<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/NCT03834909</url>
  </required_header>
  <id_info>
    <nct_id>NCT03834909</nct_id>
  </id_info>
  <brief_title>Pre-Exposure Prophylaxis Dosing in Pregnancy to Optimize HIV Prevention (PREP-P)</brief_title>
  <official_title>Correcting Pre-Exposure Prophylaxis (PrEP) Dosing and Adherence Benchmarks in Pregnancy to Optimize HIV Prevention (PrEP-P): A Randomized Comparative Pharmacokinetic Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial is a prospective, multi-center, randomized comparison study of 2 Pre-Exposure&#xD;
      Prophylaxis (PrEP) pharmacokinetic (PK) dosing regimens from 1st trimester through 12 weeks&#xD;
      following delivery (postpartum) to achieve study objectives which include PK, safety&#xD;
      monitoring for maternal and fetal/infant safety signals, and adherence.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study participants will be randomized to one of two parallel study arms, involving dosing of&#xD;
      tenofovir disoproxil sodium/emtricitabine (TDF/FTC). The investigators will be recruiting and&#xD;
      enrolling in the late 1st (preferred) and 2nd trimesters of pregnancy to capture the changes&#xD;
      in kidney function and blood flow through the kidneys that appear to start in the late 1st&#xD;
      trimester and are most significant in the 2nd and 3rd trimesters of pregnancy. Given the&#xD;
      unknown time frame for the return to pre-pregnancy physiologic state and the increased risk&#xD;
      of HIV acquisition postpartum, participants will be continued on study dose PrEP until after&#xD;
      participants' 1-3 week postpartum visit, after which all participants will be dispensed&#xD;
      standard dose PrEP. A 6-12 week postpartum study visit will also be performed to evaluate the&#xD;
      timing of return to non-pregnant plasma drug levels during the postpartum period.&#xD;
&#xD;
      PK Sampling. Primary PK data will be derived from up to 7 study visits with PK sampling,&#xD;
      including two PK visits in each trimester and postpartum. All PK visits sample blood before&#xD;
      an observed PrEP dose. .&#xD;
&#xD;
      Safety Sampling. Maternal safety assessments will continue until 6 months postpartum. Fetal&#xD;
      evaluation includes non-invasive limited ultrasound (US) and biophysical profiles (BPP) at&#xD;
      study visits and 2nd and 3rd trimester interval growth US, and chart review of all before&#xD;
      birth assessments. At birth, the investigators will obtain cord blood plasma to assess for&#xD;
      mitochondrial function. Infant safety assessments will continue until 1 year of life. Infants&#xD;
      will undergo swaddled Dual-energy X-ray absorptiometry (DXA) scans (without sedation) at 3-6,&#xD;
      24-28, and 50-54 weeks of age. The investigators will assess kidney function by blood sample&#xD;
      at 3-6 weeks of life and repeated at 24-28 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study was not funded&#xD;
  </why_stopped>
  <start_date type="Anticipated">April 2022</start_date>
  <completion_date type="Anticipated">April 2028</completion_date>
  <primary_completion_date type="Anticipated">September 2027</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>
    <intervention_model_description>The investigators will randomly allocate participants in a 1:1 ratio to two parallel study arms (based on a computer generated randomization scheme).</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma Tenofovir (TFV) Concentration</measure>
    <time_frame>36 weeks</time_frame>
    <description>Plasma Tenofovir (TFV) Concentration in nanograms per milliliter (ng/mL)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Emtricitabine (FTC) Concentration</measure>
    <time_frame>36 weeks</time_frame>
    <description>Plasma Emtricitabine (FTC) Concentration in nanograms per milliliter (ng/mL)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peripheral Blood Mononuclear Cell (PBMC) TFV-Diphosphate (TFV-DP)Concentration</measure>
    <time_frame>36 weeks</time_frame>
    <description>PBMC TFV-DP concentration in femtomoles/million cells (fmol/10E6 cells)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peripheral Blood Mononuclear Cell (PBMC) FTC-Triphosphate (FTC-TP)Concentration</measure>
    <time_frame>36 weeks</time_frame>
    <description>PBMC TFV-DP concentration in femtomoles/million cells (fmol/10E6 cells)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Pregnancy</condition>
  <condition>HIV-1-infection</condition>
  <arm_group>
    <arm_group_label>Standard Dose Truvada®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard Dose Truvada® - Tenofovir disoproxil fumarate (TDF) 300 mg/Emtricitabine (FTC) 200 mg fixed dose combination (Truvada®), one tablet each day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pregnancy-Adjusted Truvada®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pregnancy-Adjusted dose Truvada® - Tenofovir disoproxil fumarate (TDF) 300 mg/Emtricitabine (FTC) 200 mg fixed dose combination (Truvada®), two tablets each day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard dose Truvada®</intervention_name>
    <description>TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, one tablet each day</description>
    <arm_group_label>Standard Dose Truvada®</arm_group_label>
    <other_name>Tenofovir Disoproxil Fumarate/Emtricitabine</other_name>
    <other_name>TDF/FTC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pregnancy-adjusted dose Truvada®</intervention_name>
    <description>TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, two tablets each day</description>
    <arm_group_label>Pregnancy-Adjusted Truvada®</arm_group_label>
    <other_name>Tenofovir Disoproxil Fumarate/Emtricitabine</other_name>
    <other_name>TDF/FTC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age 18 years or older&#xD;
&#xD;
          -  Able to speak English, French, or Spanish&#xD;
&#xD;
          -  Able and willing to provide written informed consent&#xD;
&#xD;
          -  Viable first (preferable) or second trimester intrauterine pregnancy&#xD;
&#xD;
          -  Creatinine clearance &gt;70 ml/min&#xD;
&#xD;
          -  Negative HIV test and no signs/symptoms of acute HIV infection,&#xD;
&#xD;
          -  Documented negative hepatitis B virus status.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HIV positive at any time in the study. All neonates of mothers participating in the&#xD;
             trial will be recruited, regardless of gestational age at delivery or congenital&#xD;
             anomalies/comorbidities.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Must have documented evidence of pregnancy</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Craig Hendrix, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>February 6, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>March 28, 2022</last_update_submitted>
  <last_update_submitted_qc>March 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV Prevention</keyword>
  <keyword>Healthy Volunteer</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Emtricitabine</mesh_term>
    <mesh_term>Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03834909
nct id: NCT03834909
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This trial is a prospective, multi-center, randomized comparison study of 2 Pre-Exposure
      Prophylaxis (PrEP) pharmacokinetic (PK) dosing regimens from 1st trimester through 12 weeks
      following delivery (postpartum) to achieve study objectives which include PK, safety
      monitoring for maternal and fetal/infant safety signals, and adherence.
Study participants will be randomized to one of two parallel study arms, involving dosing of
      tenofovir disoproxil sodium/emtricitabine (TDF/FTC). The investigators will be recruiting and
      enrolling in the late 1st (preferred) and 2nd trimesters of pregnancy to capture the changes
      in kidney function and blood flow through the kidneys that appear to start in the late 1st
      trimester and are most significant in the 2nd and 3rd trimesters of pregnancy. Given the
      unknown time frame for the return to pre-pregnancy physiologic state and the increased risk
      of HIV acquisition postpartum, participants will be continued on study dose PrEP until after
      participants' 1-3 week postpartum visit, after which all participants will be dispensed
      standard dose PrEP. A 6-12 week postpartum study visit will also be performed to evaluate the
      timing of return to non-pregnant plasma drug levels during the postpartum period.

      PK Sampling. Primary PK data will be derived from up to 7 study visits with PK sampling,
      including two PK visits in each trimester and postpartum. All PK visits sample blood before
      an observed PrEP dose. .

      Safety Sampling. Maternal safety assessments will continue until 6 months postpartum. Fetal
      evaluation includes non-invasive limited ultrasound (US) and biophysical profiles (BPP) at
      study visits and 2nd and 3rd trimester interval growth US, and chart review of all before
      birth assessments. At birth, the investigators will obtain cord blood plasma to assess for
      mitochondrial function. Infant safety assessments will continue until 1 year of life. Infants
      will undergo swaddled Dual-energy X-ray absorptiometry (DXA) scans (without sedation) at 3-6,
      24-28, and 50-54 weeks of age. The investigators will assess kidney function by blood sample
      at 3-6 weeks of life and repeated at 24-28 weeks.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The investigators will randomly allocate participants in a 1:1 ratio to two parallel study arms (based on a computer generated randomization scheme).
primary purpose: Prevention
masking: None (Open Label)
measure: Plasma Tenofovir (TFV) Concentration
time frame: 36 weeks
description: Plasma Tenofovir (TFV) Concentration in nanograms per milliliter (ng/mL)
measure: Plasma Emtricitabine (FTC) Concentration
time frame: 36 weeks
description: Plasma Emtricitabine (FTC) Concentration in nanograms per milliliter (ng/mL)
measure: Peripheral Blood Mononuclear Cell (PBMC) TFV-Diphosphate (TFV-DP)Concentration
time frame: 36 weeks
description: PBMC TFV-DP concentration in femtomoles/million cells (fmol/10E6 cells)
measure: Peripheral Blood Mononuclear Cell (PBMC) FTC-Triphosphate (FTC-TP)Concentration
time frame: 36 weeks
description: PBMC TFV-DP concentration in femtomoles/million cells (fmol/10E6 cells)
arm group label: Standard Dose Truvada®
arm group type: Active Comparator
description: Standard Dose Truvada® - Tenofovir disoproxil fumarate (TDF) 300 mg/Emtricitabine (FTC) 200 mg fixed dose combination (Truvada®), one tablet each day
arm group label: Pregnancy-Adjusted Truvada®
arm group type: Experimental
description: Pregnancy-Adjusted dose Truvada® - Tenofovir disoproxil fumarate (TDF) 300 mg/Emtricitabine (FTC) 200 mg fixed dose combination (Truvada®), two tablets each day
intervention type: Drug
intervention name: Standard dose Truvada®
description: TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, one tablet each day
arm group label: Standard Dose Truvada®
other name: Tenofovir Disoproxil Fumarate/Emtricitabine
other name: TDF/FTC
intervention type: Drug
intervention name: Pregnancy-adjusted dose Truvada®
description: TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, two tablets each day
arm group label: Pregnancy-Adjusted Truvada®
other name: Tenofovir Disoproxil Fumarate/Emtricitabine
other name: TDF/FTC
criteria: 
gender: Female
gender based: Yes
gender description: Must have documented evidence of pregnancy
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Craig Hendrix, MD
role: Principal Investigator
affiliation: Johns Hopkins University
responsible party type: Sponsor
mesh term: Tenofovir
mesh term: Emtricitabine
mesh term: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
sharing ipd: No