ODYSSEY (PENTA 20)

PENTA Foundation

Status and phase: Completed; Phase 3; Phase 2

Conditions: HIV Infection

Treatments: Drug: Standard of Care; Drug: Dolutegravir

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT02259127

ODYSSEY (PENTA 20)

2014-002632-14 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

The ODYSSEY study was an international randomised trial evaluating dolutegravir based antiretroviral therapy (ART) versus standard of care in HIV-infected children aged less than 18 years who were starting first line treatment (ODYSSEY A) or switching to second line treatment (ODYSSEY B). Participants had visits 4 weeks and 12 weeks after randomisation and every 12 weeks subsequent of that. They were followed up for a minimum of 96 weeks. The primary objective of the study was 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 were invited to consent to extended follow-up. Children's visit schedules and care were as per local clinic guidelines. Participants were followed up until July 2023 in this phase of the trial. The objectives of the extended follow-up were 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 was not available through their country's national HIV treatment programme; 2. to monitor long-term safety and effectiveness of dolutegravir versus standard of care.

Enrollment: 792 patients

Sex: All

Ages: 28 days to 18 years old

Volunteers: No Healthy Volunteers

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)-Pharmacokinetics (PK)1 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 Nucleoside Reverse Transcriptase Inhibitor (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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

792 participants in 2 patient groups

SOC arm

Active Comparator group

Description:

Standard of Care (SOC) for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors

Treatment:

Drug: Standard of Care

DTG arm

Experimental group

Description:

DTG + 2 nucleoside transcriptase inhibitors

Treatment:

Drug: Dolutegravir