<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02259127</url>
  </required_header>
  <id_info>
    <org_study_id>ODYSSEY (PENTA 20)</org_study_id>
    <secondary_id>2014-002632-14</secondary_id>
    <nct_id>NCT02259127</nct_id>
  </id_info>
  <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</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>PENTA Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Program for HIV Prevention and Treatment (PHPT)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical Research Council Clinical Trials Unit at University College London (MRC CTU at UCL)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>PENTA Foundation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A new anti-HIV medicine (Dolutegravir) combined with 2 currently used anti-HIV medicines is&#xD;
      non-inferior to the standard combination of medicines used in terms of efficacy and better in&#xD;
      terms of toxicity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The ODYSSEY study is an ongoing international randomised trial evaluating dolutegravir based&#xD;
      antiretroviral therapy versus standard of care in HIV-infected children aged less than 18&#xD;
      years who are starting first line treatment (ODYSSEY A) or switching to second line treatment&#xD;
      (ODYSSEY B). Participants have visits 4 weeks and 12 weeks after randomisation and every 12&#xD;
      weeks subsequent of that. They are followed up for a minimum of 96 weeks. The primary&#xD;
      objective of the study is to assess the difference in virological or clinical failure by 96&#xD;
      weeks between children receiving a DTG-based regimen and those on standard of care.&#xD;
&#xD;
      At the end of study visit for the randomised phase, children and carers will be invited to&#xD;
      consent to extended follow-up. Children's visit schedules and care will be as per local&#xD;
      clinic guidelines. Participants will be followed up until May 2023 in this phase of the&#xD;
      trial. The objectives of the extended follow-up are two-fold: 1. to provide safety data for&#xD;
      ViiV Healthcare for participants who, in the opinion of the treating physician, continue to&#xD;
      derive benefit from dolutegravir and receive dolutegravir from ViiV Healthcare where it is&#xD;
      not available through their country's national HIV treatment programme; 2. to monitor&#xD;
      long-term safety and effectiveness of dolutegravir versus standard of care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">September 20, 2016</start_date>
  <completion_date type="Anticipated">May 2023</completion_date>
  <primary_completion_date type="Anticipated">June 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in proportion with failure (clinical or virological)</measure>
    <time_frame>96 weeks</time_frame>
    <description>estimated using time to the first occurrence of any of the following components:&#xD;
Insufficient virological response defined as &lt; 1 log10 drop at week 24 and switch to second/third line ART for treatment failure&#xD;
VL&gt;400 c/ml at or after 36 weeks confirmed by next visit&#xD;
Death due to any cause&#xD;
Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, adjudicated by the Endpoint Review Committee</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in proportion with clinical or virological failure (as defined above)</measure>
    <time_frame>over 48 weeks.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events adjudicated by the Endpoint Review Committee</measure>
    <time_frame>after 24 weeks from randomisation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children with viral load suppression &lt;50 c/ml</measure>
    <time_frame>at 48 and 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children with viral load suppression &lt;400 c/ml</measure>
    <time_frame>at 48 and 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of clinical events : WHO 4, severe WHO 3 events and death</measure>
    <time_frame>over 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CD4 count and percentage and CD4/CD8 ratio from baseline</measure>
    <time_frame>to weeks 48 and 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion developing new resistance mutations in those with viral load &gt; 400 c/ml</measure>
    <time_frame>96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in total cholesterol, triglycerides and lipid fractions (LDL, HDL)</measure>
    <time_frame>from baseline to weeks 48 and 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of serious adverse events</measure>
    <time_frame>Through study completion, at least 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of new clinical and laboratory grade 3 and 4 adverse events</measure>
    <time_frame>Through study completion, at least 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events (of any grade) leading to treatment modification</measure>
    <time_frame>Through study completion, at least 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related Quality of Life Questionnaire</measure>
    <time_frame>Through study completion, at least 96 weeks</time_frame>
    <description>Adapted from the EuroQol-5D questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence Questionnaire</measure>
    <time_frame>Through study completion, at least 96 weeks</time_frame>
    <description>The proportion of adherence questionnaires where the participant/carer reports missing a dose within the last week will be compared between randomised groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability Questionnaire</measure>
    <time_frame>Through study completion, at least 96 weeks</time_frame>
    <description>Number of participants reported to have problems with size, taste or swallowing of the medicines as assessed by Acceptability questionnaire</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">792</enrollment>
  <condition>HIV Infection</condition>
  <arm_group>
    <arm_group_label>SOC arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DTG arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DTG + 2 nucleoside transcriptase inhibitors</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DTG</intervention_name>
    <arm_group_label>DTG arm</arm_group_label>
    <arm_group_label>SOC arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        ALL PATIENTS:&#xD;
&#xD;
          -  Children ≥28 days and &lt;18 years weighing ≥3kg with confirmed HIV-1 infection&#xD;
&#xD;
          -  Parents/carers and children, where applicable, give informed written consent&#xD;
&#xD;
          -  Girls aged 12 years or older who have reached menses must have a negative pregnancy&#xD;
             test at screening and be willing to adhere to effective methods of contraception if&#xD;
             sexually active&#xD;
&#xD;
          -  Children with co-infections who need to start ART can be enrolled into ODYSSEY&#xD;
             according to local/national guidelines&#xD;
&#xD;
          -  Parents/carers and children, where applicable, willing to adhere to a minimum of 96&#xD;
             weeks' follow-up&#xD;
&#xD;
               -  Children weighing 3 to &lt;14kg must be eligible and willing to participate in the&#xD;
                  Weight band (WB)-PK1 substudy unless direct enrolment for the child's weight band&#xD;
                  has opened following the WB-PK1 substudy and/or dosing information has become&#xD;
                  available from the IMPAACT P1093 DTG dose-finding study.&#xD;
&#xD;
        ADDITIONAL CRITERIA FOR ODYSSEY A:&#xD;
&#xD;
        • Planning to start first-line ART&#xD;
&#xD;
        ADDITIONAL CRITERIA FOR ODYSSEY B:&#xD;
&#xD;
          -  Planning to start second-line ART defined as either: (i) switch of at least 2 ART&#xD;
             drugs due to treatment failure; or (ii) switch of only the third agent due to&#xD;
             treatment failure where drug sensitivity tests show no mutations conferring NRTI&#xD;
             resistance&#xD;
&#xD;
          -  Treated with only one previous ART regimen. Single drug substitutions for toxicity,&#xD;
             simplification, changes in national guidelines or drug availability are allowed&#xD;
&#xD;
          -  At least one NRTI with predicted preserved activity available for a background regimen&#xD;
&#xD;
          -  In settings where resistance tests are routinely available, at least one new active&#xD;
             NRTI from tenofovir disoproxil fumarate, abacavir or zidovudine should have preserved&#xD;
             activity based on cumulative results of resistance tests&#xD;
&#xD;
          -  In settings where resistance tests are not routinely available, children who are due&#xD;
             to switch according to national guidelines should have at least one new NRTI predicted&#xD;
             to be available from tenofovir disoproxil fumarate, abacavir or zidovudine&#xD;
&#xD;
          -  Viral load ≥ 500 c/ml at screening visit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or presence of known allergy or contraindications to dolutegravir&#xD;
&#xD;
          -  History or presence of known allergy or contraindications to proposed available NRTI&#xD;
             backbone or proposed available SOC third agent.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal, OR ALT ≥3x upper&#xD;
             limit of normal and bilirubin ≥2x upper limit of normal&#xD;
&#xD;
          -  Patients with severe hepatic impairment or unstable liver disease (as defined by the&#xD;
             presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or&#xD;
             gastric varices, or persistent jaundice), known biliary abnormalities (with the&#xD;
             exception of Gilbert's syndrome or asymptomatic gallstones)&#xD;
&#xD;
          -  Anticipated need for Hepatitis C virus (HCV) therapy during the study&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Evidence of lack of susceptibility to integrase inhibitors or more than a 2-week&#xD;
             exposure to antiretrovirals of this class&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>28 Days</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Universitata Frankfurt</name>
      <address>
        <city>Frankfurt</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UkE Eppendorf Hamburg</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Materno-Infantil de Norte</name>
      <address>
        <city>Porto</city>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Edward VIII Hospital</name>
      <address>
        <city>Durban</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Africa Health Research Institute (AHRI)</name>
      <address>
        <city>Hlabisa</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PHRU Klerksdorp</name>
      <address>
        <city>Klerksdorp</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kid-Cru</name>
      <address>
        <city>Parow</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PHRU</name>
      <address>
        <city>Soweto</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital San Joan de Defu</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital La Paz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nakornping Hospital</name>
      <address>
        <city>Chiang Mai</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chiangrai Prachanukroh Hospital</name>
      <address>
        <city>Chiang Rai</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Khon Kaen Hospital</name>
      <address>
        <city>Khon Kaen</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mahasarakam Hospital</name>
      <address>
        <city>Maha Sarakham</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prapokklao Hospital</name>
      <address>
        <city>Mueang Chanthaburi District</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Phayao Hospital</name>
      <address>
        <city>Phayao</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor</name>
      <address>
        <city>Kampala</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JCRC</name>
      <address>
        <city>Kampala</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MUJHU</name>
      <address>
        <city>Kampala</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JCRC</name>
      <address>
        <city>Mbarara</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Birmingham Heartlands Hospital</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leeds General Infirmary</name>
      <address>
        <city>Leeds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leicester Royal Infirmary</name>
      <address>
        <city>Leicester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Great Ormand Street Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kings College Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Mary's Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZCRC</name>
      <address>
        <city>Harare</city>
        <country>Zimbabwe</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Portugal</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Thailand</country>
    <country>Uganda</country>
    <country>United Kingdom</country>
    <country>Zimbabwe</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>September 30, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02259127
org study id: ODYSSEY (PENTA 20)
secondary id: 2014-002632-14
nct id: NCT02259127
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Difference in proportion with failure (clinical or virological)
time frame: 96 weeks
description: 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
measure: Difference in proportion with clinical or virological failure (as defined above)
time frame: over 48 weeks.
measure: 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
measure: Proportion of children with viral load suppression <50 c/ml
time frame: at 48 and 96 weeks
measure: Proportion of children with viral load suppression <400 c/ml
time frame: at 48 and 96 weeks
measure: Rate of clinical events : WHO 4, severe WHO 3 events and death
time frame: over 96 weeks
measure: Change in CD4 count and percentage and CD4/CD8 ratio from baseline
time frame: to weeks 48 and 96
measure: Proportion developing new resistance mutations in those with viral load > 400 c/ml
time frame: 96 weeks
measure: Change in total cholesterol, triglycerides and lipid fractions (LDL, HDL)
time frame: from baseline to weeks 48 and 96
measure: Incidence of serious adverse events
time frame: Through study completion, at least 96 weeks
measure: Incidence of new clinical and laboratory grade 3 and 4 adverse events
time frame: Through study completion, at least 96 weeks
measure: Incidence of adverse events (of any grade) leading to treatment modification
time frame: Through study completion, at least 96 weeks
measure: Health-related Quality of Life Questionnaire
time frame: Through study completion, at least 96 weeks
description: Adapted from the EuroQol-5D questionnaire
measure: Adherence Questionnaire
time frame: Through study completion, at least 96 weeks
description: The proportion of adherence questionnaires where the participant/carer reports missing a dose within the last week will be compared between randomised groups.
measure: Acceptability Questionnaire
time frame: Through study completion, at least 96 weeks
description: Number of participants reported to have problems with size, taste or swallowing of the medicines as assessed by Acceptability questionnaire
arm group label: SOC arm
arm group type: Active Comparator
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
arm group label: DTG arm
arm group type: Experimental
description: DTG + 2 nucleoside transcriptase inhibitors
intervention type: Drug
intervention name: DTG
arm group label: DTG arm
arm group label: SOC arm
criteria: 
gender: All
minimum age: 28 Days
maximum age: 18 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Portugal
country: South Africa
country: Spain
country: Thailand
country: Uganda
country: United Kingdom
country: Zimbabwe
responsible party type: Sponsor
mesh term: Infections
mesh term: HIV Infections
mesh term: Acquired Immunodeficiency Syndrome