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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

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ClinicalTrials.gov Identifier: NCT02259127
Recruitment Status : Active, not recruiting
First Posted : October 8, 2014
Last Update Posted : October 20, 2020
Sponsor:
Collaborators:
Institut National de la Santé Et de la Recherche Médicale, France
Program for HIV Prevention and Treatment (PHPT)
Information provided by (Responsible Party):
PENTA Foundation

Tracking Information
First Submitted Date  ICMJE September 30, 2014
First Posted Date  ICMJE October 8, 2014
Last Update Posted Date October 20, 2020
Actual Study Start Date  ICMJE September 20, 2016
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2020)
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
Original Primary Outcome Measures  ICMJE
 (submitted: October 7, 2014)
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
  • 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2020)
  • 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 ]
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2014)
  • 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 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: 96 weeks ]
  • Incidence of new clinical and laboratory grade 3 and 4 adverse events [ Time Frame: 96 weeks ]
  • Incidence of adverse events (of any grade) leading to treatment modification [ Time Frame: 96 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE Not Provided
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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Infection
Intervention  ICMJE Drug: DTG
Study Arms  ICMJE
  • 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
    Intervention: Drug: DTG
  • Experimental: DTG arm
    DTG + 2 nucleoside transcriptase inhibitors
    Intervention: Drug: DTG
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 16, 2020)
792
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2014)
700
Estimated Study Completion Date  ICMJE May 2023
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Portugal,   South Africa,   Spain,   Thailand,   Uganda,   United Kingdom,   Zimbabwe
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02259127
Other Study ID Numbers  ICMJE ODYSSEY (PENTA 20)
2014-002632-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PENTA Foundation
Study Sponsor  ICMJE PENTA Foundation
Collaborators  ICMJE
  • Institut National de la Santé Et de la Recherche Médicale, France
  • Program for HIV Prevention and Treatment (PHPT)
Investigators  ICMJE Not Provided
PRS Account PENTA Foundation
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP