A randomised trial of dolutegravir (DTG)-based antiretroviral treatment vs standard of care (SOC) in children with HIV infection starting first treatment or switching to second-line antiretrovirals

Phase 1

Conditions: Paediatric HIV infection
MedDRA version: 20.1Level: PTClassification code 10020161Term: HIV infectionSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2014-002632-14-DE

Lead Sponsor: PENTA Foundation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 792

Inclusion Criteria

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

• Parents/carers and children, where applicable, give informed written consent
• Girls who have reached menses must have a negative pregnancy test at screening and
randomisation and be willing to adhere to effective methods of contraception if sexually
active
• Children with co-infections who need to start ART 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 (these children will not be recruited in Germany) unless enrolment for this weight band directly into the main trial has opened following
the WB-PK1 substudy (see Section 5.3.1 and Appendix XIII) 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 (see Section 5.2.2)
• 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 active NRTI from TDF,
ABC or ZDV should have preserved activity based on cumulative results of resistance tests
(see Section 5.2.2)
• 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 TDF, ABC or ZDV (see Section 5.2.2)
• Viral load =500 c/ml at screening visit or within 4 weeks prior to screening

Are the trial subjects under 18? yes
Number of subjects for this age range: 700
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

• History or presence of known allergy or contraindications to DTG
• 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 (ULN), OR ALT =3xULN
and bilirubin =2xULN
• 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate whether treatment with DTG works as well as the standard anti-HIV treatment in children.;Secondary Objective: • To evaluate if treatment with DTG is better in terms of safety than standard anti-HIV treatment in children.<br>• To compare the adherence to treatment and the quality of life of children receiving DTG to those receiving standard anti-HIV treatment.<br>;Primary end point(s): Difference in the probability of virological or clinical failure by 96 weeks, estimated by Kaplan-Meier<br>methods using time to the first occurrence of any of the following components (note, this does not<br>mean VL must be performed in real time):<br>• Insufficient virological response defined as <1 log10 drop at week 24<br>• VL =400 c/ml at or after 36 weeks confirmed by next visit<br>• Death due to any cause<br>• Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, confirmed by<br>the Endpoint Review Committee;Timepoint(s) of evaluation of this end point: 96 weeks

Secondary Outcome Measures

Name	Time	Method

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