<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/NCT03033368</url>
  </required_header>
  <id_info>
    <org_study_id>RPV</org_study_id>
    <nct_id>NCT03033368</nct_id>
  </id_info>
  <brief_title>Rilpivirine in Virologically Suppressed Adolescents</brief_title>
  <official_title>Treatment Switch From Efavirenz to Rilpivirine in Virologically-suppressed HIV-infected Thai Adolescents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mahidol University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>amfAR, The Foundation for AIDS Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mahidol University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To describe the immunologic and virologic outcomes (HIV RNA, CD4) following switching from&#xD;
      EFV to RPV in virologically suppressed adolescents&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Procedures:&#xD;
&#xD;
      At screening, the informed consent process will be provided to participant, or participant&#xD;
      legally acceptable representatives before any study procedure. Only adolescents who know&#xD;
      their HIV status will be asked to give assent.&#xD;
&#xD;
      Twenty adolescents followed at HIV-NAT and the Department of Pediatrics, Faculty of Medicine,&#xD;
      Chulalongkorn University will be asked to participate in the PK sub study. Participant who&#xD;
      are enrolled in the PK substudy will be asked to take RPV in the morning after breakfast and&#xD;
      then commence the PK evaluations after this witnessed dose. After the PK study at week 4,&#xD;
      Participant will be followed with the other 80 adolescents until the end of the study.&#xD;
      Participant will be asked to provide a small hair sample for RPV concentrations at weeks 4,&#xD;
      12, 24, and 48 after switching. This is an option therefore participant can refuse to provide&#xD;
      their hair samples at any visits. HIV RNA levels will be performed at baseline, week 12, 24&#xD;
      and 48 visits. If the HIV-RNA at any visits is between &gt;50 copies/ml, the HIV-RNA test will&#xD;
      be repeated within 4-8 weeks with adherence improvement counseling. At any visit, if HIV-RNA&#xD;
      is ≥1000 copies/ml, genotypic resistance testing will be performed. Modification of treatment&#xD;
      both for resistance and safety consideration will be subject to the site principal&#xD;
      investigator's decision.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date>July 2015</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">June 2017</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>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 adolescents with HIV-RNA &lt;50 copies/ml at 48 weeks after switching.</measure>
    <time_frame>48 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in neuropsychiatric test scores</measure>
    <time_frame>Baseline and week 24</time_frame>
    <description>Using Trail Making Test and Coding subtest of WISC-III Wisconsin Card Sorting Test (WCST) Non-verbal part of Standard Progressive Matrices</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life (QOL) score</measure>
    <time_frame>Baseline, week 4 and week 24</time_frame>
    <description>Using PedsQLTM 4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in lipid profiles after switching to RPV-containing regimens</measure>
    <time_frame>Baseline, week 24, and week 48</time_frame>
    <description>Measure cholesterol (mg/dl), LDL (mg/dl), HDL (mg/dl), triglyceride (mg/dl)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fasting blood sugar after switching to RPV-containing regime</measure>
    <time_frame>Baseline, week 24, and week 48</time_frame>
    <description>Measue fasting blood sugar (mg/dl)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive PK parameter (Area under the plasma concentration-time curve; AUC0-24) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.</measure>
    <time_frame>week 4</time_frame>
    <description>Measure area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24): unit; ng.h/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive PK parameter (maximum observed concentration of drug in plasma ;(Cmax) ) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.</measure>
    <time_frame>week 4</time_frame>
    <description>Measue maximum observed concentration of drug in plasma (Cmax) : unit; ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive PK parameter (Minimum concentration of drug in plasma; (Ctrough)) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.</measure>
    <time_frame>week 4</time_frame>
    <description>Measure minimum concentration of drug in plasma (Ctrough) : unit; ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Description of resistance mutations in the adolescents with RPV treatment failure</measure>
    <time_frame>baseline, week 12, week 24 and week 48</time_frame>
    <description>At any visit, if HIV-RNA is ≥1000 copies/ml, genotypic resistance testing will be performed. Using HIV-1 Antiretroviral drug resistance ViriSeq HIV-1 genotyping</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>opened label</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open-label, single-arm study, rilpivirine is the study drug</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rilpivirine</intervention_name>
    <description>Rilpivirine 25 mg tablet</description>
    <arm_group_label>opened label</arm_group_label>
    <other_name>Edurant</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV-infected adolescents aged 12-18 years;&#xD;
&#xD;
          -  Body weight &gt;25 kilograms;&#xD;
&#xD;
          -  Currently treated with stable EFV-based HAART (EFV plus two nucleoside or nucleotide&#xD;
             reverse transcriptase inhibitors [N(t)RTI]) for &gt;3 months prior to enrollment;&#xD;
&#xD;
          -  Plasma HIV RNA &lt;50 copies/ml within the last 12 months;&#xD;
&#xD;
          -  ALT &lt;200 IU/L within the last 12 months;&#xD;
&#xD;
          -  Caregivers give written informed consent and adolescents who know their HIV status&#xD;
             (i.e., have been fully disclosed to) give assent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has evidence of NNRTI-associated resistance mutation(s) from previous genotypic&#xD;
             resistance testing;&#xD;
&#xD;
          -  Currently has PI(s) in the HAART regimen;&#xD;
&#xD;
          -  Has currently active HIV-related infection(s), (The subject can be enrolled after the&#xD;
             infection is under controlled);&#xD;
&#xD;
          -  Has significant medical problem(s) that would compromise study results (in the site&#xD;
             principal investigator's opinion);&#xD;
&#xD;
          -  Pregnancy (postpartum women are allowed);&#xD;
&#xD;
          -  Concomitant treatment with drugs known to effect the PK of RPV (carbamazepine,&#xD;
             phenobarbital, phenytoin, rifampicin, rifabutin, omeprazole, esomeprazole,&#xD;
             lansoprazole, erythromycin, clarithromycin, azithromycin, roxithromycin)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>October 22, 2016</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>January 24, 2017</last_update_submitted>
  <last_update_submitted_qc>January 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>immunological outcome</keyword>
  <keyword>virologic outcomes</keyword>
  <keyword>HIV-1 infected adolescents</keyword>
  <keyword>EFV switch to RPV</keyword>
  <keyword>Rilpivirine pharmacokinetic</keyword>
  <keyword>neuropsychiatric adverse events</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rilpivirine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Investigator plan to the clinical data</ipd_description>
  </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/NCT03033368
org study id: RPV
nct id: NCT03033368
lead sponsor: 
collaborator: 
has dmc: No
To describe the immunologic and virologic outcomes (HIV RNA, CD4) following switching from
      EFV to RPV in virologically suppressed adolescents
Study Procedures:

      At screening, the informed consent process will be provided to participant, or participant
      legally acceptable representatives before any study procedure. Only adolescents who know
      their HIV status will be asked to give assent.

      Twenty adolescents followed at HIV-NAT and the Department of Pediatrics, Faculty of Medicine,
      Chulalongkorn University will be asked to participate in the PK sub study. Participant who
      are enrolled in the PK substudy will be asked to take RPV in the morning after breakfast and
      then commence the PK evaluations after this witnessed dose. After the PK study at week 4,
      Participant will be followed with the other 80 adolescents until the end of the study.
      Participant will be asked to provide a small hair sample for RPV concentrations at weeks 4,
      12, 24, and 48 after switching. This is an option therefore participant can refuse to provide
      their hair samples at any visits. HIV RNA levels will be performed at baseline, week 12, 24
      and 48 visits. If the HIV-RNA at any visits is between >50 copies/ml, the HIV-RNA test will
      be repeated within 4-8 weeks with adherence improvement counseling. At any visit, if HIV-RNA
      is ≥1000 copies/ml, genotypic resistance testing will be performed. Modification of treatment
      both for resistance and safety consideration will be subject to the site principal
      investigator's decision.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of adolescents with HIV-RNA <50 copies/ml at 48 weeks after switching.
time frame: 48 weeks
measure: Change in neuropsychiatric test scores
time frame: Baseline and week 24
description: Using Trail Making Test and Coding subtest of WISC-III Wisconsin Card Sorting Test (WCST) Non-verbal part of Standard Progressive Matrices
measure: Change in quality of life (QOL) score
time frame: Baseline, week 4 and week 24
description: Using PedsQLTM 4.0
measure: Change in lipid profiles after switching to RPV-containing regimens
time frame: Baseline, week 24, and week 48
description: Measure cholesterol (mg/dl), LDL (mg/dl), HDL (mg/dl), triglyceride (mg/dl)
measure: Change in fasting blood sugar after switching to RPV-containing regime
time frame: Baseline, week 24, and week 48
description: Measue fasting blood sugar (mg/dl)
measure: Intensive PK parameter (Area under the plasma concentration-time curve; AUC0-24) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.
time frame: week 4
description: Measure area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24): unit; ng.h/ml
measure: Intensive PK parameter (maximum observed concentration of drug in plasma ;(Cmax) ) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.
time frame: week 4
description: Measue maximum observed concentration of drug in plasma (Cmax) : unit; ng/ml
measure: Intensive PK parameter (Minimum concentration of drug in plasma; (Ctrough)) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.
time frame: week 4
description: Measure minimum concentration of drug in plasma (Ctrough) : unit; ng/ml
measure: Description of resistance mutations in the adolescents with RPV treatment failure
time frame: baseline, week 12, week 24 and week 48
description: At any visit, if HIV-RNA is ≥1000 copies/ml, genotypic resistance testing will be performed. Using HIV-1 Antiretroviral drug resistance ViriSeq HIV-1 genotyping
arm group label: opened label
arm group type: Experimental
description: Open-label, single-arm study, rilpivirine is the study drug
intervention type: Drug
intervention name: Rilpivirine
description: Rilpivirine 25 mg tablet
arm group label: opened label
other name: Edurant
criteria: 
gender: All
minimum age: 12 Years
maximum age: 18 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Rilpivirine
sharing ipd: Yes
ipd description: Investigator plan to the clinical data