DTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old (D3 (Penta21))

September 15, 2023 updated by: PENTA Foundation

A Randomised Non-inferiority Trial With Nested PK to Assess DTG/3TC Fixed Dose Formulations for the Maintenance of Virological Suppression in Children With HIV Infection Aged 2 to <15 Years Old

This study aims to find out whether treating children and young people living with HIV with two anti HIV medicines, dolutegravir and lamivudine, is safe and as effective as the three-medicine anti-HIV treatments currently used in routine practice.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study will include 370 children and young people aged 2 to less than 15 years old who are living with HIV and are being treated with anti-HIV medicines for the first time. Participants will be split into two groups, by chance, by a process called "randomisation". One group will continue to receive the anti-HIV medicines already taken according to country-specific routine practice. The second group will change to the new combination of medicine, dolutegravir and lamivudine (with the combination written usually as "DTG/3TC"). Depending on the weight, participants in the second group will be able take the new medicine either as one tablet a day or as a small number of dispersible tablets that are also taken once a day. All children and young people in the study will have regular clinic assessments that are at a similar frequency to the clinic visits that participants would have outside of the study. Blood tests will be performed to check that the medicine is safe and, at some visits, participants and their carers will also be asked to answer some questions on how they feel about taking their medicine. All children and young people will be followed until the last participant who joins the study has been in the study for 96 weeks.

Study Type

Interventional

Enrollment (Estimated)

370

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 months to 13 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolment
  2. Aged 2 to <15 years old
  3. Weight 6 kg or higher
  4. Children on the same triple-drug PI/r, NNRTI or INSTI containing ART regimen for at least 3 months
  5. Girls who have reached menarche must have a negative pregnancy test at screening and randomisation
  6. Girls who are sexually active must be willing to adhere to highly effective methods of contraception
  7. A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the protocol
  8. Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information about participation in the study

Exclusion Criteria:

  1. Any previous switch in ART regimen for virological, immunological or clinical treatment failure
  2. Any changes in ART in the last 6 months for reasons other than due to child's growth, drug stock-outs, changes in country guidelines and treatment simplification
  3. Evidence of previous resistance to 3TC or INSTI
  4. Any prior use of regimens consisting of single or dual NRTIs with the exception of a course of zidovudine for PMTCT
  5. Known allergy or contraindications to dolutegravir or lamivudine
  6. Diagnosis of tuberculosis and on anti-tuberculosis treatment; children can be enrolled after successful tuberculosis treatment
  7. Treatment of co-morbidities with drugs which have significant interactions with antiretroviral treatment, requiring dose adjustment of the study drugs (children can be enrolled after the illness resolves)
  8. Randomisation visit more than 12 weeks after the most recent screening visit
  9. Evidence of hepatitis B infection with no protective immunity against hepatitis B: participants positive for HBsAg or HBcAb and negative for HBsAb
  10. Anticipated need for hepatitis C virus therapy with interferon-based regimen prior to the primary endpoint.
  11. Screening ALT equal to 3 or more times the upper limit of normal AND bilirubin equal to 2 or more times the upper limit of normal (ALT ≥3xULN AND bilirubin ≥2xULN)
  12. Screening ALT equal to 5 or more times the upper limit of normal ALT (≥5xULN)
  13. Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  14. Screening creatinine clearance <50 mL/min/1.73m2
  15. Patients aged ≥6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)
  16. Girls who are pregnant or breastfeeding
  17. Children who are in the legal custody of the State and do not have a parent or guardian able to provide informed consent on their behalf.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: SOC
Standard-of-care (SOC)
Drug: SOC
2 nucleos(t)ide reverse transcriptase inhibitor (NRTI) and a third (anchor) drug (either an integrase strand transfer inhibitor (INSTI), a protease inhibitor (PI) or a non- nucleoside reverse transcriptase inhibitor (NNRTI)
Experimental: DTG/3TC
Dolutegravir (DTG) and lamivudine (3TC) (known as DTG/3TC)
Drug: Dolutegravir (DTG) and lamivudine (3TC)
Children randomised to the DTG/3TC arm will receive once daily DTG/3TC fixed dose combination dispersible or film-coated tablets dosed using WHO weight bands criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 96
Time Frame: by Week 96
by Week 96

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 48
Time Frame: by Week 48
by Week 48
Proportion of children with confirmed HIV-1 RNA ≥50c/mL at weeks 48 and 96 (modified FDA snapshot)
Time Frame: at Week 48 and 96
at Week 48 and 96
Proportion of children with HIV-1 RNA ≥50c/mL at weeks 24, 48 and 96 (including blips and confirmed measures ≥50c/mL)
Time Frame: at Week 24, 48 and 96
at Week 24, 48 and 96
New resistance-associated mutations in those with confirmed HIV-1 RNA ≥50c/mL
Time Frame: by Week 96
by Week 96
Time to any new or recurrent WHO 3 or WHO 4 event or death
Time Frame: through study completion, up to 5 years
through study completion, up to 5 years
Change in CD4 (absolute and percentage) from baseline to weeks 24, 48 and 96
Time Frame: Week 24, 48 and 96
Week 24, 48 and 96
Incidence of serious adverse events, grade 3 and 4 clinical and laboratory adverse events
Time Frame: through study completion, up to 5 years
through study completion, up to 5 years
Incidence of adverse events leading to discontinuation or modification of the treatment regimen
Time Frame: through study completion, up to 5 years
through study completion, up to 5 years
Proportion of children with a change in ART for toxicity or switch to second-line
Time Frame: through study completion, up to 5 years
through study completion, up to 5 years
Change in blood lipids from baseline to weeks 48 and 96
Time Frame: Week 48 and 96
Week 48 and 96
Change in creatinine clearance estimated using bedside-Schwartz to weeks 48 and 96
Time Frame: Week 48 and 96
Week 48 and 96

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PENTA Foundation

Collaborators

Baylor College of Medicine
University Hospital Birmingham NHS Foundation Trust
Hospital Universitario 12 de Octubre
Great Ormond Street Hospital for Children NHS Foundation Trust
Chiang Mai University
Joint Clinical Research Center
MRC CTU at UCL
MU-JHU CARE
Khon Kaen Hospital
Chris Hani Baragwanath Academic Hospital
Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands.
Chiangrai Prachanukroh Hospital
AMS-CMU/IRD (PHPT)
Durban International Clinical Research Site
Prapokklao Hospital, Chantaburi
Nakornping Hospital
Kalasin Hospital, Kalasin
Imperial College Healthcare Trust, St Mary's Hospital
Advanced Pathogens Diagnostics Unit, University College London Hospitals
Centre for Health Economics, University of York
Department of Molecular and Clinical Pharmacology, University of Liverpool

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 22, 2022

Primary Completion (Estimated)

September 15, 2024

Study Completion (Estimated)

July 31, 2025

Study Registration Dates

First Submitted

March 27, 2020

First Submitted That Met QC Criteria

April 6, 2020

First Posted (Actual)

April 7, 2020

Study Record Updates

Last Update Posted (Actual)

September 18, 2023

Last Update Submitted That Met QC Criteria

September 15, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D3 (Penta21)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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