<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/NCT04429152</url>
  </required_header>
  <id_info>
    <org_study_id>EZMiM018</org_study_id>
    <nct_id>NCT04429152</nct_id>
  </id_info>
  <brief_title>ADORE: Efficacy of DORavirine in Adults Living With HIV Experiencing Virological Failure on First-line Efavirenz-based Antiretroviral Therapy With NNRTI Resistance</brief_title>
  <acronym>ADORE</acronym>
  <official_title>ADORE: A Single-arm, Phase 3, Pilot Study Investigating the Efficacy of Doravirine in Adults Living With HIV Experiencing Virological Failure on First-line Efavirenz-based Antiretroviral Therapy With Non-nucleoside Reverse Transcriptase Inhibitor Resistance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Professor Francois Venter</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Witwatersrand, South Africa</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study investigating the efficacy of Doravirine (DOR) in combination with&#xD;
      Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in adults&#xD;
      living with HIV-1 experiencing virological failure on first-line Efavirenz-based&#xD;
      antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor resistance&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-arm, phase 3 pilot study investigating the efficacy of Doravirine (DOR) in&#xD;
      combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over&#xD;
      48 weeks in adults living with HIV-1 experiencing virological failure on first-line&#xD;
      Efavirenz-based antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor&#xD;
      resistance.&#xD;
&#xD;
      Approximately 25 male and female participants 18 years and older infected with HIV-1 and&#xD;
      experiencing virological failure on efavirenz-based ART will be administered a once-daily,&#xD;
      fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil&#xD;
      fumarate 300 mg (DOR/3TC/TDF). The study includes screening and baseline visits, 4 study&#xD;
      visits from Week 4 to Week 36, and an end of study visit at Week 48.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 9, 2021</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of participants with undetectable plasma HIV-1 RNA levels (&lt;50 copies/mL) at week 24</measure>
    <time_frame>24 weeks</time_frame>
    <description>The proportion of participants with undetectable plasma HIV-1 RNA levels at Week 24 will be recorded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with undetectable plasma HIV-1 RNA levels (&lt;50 copies/mL) at weeks 4, 12 and 48</measure>
    <time_frame>At week 4, 12, 48</time_frame>
    <description>Evaluation of viral suppression by recording the proportion of patients with undetectable plasma HIV-1 RNA levels (&lt;50 copies/mL) at weeks 4, 12 and 48</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in plasma CD4 levels at weeks 24 and 48</measure>
    <time_frame>At week 24, 48</time_frame>
    <description>Evaluation of changes in CD4 count from baseline recorded at weeks 24 and 48.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emergence of antiretroviral resistance mutations in participants with virological failure</measure>
    <time_frame>48 weeks</time_frame>
    <description>Evaluation of the number of antiretroviral resistance mutations that emerge in participants with virological failure</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>HIV-1-infection</condition>
  <arm_group>
    <arm_group_label>Doravirine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once-daily, fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doravirine/Lamivudine/Tenofovir</intervention_name>
    <description>DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination</description>
    <arm_group_label>Doravirine</arm_group_label>
    <other_name>Delstrigo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults living with HIV-1, 18 years and older&#xD;
&#xD;
          -  Viral load 5000 - 60 000 copies/mL on first-line efavirenz-based antiretroviral&#xD;
             therapy&#xD;
&#xD;
          -  HIV genotype resistance test with first generation NNRTI resistance (e.g. K103N,&#xD;
             Y181C, etc as listed in the protocol)&#xD;
&#xD;
          -  CD4 &gt; 200 cells/uL&#xD;
&#xD;
          -  Creatinine clearance &gt; 50 mL/min&#xD;
&#xD;
          -  Body mass ≥ 35 kg.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Resistance to TDF on genotype (K65R)&#xD;
&#xD;
          -  &quot;Significant resistance&quot; to doravirine, denoted by a Stanford Score ≥ 15 on genotype&#xD;
&#xD;
          -  Virologic failure on any other regimen&#xD;
&#xD;
          -  Women who are pregnant at the time of the screening or enrolment visits&#xD;
&#xD;
          -  Active tuberculosis and/or are on anti-tuberculous therapy at the time of the&#xD;
             screening or enrolment visits&#xD;
&#xD;
          -  Taking and cannot discontinue prohibited concomitant medications listed in protocol at&#xD;
             least two weeks prior to the enrolment visit and for the duration of the study period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Simiso Sokhela, MBBCh</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Simiso Sokhela, MBBCh</last_name>
    <phone>+27113585437</phone>
    <email>ssokhela@wrhi.ac.za</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Bronwyn Bosch, MBBCh</last_name>
    <phone>+27113585300</phone>
    <email>bbosch@wrhi.ac.za</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Charlotte Maxeke Johannesburg Academic Hospital</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2196</zip>
        <country>South Africa</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Natasha Arulappan</last_name>
      <phone>+27113585542</phone>
      <email>gakpomiemie@wrhi.ac.za</email>
    </contact>
    <contact_backup>
      <last_name>Nonkululeko Mashabane, BPharm</last_name>
      <phone>+27113585543</phone>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Sunnyside Office Park</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <country>South Africa</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Bronwyn Bosch, MBBCh</last_name>
      <phone>+27113585300</phone>
      <email>bbosch@wrhi.ac.za</email>
    </contact>
    <contact_backup>
      <last_name>Godspower Akpomiemie, MPH</last_name>
      <phone>+2711358 5370</phone>
      <email>gakpomiemie@wrhi.ac.za</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Wits RHI Yeoville Clinic</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <country>South Africa</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Simiso Sokhela, MBBCh</last_name>
      <phone>+27113585500</phone>
      <email>ssokhela@wrhi.ac.za</email>
    </contact>
    <contact_backup>
      <last_name>Nonkululeko Mashabane, BPharm</last_name>
      <phone>+27113585543</phone>
      <email>nmashabane@wrhi.ac.za</email>
    </contact_backup>
    <investigator>
      <last_name>Simiso Sokhela, MBBCh</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nomathemba Chandiwana, MBBCh</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>June 5, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>June 6, 2022</last_update_submitted>
  <last_update_submitted_qc>June 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Witwatersrand, South Africa</investigator_affiliation>
    <investigator_full_name>Professor Francois Venter</investigator_full_name>
    <investigator_title>Divisional Director: Ezintsha</investigator_title>
  </responsible_party>
  <keyword>Virological failure, first-line antiretroviral therapy</keyword>
  <keyword>Doravirine</keyword>
  <keyword>Delstrigo</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Lamivudine</mesh_term>
  </intervention_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/NCT04429152
org study id: EZMiM018
nct id: NCT04429152
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a pilot study investigating the efficacy of Doravirine (DOR) in combination with
      Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in adults
      living with HIV-1 experiencing virological failure on first-line Efavirenz-based
      antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor resistance
This is a single-arm, phase 3 pilot study investigating the efficacy of Doravirine (DOR) in
      combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over
      48 weeks in adults living with HIV-1 experiencing virological failure on first-line
      Efavirenz-based antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor
      resistance.

      Approximately 25 male and female participants 18 years and older infected with HIV-1 and
      experiencing virological failure on efavirenz-based ART will be administered a once-daily,
      fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil
      fumarate 300 mg (DOR/3TC/TDF). The study includes screening and baseline visits, 4 study
      visits from Week 4 to Week 36, and an end of study visit at Week 48.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of participants with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at week 24
time frame: 24 weeks
description: The proportion of participants with undetectable plasma HIV-1 RNA levels at Week 24 will be recorded.
measure: Proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48
time frame: At week 4, 12, 48
description: Evaluation of viral suppression by recording the proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48
measure: Change from baseline in plasma CD4 levels at weeks 24 and 48
time frame: At week 24, 48
description: Evaluation of changes in CD4 count from baseline recorded at weeks 24 and 48.
measure: Emergence of antiretroviral resistance mutations in participants with virological failure
time frame: 48 weeks
description: Evaluation of the number of antiretroviral resistance mutations that emerge in participants with virological failure
arm group label: Doravirine
arm group type: Experimental
description: Once-daily, fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF).
intervention type: Drug
intervention name: Doravirine/Lamivudine/Tenofovir
description: DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination
arm group label: Doravirine
other name: Delstrigo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Simiso Sokhela, MBBCh
role: Principal Investigator
affiliation: Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)
last name: Simiso Sokhela, MBBCh
phone: +27113585437
email: ssokhela@wrhi.ac.za
last name: Bronwyn Bosch, MBBCh
phone: +27113585300
email: bbosch@wrhi.ac.za
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Not yet recruiting
contact: 
contact backup: 
facility: 
status: Not yet recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: South Africa
responsible party type: Sponsor-Investigator
investigator affiliation: University of Witwatersrand, South Africa
investigator full name: Professor Francois Venter
investigator title: Divisional Director: Ezintsha
mesh term: Tenofovir
mesh term: Lamivudine