<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/NCT04433780</url>
  </required_header>
  <id_info>
    <org_study_id>EZMiM017</org_study_id>
    <nct_id>NCT04433780</nct_id>
  </id_info>
  <brief_title>DORA: A Doravirine-based First-line Antiretroviral Therapy for Women of Reproductive Potential Living With HIV</brief_title>
  <acronym>DORA</acronym>
  <official_title>A Single Arm, Phase 3 Study, Exploring the Safety of Doravirine-based First-line Antiretroviral Therapy for Women of Reproductive Potential Living With HIV, a Pilot Switch Study Strategy in South Africa</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study investigating the safety of Doravirine (DOR) in combination with&#xD;
      Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in women&#xD;
      of reproductive potential living with HIV-1 switched from Efavirenz or Dolutegravir-based&#xD;
      antiretroviral therapy on metabolic and neuropsychiatric outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pilot, open label, single-arm, single centre, phase 3, switch study exploring the&#xD;
      safety of of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil&#xD;
      Fumarate (TDF) administered over 48 weeks in women of reproductive potential living with&#xD;
      HIV-1 switched from Efavirenz or Dolutegravir-based antiretroviral therapy. The metabolic and&#xD;
      neuropsychiatric outcomes among women (and their infants) in a representative African female&#xD;
      population of reproductive potential will be investigated.&#xD;
&#xD;
      Approximately 100 women aged between 18 and 49 years old 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>Completed</overall_status>
  <start_date type="Actual">January 4, 2021</start_date>
  <completion_date type="Actual">March 31, 2023</completion_date>
  <primary_completion_date type="Actual">February 20, 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>The proportion of participants with neuropsychiatric adverse events (AEs)</measure>
    <time_frame>48 weeks</time_frame>
    <description>The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories (dizziness, sleep disorders/ disturbances, and altered sensorium) at Week 48</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in fasting lipids from baseline to Week 48</measure>
    <time_frame>48 weeks</time_frame>
    <description>Changes in fasting lipids from baseline to Week 48 assessed using lipid profile blood test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in weight from baseline to Week 48</measure>
    <time_frame>48 weeks</time_frame>
    <description>Changes in weight from baseline to Week 48 assessed</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in body mass index from baseline to Week 48</measure>
    <time_frame>48 weeks</time_frame>
    <description>Changes in body mass index from baseline to Week 48 assessed</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in glucose from baseline to Week 48</measure>
    <time_frame>48 weeks</time_frame>
    <description>Changes in glucose from baseline to Week 48 assessed using blood test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL)</measure>
    <time_frame>At week 24, 48</time_frame>
    <description>The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL) at weeks 24 and 48</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories</measure>
    <time_frame>24 weeks</time_frame>
    <description>The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories (dizziness, sleep disorders/ disturbances, and altered sensorium) at Week 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in glucose from baseline to week 24</measure>
    <time_frame>24 weeks</time_frame>
    <description>Changes in glucose from baseline to Week 24 using blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in fasting lipids from baseline to week 24</measure>
    <time_frame>24 weeks</time_frame>
    <description>Changes in fasting lipids from baseline to Week 24 using lipid profile blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in weight and from baseline to week 24</measure>
    <time_frame>24 weeks</time_frame>
    <description>Changes in weight from baseline to Week 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in body mass index from baseline to week 24</measure>
    <time_frame>24 weeks</time_frame>
    <description>Changes in body mass index from baseline to Week 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of infants evaluated for HIV-positive tests using HIV DNA polymerase chain reaction test (PCR)</measure>
    <time_frame>48 weeks</time_frame>
    <description>The proportion of infants evaluated for HIV-positive tests using HIV DNA polymerase chain reaction test (PCR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in quality of life from baseline</measure>
    <time_frame>At weeks 24, 48</time_frame>
    <description>Changes in quality of life from baseline to Weeks 24 and 48 measured using a traditional clinical, validated quality of life questionairre. Higher scores mean a better outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median adherence by each adherence measure</measure>
    <time_frame>At weeks 24, 48</time_frame>
    <description>Median adherence by each adherence measure at Weeks 24 and 48 using a validated adherence questionairre</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emergence of antiretroviral resistance mutations in participants with virological failure</measure>
    <time_frame>48 weeks</time_frame>
    <description>Evaluating 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="Actual">133</enrollment>
  <condition>HIV-1-infection</condition>
  <arm_group>
    <arm_group_label>Delstrigo</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 Disoproxil Fumarate</intervention_name>
    <description>DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination switched from either EFV/TDF/FTC or DTG/TDF/3TC</description>
    <arm_group_label>Delstrigo</arm_group_label>
    <other_name>Delstrigo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Females, aged 18-49 years and ≥ 40 kg&#xD;
&#xD;
          -  On a first-line EFV or DTG-containing regimen for at least six months and not more&#xD;
             than 3 years&#xD;
&#xD;
          -  Plasma HIV-1 RNA &lt; 50 copies/mL in last 60 days&#xD;
&#xD;
          -  Calculated creatinine clearance (CrCl) &gt; 50 mL/min (Cockcroft-Gault formula)&#xD;
&#xD;
          -  Baseline weight measurement available at ART initiation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Virological failure on any other regimen&#xD;
&#xD;
          -  Women who are pregnant at the time of the screening or enrolment visits or have had a&#xD;
             pregnancy gestation ≥ 28 weeks in the preceding 2 years&#xD;
&#xD;
          -  Active tuberculosis and/or are on antituberculosis therapy at the time of the&#xD;
             screening or enrolment visits&#xD;
&#xD;
          -  Taking (and cannot discontinue) prohibited concomitant medications listed in protocol&#xD;
             at least two weeks prior to the enrolment visit and for the duration of the study&#xD;
             period (see potential drug interactions section for list).&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female HIV-positive participants of reproductive potential age</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Simiso Sokhela</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)</affiliation>
  </overall_official>
  <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>
  </location>
  <location>
    <facility>
      <name>Sunnyside Office Park</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 5, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>July 31, 2023</last_update_submitted>
  <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</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 of Ezintsha</investigator_title>
  </responsible_party>
  <keyword>Doravirine</keyword>
  <keyword>Delstrigo</keyword>
  <keyword>DOR/3TC/TDF</keyword>
  <keyword>Women of reproductive potential</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>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data that will be shared is all of the individual participant data collected during the trial, after deidentification.The data that will be shared is all of the individual participant data collected during the trial, after identification. The data that will be shared is all of the individual participant data collected during the trial, after deidentification.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Immediately following publication</ipd_time_frame>
    <ipd_access_criteria>Anyone who wishes to access the data</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT04433780
org study id: EZMiM017
nct id: NCT04433780
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a pilot study investigating the safety of Doravirine (DOR) in combination with
      Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in women
      of reproductive potential living with HIV-1 switched from Efavirenz or Dolutegravir-based
      antiretroviral therapy on metabolic and neuropsychiatric outcomes.
This is a pilot, open label, single-arm, single centre, phase 3, switch study exploring the
      safety of of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil
      Fumarate (TDF) administered over 48 weeks in women of reproductive potential living with
      HIV-1 switched from Efavirenz or Dolutegravir-based antiretroviral therapy. The metabolic and
      neuropsychiatric outcomes among women (and their infants) in a representative African female
      population of reproductive potential will be investigated.

      Approximately 100 women aged between 18 and 49 years old 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: The proportion of participants with neuropsychiatric adverse events (AEs)
time frame: 48 weeks
description: The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories (dizziness, sleep disorders/ disturbances, and altered sensorium) at Week 48
measure: Changes in fasting lipids from baseline to Week 48
time frame: 48 weeks
description: Changes in fasting lipids from baseline to Week 48 assessed using lipid profile blood test
measure: Changes in weight from baseline to Week 48
time frame: 48 weeks
description: Changes in weight from baseline to Week 48 assessed
measure: Changes in body mass index from baseline to Week 48
time frame: 48 weeks
description: Changes in body mass index from baseline to Week 48 assessed
measure: Changes in glucose from baseline to Week 48
time frame: 48 weeks
description: Changes in glucose from baseline to Week 48 assessed using blood test
measure: The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL)
time frame: At week 24, 48
description: The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL) at weeks 24 and 48
measure: The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories
time frame: 24 weeks
description: The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories (dizziness, sleep disorders/ disturbances, and altered sensorium) at Week 24
measure: Changes in glucose from baseline to week 24
time frame: 24 weeks
description: Changes in glucose from baseline to Week 24 using blood test
measure: Changes in fasting lipids from baseline to week 24
time frame: 24 weeks
description: Changes in fasting lipids from baseline to Week 24 using lipid profile blood test
measure: Changes in weight and from baseline to week 24
time frame: 24 weeks
description: Changes in weight from baseline to Week 24
measure: Changes in body mass index from baseline to week 24
time frame: 24 weeks
description: Changes in body mass index from baseline to Week 24
measure: The proportion of infants evaluated for HIV-positive tests using HIV DNA polymerase chain reaction test (PCR)
time frame: 48 weeks
description: The proportion of infants evaluated for HIV-positive tests using HIV DNA polymerase chain reaction test (PCR)
measure: Changes in quality of life from baseline
time frame: At weeks 24, 48
description: Changes in quality of life from baseline to Weeks 24 and 48 measured using a traditional clinical, validated quality of life questionairre. Higher scores mean a better outcome
measure: Median adherence by each adherence measure
time frame: At weeks 24, 48
description: Median adherence by each adherence measure at Weeks 24 and 48 using a validated adherence questionairre
measure: Emergence of antiretroviral resistance mutations in participants with virological failure
time frame: 48 weeks
description: Evaluating the number of antiretroviral resistance mutations that emerge in participants with virological failure
arm group label: Delstrigo
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 Disoproxil Fumarate
description: DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination switched from either EFV/TDF/FTC or DTG/TDF/3TC
arm group label: Delstrigo
other name: Delstrigo
criteria: 
gender: Female
gender based: Yes
gender description: Female HIV-positive participants of reproductive potential age
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: No
last name: Simiso Sokhela
role: Principal Investigator
affiliation: Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)
facility: 
facility: 
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 of Ezintsha
mesh term: Tenofovir
mesh term: Lamivudine
sharing ipd: Yes
ipd description: The data that will be shared is all of the individual participant data collected during the trial, after deidentification.The data that will be shared is all of the individual participant data collected during the trial, after identification. The data that will be shared is all of the individual participant data collected during the trial, after deidentification.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: Immediately following publication
ipd access criteria: Anyone who wishes to access the data