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
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| ClinicalTrials.gov Identifier: NCT02259127 |
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Recruitment Status : Unknown
Verified April 2021 by PENTA Foundation.
Recruitment status was: Active, not recruiting
First Posted : October 8, 2014
Last Update Posted : April 29, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infection | Drug: DTG | Phase 2 Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 792 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Actual Study Start Date : | September 20, 2016 |
| Estimated Primary Completion Date : | June 2021 |
| Estimated Study Completion Date : | May 2023 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: SOC arm
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
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Drug: DTG |
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Experimental: DTG arm
DTG + 2 nucleoside transcriptase inhibitors
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Drug: DTG |
- Difference in proportion with failure (clinical or virological) [ Time Frame: 96 weeks ]
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
- Difference in proportion with clinical or virological failure (as defined above) [ Time Frame: over 48 weeks. ]
- 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 ]
- Proportion of children with viral load suppression <50 c/ml [ Time Frame: at 48 and 96 weeks ]
- Proportion of children with viral load suppression <400 c/ml [ Time Frame: at 48 and 96 weeks ]
- Rate of clinical events : WHO 4, severe WHO 3 events and death [ Time Frame: over 96 weeks ]
- Change in CD4 count and percentage and CD4/CD8 ratio from baseline [ Time Frame: to weeks 48 and 96 ]
- Proportion developing new resistance mutations in those with viral load > 400 c/ml [ Time Frame: 96 weeks ]
- Change in total cholesterol, triglycerides and lipid fractions (LDL, HDL) [ Time Frame: from baseline to weeks 48 and 96 ]
- Incidence of serious adverse events [ Time Frame: Through study completion, at least 96 weeks ]
- Incidence of new clinical and laboratory grade 3 and 4 adverse events [ Time Frame: Through study completion, at least 96 weeks ]
- Incidence of adverse events (of any grade) leading to treatment modification [ Time Frame: Through study completion, at least 96 weeks ]
- Health-related Quality of Life Questionnaire [ Time Frame: Through study completion, at least 96 weeks ]Adapted from the EuroQol-5D questionnaire
- Adherence Questionnaire [ Time Frame: Through study completion, at least 96 weeks ]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 [ Time Frame: Through study completion, at least 96 weeks ]Number of participants reported to have problems with size, taste or swallowing of the medicines as assessed by Acceptability questionnaire
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| Ages Eligible for Study: | 28 Days to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02259127
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| Responsible Party: | PENTA Foundation |
| ClinicalTrials.gov Identifier: | NCT02259127 |
| Other Study ID Numbers: |
ODYSSEY (PENTA 20) 2014-002632-14 ( EudraCT Number ) |
| First Posted: | October 8, 2014 Key Record Dates |
| Last Update Posted: | April 29, 2021 |
| Last Verified: | April 2021 |
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Infections HIV Infections Acquired Immunodeficiency Syndrome Communicable Diseases Blood-Borne Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Lentivirus Infections |
Retroviridae Infections RNA Virus Infections Virus Diseases Genital Diseases Urogenital Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases |