<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/NCT03240822</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00027539</org_study_id>
    <nct_id>NCT03240822</nct_id>
  </id_info>
  <brief_title>Human Penile Tissue Allotransplantation for Devastating Penile and Concomitant Genital Trauma</brief_title>
  <official_title>Vascularized Composite Allotransplantation (VCA) for Devastating Penile and Concomitant Genital Trauma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a 4-year, non-randomized, single center, patient self-controlled, clinical trial&#xD;
      (though enrolled subjects will be followed for life as are all transplant patients) for&#xD;
      patients seeking allotransplantation of the male external genitalia (MEG), or penile tissue,&#xD;
      as a feasible reconstructive strategy for the treatment of devastating and irreversible&#xD;
      injuries to the genitalia. In addition to receiving penile allotransplantation and&#xD;
      post-operative monitoring and support, enrolled patients will receive an innovative and&#xD;
      clinically proven immunomodulatory protocol that combines lymphocyte depletion of the&#xD;
      recipient with donor bone marrow cell infusion. Patients will be treated with lymphocyte&#xD;
      depleting induction therapy, donor bone marrow cell infusion and tacrolimus. After the first&#xD;
      year, maintenance immunosuppression will be modified gradually and cautiously (tapered dose&#xD;
      reduction or spaced frequency dosing of tacrolimus) in selected patients based on a critical&#xD;
      evaluation of clinical and immunologic outcomes. Outcomes will include but not be limited to&#xD;
      functional metrics (sensation, erection, voiding), psychosocial (body integrity, adaptation&#xD;
      to transplant) and health related quality of life (HRQOL) measures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Initial treatment with an antibody targeting recipient immune cells followed by triple-drug&#xD;
      maintenance therapy represents the current standard in clinical VCA. Our protocol is&#xD;
      different from the existing conventional drug treatments used in MEG allotransplantation in&#xD;
      that it combines donor bone marrow infusion with an immunosuppression sparing protocol. The&#xD;
      primary goal of this pilot clinical trial is to determine the feasibility of using allogeneic&#xD;
      penile tissue to repair/replace irreversibly damaged external genitalia. Enrolled and&#xD;
      transplanted subjects will be followed for their lifetime as a transplant patient.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of Funding&#xD;
  </why_stopped>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>All subjects receive transplant and immunosuppression therapy</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Need for Immunosuppressive drug therapy</measure>
    <time_frame>6 months</time_frame>
    <description>The amount of immunosuppressive drug therapy will be recorded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>erectile function</measure>
    <time_frame>6 months</time_frame>
    <description>This will be assessed following intracorporal injection of vaso-active agents, such as prostaglandin, phentolamine, papaverine, or some mixture of these drugs (i.e. Trimix). and through high-resolution duplex Doppler ultrasonography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of sensory return and sensory thresholds</measure>
    <time_frame>6 months</time_frame>
    <description>This will be accomplished by penile biothesiometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determination of hemodynamic status</measure>
    <time_frame>6 months</time_frame>
    <description>Dynamic infusion pharmaco-cavernosometry and cavernosography will be utilized to better understand these changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Reintegration to Normal Living (RNL) Index</measure>
    <time_frame>6 months</time_frame>
    <description>The RNL is an 11-item questionnaire that asks how a person manages activities, roles, and relationships on a day-to-day basis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Situational Inventory of Body-Image Dysphoria (SIBID)</measure>
    <time_frame>6 months</time_frame>
    <description>The SIBID is a multidimensional body-image survey assessment of people's negative body-image emotions in everyday situations and physical experiences.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Function and Body Image Survey</measure>
    <time_frame>6 months</time_frame>
    <description>This survey consists of six open-ended questions regarding personal thoughts, opinions, and experiences about the transplant, and the individual's current functional abilities.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Urologic Injuries</condition>
  <condition>Genital Diseases, Male</condition>
  <condition>Amputation</condition>
  <arm_group>
    <arm_group_label>Penile Allotransplant and Immunosuppression Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Penile transplantation with monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Penile Transplant</intervention_name>
    <description>Penile Allotransplantation</description>
    <arm_group_label>Penile Allotransplant and Immunosuppression Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Monoclonal Antibody (Humanized Anti-CD52)</intervention_name>
    <arm_group_label>Penile Allotransplant and Immunosuppression Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <arm_group_label>Penile Allotransplant and Immunosuppression Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: For Recipients&#xD;
&#xD;
          1. Male&#xD;
&#xD;
          2. 18-40 years&#xD;
&#xD;
          3. Irreversible and devastating genitalia damage not amenable to conventional&#xD;
             reconstruction.&#xD;
&#xD;
          4. Patent main vessels leading into the remaining penile stump, as confirmed by&#xD;
             angiography.&#xD;
&#xD;
          5. Adequate penile stump (&gt; 2.5cm) to facilitate placement of a tourniquet, debridement&#xD;
             of the distal portion and sufficient distal mobilization of the structures requiring&#xD;
             anastomosis&#xD;
&#xD;
          6. Eligible for long term standard of care coverage&#xD;
&#xD;
        Exclusion Criteria: For Recipients&#xD;
&#xD;
          1. Documented history of:&#xD;
&#xD;
               1. cancer&#xD;
&#xD;
               2. renal impairment&#xD;
&#xD;
               3. hepatic disorders&#xD;
&#xD;
               4. neurologic disorders (sensory or motor function deficits)&#xD;
&#xD;
               5. severe scarring with poor host tissue bed&#xD;
&#xD;
               6. penile resection or implant surgery&#xD;
&#xD;
               7. diabetes&#xD;
&#xD;
               8. hypertension&#xD;
&#xD;
               9. hyperlipidemia&#xD;
&#xD;
              10. coronary artery disease&#xD;
&#xD;
              11. untreated genital cancer&#xD;
&#xD;
              12. HIV, Hepatitis B or C, or any infectious disease&#xD;
&#xD;
              13. erectile dysfunction&#xD;
&#xD;
              14. Peyronie's disease&#xD;
&#xD;
              15. urethral stricture disease&#xD;
&#xD;
              16. balanitis&#xD;
&#xD;
              17. xerotica obliterans&#xD;
&#xD;
              18. pelvic embolization&#xD;
&#xD;
              19. pelvic radiation&#xD;
&#xD;
              20. untreated hypogonadism&#xD;
&#xD;
              21. prior prostate surgery&#xD;
&#xD;
              22. recurrent urinary tract infections (UTIs)&#xD;
&#xD;
              23. nephrolithiasis&#xD;
&#xD;
              24. connective tissue disease or collagen disease&#xD;
&#xD;
              25. lipopolysaccharidosis or amyloidosis&#xD;
&#xD;
          2. Use of 5-alpha-reductase inhibitors&#xD;
&#xD;
          3. External signs, sequelae or positive serology of sexually transmitted disease&#xD;
             (including HPV)&#xD;
&#xD;
          4. Active UTI, stones, urethral edema and other pathology that prevents urethral&#xD;
             anastomosis&#xD;
&#xD;
          5. Current or past substance abuse&#xD;
&#xD;
          6. Current or past smoker (within past 3 months)&#xD;
&#xD;
          7. Use of any medications known to cause vasoconstriction&#xD;
&#xD;
          8. Psychiatric illness or psychological problems, or deemed unsuitable on psychiatric&#xD;
             evaluation&#xD;
&#xD;
          9. Any condition that may prevent transplantation (positive cross match, high panel&#xD;
             reactive antibody (PRA), etc.)&#xD;
&#xD;
         10. Uncontrolled bleeding disorder, platelet count &gt; 50,000, hemophilia or any other&#xD;
             inherited coagulopathy or need to routinely receive blood products for bleeding&#xD;
             disorders&#xD;
&#xD;
         11. Concurrent participation in any other clinical investigation during the period of this&#xD;
             investigation&#xD;
&#xD;
         12. Inability to undergo leukapheresis&#xD;
&#xD;
         13. Inability to participate in all necessary study activities due to physical or mental&#xD;
             limitations&#xD;
&#xD;
         14. Inability or unwillingness to return for all required follow-up visits.&#xD;
&#xD;
         15. Inability or unwillingness to sign the patient informed consent document.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>This is a male, penile transplantation study.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anthony Atala, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>April 9, 2021</last_update_submitted>
  <last_update_submitted_qc>April 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Penile Trauma</keyword>
  <keyword>Allotransplantation</keyword>
  <keyword>Vascularized Composite Allotransplantation</keyword>
  <keyword>VCA</keyword>
  <keyword>Genital Trauma</keyword>
  <keyword>Penile Transplantation</keyword>
  <keyword>Amputation</keyword>
  <keyword>Penile Injury</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Genital Diseases</mesh_term>
    <mesh_term>Genital Diseases, Male</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Tacrolimus</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/NCT03240822
org study id: IRB00027539
nct id: NCT03240822
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a 4-year, non-randomized, single center, patient self-controlled, clinical trial
      (though enrolled subjects will be followed for life as are all transplant patients) for
      patients seeking allotransplantation of the male external genitalia (MEG), or penile tissue,
      as a feasible reconstructive strategy for the treatment of devastating and irreversible
      injuries to the genitalia. In addition to receiving penile allotransplantation and
      post-operative monitoring and support, enrolled patients will receive an innovative and
      clinically proven immunomodulatory protocol that combines lymphocyte depletion of the
      recipient with donor bone marrow cell infusion. Patients will be treated with lymphocyte
      depleting induction therapy, donor bone marrow cell infusion and tacrolimus. After the first
      year, maintenance immunosuppression will be modified gradually and cautiously (tapered dose
      reduction or spaced frequency dosing of tacrolimus) in selected patients based on a critical
      evaluation of clinical and immunologic outcomes. Outcomes will include but not be limited to
      functional metrics (sensation, erection, voiding), psychosocial (body integrity, adaptation
      to transplant) and health related quality of life (HRQOL) measures.
Initial treatment with an antibody targeting recipient immune cells followed by triple-drug
      maintenance therapy represents the current standard in clinical VCA. Our protocol is
      different from the existing conventional drug treatments used in MEG allotransplantation in
      that it combines donor bone marrow infusion with an immunosuppression sparing protocol. The
      primary goal of this pilot clinical trial is to determine the feasibility of using allogeneic
      penile tissue to repair/replace irreversibly damaged external genitalia. Enrolled and
      transplanted subjects will be followed for their lifetime as a transplant patient.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: All subjects receive transplant and immunosuppression therapy
primary purpose: Treatment
masking: None (Open Label)
measure: Need for Immunosuppressive drug therapy
time frame: 6 months
description: The amount of immunosuppressive drug therapy will be recorded.
measure: erectile function
time frame: 6 months
description: This will be assessed following intracorporal injection of vaso-active agents, such as prostaglandin, phentolamine, papaverine, or some mixture of these drugs (i.e. Trimix). and through high-resolution duplex Doppler ultrasonography
measure: Assessment of sensory return and sensory thresholds
time frame: 6 months
description: This will be accomplished by penile biothesiometry
measure: Determination of hemodynamic status
time frame: 6 months
description: Dynamic infusion pharmaco-cavernosometry and cavernosography will be utilized to better understand these changes
measure: The Reintegration to Normal Living (RNL) Index
time frame: 6 months
description: The RNL is an 11-item questionnaire that asks how a person manages activities, roles, and relationships on a day-to-day basis.
measure: The Situational Inventory of Body-Image Dysphoria (SIBID)
time frame: 6 months
description: The SIBID is a multidimensional body-image survey assessment of people's negative body-image emotions in everyday situations and physical experiences.
measure: The Function and Body Image Survey
time frame: 6 months
description: This survey consists of six open-ended questions regarding personal thoughts, opinions, and experiences about the transplant, and the individual's current functional abilities.
arm group label: Penile Allotransplant and Immunosuppression Treatment
arm group type: Experimental
description: Penile transplantation with monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.
intervention type: Procedure
intervention name: Penile Transplant
description: Penile Allotransplantation
arm group label: Penile Allotransplant and Immunosuppression Treatment
intervention type: Biological
intervention name: Monoclonal Antibody (Humanized Anti-CD52)
arm group label: Penile Allotransplant and Immunosuppression Treatment
intervention type: Drug
intervention name: Tacrolimus
arm group label: Penile Allotransplant and Immunosuppression Treatment
criteria: 
gender: Male
gender based: Yes
gender description: This is a male, penile transplantation study.
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: No
last name: Anthony Atala, MD
role: Principal Investigator
affiliation: Professor
country: United States
responsible party type: Sponsor
mesh term: Genital Diseases
mesh term: Genital Diseases, Male
mesh term: Antibodies
mesh term: Antibodies, Monoclonal
mesh term: Tacrolimus
sharing ipd: No