<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/NCT01674569</url>
  </required_header>
  <id_info>
    <org_study_id>X82-OPH-102</org_study_id>
    <nct_id>NCT01674569</nct_id>
  </id_info>
  <brief_title>Pilot Study of X-82 in Patients With Wet AMD</brief_title>
  <official_title>A Phase 1 Open-label, Dose Escalation Clinical Trial to Evaluate the Safety and Preliminary Biologic Activity/Efficacy of the VEGFR/PDGFR Inhibitor X-82 Administered Per Os in Subjects With Neovascular Age-related Macular Degeneration (AMD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tyrogenex</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tyrogenex</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to evaluate the safety and preliminary biologic&#xD;
      activity/efficacy of X-82 in patients with wet Age-related Macular Degeneration (AMD).&#xD;
      Preliminary efficacy will be assessed by change from baseline in visual acuity, fluorescein&#xD;
      leakage, retinal thickness and fibrosis, if detectable, based on fundus examination, fundus&#xD;
      photography, fluorescein angiography and optical coherence tomography (OCT).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline Visual Acuity at 6 Months</measure>
    <time_frame>6 months</time_frame>
    <description>The best corrected visual acuity by the Early Treatment Diabetic Retinopathy Study (ETDRS) method was determined at baseline and at various times during the study. The ETDRS method records the number of letters of decreasing size on a chart that a subject can read from a defiend distance.&#xD;
During the study the ETDRS visual acuity was used to monitor the need for rescue therapy. The primary endpoint of the study was the change from baseline visual ETDRS visual acuity at 6 months. It was calculated by subtracting the baseline visual acuity from the visual acuity at 6 months for each individual subject. A positive change from baseline indicates improvement in visual acuity.</description>
  </primary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Exudative Macular Degeneration</condition>
  <arm_group>
    <arm_group_label>50 mg X-82 oral alternate days</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity develops</description>
  </arm_group>
  <arm_group>
    <arm_group_label>50 mg X-82 oral QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria.for 24 weeks or until unacceptable toxicity develops</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100 mg X-82 oral alternate days</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria.for 24 weeks or until unacceptable toxicty develops</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100 mg X-82 oral QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200 mg X-82 oral QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>300 mg X-82 oral QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>300 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>X-82 oral</intervention_name>
    <description>X-82 oral for 24 weeks or until unacceptable toxicity develops</description>
    <arm_group_label>100 mg X-82 oral QD</arm_group_label>
    <arm_group_label>100 mg X-82 oral alternate days</arm_group_label>
    <arm_group_label>200 mg X-82 oral QD</arm_group_label>
    <arm_group_label>300 mg X-82 oral QD</arm_group_label>
    <arm_group_label>50 mg X-82 oral QD</arm_group_label>
    <arm_group_label>50 mg X-82 oral alternate days</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ranibizumab (Lucentis)</intervention_name>
    <description>Rescue treatment with intravitreal ranibizumab (Lucentis) as needed</description>
    <arm_group_label>100 mg X-82 oral QD</arm_group_label>
    <arm_group_label>100 mg X-82 oral alternate days</arm_group_label>
    <arm_group_label>200 mg X-82 oral QD</arm_group_label>
    <arm_group_label>300 mg X-82 oral QD</arm_group_label>
    <arm_group_label>50 mg X-82 oral QD</arm_group_label>
    <arm_group_label>50 mg X-82 oral alternate days</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Active choroidal neovascularization (CNV) associated with AMD, as evidenced on&#xD;
             fluorescein angiography (FA) and OCT.&#xD;
&#xD;
          2. No previous treatment with anti-VEGF therapy or prior anti-VEGF therapy with evidence&#xD;
             of response to treatment and the need for additional treatment.&#xD;
&#xD;
          3. Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA 20/32 to 20/320 in the study&#xD;
             eye(s).&#xD;
&#xD;
          4. Adequate bone marrow function.&#xD;
&#xD;
          5. PT within the institutional upper limit of normal.&#xD;
&#xD;
          6. Adequate hepatic function.&#xD;
&#xD;
          7. Adequate renal function; serum creatinine.&#xD;
&#xD;
          8. Ability to swallow oral medication.&#xD;
&#xD;
          9. Age ≥ 50 years.&#xD;
&#xD;
         10. Willing and able to provide written informed consent, comply with the investigational&#xD;
             study protocol and return for all study visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous treatment with photodynamic therapy (PDT) within 4 months of screening in the&#xD;
             study eye.&#xD;
&#xD;
          2. CNV due to causes other than AMD.&#xD;
&#xD;
          3. Geographic atrophy involving the foveal center in the study eye.&#xD;
&#xD;
          4. Any retinal vascular disease or retinal degeneration other than AMD in the study eye.&#xD;
&#xD;
          5. In the opinion of the investigator, any significant disease in the study eye that&#xD;
             could compromise best-corrected visual acuity.&#xD;
&#xD;
          6. Cataract surgery in the study eye within three months of screening.&#xD;
&#xD;
          7. Trabeculectomy or aqueous shunt or valve in the study eye.&#xD;
&#xD;
          8. Intraocular surgery in the study eye within three months of screening; Nd:YAG&#xD;
             capsulotomy or laser iridotomy within 30 days of screening.&#xD;
&#xD;
          9. Inadequate pupillary dilation or significant media opacities in the study eye.&#xD;
&#xD;
         10. Use of any investigational agent or participation in any other clinical trial of an&#xD;
             investigational agent or investigational therapy within thirty (30) days of baseline&#xD;
             with the exception of subjects who are participating in the AREDS2 study.&#xD;
&#xD;
         11. Females of child bearing potential that are pregnant or not using medically acceptable&#xD;
             contraception; males unwilling to take adequate contraceptive measures. Females that&#xD;
             are breastfeeding are also excluded.&#xD;
&#xD;
         12. Serious allergy to or prior significant adverse reaction to fluorescein.&#xD;
&#xD;
         13. Undiagnosed acute illness first observed during screening or between screening and&#xD;
             baseline, or severe concurrent medical conditions that, in the investigators judgment,&#xD;
             represent a safety concern.&#xD;
&#xD;
         14. Severe cardiac disease, symptomatic congestive heart failure, unstable angina, acute&#xD;
             coronary syndrome, myocardial infarction or coronary artery revascularization, or&#xD;
             arterial thrombosis within 12 months of start of study drug, inadequately controlled&#xD;
             hypertension, or ventricular tachyarrhythmias requiring ongoing treatment.&#xD;
&#xD;
         15. QTc ≥450 msec or subjects with a history of risk factors for Torsades de Pointes or&#xD;
             other clinically significant ECG abnormalities as determined by the investigator.&#xD;
&#xD;
         16. Stroke or transient ischemic attack within 12 months of trial entry.&#xD;
&#xD;
         17. Clinically significant impaired renal or hepatic function.&#xD;
&#xD;
         18. Any major surgical procedure within one month of trial entry.&#xD;
&#xD;
         19. Presence of active gastrointestinal (GI) disease or other condition that will&#xD;
             interfere significantly with the absorption, distribution, metabolism, or excretion of&#xD;
             X-82.&#xD;
&#xD;
         20. Receiving treatment with anti-coagulants other than 325 mg of aspirin per day.&#xD;
&#xD;
         21. Serious active infection, other serious medical condition or any other condition that&#xD;
             would impair the ability of the subject to administer the investigational drug or to&#xD;
             adhere to the study protocol requirements.&#xD;
&#xD;
         22. Presence of any condition which, in the judgment of the investigator, would prevent&#xD;
             the subject from completing the study.&#xD;
&#xD;
         23. No herbal medications with the exception of bilberry are allowed within 7 days of&#xD;
             start of study drug.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Retina Vitreous Associates Medical Group</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New England Retina Associates</name>
      <address>
        <city>New London</city>
        <state>Connecticut</state>
        <zip>06320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elman Retina Group</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Research Institute of Texas</name>
      <address>
        <city>Abilene</city>
        <state>Texas</state>
        <zip>79606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Jackson TL, Boyer D, Brown DM, Chaudhry N, Elman M, Liang C, O'Shaughnessy D, Parsons EC, Patel S, Slakter JS, Rosenfeld PJ. Oral Tyrosine Kinase Inhibitor for Neovascular Age-Related Macular Degeneration: A Phase 1 Dose-Escalation Study. JAMA Ophthalmol. 2017 Jul 1;135(7):761-767. doi: 10.1001/jamaophthalmol.2017.1571.</citation>
    <PMID>28570723</PMID>
  </results_reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>August 23, 2012</study_first_submitted>
  <study_first_submitted_qc>August 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2012</study_first_posted>
  <results_first_submitted>May 24, 2018</results_first_submitted>
  <results_first_submitted_qc>May 24, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">June 27, 2018</results_first_posted>
  <last_update_submitted>July 31, 2018</last_update_submitted>
  <last_update_submitted_qc>July 31, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>VEGF</keyword>
  <keyword>PDGF</keyword>
  <keyword>AMD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Degeneration</mesh_term>
    <mesh_term>Wet Macular Degeneration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ranibizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects with wet age related macular degeneration were enrolled at 5 US retinal clinics between November 2012 and March 2015</recruitment_details>
      <pre_assignment_details>110 subjects were screened for entry into the study. 52 did not meet inclusion criteria, 19 declined to participate and 4 were excluded for other reasons</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>50 mg X82 Alternate Days</title>
          <description>Participants were assigned to 50 mg X-82 on alternate days for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.</description>
        </group>
        <group group_id="P2">
          <title>50 mg X82 QD</title>
          <description>Participants were assigned to 50 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.</description>
        </group>
        <group group_id="P3">
          <title>100 mg X82 on Alternate Days</title>
          <description>Participants were assigned to 100 mg X-82 on alternate days for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.</description>
        </group>
        <group group_id="P4">
          <title>100 mg X82 QD</title>
          <description>Participants were assigned to 100 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.</description>
        </group>
        <group group_id="P5">
          <title>200 mg X82 QD</title>
          <description>Participants were assigned to 200 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.</description>
        </group>
        <group group_id="P6">
          <title>300 mg X82 QD</title>
          <description>Participants were assigned to 300 mg X-82 QD for 24 weeks. After treatment discontinuation subjects were followed for an additional 4 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="7"/>
                <participants group_id="P6" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="9"/>
                <participants group_id="P5" count="5"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Dose Escalation of X-82 and Ranibizumab Rescue</title>
          <description>Groups of participants were assigned to 1 of 6 X-82 doses over 24weeks,with an additional 4 weeks for follow-up. The dose escalated from one level to the next in the absence of any dose-limiting toxicity (DLT) defined as a drug-related safety event during the first 2 weeks of treatment that was severe enough to require removal of the participant from the study.&#xD;
The escalating X82 oral dose regimens were 50 mg alternate days, 50 mg daily, 100 mg alternate days, 100mg daily, 200mg daily, and 300mg daily.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="35"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="76.8" spread="8.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Best corrected visual acuity</title>
          <units>Number of letters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.4" spread="12.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline Visual Acuity at 6 Months</title>
        <description>The best corrected visual acuity by the Early Treatment Diabetic Retinopathy Study (ETDRS) method was determined at baseline and at various times during the study. The ETDRS method records the number of letters of decreasing size on a chart that a subject can read from a defiend distance.&#xD;
During the study the ETDRS visual acuity was used to monitor the need for rescue therapy. The primary endpoint of the study was the change from baseline visual ETDRS visual acuity at 6 months. It was calculated by subtracting the baseline visual acuity from the visual acuity at 6 months for each individual subject. A positive change from baseline indicates improvement in visual acuity.</description>
        <time_frame>6 months</time_frame>
        <population>The mean and standard deviation was calculated for all subjects who completed 6 months of treatment with oral X82</population>
        <group_list>
          <group group_id="O1">
            <title>All Completers</title>
            <description>All subjects who successfully completed 6 months of treatment with oral X82</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Visual Acuity at 6 Months</title>
          <description>The best corrected visual acuity by the Early Treatment Diabetic Retinopathy Study (ETDRS) method was determined at baseline and at various times during the study. The ETDRS method records the number of letters of decreasing size on a chart that a subject can read from a defiend distance.&#xD;
During the study the ETDRS visual acuity was used to monitor the need for rescue therapy. The primary endpoint of the study was the change from baseline visual ETDRS visual acuity at 6 months. It was calculated by subtracting the baseline visual acuity from the visual acuity at 6 months for each individual subject. A positive change from baseline indicates improvement in visual acuity.</description>
          <population>The mean and standard deviation was calculated for all subjects who completed 6 months of treatment with oral X82</population>
          <units>number of letters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" spread="9.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were recorded for the duration of the study beginning at participant randomization and continuing till participant completion of the study. The participation of individual subjects in the study ranged from 1-7 months.</time_frame>
      <desc>Since the sample size for each dose group of X82 was limited, the frequency of adverse events are reported for all patients enrolled in the study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Dose Escalation of X-82 and Ranibizumab Rescue</title>
          <description>Groups of participants were assigned to 1 of 6 X-82 doses over 24 weeks,with an additional 4 weeks for follow-up. The dose escalated from one level to the next in the absence of any dose-limiting toxicity (DLT) defined as a drug-related safety event during the first 2 weeks of treatment that was severe enough to require removal of the participant from the study.&#xD;
The escalating X82 oral dose regimens were 50 mg alternate days, 50 mg daily, 100 mg alternate days, 100mg daily, 200mg daily, and 300mg daily.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedRA 17.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Congestive heart failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>multiple myeloma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedRA 17.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Gastrointestinal reflux</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>decrease body weight</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Alanine amino transferase elevation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Aspartate amino transferase elevation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>muscle spasma</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>arthritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Sr Vice President, Development</name_or_title>
      <organization>Tyrogenex, Inc</organization>
      <phone>240-403-7153</phone>
      <email>Dan@tyrogenex.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01674569
org study id: X82-OPH-102
nct id: NCT01674569
lead sponsor: 
has dmc: No
The objective of this study is to evaluate the safety and preliminary biologic
      activity/efficacy of X-82 in patients with wet Age-related Macular Degeneration (AMD).
      Preliminary efficacy will be assessed by change from baseline in visual acuity, fluorescein
      leakage, retinal thickness and fibrosis, if detectable, based on fundus examination, fundus
      photography, fluorescein angiography and optical coherence tomography (OCT).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline Visual Acuity at 6 Months
time frame: 6 months
description: The best corrected visual acuity by the Early Treatment Diabetic Retinopathy Study (ETDRS) method was determined at baseline and at various times during the study. The ETDRS method records the number of letters of decreasing size on a chart that a subject can read from a defiend distance.
During the study the ETDRS visual acuity was used to monitor the need for rescue therapy. The primary endpoint of the study was the change from baseline visual ETDRS visual acuity at 6 months. It was calculated by subtracting the baseline visual acuity from the visual acuity at 6 months for each individual subject. A positive change from baseline indicates improvement in visual acuity.
arm group label: 50 mg X-82 oral alternate days
arm group type: Experimental
description: 50 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity develops
arm group label: 50 mg X-82 oral QD
arm group type: Experimental
description: 50 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria.for 24 weeks or until unacceptable toxicity develops
arm group label: 100 mg X-82 oral alternate days
arm group type: Experimental
description: 100 mg X-82 oral on alternate days with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria.for 24 weeks or until unacceptable toxicty develops
arm group label: 100 mg X-82 oral QD
arm group type: Experimental
description: 100 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs
arm group label: 200 mg X-82 oral QD
arm group type: Experimental
description: 200 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs
arm group label: 300 mg X-82 oral QD
arm group type: Experimental
description: 300 mg X-82 oral QD with intravitreous ranibizumab (Lucentis) therapy using predefined retreatment criteria for 24 weeks or until unacceptable toxicity occurs.
intervention type: Drug
intervention name: X-82 oral
description: X-82 oral for 24 weeks or until unacceptable toxicity develops
arm group label: 100 mg X-82 oral QD
arm group label: 100 mg X-82 oral alternate days
arm group label: 200 mg X-82 oral QD
arm group label: 300 mg X-82 oral QD
arm group label: 50 mg X-82 oral QD
arm group label: 50 mg X-82 oral alternate days
intervention type: Drug
intervention name: ranibizumab (Lucentis)
description: Rescue treatment with intravitreal ranibizumab (Lucentis) as needed
arm group label: 100 mg X-82 oral QD
arm group label: 100 mg X-82 oral alternate days
arm group label: 200 mg X-82 oral QD
arm group label: 300 mg X-82 oral QD
arm group label: 50 mg X-82 oral QD
arm group label: 50 mg X-82 oral alternate days
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Jackson TL, Boyer D, Brown DM, Chaudhry N, Elman M, Liang C, O'Shaughnessy D, Parsons EC, Patel S, Slakter JS, Rosenfeld PJ. Oral Tyrosine Kinase Inhibitor for Neovascular Age-Related Macular Degeneration: A Phase 1 Dose-Escalation Study. JAMA Ophthalmol. 2017 Jul 1;135(7):761-767. doi: 10.1001/jamaophthalmol.2017.1571.
PMID: 28570723
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Wet Macular Degeneration
mesh term: Ranibizumab
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 