<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/NCT03234400</url>
  </required_header>
  <id_info>
    <org_study_id>MTN-036/IPM 047</org_study_id>
    <secondary_id>5UM1AI068633</secondary_id>
    <nct_id>NCT03234400</nct_id>
  </id_info>
  <brief_title>A Phase 1, Randomized Pharmacokinetics and Safety Study of Extended Duration Dapivirine Vaginal Rings</brief_title>
  <official_title>A Phase 1, Randomized Pharmacokinetics and Safety Study of Extended Duration Dapivirine Vaginal Rings</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>International Partnership for Microbicides, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>International Partnership for Microbicides, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Participants will be randomized to one of three study vaginal rings (VRs) in a 1:1:1 ratio,&#xD;
      25 mg, 100 mg or 200 mg VRs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants will be randomized to one of three study vaginal rings (VRs) in a 1:1:1 ratio,&#xD;
      and those randomized to the 100 mg and 200 mg VRs will not be told their group assignment.&#xD;
      Participants will insert one VR to be used continuously for 13 weeks (100 mg VR or 200 mg VR)&#xD;
      or one VR (25 mg VR) to be replaced every 4 weeks for 8 weeks, then worn for an additional 5&#xD;
      weeks for a total of 13 weeks. Participants will continue follow-up for an additional one to&#xD;
      three days after final VR removal.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 4, 2017</start_date>
  <completion_date type="Actual">January 23, 2019</completion_date>
  <primary_completion_date type="Actual">October 23, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>DPV concentration in plasma.</measure>
    <time_frame>13 weeks</time_frame>
    <description>To compare the local and systemic pharmacokinetics (PK) of two extended duration DPV VRs (100 mg and 200 mg) when used continuously for 13 weeks to the current 25 mg DPV VR when replaced every 4 weeks for 8 weeks and then worn for an additional 5 weeks for a total of 13 weeks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DPV concentration in cervicovaginal fluid</measure>
    <time_frame>13 weeks</time_frame>
    <description>To compare the local and systemic pharmacokinetics (PK) of two extended duration DPV VRs (100 mg and 200 mg) when used continuously for 13 weeks to the current 25 mg DPV VR when replaced every 4 weeks for 8 weeks and then worn for an additional 5 weeks for a total of 13 weeks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DPV concentration in cervical tissue</measure>
    <time_frame>13 weeks</time_frame>
    <description>To compare the local and systemic pharmacokinetics (PK) of two extended duration DPV VRs (100 mg and 200 mg) when used continuously for 13 weeks to the current 25 mg DPV VR when replaced every 4 weeks for 8 weeks and then worn for an additional 5 weeks for a total of 13 weeks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety comparison of the two extended duration DPV VRs (100 mg and 200 mg) to the current 25 mg DPV VR</measure>
    <time_frame>13 weeks</time_frame>
    <description>Proportions of participants with Grade 2 or higher genitourinary adverse events as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017, and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies [Dated November 2007])&#xD;
Proportions of participants with Grade 3 or higher adverse events as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adherence</measure>
    <time_frame>13 weeks</time_frame>
    <description>• Frequency of study VR removal/expulsions (voluntary and involuntary) and duration without VR in vagina (by self-report)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence</measure>
    <time_frame>13 weeks</time_frame>
    <description>• VR use initiation and persistence (whether the VR is in place when participants come to the clinic for their study visits)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability</measure>
    <time_frame>13 weeks</time_frame>
    <description>Degree to which study participants liked or disliked using the three DPV VRs (by self-report)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>HIV-1-infection</condition>
  <arm_group>
    <arm_group_label>25 mg Dapivirine Vaginal Ring</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will insert one Dapivirine Vaginal Ring, 25 mg to be replaced every 4 weeks for 8 weeks, then worn for an additional 5 weeks for a total of 13 weeks. Participants will continue follow-up for an additional one to three days after final VR removal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100 mg Dapivirine Vaginal Ring</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will insert one Dapivirine Vaginal Ring, 100 mg to be used continuously for 13 weeks. Participants will continue follow-up for an additional one to three days after final VR removal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200 mg Dapivirine Vaginal Ring</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will insert one Dapivirine Vaginal Ring, 200 mg to be used continuously for 13 weeks. Participants will continue follow-up for an additional one to three days after final VR removal.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Dapivirine Vaginal Ring, 25 mg</intervention_name>
    <description>Vaginal Ring containing 25 mg dapivirine</description>
    <arm_group_label>25 mg Dapivirine Vaginal Ring</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Dapivirine Vaginal Ring, 100 mg</intervention_name>
    <description>Vaginal Ring containing 100 mg dapivirine</description>
    <arm_group_label>100 mg Dapivirine Vaginal Ring</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Dapivirine Vaginal Ring, 200 mg</intervention_name>
    <description>Vaginal Ring containing 200 mg dapivirine</description>
    <arm_group_label>200 mg Dapivirine Vaginal Ring</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Assigned female sex at birth Note: Participants who are female at birth, who now&#xD;
             identify as male, will not be excluded so long as they are not on female-to-male&#xD;
             transition therapy.&#xD;
&#xD;
          -  Age 18 through 45 years (inclusive) at Screening, verified per site SOPs&#xD;
&#xD;
          -  Able and willing to provide written informed consent to be screened for and enrolled&#xD;
             in MTN-036/IPM 047&#xD;
&#xD;
          -  Able and willing to provide adequate locator information, as defined in site SOPs&#xD;
&#xD;
          -  Able to communicate in spoken and written English&#xD;
&#xD;
          -  Available for all visits and able and willing to comply with all study procedural&#xD;
             requirements&#xD;
&#xD;
          -  Willing to comply with abstinence and other protocol requirements&#xD;
&#xD;
          -  Willing to use male condoms for penile-vaginal intercourse (PVI) and penile-rectal&#xD;
             intercourse for the duration of study participation&#xD;
&#xD;
          -  Per participant report, using an effective method of contraception for at least 30&#xD;
             days (inclusive) prior to Enrollment, and intending to continue use of an effective&#xD;
             method for the duration of study participation; effective methods include:&#xD;
&#xD;
               1. hormonal methods (except contraceptive ring)&#xD;
&#xD;
               2. intrauterine device (IUD)&#xD;
&#xD;
               3. sterilization (of participant or partner, as defined in site SOPs)&#xD;
&#xD;
               4. having sex exclusively with cis-women&#xD;
&#xD;
               5. abstinence from PVI for 90 days prior to Enrollment, and intending to remain&#xD;
                  abstinent from PVI for the duration of study participation&#xD;
&#xD;
          -  HIV-uninfected based on testing performed at Screening and Enrollment&#xD;
&#xD;
          -  Per participant report at Screening, regular menstrual cycles with at least 21 days&#xD;
             between menses Note: This criterion is not applicable to participants who report using&#xD;
             a progestin-only method of contraception at Screening (e.g., Depo-Provera or&#xD;
             levonorgestrel-releasing IUD) nor to participants using continuous combination oral&#xD;
             contraceptive pills, as the absence of regular menstrual cycles is an expected, normal&#xD;
             consequence in this context.&#xD;
&#xD;
          -  Per participant report at Screening and Enrollment, states a willingness to refrain&#xD;
             from inserting any non-study vaginal products or objects into the vagina including,&#xD;
             but not limited to spermicides, female condoms, diaphragms, intravaginal rings,&#xD;
             vaginal medications, menstrual cups, cervical caps, douches, lubricants, and sex toys&#xD;
             (vibrators, dildos, etc.) for the 24 hours preceding the Enrollment Visit and for the&#xD;
             duration of study participation.&#xD;
&#xD;
        Note: Use of tampons is permitted except for 24 hours prior to clinic visits in which CVF&#xD;
        samples are scheduled to be collected.&#xD;
&#xD;
          -  Participants over the age of 21 (inclusive) must have documentation of a satisfactory&#xD;
             Pap within the past 3 years prior to Enrollment consistent with Grade 0 according to&#xD;
             the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (Dated&#xD;
             November 2007) to the DAIDS Table for Grading Adult and Pediatric Adverse Events,&#xD;
             Version 2.1, March 2017, or satisfactory evaluation with no treatment required of&#xD;
             Grade 1 or higher Pap result&#xD;
&#xD;
          -  At Screening and Enrollment, agrees not to participate in other research studies&#xD;
             involving drugs, medical devices, vaginal products or vaccines after the Screening&#xD;
             Visit and for the duration of study participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant at Screening or Enrollment or plans to become pregnant during the study&#xD;
             period&#xD;
&#xD;
          -  Diagnosed with a UTI or reproductive tract infection (RTI) at Screening or Enrollment&#xD;
&#xD;
          -  Diagnosed with an acute STI requiring treatment per current Centers for Disease&#xD;
             Control and Prevention (CDC) guidelines (http://www.cdc.gov/std/treatment/) at&#xD;
             Screening or Enrollment such as gonorrhea (GC), CT, trichomonas, PID, and/or syphilis&#xD;
&#xD;
          -  Has a clinically apparent Grade 2 or higher pelvic exam finding (observed by study&#xD;
             staff) at Screening or Enrollment, as per the DAIDS Table for Grading the Severity of&#xD;
             Adult and Pediatric Adverse Events, Version 2.1, March 2017, and/or Addendum 1 (Female&#xD;
             Genital Grading Table for Use in Microbicide Studies [Dated November 2007])&#xD;
&#xD;
          -  5) Participant report and/or clinical evidence of any of the following:&#xD;
&#xD;
               1. Known adverse reaction to any of the study products (ever)&#xD;
&#xD;
               2. Chronic and/or recurrent vaginal candidiasis&#xD;
&#xD;
               3. Non-therapeutic injection drug use in the 12 months prior to Enrollment&#xD;
&#xD;
               4. Last pregnancy outcome less than 90 days prior to Enrollment&#xD;
&#xD;
               5. Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage,&#xD;
                  piercing) 45 days or less prior to Enrollment Note: Colposcopy and cervical&#xD;
                  biopsies for evaluation of an abnormal Pap test as well as IUD insertion/removal&#xD;
                  are not exclusionary.&#xD;
&#xD;
               6. Currently breastfeeding or planning to breastfeed during the study period&#xD;
&#xD;
               7. Participation in any other research study involving drugs, medical devices,&#xD;
                  vaginal products or vaccines, in the 60 days prior to Enrollment&#xD;
&#xD;
          -  Use of pre-exposure prophylaxis (PrEP) for HIV prevention and/or post-exposure&#xD;
             prophylaxis (PEP) for potential HIV exposure within the 3 months prior to Enrollment,&#xD;
             and/or anticipated use and/or unwillingness to abstain from PrEP during trial&#xD;
             participation&#xD;
&#xD;
          -  Has any of the following Grade 1 or higher laboratory abnormalities at Screening&#xD;
             Visit:&#xD;
&#xD;
               1. AST or ALT&#xD;
&#xD;
               2. Hemoglobin&#xD;
&#xD;
          -  Has any other condition that, in the opinion of the IoR/designee, would preclude&#xD;
             informed consent, make study participation unsafe, complicate the interpretation of&#xD;
             study outcome data, or otherwise interfere with achieving the study objectives&#xD;
             including any significant uncontrolled active or chronic medical condition.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bridge HIV CRS San Francisco Department of Public Health</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>January 25, 2019</last_update_submitted>
  <last_update_submitted_qc>January 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dapivirine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03234400
org study id: MTN-036/IPM 047
secondary id: 5UM1AI068633
nct id: NCT03234400
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: Yes
is unapproved device: Yes
Participants will be randomized to one of three study vaginal rings (VRs) in a 1:1:1 ratio,
      25 mg, 100 mg or 200 mg VRs.
Participants will be randomized to one of three study vaginal rings (VRs) in a 1:1:1 ratio,
      and those randomized to the 100 mg and 200 mg VRs will not be told their group assignment.
      Participants will insert one VR to be used continuously for 13 weeks (100 mg VR or 200 mg VR)
      or one VR (25 mg VR) to be replaced every 4 weeks for 8 weeks, then worn for an additional 5
      weeks for a total of 13 weeks. Participants will continue follow-up for an additional one to
      three days after final VR removal.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: DPV concentration in plasma.
time frame: 13 weeks
description: To compare the local and systemic pharmacokinetics (PK) of two extended duration DPV VRs (100 mg and 200 mg) when used continuously for 13 weeks to the current 25 mg DPV VR when replaced every 4 weeks for 8 weeks and then worn for an additional 5 weeks for a total of 13 weeks.
measure: DPV concentration in cervicovaginal fluid
time frame: 13 weeks
description: To compare the local and systemic pharmacokinetics (PK) of two extended duration DPV VRs (100 mg and 200 mg) when used continuously for 13 weeks to the current 25 mg DPV VR when replaced every 4 weeks for 8 weeks and then worn for an additional 5 weeks for a total of 13 weeks.
measure: DPV concentration in cervical tissue
time frame: 13 weeks
description: To compare the local and systemic pharmacokinetics (PK) of two extended duration DPV VRs (100 mg and 200 mg) when used continuously for 13 weeks to the current 25 mg DPV VR when replaced every 4 weeks for 8 weeks and then worn for an additional 5 weeks for a total of 13 weeks.
measure: Safety comparison of the two extended duration DPV VRs (100 mg and 200 mg) to the current 25 mg DPV VR
time frame: 13 weeks
description: Proportions of participants with Grade 2 or higher genitourinary adverse events as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017, and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies [Dated November 2007])
Proportions of participants with Grade 3 or higher adverse events as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017
measure: Adherence
time frame: 13 weeks
description: • Frequency of study VR removal/expulsions (voluntary and involuntary) and duration without VR in vagina (by self-report)
measure: Adherence
time frame: 13 weeks
description: • VR use initiation and persistence (whether the VR is in place when participants come to the clinic for their study visits)
measure: Acceptability
time frame: 13 weeks
description: Degree to which study participants liked or disliked using the three DPV VRs (by self-report)
arm group label: 25 mg Dapivirine Vaginal Ring
arm group type: Experimental
description: Participants will insert one Dapivirine Vaginal Ring, 25 mg to be replaced every 4 weeks for 8 weeks, then worn for an additional 5 weeks for a total of 13 weeks. Participants will continue follow-up for an additional one to three days after final VR removal.
arm group label: 100 mg Dapivirine Vaginal Ring
arm group type: Experimental
description: Participants will insert one Dapivirine Vaginal Ring, 100 mg to be used continuously for 13 weeks. Participants will continue follow-up for an additional one to three days after final VR removal.
arm group label: 200 mg Dapivirine Vaginal Ring
arm group type: Experimental
description: Participants will insert one Dapivirine Vaginal Ring, 200 mg to be used continuously for 13 weeks. Participants will continue follow-up for an additional one to three days after final VR removal.
intervention type: Combination Product
intervention name: Dapivirine Vaginal Ring, 25 mg
description: Vaginal Ring containing 25 mg dapivirine
arm group label: 25 mg Dapivirine Vaginal Ring
intervention type: Combination Product
intervention name: Dapivirine Vaginal Ring, 100 mg
description: Vaginal Ring containing 100 mg dapivirine
arm group label: 100 mg Dapivirine Vaginal Ring
intervention type: Combination Product
intervention name: Dapivirine Vaginal Ring, 200 mg
description: Vaginal Ring containing 200 mg dapivirine
arm group label: 200 mg Dapivirine Vaginal Ring
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dapivirine
sharing ipd: Undecided