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

NCT04337450 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: D3 (Penta21)
• Study Type: interventional
• Target: 386
• Locations: 5 countries
• Sites: 14

Brief Summary

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 96

  by Week 96

Secondary Outcomes (11)

• Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 48

  by Week 48

• Proportion of children with confirmed HIV-1 RNA ≥50c/mL at weeks 48 and 96 (modified FDA snapshot)

  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)

  at Week 24, 48 and 96

• New resistance-associated mutations in those with confirmed HIV-1 RNA ≥50c/mL

  by Week 96

• Time to any new or recurrent WHO 3 or WHO 4 event or death

  through study completion, up to 5 years

Study Arms (2)

SOC

ACTIVE COMPARATOR

Standard-of-care (SOC)

Drug: SOC

DTG/3TC

EXPERIMENTAL

Dolutegravir (DTG) and lamivudine (3TC) (known as DTG/3TC)

Drug: Dolutegravir (DTG) and lamivudine (3TC)

Interventions

Dolutegravir (DTG) and lamivudine (3TC) DRUG

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

DTG/3TC

SOC DRUG

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)

SOC

Eligibility Criteria

• Age: 2 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolment
• Aged 2 to \<15 years old
• Weight 6 kg or higher
• Children on the same triple-drug PI/r, NNRTI or INSTI containing ART regimen for at least 3 months
• Girls who have reached menarche must have a negative pregnancy test at screening and randomisation
• Girls who are sexually active must be willing to adhere to highly effective methods of contraception
• 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
• 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
• Participants remain on DTG/3TC at the end of the randomised phase, and in the opinion of the treating physician, derive ongoing benefit from DTG/3TC
• Participants have no access to weight-appropriate DTG/3TC formulation via their national programme

You may not qualify if:

• Any previous switch in ART regimen for virological, immunological or clinical treatment failure
• 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
• Evidence of previous resistance to 3TC or INSTI
• Any prior use of regimens consisting of single or dual NRTIs with the exception of a course of zidovudine for PMTCT
• Known allergy or contraindications to dolutegravir or lamivudine
• Diagnosis of tuberculosis and on anti-tuberculosis treatment; children can be enrolled after successful tuberculosis treatment
• 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)
• Randomisation visit more than 12 weeks after the most recent screening visit
• Evidence of hepatitis B infection with no protective immunity against hepatitis B: participants positive for HBsAg or HBcAb and negative for HBsAb
• Anticipated need for hepatitis C virus therapy with interferon-based regimen prior to the primary endpoint.
• 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)
• Screening ALT equal to 5 or more times the upper limit of normal ALT (≥5xULN)
• 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)
• Screening creatinine clearance \<50 mL/min/1.73m2
• Patients aged ≥6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)

Sponsors & Collaborators

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

Study Sites (14)

King Edward VIII Hospital

Durban, South Africa

Location

PHRU Klerksdorp

Klerksdorp, South Africa

Location

PHRU

Soweto, South Africa

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Prapokklao Hospital

Chanthaburi, Thailand

Location

Nakornping Hospital

Chiang Mai, Thailand

Location

Chiangrai Prachanukroh Hospital

Chiang Rai, Thailand

Location

Khon Kaen Hospital

Khon Kaen, Thailand

Location

Baylor

Kampala, Uganda

Location

Joint Clinical Research Centre

Kampala, Uganda

Location

MUJHU

Kampala, Uganda

Location

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

Great Ormand Street Hospital

London, United Kingdom

Location

St. Mary's Hospital

London, United Kingdom

Location

Related Publications (2)

• Turkova A, Chan MK, Kityo C, Kekitiinwa AR, Musoke P, Violari A, Variava E, Archary M, Cressey TR, Chalermpantmetagul S, Sawasdichai K, Ounchanum P, Kanjanavanit S, Srirojana S, Srirompotong U, Welch S, Bamford A, Epalza C, Fortuny C, Colbers A, Nastouli E, Walker S, Carr D, Conway M, Spyer MJ, Parkar N, White I, Nardone A, Thomason MJ, Ferrand RA, Giaquinto C, Ford D; D3 trial team. D3/Penta 21 clinical trial design: A randomised non-inferiority trial with nested drug licensing substudy to assess dolutegravir and lamivudine fixed dose formulations for the maintenance of virological suppression in children with HIV-1 infection, aged 2 to 15 years. Contemp Clin Trials. 2024 Jul;142:107540. doi: 10.1016/j.cct.2024.107540. Epub 2024 Apr 16.

  PMID: 38636725 DERIVED

• Botha JC, Byott M, Spyer MJ, Grant PR, Gartner K, Chen WX, Burton J, Bamford A, Waters LJ, Giaquinto C, Turkova A, Vavro CL, Nastouli E. Sensitive HIV-1 DNA Pol Next-Generation Sequencing for the Characterisation of Archived Antiretroviral Drug Resistance. Viruses. 2023 Aug 25;15(9):1811. doi: 10.3390/v15091811.

  PMID: 37766218 DERIVED

Related Links

• Related Info
• Related Info

MeSH Terms

Conditions

HIV Infections

Interventions

dolutegravir; Lamivudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2020
• First Posted: April 7, 2020
• Study Start: April 22, 2022
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

ES (1); ZA (3); TH (4); UG (3); GB (3)