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

• Register: EUCTR
• Last refreshed on: 19 February 2024
• Main ID: EUCTR2014-002632-14-DE
• Date of registration: 07/10/2016
• Prospective Registration: Yes
• Primary sponsor: PENTA Foundation
• Public title: 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
• Scientific title: 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 - ODYSSEY (Once daily DTG-based ART in young people vs standard therapy)
• Date of first enrolment: 21/02/2017
• Target sample size: 700
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002632-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, France, Germany, Italy, Portugal, Spain, Thailand, Uganda, United Kingdom, United States, Zimbabwe

Contacts

• Name: Anna Parker
• Affiliation: MRC Clinical Trials Unit at UCL

• Name: Anna Parker
• Affiliation: MRC Clinical Trials Unit at UCL

Key inclusion & exclusion criteria

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Paediatric HIV infection
MedDRA version: 20.1 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Trade Name: Tivicay 50mg film-coated tablets
Product Name: Tivicay (dolutegravir) 50mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dolutegravir (as sodium)
CAS Number: 1051375-19-9
Current Sponsor code: GSK1349572
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Dolutegravir 25mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dolutegravir (as sodium)
CAS Number: 1051375-19-9
Current Sponsor code: GSK1349572
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Name: Dolutegravir 10mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dolutegravir (as sodium)
CAS Number: 1051375-19-9
Current Sponsor code: GSK1349572
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Triumeq 50mg/600mg/300mg film-coated tablets
Product Name: Triumeq 50mg/600mg/300mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dolutegravir (as sodium)
CAS Number: 1051375-19-9
Current Sponsor code: GSK1349572
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Abacavir (as sulphate)
CAS Number: 188062-50-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
INN or Proposed INN: Lamivudine
CAS Number: 134678-17-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Trade Name: Standard of care 3rd agent antiretrovirals (NNRTI/bPI/RAL)
Product Name: standard of care 3rd agent antiretrovirals (NNRTI/bPI/RAL)
Pharmaceutical Form:

Trade Name: Tivicay 50mg film-coated tablets
Product Name: Tivicay (dolutegravir) 50mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dol

Primary Outcome(s)

Main Objective: To evaluate whether treatment with DTG works as well as the standard anti-HIV treatment in children.

Timepoint(s) of evaluation of this end point: 96 weeks

Secondary Objective: • To evaluate if treatment with DTG is better in terms of safety than standard anti-HIV treatment in children.
• To compare the adherence to treatment and the quality of life of children receiving DTG to those receiving standard anti-HIV treatment.

Primary end point(s): Difference in the probability of virological or clinical failure by 96 weeks, estimated by Kaplan-Meier
methods using time to the first occurrence of any of the following components (note, this does not
mean VL must be performed in real time):
• Insufficient virological response defined as <1 log10 drop at week 24
• VL =400 c/ml at or after 36 weeks confirmed by next visit
• Death due to any cause
• Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, confirmed by
the Endpoint Review Committee

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 48 weeks and 96 weeks

Secondary end point(s): SECONDARY EFFICACY OUTCOMES
• Difference in proportion with clinical or virological failure (as defined above) by 48 weeks
• Time to any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events,
confirmed by the Endpoint Review Committee
• Proportion of children with VL <50 c/ml at 48 and 96 weeks
• Proportion of children with VL <400 c/ml at 48 and 96 weeks
• Rate of clinical events over 96 weeks: WHO 4, severe WHO 3 events and death
• Change in CD4 count and percentage and CD4/CD8 ratio from baseline to weeks 48 and 96
• Proportion developing new resistance mutations

SECONDARY SAFETY OUTCOMES
• Change in total cholesterol, triglycerides and lipid fractions (LDL, HDL) from baseline to
weeks 48 and 96 (change in total cholesterol from baseline to week 96 will be used to
formally assess superiority of DTG based regimen vs. SOC)
• Incidence of serious adverse events
• Incidence of new clinical and laboratory grade 3 and 4 adverse events
• Incidence of adverse events (of any grade) leading to treatment modification

OTHER SECONDARY OUTCOMES
• Quality of life
Adherence and acceptability

Secondary ID(s)

2014-002632-14-ES

NCT02259127

ISRCTN91737921

ODYSSEY(PENTA20)

Source(s) of Monetary Support

Viiv Healthcare Ltd

Ethics review

Status: Approved
Approval date: 02/01/2017
Contact: