<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/NCT03298815</url>
  </required_header>
  <id_info>
    <org_study_id>103515</org_study_id>
    <nct_id>NCT03298815</nct_id>
  </id_info>
  <brief_title>Study for the Treatment of Ocular Chronic Graft-Versus-Host Disease (GVHD) With Amniotic Fluid Eye Drops (AFED)</brief_title>
  <official_title>A Randomized, Double-Blinded, Placebo-Controlled Study for the Treatment of Ocular Chronic Graft-Versus-Host Disease (GVHD) With Amniotic Fluid Eye Drops (AFED)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Utah</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>
      A Randomized, Double-blinded, Placebo-Controlled Study for the Treatment of Ocular Chronic&#xD;
      Graft Verses Host Disease with Processed Amniotic Fluid (pAF) Drops.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized (to each eye, within patient), double-blinded, placebo-controlled study&#xD;
      of the efficacy of Processed Amniotic Fluid (pAF) in patients with hematologic malignancies&#xD;
      who have undergone Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and are&#xD;
      diagnosed with Chronic Graft Verses Host Disease of the eye.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2019</start_date>
  <completion_date type="Actual">February 24, 2023</completion_date>
  <primary_completion_date type="Actual">December 16, 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>100 days</time_frame>
    <description>Response is a composite of the NIH Consensus Conference (CC) for assessment of response in chronic GVHD (eye score) and the International Dry Eye Workshop (DEWS) grading scale. Responders would be defined as a one point improvement in the dry eye grading scale (DEWS), without worsening in the eye score.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety of pAF in patients with chronic ocular GVHD: CTCAE version 4</measure>
    <time_frame>100 days</time_frame>
    <description>Serious adverse events and ocular adverse events using CTCAE version 4</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Functional Assessment of Cancer Therapy: General (FACT-G)</measure>
    <time_frame>30 days</time_frame>
    <description>Change in Quality of Life questionnaire using a five-point scale from 0 (not at all) to 4 (very much).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Assessment of Cancer Therapy: General (FACT-G)</measure>
    <time_frame>60 days</time_frame>
    <description>Change in Quality of Life questionnaire using a five-point scale from 0 (not at all) to 4 (very much).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Assessment of Cancer Therapy: General (FACT-G)</measure>
    <time_frame>100 days</time_frame>
    <description>Change in Quality of Life questionnaire using a five-point scale from 0 (not at all) to 4 (very much).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>National Institutes of Health (NIH) Consensus Criteria (CC) ocular score of chronic GVHD</measure>
    <time_frame>30 days</time_frame>
    <description>Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>National Institutes of Health (NIH) Consensus Criteria (CC) ocular score of chronic GVHD</measure>
    <time_frame>60 days</time_frame>
    <description>Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>National Institutes of Health (NIH) Consensus Criteria (CC) ocular score of chronic GVHD</measure>
    <time_frame>100 days</time_frame>
    <description>Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading</measure>
    <time_frame>30 days</time_frame>
    <description>Ophthalmologic assessment to determine changes in dry eye signs/symptoms each graded on a scale of 1 to 4 with 1 being non/mild to 4 being most severe for a total score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading</measure>
    <time_frame>60 days</time_frame>
    <description>Ophthalmologic assessment to determine changes in dry eye signs/symptoms each graded on a scale of 1 to 4 with 1 being non/mild to 4 being most severe for a total score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading</measure>
    <time_frame>100 days</time_frame>
    <description>Ophthalmologic assessment to determine changes in dry eye signs/symptoms each graded on a scale of 1 to 4 with 1 being non/mild to 4 being most severe for a total score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Assessment</measure>
    <time_frame>60 days</time_frame>
    <description>Change in patient reported pain level using 0-10 pain rating scale with zero being no pain to 10 being very severe pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Visual Acuity</measure>
    <time_frame>Up to 100 days</time_frame>
    <description>Ophthalmologic assessment to determine changes in visual acuity related to the administration of pAF.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects on the Corneal Surface</measure>
    <time_frame>Up to 100 days</time_frame>
    <description>Ophthalmologic assessment to determine the effects of treatment with pAF on the corneal surface of patients with ocular chronic GVHD.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Ocular Graft Versus Host Disease</condition>
  <arm_group>
    <arm_group_label>Amniotic Fluid Eye Drops (AFED) - All participants, One eye</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline Solution - All participants, One eye</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Amniotic Fluid Eye Drops (AFED)</intervention_name>
    <description>One drop (0.25 mL) in one eye twice daily for up to 3 months</description>
    <arm_group_label>Amniotic Fluid Eye Drops (AFED) - All participants, One eye</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Saline Solution</intervention_name>
    <description>One drop (0.25 mL) in the other eye twice daily for up to 3 months</description>
    <arm_group_label>Saline Solution - All participants, One eye</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed within 5 years after hematopoietic stem cell transplant for any&#xD;
             disease, with any graft and any conditioning regimen with at least one of the&#xD;
             following symptoms:&#xD;
&#xD;
               1. Dry eye symptoms partially affecting (requiring lubricant drops &gt; 3 x per day or&#xD;
                  punctal plugs, or thermally cauterized puncta) or significantly affecting&#xD;
                  (special eyeware to relieve pain) activities of daily living (ADL)&#xD;
&#xD;
               2. Unable to work because of ocular symptoms&#xD;
&#xD;
               3. Loss of vision due to keratoconjunctivitis sicca (KCS)&#xD;
&#xD;
          -  Patients may be using bilateral scleral lenses and/or bilateral punctal plugs at the&#xD;
             time of accrual.&#xD;
&#xD;
          -  Patients who are 18 years of age or older.&#xD;
&#xD;
          -  Willing and able to provide informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have any other reversible cause for dry eye at the time of accrual.&#xD;
&#xD;
          -  More than 3 lines of therapy beyond corticosteroids with or without calcineurin&#xD;
             inhibitors or sirolimus&#xD;
&#xD;
          -  Relapsed malignancy after transplantation&#xD;
&#xD;
          -  A difference in dryness between both eyes of more than 2 points of the grading&#xD;
             provided by the International Dry Eye Workshop (DEWS) 2007 report&#xD;
&#xD;
          -  Patients who are pregnant or plan to become pregnant while participating in the study.&#xD;
             - Patients who are not willing to discontinue the use of any eye drops, with the&#xD;
             exception of non-medicated lubricant eye drops (artificial tears). All eye drops&#xD;
             (excluding non-medicated lubricant eye drops) must be stopped at least seven days&#xD;
             before treatment with pAF.&#xD;
&#xD;
          -  Inability to comply with the investigational plan and visit schedule for any&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Catherine J. Lee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Utah Huntsman Cancer Institute</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>July 2023</verification_date>
  <study_first_submitted>September 13, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <last_update_submitted>July 5, 2023</last_update_submitted>
  <last_update_submitted_qc>July 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Utah</investigator_affiliation>
    <investigator_full_name>Catherine Lee</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchiolitis Obliterans Syndrome</mesh_term>
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ophthalmic Solutions</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03298815
org study id: 103515
nct id: NCT03298815
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
A Randomized, Double-blinded, Placebo-Controlled Study for the Treatment of Ocular Chronic
      Graft Verses Host Disease with Processed Amniotic Fluid (pAF) Drops.
This is a randomized (to each eye, within patient), double-blinded, placebo-controlled study
      of the efficacy of Processed Amniotic Fluid (pAF) in patients with hematologic malignancies
      who have undergone Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and are
      diagnosed with Chronic Graft Verses Host Disease of the eye.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Overall Response Rate
time frame: 100 days
description: Response is a composite of the NIH Consensus Conference (CC) for assessment of response in chronic GVHD (eye score) and the International Dry Eye Workshop (DEWS) grading scale. Responders would be defined as a one point improvement in the dry eye grading scale (DEWS), without worsening in the eye score.
measure: Safety of pAF in patients with chronic ocular GVHD: CTCAE version 4
time frame: 100 days
description: Serious adverse events and ocular adverse events using CTCAE version 4
measure: Functional Assessment of Cancer Therapy: General (FACT-G)
time frame: 30 days
description: Change in Quality of Life questionnaire using a five-point scale from 0 (not at all) to 4 (very much).
measure: Functional Assessment of Cancer Therapy: General (FACT-G)
time frame: 60 days
description: Change in Quality of Life questionnaire using a five-point scale from 0 (not at all) to 4 (very much).
measure: Functional Assessment of Cancer Therapy: General (FACT-G)
time frame: 100 days
description: Change in Quality of Life questionnaire using a five-point scale from 0 (not at all) to 4 (very much).
measure: National Institutes of Health (NIH) Consensus Criteria (CC) ocular score of chronic GVHD
time frame: 30 days
description: Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms).
measure: National Institutes of Health (NIH) Consensus Criteria (CC) ocular score of chronic GVHD
time frame: 60 days
description: Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms).
measure: National Institutes of Health (NIH) Consensus Criteria (CC) ocular score of chronic GVHD
time frame: 100 days
description: Change in ocular score using a four-point scale from 0 (no dry eye symptoms) to 3 (severe dry eye symptoms).
measure: Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading
time frame: 30 days
description: Ophthalmologic assessment to determine changes in dry eye signs/symptoms each graded on a scale of 1 to 4 with 1 being non/mild to 4 being most severe for a total score.
measure: Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading
time frame: 60 days
description: Ophthalmologic assessment to determine changes in dry eye signs/symptoms each graded on a scale of 1 to 4 with 1 being non/mild to 4 being most severe for a total score.
measure: Dry Eye Workshop (DEWS) 2007 Dry Eye Severity Grading
time frame: 100 days
description: Ophthalmologic assessment to determine changes in dry eye signs/symptoms each graded on a scale of 1 to 4 with 1 being non/mild to 4 being most severe for a total score.
measure: Pain Assessment
time frame: 60 days
description: Change in patient reported pain level using 0-10 pain rating scale with zero being no pain to 10 being very severe pain.
measure: Changes in Visual Acuity
time frame: Up to 100 days
description: Ophthalmologic assessment to determine changes in visual acuity related to the administration of pAF.
measure: Effects on the Corneal Surface
time frame: Up to 100 days
description: Ophthalmologic assessment to determine the effects of treatment with pAF on the corneal surface of patients with ocular chronic GVHD.
arm group label: Amniotic Fluid Eye Drops (AFED) - All participants, One eye
arm group type: Active Comparator
arm group label: Saline Solution - All participants, One eye
arm group type: Placebo Comparator
intervention type: Biological
intervention name: Amniotic Fluid Eye Drops (AFED)
description: One drop (0.25 mL) in one eye twice daily for up to 3 months
arm group label: Amniotic Fluid Eye Drops (AFED) - All participants, One eye
intervention type: Other
intervention name: Saline Solution
description: One drop (0.25 mL) in the other eye twice daily for up to 3 months
arm group label: Saline Solution - All participants, One eye
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Catherine J. Lee, MD
role: Principal Investigator
affiliation: University of Utah
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Utah
investigator full name: Catherine Lee
investigator title: MD
mesh term: Bronchiolitis Obliterans Syndrome
mesh term: Graft vs Host Disease
mesh term: Ophthalmic Solutions