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Completed

NCT Number: NCT02259127

ODYSSEY (PENTA 20)

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.

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Key information

Conditions

HIV Infection Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

28 day–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Universitata Frankfurt, Frankfurt, Germany

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Dolutegravir

Drug

Other names: DTG

Standard of care

Drug

PI or non nucleoside transcriptase inhibitors

Other names: SOC

Primary outcomes

  1. Difference in Proportion With Failure (Clinical or Virological)

    Time frame: 96 weeks post randomisation

    Treatment failure by 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
    • Viral Load (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 outcomes

  1. HIV-1 RNA <50c/ml at 96 Weeks

    Time frame: 96 weeks post randomisation

    Proportion of children with viral load suppression <50 c/ml at 96 weeks.

  2. HIV-1 RNA <400c/mL at 96 Weeks

    Time frame: 96 weeks post randomisation

    Proportion of children with viral load suppression <400 c/ml at 96 weeks

  3. Mean Change in CD4 Count From Baseline to Week 96

    Time frame: 96 weeks post randomisation

    Reporting mean change from the global baseline value across both arms.

  4. Mean Change in Total Cholesterol From Baseline to Week 96

    Time frame: 96 weeks post randomisation

    Reporting mean change from global baseline value across both arms.

  5. Serious Adverse Events

    Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

    Incidence of serious adverse events

  6. Grade 3 or Above Clinical and Laboratory Adverse Events

    Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

    Incidence of new clinical and laboratory grade 3 and 4 adverse events

  7. Adverse Events Leading to ART Modification Any Grade

    Time frame: Randomised Phase

    Incidence of adverse events (of any grade) leading to treatment modification

  8. Treatment Failure by 48 Weeks

    Time frame: 48 weeks post randomisation

    Treatment failure by 48 weeks. Difference in proportion with clinical or virological failure (as defined above)

  9. Treatment Failure by 144 Weeks

    Time frame: 144 weeks post randomisation

    Treatment failure by 144 weeks. Difference in proportion with clinical or virological failure (as defined above)

  10. WHO 4, Severe WHO 3 Events and Death

    Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

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

  11. Per Protocol: Treatment Failure by 96 Weeks

    Time frame: 96 weeks post randomisation

    Per protocol: treatment failure by 96 weeks post randomisation

  12. Any Drug Class Resistance After Virologic Failure

    Time frame: 96 weeks post randomisation

    Any drug class resistance after virologic failure 96 weeks post randomisation

    Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

  13. NRTI Resistance After Virologic Failure

    Time frame: 96 weeks post randomisation

    NRTI resistance after virologic failure 96 weeks post randomisation.

    Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

  14. NNRTI Resistance After Virologic Failure

    Time frame: 96 weeks post randomisation

    NNRTI resistance after virologic failure 96 weeks post randomisation.

    Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

  15. PI Resistance After Virologic Failure

    Time frame: 96 weeks post randomisation

    PI resistance after virologic failure 96 weeks post randomisation.

    Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

  16. INSTI Resistance After Virologic Failure

    Time frame: 96 weeks post randomisation

    INSTI resistance after virologic failure 96 weeks post randomisation

    Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

  17. Emerging Resistance to Any Drug Class After Virologic Failure

    Time frame: 96 weeks post randomisation

    Emerging resistance to any drug class after virologic failure 96 weeks post randomisation

    Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

    >=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.

    <14kg cohort: percentage reported for participants with whom resistance test was available post-failure and at baseline, and exposed to drug-class during trial.

  18. NRTI Emerging Resistance After Virologic Failure

    Time frame: 96 weeks post randomisation

    NRTI emerging resistance after virologic failure 96 weeks post randomisation

    Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

    >=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.

    <14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.

  19. NNRTI Emerging Resistance After Virologic Failure

    Time frame: 96 weeks post randomisation

    NNRTI emerging resistance after virologic failure 96 weeks post randomisation

    Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

    >=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.

    <14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.

  20. PI Emerging Resistance After Virologic Failure

    Time frame: 96 weeks post randomisation

    PI emerging resistance after virologic failure 96 weeks post randomisation

    Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

    >=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.

    <14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.

  21. INSTI Emerging Resistance After Virologic Failure

    Time frame: 96 weeks post randomisation

    INSTI emerging resistance after virologic failure 96 weeks post randomisation

    Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

    >=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.

    <14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.

    The integrase gene was not sequenced for the standard of care arm.

  22. Time to Any New or Recurrent AIDS Defining Event (WHO 4) or Severe WHO 3 Events

    Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

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

    Reported in >=14kg and <14kg papers. >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) <14kg cohort paper (https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)

  23. Adherence Questionnaire

    Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

    The proportion of adherence questionnaires where the participant/carer reports missing a dose within the last week will be compared between randomised groups.

    Reported in >=14kg and <14kg papers. >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) <14kg cohort paper (https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)

  24. Health-related Quality of Life Questionnaire

    Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

    Adapted from the Euro Quality of Life Questionnaire (Qol)-5D questionnaire The EQ5D-3L (3-level version of EQ-5D) questionnaire contains five questions about the participants' quality of life: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

    Each question has three dimensions: no problems, some problems, and extreme problems.

    This analysis reports whether the participant reports any problems (some or extreme). Percentages are of participants completing at least one EQ5D-3L questionnaire during follow-up.

    Reported in >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793)

  25. Acceptability Questionnaire

    Time frame: Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

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

    Reported in >=14kg and <14kg papers. >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) <14kg cohort paper (https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)

Other outcomes

  1. Mean Change in Weight From Baseline

    Time frame: 96 weeks post randomisation

    Mean change in weight from baseline to week 96

  2. Mean Change in BMI-for-age Z-score From Baseline

    Time frame: 96 weeks post randomisation

    Mean change in BMI-for-age from baseline to week 96. Reporting mean change from the global baseline value across both arms.

    z-scores (standard scores) are the number of standard deviations the observed data is above or below the population (z-score of 0 represents the population median). Positive z-scores represent the standard deviations above the median and negative z-scores represent the standard deviations below the median. BMI-for-age Z scores indicate: <-3SD severe thinness; <-2SD thinness; -2 to 1SD healthy weight; >1SD overweight; >2SD obese.

Sponsors and collaborators

Lead sponsor

PENTA Foundation

Network

Collaborators

  • Institut National de la Santé Et de la Recherche Médicale, France
  • MRC CTU at UCL
  • Program for HIV Prevention and Treatment (PHPT)
  • ViiV Healthcare

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2021
Study completion
2023
First posted
Oct 8, 2014
Registry last updated
Jul 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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