<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/NCT03258658</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00043624</org_study_id>
    <nct_id>NCT03258658</nct_id>
  </id_info>
  <brief_title>Safety and Feasibility Study of Autologous Engineered Urethral Constructs for the Treatment of Strictures</brief_title>
  <official_title>A Phase 1 Pilot Safety and Feasibility Study of Autologous Engineered Urethral</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>Yes</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 is a Phase I clinical study to determine the safety and efficacy of using autologous,&#xD;
      engineered urethral constructs for the treatment of urethral strictures in adult males.&#xD;
&#xD;
      The proposed study design is a prospective non-randomized and uncontrolled single-center&#xD;
      investigation. Autologous urothelial cells (UCs) and smooth muscle cells (SMCs), obtained&#xD;
      from enrolled male subjects' bladder tissue samples, will be culture expanded in vitro and&#xD;
      used to seed tubular PGA scaffolds to create autologous urethral constructs for the repair of&#xD;
      urethral strictures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I clinical study to determine the safety and efficacy of using autologous,&#xD;
      engineered urethral constructs for the treatment of urethral strictures in adult males.&#xD;
&#xD;
      The proposed study design is a prospective non-randomized and uncontrolled single-center&#xD;
      investigation. Autologous urothelial cells (UCs) and smooth muscle cells (SMCs), obtained&#xD;
      from enrolled male subjects' bladder tissue samples, will be culture expanded in vitro and&#xD;
      used to seed tubular Polyglycolic Acid (PGA) scaffolds to create autologous urethral&#xD;
      constructs for the repair of urethral strictures.&#xD;
&#xD;
      Male patients, aged 21-65 years old, seen in the Wake Forest Baptist Health urology clinic,&#xD;
      referred to or self-referred to the study team, with recurrent urethral stricture, previously&#xD;
      treated with dilation, internal urethrotomy, or urethroplasty, will be approached and offered&#xD;
      consent to participate in in the trial. Up to 20 men may undergo screening procedures to&#xD;
      identify 10 eligible subjects meeting all inclusion and exclusion criteria. All eligible&#xD;
      subjects will undergo full thickness bladder tissue biopsies at Wake Forest Baptist Medical&#xD;
      Center in Winston-Salem, North Carolina to obtain UCs and SMCs, which will be cultured and&#xD;
      expanded and then seeded on tubular PGA scaffolds. Approximately 6 weeks after biopsy, the&#xD;
      subjects will return to undergo surgical removal of the stricture and implant of the urethral&#xD;
      construct. Subjects will be followed through 36 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">September 2023</start_date>
  <completion_date type="Anticipated">May 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <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>Incidence of product-related, biopsy procedure-related, and injection procedure-related adverse events</measure>
    <time_frame>monitored through 36 months post treatment</time_frame>
    <description>Rate of adverse events reported for each patient</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of urethral construct in repairing urethral stricture</measure>
    <time_frame>monitored through 36 months post construct implant</time_frame>
    <description>Improvement in peak urinary flow rate defined as Qmax improvement from baseline</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Urologic Diseases</condition>
  <condition>Male Urogenital Diseases</condition>
  <condition>Urethral Stricture</condition>
  <condition>Urethral Injury</condition>
  <arm_group>
    <arm_group_label>Autologous Engineered Urethral Construct</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects enrolled will undergo a full-thickness bladder biopsy as an out-patient surgical procedure. Urothelial and Smooth Muscle Cells recovered from the biopsy will be isolated and expanded over the next 4-6 weeks, and then seeded onto a tubular scaffold to create the autologous engineered urethral construct. Subjects will undergo a second surgical procedure to excise the urethral stricture and implant the urethral construct. All subjects will be followed for 3 years for safety and efficacy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous Engineered Urethral Construct</intervention_name>
    <description>urethral construct</description>
    <arm_group_label>Autologous Engineered Urethral Construct</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Stricture of the anterior urethra meeting the following criteria:&#xD;
&#xD;
               1. History of at least one previously failed attempt at conservative management, at&#xD;
                  least 6 months prior to study.&#xD;
&#xD;
               2. Urethral stricture of 10-60 mm in length, as determined by urethrography.&#xD;
&#xD;
               3. Contains at least 1 strictured segment through which a 16 Fr flexible cystoscope&#xD;
                  cannot be atraumatically passed.&#xD;
&#xD;
          2. Patients must be available for all follow-up visits.&#xD;
&#xD;
          3. Ability to speak English.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Any of the following is regarded as a criterion for excluding a subject from the study:&#xD;
&#xD;
          1. Strictures of the meatus or prostatic urethra; any urethral stricture associated with&#xD;
             or suspected to be urethral carcinoma, or strictures due to pelvic distraction&#xD;
             injuries. Strictures &lt;10 mm or &gt;60 mm, as determined by urethrography, and criteria&#xD;
             for bulbar urethral strictures excluding those with strictures &lt;20 mm and &gt;60 mm, as&#xD;
             described by urethrography.&#xD;
&#xD;
          2. Presence of untreated urinary tract infection.&#xD;
&#xD;
          3. Presence or prior history of lichen sclerosus et atrophicus (previously termed&#xD;
             'balanitis xerotica obliterans').&#xD;
&#xD;
          4. Uncontrolled bleeding disorder or patients with a platelet count less than 50,000,&#xD;
             hemophilia or patients routinely receiving blood products for bleeding disorders.&#xD;
&#xD;
          5. Any urological condition that would be likely to require additional urethral&#xD;
             instrumentation during the period of investigation, including, but not limited to&#xD;
             benign prostatic hyperplasia requiring treatment, use of alpha blockers, active&#xD;
             prostate cancer, an unevaluated elevated prostate surface antigen (PSA), bladder&#xD;
             cancer, or any recurrent urinary stone formation. Patients with evidence or diagnosis&#xD;
             of any coagulation disorder (including concomitant anti-coagulation therapy at&#xD;
             enrollment).&#xD;
&#xD;
          6. Serum creatinine &gt; 2.0 mg/dl or evidence of progressive renal disease.&#xD;
&#xD;
          7. Patients with abnormal urologic conditions, including vesicoureteral reflux, bladder&#xD;
             stones, bladder tumors and renal impairment.&#xD;
&#xD;
          8. Subjects with an alanine aminotransferase (ALT) or aspartate aminotransferase (AST)&#xD;
             value &gt;3 times the upper limit of normal.&#xD;
&#xD;
          9. Subjects with an albumin value &lt;3.0 g/dL.&#xD;
&#xD;
         10. Subjects with uncontrolled diabetes, unstable cardiac and/or pulmonary disorders.&#xD;
&#xD;
         11. Subjects with active tuberculosis (TB) requiring treatment in the past 3 years.&#xD;
             Subjects with a current positive (≥5 mm induration for high-risk subjects; otherwise&#xD;
             ≥10 mm of induration) purified protein derivative (PPD) test are excluded unless they&#xD;
             have completed a full course of treatment for latent TB and have a negative chest&#xD;
             x-ray film at enrollment.&#xD;
&#xD;
         12. Subjects known to be colonized with either methicillin-resistant Staphylococcus aureus&#xD;
             (MRSA) or vancomycin-resistant Enterococcus (VRE), or gentamicin-resistant organisms.&#xD;
&#xD;
         13. Immunocompromised subjects or subjects receiving immunosuppressive agents (inhaled&#xD;
             corticosteroids and chronic low-dose corticosteroids [≤0.25 mg/kg prednisone or&#xD;
             equivalent per day] are permitted).&#xD;
&#xD;
         14. Any history of alcohol and/or drug abuse.&#xD;
&#xD;
         15. Current smoker.&#xD;
&#xD;
         16. Documented history of, or positive result of HIV, Hepatitis B or C, or any infectious&#xD;
             disease. External signs, sequelae, or positive serology of sexually transmitted&#xD;
             disease (including HPV). Patients with a history of systemic conditions, including but&#xD;
             not limited to HIV, diabetes and chronic liver disease (including Hepatitis B or C),&#xD;
             that the Investigator believes may jeopardize the safety of the patient to participate&#xD;
             in the study.&#xD;
&#xD;
         17. Concurrent participation in any other clinical investigation during the period of this&#xD;
             investigation. Patients who have been treated with any other investigational drug or&#xD;
             participated in any investigational study within 30 days prior to enrollment in this&#xD;
             study.&#xD;
&#xD;
         18. Any current illness that might confound the results of this investigation, including&#xD;
             but not limited to bladder atonia, neuropathic/neurogenic bladder, bladder outlet&#xD;
             obstruction (other than urethral stricture), sphincteric dysfunction, or spinal cord&#xD;
             injury.&#xD;
&#xD;
         19. Any circumstance in which the investigator deems participation in the study is not in&#xD;
             the subject's best interest.&#xD;
&#xD;
         20. Inability to participate in all necessary study activities due to physical or mental&#xD;
             limitations.&#xD;
&#xD;
         21. Inability or unwillingness to return for all required follow-up visits.&#xD;
&#xD;
         22. Inability or unwillingness to sign informed consent.&#xD;
&#xD;
         23. Patients requiring concomitant use of or treatment with immunosuppressive agents.&#xD;
&#xD;
         24. Patients with neurological disorders (e.g., multiple sclerosis, Parkinson's disease).&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James Yoo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest Institute for Regenerative Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mary-Clare Day, RN, BSN</last_name>
    <phone>336-713-1343</phone>
    <email>mday@wakehealth.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Ben Breyer, MD</last_name>
      <phone>628-476-3372</phone>
      <email>Benjamin.Breyer@ucsf.edu</email>
    </contact>
    <investigator>
      <last_name>Ben Breyer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Wake Forest Institute for Regenerative Medicine (WFIRM)</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>July 28, 2023</last_update_submitted>
  <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Urethral Stricture</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urologic Diseases</mesh_term>
    <mesh_term>Urethral Stricture</mesh_term>
    <mesh_term>Urogenital Diseases</mesh_term>
    <mesh_term>Male Urogenital Diseases</mesh_term>
    <mesh_term>Constriction, Pathologic</mesh_term>
  </condition_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/NCT03258658
org study id: IRB00043624
nct id: NCT03258658
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase I clinical study to determine the safety and efficacy of using autologous,
      engineered urethral constructs for the treatment of urethral strictures in adult males.

      The proposed study design is a prospective non-randomized and uncontrolled single-center
      investigation. Autologous urothelial cells (UCs) and smooth muscle cells (SMCs), obtained
      from enrolled male subjects' bladder tissue samples, will be culture expanded in vitro and
      used to seed tubular PGA scaffolds to create autologous urethral constructs for the repair of
      urethral strictures.
This is a Phase I clinical study to determine the safety and efficacy of using autologous,
      engineered urethral constructs for the treatment of urethral strictures in adult males.

      The proposed study design is a prospective non-randomized and uncontrolled single-center
      investigation. Autologous urothelial cells (UCs) and smooth muscle cells (SMCs), obtained
      from enrolled male subjects' bladder tissue samples, will be culture expanded in vitro and
      used to seed tubular Polyglycolic Acid (PGA) scaffolds to create autologous urethral
      constructs for the repair of urethral strictures.

      Male patients, aged 21-65 years old, seen in the Wake Forest Baptist Health urology clinic,
      referred to or self-referred to the study team, with recurrent urethral stricture, previously
      treated with dilation, internal urethrotomy, or urethroplasty, will be approached and offered
      consent to participate in in the trial. Up to 20 men may undergo screening procedures to
      identify 10 eligible subjects meeting all inclusion and exclusion criteria. All eligible
      subjects will undergo full thickness bladder tissue biopsies at Wake Forest Baptist Medical
      Center in Winston-Salem, North Carolina to obtain UCs and SMCs, which will be cultured and
      expanded and then seeded on tubular PGA scaffolds. Approximately 6 weeks after biopsy, the
      subjects will return to undergo surgical removal of the stricture and implant of the urethral
      construct. Subjects will be followed through 36 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of product-related, biopsy procedure-related, and injection procedure-related adverse events
time frame: monitored through 36 months post treatment
description: Rate of adverse events reported for each patient
measure: Effectiveness of urethral construct in repairing urethral stricture
time frame: monitored through 36 months post construct implant
description: Improvement in peak urinary flow rate defined as Qmax improvement from baseline
arm group label: Autologous Engineered Urethral Construct
arm group type: Experimental
description: All subjects enrolled will undergo a full-thickness bladder biopsy as an out-patient surgical procedure. Urothelial and Smooth Muscle Cells recovered from the biopsy will be isolated and expanded over the next 4-6 weeks, and then seeded onto a tubular scaffold to create the autologous engineered urethral construct. Subjects will undergo a second surgical procedure to excise the urethral stricture and implant the urethral construct. All subjects will be followed for 3 years for safety and efficacy.
intervention type: Biological
intervention name: Autologous Engineered Urethral Construct
description: urethral construct
arm group label: Autologous Engineered Urethral Construct
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: No
last name: James Yoo, MD
role: Principal Investigator
affiliation: Wake Forest Institute for Regenerative Medicine
last name: Mary-Clare Day, RN, BSN
phone: 336-713-1343
email: mday@wakehealth.edu
facility: 
contact: 
investigator: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Urologic Diseases
mesh term: Urethral Stricture
mesh term: Urogenital Diseases
mesh term: Male Urogenital Diseases
mesh term: Constriction, Pathologic
sharing ipd: No