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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

Primary Purpose

HIV Infection

Status

Unknown status

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

DTG

About this trial

This is an interventional treatment trial for HIV Infection

Eligibility Criteria

28 Days - 18 Years (Child, Adult)All SexesDoes not accept 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)-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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

SOC arm

DTG arm

Arm Description

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

DTG + 2 nucleoside transcriptase inhibitors

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Difference in proportion with clinical or virological failure (as defined above)

Time to any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events adjudicated by the Endpoint Review Committee

Proportion of children with viral load suppression <50 c/ml

Proportion of children with viral load suppression <400 c/ml

Rate of clinical events : WHO 4, severe WHO 3 events and death

Change in CD4 count and percentage and CD4/CD8 ratio from baseline

Proportion developing new resistance mutations in those with viral load > 400 c/ml

Change in total cholesterol, triglycerides and lipid fractions (LDL, HDL)

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

Health-related Quality of Life Questionnaire

Adapted from the EuroQol-5D questionnaire

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.

Acceptability Questionnaire

Number of participants reported to have problems with size, taste or swallowing of the medicines as assessed by Acceptability questionnaire

Full Information

NCT ID

NCT02259127

First Posted

September 30, 2014

Last Updated

April 27, 2021

Sponsor

PENTA Foundation

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France, Program for HIV Prevention and Treatment (PHPT), Medical Research Council Clinical Trials Unit at University College London (MRC CTU at UCL)

1. Study Identification

Unique Protocol Identification Number

NCT02259127

Brief 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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Unknown status

Study Start Date

September 20, 2016 (Actual)

Primary Completion Date

June 2021 (Anticipated)

Study Completion Date

May 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PENTA Foundation

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

792 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SOC arm

Arm Type

Active Comparator

Arm Description

Arm Title

DTG arm

Arm Type

Experimental

Arm Description

DTG + 2 nucleoside transcriptase inhibitors

Intervention Type

Drug

Intervention Name(s)

DTG

Primary Outcome Measure Information:

Title

Difference in proportion with failure (clinical or virological)

Description

Time Frame

96 weeks

Secondary Outcome Measure Information:

Title

Difference in proportion with clinical or virological failure (as defined above)

Time Frame

over 48 weeks.

Title

Time to any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events adjudicated by the Endpoint Review Committee

Time Frame

after 24 weeks from randomisation

Title

Proportion of children with viral load suppression <50 c/ml

Time Frame

at 48 and 96 weeks

Title

Proportion of children with viral load suppression <400 c/ml

Time Frame

at 48 and 96 weeks

Title

Rate of clinical events : WHO 4, severe WHO 3 events and death

Time Frame

over 96 weeks

Title

Change in CD4 count and percentage and CD4/CD8 ratio from baseline

Time Frame

to weeks 48 and 96

Title

Proportion developing new resistance mutations in those with viral load > 400 c/ml

Time Frame

96 weeks

Title

Change in total cholesterol, triglycerides and lipid fractions (LDL, HDL)

Time Frame

from baseline to weeks 48 and 96

Title

Incidence of serious adverse events

Time Frame