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

Phase 3

Active, not recruiting

Conditions: HIV-infected

Registration Number: 2024-520388-15-00

Lead Sponsor: Fondazione Penta Ets, Fondazione Penta Ets

Brief Summary: To assess whether DTG/3TC is non-inferior to DTG + 2 NRTIs in terms of virological suppression

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.

Recruitment & Eligibility

Status: Ongoing, recruitment ended

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

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

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

Exclusion Criteria

Any previous switch in ART regimen for virological, immunological or clinical treatment failure

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 <30 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)

Girls who are pregnant or breastfeeding

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

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 prevention of mother to child transmission

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

Positive HBsAg

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 48.		Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 48.
Proportion of children with confirmed HIV-1 RNA ≥50c/mL at weeks 48 and 96 (modified FDA snapshot)		Proportion of children with confirmed HIV-1 RNA ≥50c/mL at weeks 48 and 96 (modified FDA snapshot)
Proportion of children with HIV-1 RNA ≥50c/mL at weeks 24, 48 and 96 (including blips and confirmed measures ≥50c/mL)		Proportion of children with HIV-1 RNA ≥50c/mL at weeks 24, 48 and 96 (including blips and confirmed measures ≥50c/mL)
New resistance-associated mutations in those with confirmed HIV-1 RNA ≥50c/mL		New resistance-associated mutations in those with confirmed HIV-1 RNA ≥50c/mL
Time to any new or recurrent WHO 3 or WHO 4 event or death		Time to any new or recurrent WHO 3 or WHO 4 event or death
Change in CD4 (absolute and percentage) from baseline to weeks 24, 48 and 96		Change in CD4 (absolute and percentage) from baseline to weeks 24, 48 and 96
Incidence of serious adverse events, grade ≥3 clinical and laboratory adverse events		Incidence of serious adverse events, grade ≥3 clinical and laboratory adverse events
Incidence of adverse events leading to discontinuation or modification of the treatment regimen		Incidence of adverse events leading to discontinuation or modification of the treatment regimen
Proportion of children with a change in ART for toxicity or switch to second-line		Proportion of children with a change in ART for toxicity or switch to second-line
Change in blood lipids from baseline to weeks 48 and 96		Change in blood lipids from baseline to weeks 48 and 96
Change in creatinine clearance estimated using bedside-Schwartz to weeks 48 and 96		Change in creatinine clearance estimated using bedside-Schwartz to weeks 48 and 96
Adherence as assessed by participant/care-giver questionnaires		Adherence as assessed by participant/care-giver questionnaires
Acceptability, sleep and mood, suicidality ideation and health-related quality of life as assessed by participant/care-giver completed questionnaires		Acceptability, sleep and mood, suicidality ideation and health-related quality of life as assessed by participant/care-giver completed questionnaires

Trial Locations

Locations (2): Hospital Sant Joan De Deu Barcelona
🇪🇸
Esplugues De Llobregat, Spain
Hospital Universitario 12 De Octubre
🇪🇸
Madrid, Spain
Hospital Sant Joan De Deu Barcelona
🇪🇸Esplugues De Llobregat, Spain
Clàudia Fortuny
Site contact
0034932532100
cfortuny@sjdhospitalbarcelona.org