Overview

A Randomised Trial of Dolutegravir (DTG)-Based Antiretroviral Therapy vs. Standard of Care (SOC) in Children With HIV Infection Starting First-line or Switching to Second-line ART

Status:
Active, not recruiting
Trial end date:
2023-05-01
Target enrollment:
0
Participant gender:
All
Summary
A new anti-HIV medicine (Dolutegravir) combined with 2 currently used anti-HIV medicines is non-inferior to the standard combination of medicines used in terms of efficacy and better in terms of toxicity.
Phase:
Phase 2/Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
PENTA Foundation
Collaborators:
Institut National de la Santé Et de la Recherche Médicale, France
Medical Research Council Clinical Trials Unit at University College London (MRC CTU at UCL)
Program for HIV Prevention and Treatment (PHPT)
Criteria
Inclusion Criteria:

ALL PATIENTS:

- Children ≥28 days and <18 years weighing ≥3kg with confirmed HIV-1 infection

- Parents/carers and children, where applicable, give informed written consent

- Girls aged 12 years or older who have reached menses must have a negative pregnancy
test at screening and be willing to adhere to effective methods of contraception if
sexually active

- Children with co-infections who need to start ART can be enrolled into ODYSSEY
according to local/national guidelines

- Parents/carers and children, where applicable, willing to adhere to a minimum of 96
weeks' follow-up

- Children weighing 3 to <14kg must be eligible and willing to participate in the
Weight band (WB)-PK1 substudy unless direct enrolment for the child's weight band
has opened following the WB-PK1 substudy and/or dosing information has become
available from the IMPAACT P1093 DTG dose-finding study.

ADDITIONAL CRITERIA FOR ODYSSEY A:

• Planning to start first-line ART

ADDITIONAL CRITERIA FOR ODYSSEY B:

- Planning to start second-line ART defined as either: (i) switch of at least 2 ART
drugs due to treatment failure; or (ii) switch of only the third agent due to
treatment failure where drug sensitivity tests show no mutations conferring NRTI
resistance

- Treated with only one previous ART regimen. Single drug substitutions for toxicity,
simplification, changes in national guidelines or drug availability are allowed

- At least one NRTI with predicted preserved activity available for a background regimen

- In settings where resistance tests are routinely available, at least one new active
NRTI from tenofovir disoproxil fumarate, abacavir or zidovudine should have preserved
activity based on cumulative results of resistance tests

- In settings where resistance tests are not routinely available, children who are due
to switch according to national guidelines should have at least one new NRTI predicted
to be available from tenofovir disoproxil fumarate, abacavir or zidovudine

- Viral load ≥ 500 c/ml at screening visit

Exclusion Criteria:

- History or presence of known allergy or contraindications to dolutegravir

- History or presence of known allergy or contraindications to proposed available NRTI
backbone or proposed available SOC third agent.

- Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal, OR ALT ≥3x upper
limit of normal and bilirubin ≥2x upper limit of normal

- 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), known biliary abnormalities (with the
exception of Gilbert's syndrome or asymptomatic gallstones)

- Anticipated need for Hepatitis C virus (HCV) therapy during the study

- Pregnancy or breastfeeding

- Evidence of lack of susceptibility to integrase inhibitors or more than a 2-week
exposure to antiretrovirals of this class