<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/NCT02245945</url>
  </required_header>
  <id_info>
    <org_study_id>A14-130</org_study_id>
    <nct_id>NCT02245945</nct_id>
  </id_info>
  <brief_title>Safety and Acceptability of Tenofovir 1% Gel in Adolescent Females</brief_title>
  <official_title>Phase I Safety and Acceptability of Tenofovir 1% Gel in Adolescent Females</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CONRAD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CONRAD</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this trial is to assess the safety and acceptability of Tenofovir (TFV) 1% gel&#xD;
      in adolescent females over 12 weeks of a minimum of twice weekly dosing following the BAT24&#xD;
      regimen.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 1</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in genitourinary adverse events (AEs)</measure>
    <time_frame>24 hours after single dose; 1, 2, 4, 8 and 12 weeks during/after repeat dosing</time_frame>
    <description>Number of genitourinary adverse events (AEs)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in soluble markers of inflammation in cervicovaginal fluid (CVF)</measure>
    <time_frame>Baseline; 24 hours after single dose; 12 weeks after repeat dosing</time_frame>
    <description>changes in soluble markers of inflammation in cervicovaginal fluid (CVF)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in vaginal microflora as assessed by Gram stain and semi-quantitative vaginal culture</measure>
    <time_frame>Baseline and 12 weeks after repeat dosing</time_frame>
    <description>Changes in vaginal microflora as assessed by Gram stain and semi-quantitative vaginal culture</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Responses to key questions on acceptability questionnaire</measure>
    <time_frame>2, 8 and 12 weeks during/after repeat dosing</time_frame>
    <description>Responses to key questions on acceptability questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TFV concentration in plasma</measure>
    <time_frame>2 and 24 hours after single dose</time_frame>
    <description>TFV concentration in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TFV concentration in CVF</measure>
    <time_frame>24 hours after single does; 2, 4, 8, and 12 weeks during/after repeat dosing</time_frame>
    <description>TFV concentration in CVF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-HIV and anti-herpes simplex virus (HSV)-2 activity in the CVF</measure>
    <time_frame>Baseline; 24 hours after single-dose; 12 weeks after repeat dosing</time_frame>
    <description>Anti-HIV and anti-HSV-2 activity in the CVF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Real time adherence via internet-based diary</measure>
    <time_frame>12 weeks</time_frame>
    <description>Real time adherence via internet-based diary</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biologic markers of adherence via returned empty applicators</measure>
    <time_frame>2, 4, 8 and 12 weeks during/after repeat dosing</time_frame>
    <description>Biologic markers of adherence via returned empty applicators</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>HIV Prevention</condition>
  <arm_group>
    <arm_group_label>TFV 1% gel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be instructed to use TFV 1% vaginal gel according to the BAT 24 regimen (2 gel doses) at least twice per week, regardless of sexual frequency.&#xD;
The BAT24 dosing regimen when used with sex is defined as one dose of gel within 12 hours before sex and a second dose of gel as soon as possible within 12 hours after sex and no more than two doses in a 24 hour period. Participants who do engage in sexual intercourse should use the BAT24 regimen with each sex act.&#xD;
If used without sex, the BAT24 dosing regimen is defined as 2 doses of gel administered 2-24 hours apart, with no more than two doses in a 24 hour period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>hydroxyethylcellulose (HEC) placebo gel</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be instructed to use HEC placebo gel according to the BAT 24 regimen (2 gel doses) at least twice per week, regardless of sexual frequency.&#xD;
The BAT24 dosing regimen when used with sex is defined as one dose of gel within 12 hours before sex and a second dose of gel as soon as possible within 12 hours after sex and no more than two doses in a 24 hour period. Participants who do engage in sexual intercourse should use the BAT24 regimen with each sex act.&#xD;
If used without sex, the BAT24 dosing regimen is defined as 2 doses of gel administered 2-24 hours apart, with no more than two doses in a 24 hour period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TFV 1% vaginal gel</intervention_name>
    <description>Tenofovir 1% gel is supplied as a clear, transparent, viscous gel packaged in pre-filled single use applicators. Each applicator contains 4.0 mL of tenofovir gel (equal to 4.4 gm) at a concentration of 1% (weight for weight) formulated in purified water with edetate disodium, citric acid, glycerin, methylparaben, propylparaben and hydroxyethylcellulose, and is pH adjusted to 4-5.</description>
    <arm_group_label>TFV 1% gel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HEC Placebo Gel</intervention_name>
    <description>Placebo gel contains hydroxyethylcellulose (HEC) as the gel thickener, purified water, sodium chloride, sorbic acid and sodium hydroxide. The gel is isotonic and formulated at a pH of 4.4. Each pre-filled applicator will contain approximately 4 mL of placebo gel for delivery.</description>
    <arm_group_label>hydroxyethylcellulose (HEC) placebo gel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 15 through 17 years, inclusive, as per site policy&#xD;
&#xD;
          -  General good health (by volunteer history and per investigator discretion) without any&#xD;
             clinically significant systemic disease (including, but not limited to significant&#xD;
             liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease,&#xD;
             osteoporosis or bone disease, and diabetes)&#xD;
&#xD;
          -  Able to communicate in spoken and written English&#xD;
&#xD;
          -  Willing to following instructions regarding vaginal activity and vaginal products as&#xD;
             follows:&#xD;
&#xD;
               1. Willing to abstain from all vaginal activity, including intercourse, for 48 hours&#xD;
                  prior to Visit 2 and 48 hours prior to Visit 7&#xD;
&#xD;
               2. Willing to abstain from the use of vaginal products other than the study product&#xD;
                  including spermicides, lubricants, and douches for the duration of study&#xD;
                  participation.&#xD;
&#xD;
        Note: Tampons may be used for menses, but pads should be used for any other intermenstrual&#xD;
        spotting or bleeding.&#xD;
&#xD;
          -  Assessment of onset and progression of puberty as measured by Tanner Stage 4 or 5&#xD;
&#xD;
          -  History of consensual penile-vaginal intercourse (at least one episode in&#xD;
             participant's lifetime)&#xD;
&#xD;
          -  Negative urine pregnancy test&#xD;
&#xD;
          -  Use of an effective method of contraception for at least the past 30 days (per&#xD;
             participant report) and intended use for the duration of study participation.&#xD;
             Effective methods include:&#xD;
&#xD;
               1. Hormonal methods (excluding contraceptive ring)&#xD;
&#xD;
               2. Intrauterine contraception (IUC)&#xD;
&#xD;
        Note: An IUC must be in place for at least 15 days prior to enrollment&#xD;
&#xD;
          -  Willing to give voluntary assent, and comply with study procedures as required by the&#xD;
             protocol assent and willing for parent/guardian to provide written informed consent&#xD;
             for participation as per Institutional Review Board (IRB) requirements. Emancipated&#xD;
             minors may give their own informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known adverse reaction to study products (ever) or latex, per participant report&#xD;
&#xD;
          -  Non-therapeutic injection drug use in the last 12 calendar months&#xD;
&#xD;
          -  Post-exposure prophylaxis (PEP) for HIV-1 exposure within the last 6 calendar months&#xD;
&#xD;
          -  Currently pregnant or within 30 days from the last pregnancy outcome.&#xD;
&#xD;
        Note: If recently pregnant must have had at least two spontaneous menses since pregnancy&#xD;
        outcome.&#xD;
&#xD;
          -  History of gynecological procedures (including genital piercing) on the external&#xD;
             genitalia, vagina or cervix within the last 14 days&#xD;
&#xD;
          -  Intention to become pregnant in the next 6 months&#xD;
&#xD;
          -  Currently breastfeeding or having breastfed an infant in the last two months, or&#xD;
             planning to breastfeed during the course of the study&#xD;
&#xD;
          -  Positive for HIV&#xD;
&#xD;
          -  Grade 2 or higher as per the Division of AIDS (DAIDS) Table for Grading Adult and&#xD;
             Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009)&#xD;
             of the following:&#xD;
&#xD;
               1. Alanine transaminase (ALT), aspartate aminotransferase (AST)&#xD;
&#xD;
               2. Creatinine&#xD;
&#xD;
               3. Hemoglobin&#xD;
&#xD;
               4. Platelet count&#xD;
&#xD;
               5. Hepatitis B surface antigen (HBsAg)&#xD;
&#xD;
        Note: Otherwise eligible participants with an exclusionary test result(s) listed above may&#xD;
        be re-tested a maximum of one time and if a non-exclusionary result is documented within&#xD;
        the 30 days of providing informed consent, they may be enrolled.&#xD;
&#xD;
          -  Clinically apparent Grade 2 or higher pelvic examination finding (observed by study&#xD;
             staff) per the Female Genital Grading Table for Use in Microbicide Studies (Addendum 1&#xD;
             to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 1.0,&#xD;
             December 2004 (Clarification dated August 2009)&#xD;
&#xD;
        Note: 1) Cervical bleeding associated with speculum insertion and/or specimen collection&#xD;
        judged to be within the range of normal according to the clinical judgment of the Principal&#xD;
        Investigator/designee is considered expected non-menstrual bleeding and is not&#xD;
        exclusionary. 2) Otherwise eligible participants with exclusionary pelvic examination&#xD;
        findings may be enrolled /randomized if improvement of findings to a non-exclusionary grade&#xD;
        or to resolution can be documented within 30 days of providing informed consent for&#xD;
        Screening.&#xD;
&#xD;
          -  Current pelvic inflammatory disease (PID) or sexually transmitted infection requiring&#xD;
             treatment per current Centers for Disease Control and Prevention (CDC) guidelines&#xD;
             (e.g., Trichomonas vaginalis, Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), or&#xD;
             active herpes outbreak)&#xD;
&#xD;
          -  Symptomatic vulvovaginal candidiasis, symptomatic bacterial vaginosis (BV) or urinary&#xD;
             tract infection (UTI)&#xD;
&#xD;
        Note: Otherwise eligible participants with symptomatic vulvovaginal candidiasis, BV or UTI&#xD;
        prior to genital sampling at Visit 2 will be offered treatment and may be continue in the&#xD;
        study after completing treatment and all symptoms and findings have resolved.&#xD;
&#xD;
          -  Systemic use in the last two weeks or anticipated use during the study of any of the&#xD;
             following: corticosteroids, antibiotics, antifungals, antivirals (e.g., acyclovir or&#xD;
             valacyclovir) or antiretrovirals (e.g., Viread®, Atripla®, Emtriva®, Complera®,&#xD;
             Stribild®).&#xD;
&#xD;
        Note: Participants should avoid non-steroidal anti-inflammatory drugs (NSAIDs) except for&#xD;
        treatment of dysmenorrhea during menses. Participants may use Tylenol® on an as-needed but&#xD;
        not daily basis during the study.&#xD;
&#xD;
          -  Participation in any other investigational trial (device, drug, or vaginal trial)&#xD;
             within the last 30 days or planned participation in any other investigational trial&#xD;
             during the study&#xD;
&#xD;
          -  Any other condition that, in the opinion of the Principal Investigator (PI) or&#xD;
             designee, would preclude informed consent, make study participation unsafe, complicate&#xD;
             interpretation of study outcome data, or otherwise interfere with achieving the study&#xD;
             objectives&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jill Schwartz, MD</last_name>
    <role>Study Director</role>
    <affiliation>CONRAD</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Albert Einstein College of Medicine</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10451</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 22, 2014</study_first_posted>
  <last_update_submitted>April 30, 2015</last_update_submitted>
  <last_update_submitted_qc>April 30, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 1, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>prevention</keyword>
  <!-- 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/NCT02245945
org study id: A14-130
nct id: NCT02245945
lead sponsor: 
has dmc: No
The purpose of this trial is to assess the safety and acceptability of Tenofovir (TFV) 1% gel
      in adolescent females over 12 weeks of a minimum of twice weekly dosing following the BAT24
      regimen.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in genitourinary adverse events (AEs)
time frame: 24 hours after single dose; 1, 2, 4, 8 and 12 weeks during/after repeat dosing
description: Number of genitourinary adverse events (AEs)
measure: Changes in soluble markers of inflammation in cervicovaginal fluid (CVF)
time frame: Baseline; 24 hours after single dose; 12 weeks after repeat dosing
description: changes in soluble markers of inflammation in cervicovaginal fluid (CVF)
measure: Changes in vaginal microflora as assessed by Gram stain and semi-quantitative vaginal culture
time frame: Baseline and 12 weeks after repeat dosing
description: Changes in vaginal microflora as assessed by Gram stain and semi-quantitative vaginal culture
measure: Responses to key questions on acceptability questionnaire
time frame: 2, 8 and 12 weeks during/after repeat dosing
description: Responses to key questions on acceptability questionnaire
measure: TFV concentration in plasma
time frame: 2 and 24 hours after single dose
description: TFV concentration in plasma
measure: TFV concentration in CVF
time frame: 24 hours after single does; 2, 4, 8, and 12 weeks during/after repeat dosing
description: TFV concentration in CVF
measure: Anti-HIV and anti-herpes simplex virus (HSV)-2 activity in the CVF
time frame: Baseline; 24 hours after single-dose; 12 weeks after repeat dosing
description: Anti-HIV and anti-HSV-2 activity in the CVF
measure: Real time adherence via internet-based diary
time frame: 12 weeks
description: Real time adherence via internet-based diary
measure: Biologic markers of adherence via returned empty applicators
time frame: 2, 4, 8 and 12 weeks during/after repeat dosing
description: Biologic markers of adherence via returned empty applicators
arm group label: TFV 1% gel
arm group type: Experimental
description: Participants will be instructed to use TFV 1% vaginal gel according to the BAT 24 regimen (2 gel doses) at least twice per week, regardless of sexual frequency.
The BAT24 dosing regimen when used with sex is defined as one dose of gel within 12 hours before sex and a second dose of gel as soon as possible within 12 hours after sex and no more than two doses in a 24 hour period. Participants who do engage in sexual intercourse should use the BAT24 regimen with each sex act.
If used without sex, the BAT24 dosing regimen is defined as 2 doses of gel administered 2-24 hours apart, with no more than two doses in a 24 hour period.
arm group label: hydroxyethylcellulose (HEC) placebo gel
arm group type: Placebo Comparator
description: Participants will be instructed to use HEC placebo gel according to the BAT 24 regimen (2 gel doses) at least twice per week, regardless of sexual frequency.
The BAT24 dosing regimen when used with sex is defined as one dose of gel within 12 hours before sex and a second dose of gel as soon as possible within 12 hours after sex and no more than two doses in a 24 hour period. Participants who do engage in sexual intercourse should use the BAT24 regimen with each sex act.
If used without sex, the BAT24 dosing regimen is defined as 2 doses of gel administered 2-24 hours apart, with no more than two doses in a 24 hour period.
intervention type: Drug
intervention name: TFV 1% vaginal gel
description: Tenofovir 1% gel is supplied as a clear, transparent, viscous gel packaged in pre-filled single use applicators. Each applicator contains 4.0 mL of tenofovir gel (equal to 4.4 gm) at a concentration of 1% (weight for weight) formulated in purified water with edetate disodium, citric acid, glycerin, methylparaben, propylparaben and hydroxyethylcellulose, and is pH adjusted to 4-5.
arm group label: TFV 1% gel
intervention type: Drug
intervention name: HEC Placebo Gel
description: Placebo gel contains hydroxyethylcellulose (HEC) as the gel thickener, purified water, sodium chloride, sorbic acid and sodium hydroxide. The gel is isotonic and formulated at a pH of 4.4. Each pre-filled applicator will contain approximately 4 mL of placebo gel for delivery.
arm group label: hydroxyethylcellulose (HEC) placebo gel
criteria: 
gender: Female
minimum age: 15 Years
maximum age: 17 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jill Schwartz, MD
role: Study Director
affiliation: CONRAD
facility: 
facility: 
country: United States
responsible party type: Sponsor