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

HIV Infection Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02259127
• Other study ID #: ODYSSEY (PENTA 20)
• Secondary ID: 2014-002632-14
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: September 20, 2016
• Est. completion date: May 2023

Study information

• Verified date: April 2021
• Source: PENTA Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The ODYSSEY study is an ongoing international randomised trial evaluating dolutegravir based antiretroviral therapy versus standard of care in HIV-infected children aged less than 18 years who are starting first line treatment (ODYSSEY A) or switching to second line treatment (ODYSSEY B). Participants have visits 4 weeks and 12 weeks after randomisation and every 12 weeks subsequent of that. They are followed up for a minimum of 96 weeks. The primary objective of the study is to assess the difference in virological or clinical failure by 96 weeks between children receiving a DTG-based regimen and those on standard of care.

At the end of study visit for the randomised phase, children and carers will be invited to consent to extended follow-up. Children's visit schedules and care will be as per local clinic guidelines. Participants will be followed up until May 2023 in this phase of the trial. The objectives of the extended follow-up are two-fold: 1. to provide safety data for ViiV Healthcare for participants who, in the opinion of the treating physician, continue to derive benefit from dolutegravir and receive dolutegravir from ViiV Healthcare where it is not available through their country's national HIV treatment programme; 2. to monitor long-term safety and effectiveness of dolutegravir versus standard of care.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 792
• Est. completion date: May 2023
• Est. primary completion date: June 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infection
• HIV Infections
• Infection

Intervention

Drug:
• DTG

Locations

Country	Name	City	State
Germany	Universitata Frankfurt	Frankfurt
Germany	UkE Eppendorf Hamburg	Hamburg
Portugal	Centro Materno-Infantil de Norte	Porto
South Africa	King Edward VIII Hospital	Durban
South Africa	Africa Health Research Institute (AHRI)	Hlabisa
South Africa	PHRU Klerksdorp	Klerksdorp
South Africa	Kid-Cru	Parow
South Africa	PHRU	Soweto
Spain	Hospital San Joan de Defu	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital La Paz	Madrid
Thailand	Nakornping Hospital	Chiang Mai
Thailand	Chiangrai Prachanukroh Hospital	Chiang Rai
Thailand	Khon Kaen Hospital	Khon Kaen
Thailand	Mahasarakam Hospital	Maha Sarakham
Thailand	Prapokklao Hospital	Mueang Chanthaburi District
Thailand	Phayao Hospital	Phayao
Uganda	Baylor	Kampala
Uganda	JCRC	Kampala
Uganda	MUJHU	Kampala
Uganda	JCRC	Mbarara
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Great Ormand Street Hospital	London
United Kingdom	Kings College Hospital	London
United Kingdom	St Mary's Hospital	London
Zimbabwe	UZCRC	Harare

Sponsors (4)

Lead Sponsor	Collaborator
PENTA Foundation	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)

Countries where clinical trial is conducted

Germany,  Portugal,  South Africa,  Spain,  Thailand,  Uganda,  United Kingdom,  Zimbabwe, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in proportion with failure (clinical or virological)	estimated using time to the first occurrence of any of the following components: Insufficient virological response defined as < 1 log10 drop at week 24 and switch to second/third line ART for treatment failure; 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, adjudicated by the Endpoint Review Committee	96 weeks
Secondary	Difference in proportion with clinical or virological failure (as defined above)		over 48 weeks.
Secondary	Time to any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events adjudicated by the Endpoint Review Committee		after 24 weeks from randomisation
Secondary	Proportion of children with viral load suppression <50 c/ml		at 48 and 96 weeks
Secondary	Proportion of children with viral load suppression <400 c/ml		at 48 and 96 weeks
Secondary	Rate of clinical events : WHO 4, severe WHO 3 events and death		over 96 weeks
Secondary	Change in CD4 count and percentage and CD4/CD8 ratio from baseline		to weeks 48 and 96
Secondary	Proportion developing new resistance mutations in those with viral load > 400 c/ml		96 weeks
Secondary	Change in total cholesterol, triglycerides and lipid fractions (LDL, HDL)		from baseline to weeks 48 and 96
Secondary	Incidence of serious adverse events		Through study completion, at least 96 weeks
Secondary	Incidence of new clinical and laboratory grade 3 and 4 adverse events		Through study completion, at least 96 weeks
Secondary	Incidence of adverse events (of any grade) leading to treatment modification		Through study completion, at least 96 weeks
Secondary	Health-related Quality of Life Questionnaire	Adapted from the EuroQol-5D questionnaire	Through study completion, at least 96 weeks
Secondary	Adherence Questionnaire	The proportion of adherence questionnaires where the participant/carer reports missing a dose within the last week will be compared between randomised groups.	Through study completion, at least 96 weeks
Secondary	Acceptability Questionnaire	Number of participants reported to have problems with size, taste or swallowing of the medicines as assessed by Acceptability questionnaire	Through study completion, at least 96 weeks