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: 17 May 2016
• Main ID: EUCTR2014-002632-14-ES
• Date of registration: 13/01/2016
• Prospective Registration: Yes
• Primary sponsor: Fondazione PENTA ONLUS
• 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: 21/03/2016
• Target sample size: 700
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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, Brazil, France, Germany, Italy, Portugal, South Africa, Spain, Thailand, Uganda, United Kingdom, United States, Zimbabwe

Contacts

• Name: Pablo Rojo
• Affiliation: Hospital doce de Octubre / PENTA

• Name: Pablo Rojo
• Affiliation: Hospital doce de Octubre / PENTA

Key inclusion & exclusion criteria

Inclusion criteria:
? Children <18 years with confirmed HIV-1 infection and DTG dose known for child?s age/weight-band*
? 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 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

*Recruitment will start from children aged ?6 and<18 years for whom dosing information and formulations are currently available. Additional formulations for younger children will become available during the trial and dosing information will be updated.

Additional criteria for ODYSSEY A:
? Planning to start first-line ART

Additional criteria for ODYSSEY B:
? Planning to start second-line ART defined as switch of at least 2 ART drugs due to treatment failure
? Treated with only one previous ART regimen. Single drug substitutions for toxicity 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, abacavir or zidovudine should have preserved activity based on cumulative results of resistance tests within 3 months
? 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 available from tenofovir, abacavir or zidovudine
? Viral load >1000 c/ml at screening visit
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 some other contraindication to the study drugs or their components
? 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
? Contraindications to proposed available NRTI backbone.


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: 18.1 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-

Primary Outcome(s)

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.

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

Primary end point(s): Difference in the probability of virological or clinical failure at 96 weeks, estimated by Kaplan-Meier methods, using time to the first occurrence of any of the following components:
? Insufficient virological response defined as <1 log10 drop at week 24
? Viral load >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)

Secondary end point(s): Secondary efficacy outcomes:
? Difference in proportion with clinical or virological failure (as defined above) over 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 with a subgroup analysis according to the activity of the background regimen

Secondary safety outcomes:
? Change in total cholesterol, triglycerides and lipid fractions (LDL, HDL) from baseline to weeks 48 and 96. These safety outcomes 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

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

Secondary ID(s)

NCT02259127

ISRCTN91737921

ODYSSEY(PENTA20)

Source(s) of Monetary Support

Fondazione PENTA ONLUS

Viiv Healthcare Ltd