViiV Healthcare
- Responsible party
- Sponsor
- Investigators
- Patricia Flynn, MD, Study chair, St. Jude Children's Research HospitalHelena Rabie, MBChB, MMED, FCPaed, Study chair, University of StellenboschJennifer Kiser, PharmD, PhD, Study chair, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03760458
- Sponsor's protocol ID
- IMPAACT 2019
- Other IDs
- 38504
- Status last verified
- May 2023
- First submitted
- 29 Nov 2018
- Last updated
- 27 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.
Publications
McKenna M, Lulic Z, Buchanan AM, Brothers C, Tan LK, Wang M, Brummel S, Ziemba L, Ruel T, Flynn PM, Rabie H, Wiznia A. Growth Outcomes After 48 Weeks of Dolutegravir in Children and Adolescents with HIV-1 in IMPAACT P1093 and IMPAACT 2019. J Pediatric Infect Dis Soc. 2026 Sep 12:piag088. doi: 10.1093/jpids/piag088. Online ahead of print.
PubMed 42731017Brooks KM, Kiser JJ, Ziemba L, Ward S, Rani Y, Cressey TR, Masheto GR, Cassim H, Deville JG, Ponatshego PL, Patel F, Aurpibul L, Barnabas SL, Mustich I, Coletti A, Heckman B, Krotje C, Lojacono M, Yin DE, Townley E, Moye J, Majji S, Acosta EP, Ryan K, Chandasana H, Brothers CH, Buchanan AM, Rabie H, Flynn PM; IMPAACT 2019 Study Team. Pharmacokinetics, safety, and tolerability of dispersible and immediate-release abacavir, dolutegravir, and lamivudine tablets in children with HIV (IMPAACT 2019): week 24 results of an open-label, multicentre, phase 1-2 dose-confirmation study. Lancet HIV. 2023 Aug;10(8):e506-e517. doi: 10.1016/S2352-3018(23)00107-8.
PubMed 37541705Singh RP, Adkison KK, Baker M, Parasrampuria R, Wolstenholme A, Davies M, Sewell N, Brothers C, Buchanan AM. Development of Dolutegravir Single-entity and Fixed-dose Combination Formulations for Children. Pediatr Infect Dis J. 2022 Mar 1;41(3):230-237. doi: 10.1097/INF.0000000000003366.
PubMed 34817414