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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Penta Ets

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

30 Jun 2023 → ongoing

Decision date (initial)

2025-01-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ViiV Healthcare UK Limited

External identifiers

EU CT number

2024-520388-15-00

EudraCT number

2020-001426-57

ClinicalTrials.gov

NCT04337450

ISRCTN

ISRCTN17157458

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenomic, Therapy, Pharmacodynamic, Safety, Pharmacogenetic, Pharmacokinetic, Pharmacoeconomic

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

Secondary objectives 6

1. To evaluate clinical and laboratory adverse events (AEs) associated with the trial antiretrovirals
2. To evaluate new resistance mutations in participants with virological rebound (confirmed VL≥50 copies/mL)
3. To assess low level viraemia and virological reservoirs
4. To evaluate adherence, tolerability, acceptability, sleep and health-related quality of life
5. To evaluate and model the pharmacokinetics and pharmacodynamics of dispersible and film-coated fixed-dose DTG/3TC formulations in children weighing 6-<40kg using WHO weight band-aligned dosing
6. To evaluate cost-effectiveness of treatment maintenance with DTG/3TC FDC if DTG/3TC is shown to be non-inferior to DTG + 2 NRTIs

Conditions and MedDRA coding

HIV-infected

Study design 4 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001940-PIP01-16

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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. Girls who have reached menarche must have a negative pregnancy test at screening and randomisation
5. Girls who are sexually active must be willing to adhere to highly effective methods of contraception
6. 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
7. 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 15

1. Any previous switch in ART regimen for virological, immunological or clinical treatment failure
2. Evidence of previous resistance to 3TC or INSTI
3. 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
4. Known allergy or contraindications to dolutegravir or lamivudine
5. Diagnosis of tuberculosis and on anti-tuberculosis treatment; children can be enrolled after successful tuberculosis treatment
6. 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)
7. Randomisation visit more than 12 weeks after the most recent screening visit
8. Positive HBsAg
9. 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)
10. Screening ALT equal to 5 or more times the upper limit of normal ALT (≥5xULN)
11. 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)
12. Screening creatinine clearance <30 mL/min/1.73m2
13. Patients aged ≥6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)
14. Girls who are pregnant or breastfeeding
15. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 13

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Penta Ets

Sponsor organisation

Fondazione Penta Ets

Address

Torre Di Ricerca Pediatrica, Corso Stati Uniti 4 Corso Stati Uniti 4

City

Padova

Postcode

35127

Country

Italy

Scientific contact point

Organisation

Fondazione Penta Ets

Contact name

Anna Turkova

Public contact point

Organisation

Fondazione Penta Ets

Contact name

Alessandra Nardone

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications