<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/NCT02239562</url>
  </required_header>
  <id_info>
    <org_study_id>20140114</org_study_id>
    <secondary_id>119219</secondary_id>
    <nct_id>NCT02239562</nct_id>
  </id_info>
  <brief_title>sPIF CLINICAL STUDY PROTOCOL IN AUTOIMMUNE HEPATITIS</brief_title>
  <official_title>A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of Synthetic PreImplantation Factor (sPIF) in Autoimmune Hepatitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Christopher O'Brien, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>BioIncept LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Miami</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to study the safety and tolerability of synthetic&#xD;
      PreImplantation Factor (sPIF) in female patients with autoimmune hepatitis. Autoimmune&#xD;
      hepatitis is a disease where the patient's immune system produces an inappropriate immune&#xD;
      response against their own liver. PreImplantation Factor is a substance that is secreted by&#xD;
      viable fetuses during pregnancy. PIF apparently initiates both maternal tolerance preventing&#xD;
      the loss/rejection of the fetus. Synthetic PIF (sPIF) successfully translates PIF endogenous&#xD;
      properties to pregnant and non-pregnant immune disorders. sPIF was found to be effective in&#xD;
      preclinical models of autoimmunity and transplantation (published). Specifically sPIF&#xD;
      protected the liver against immune attack. Toxicity studies (mice, dogs) have shown that&#xD;
      high-dose sPIF administration for 2 weeks followed by 2 weeks observation period demonstrated&#xD;
      a high safety profile. This study will evaluate the safety, tolerability and the blood level&#xD;
      of this synthetic version of this natural compound in the circulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Both sPIF as well as natural PIF appears to orchestrate a complex series of cytokine effects&#xD;
      that overall appear to cause return of proper immune function and regulation rather than a&#xD;
      nonspecific immune suppression. PIF acts on both the innate and adaptive arms of the immune&#xD;
      system in a dynamic, diverse and synergetic manner &quot;per need&quot;. In the pregnancy setting, PIF&#xD;
      maintains basal immunity required for embryo and maternal survival, and aids in tolerance for&#xD;
      self by blocking activated T cells proliferation that would otherwise harm the embryo. The&#xD;
      activity of PIF appears to have a dual complementary mode of action that is dependent on&#xD;
      whether the immune system is in the basal or the stimulated immune state. The sPIF&#xD;
      concentrations that were used are in the same range as those that are present in maternal&#xD;
      circulation of viable pregnancy. sPIF targets three major intracellular proteins that pivotal&#xD;
      in autoimmune control.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 14, 2014</start_date>
  <completion_date type="Actual">December 29, 2016</completion_date>
  <primary_completion_date type="Actual">April 25, 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety/Tolerability Measured by Clinical Laboratory Tests, Metabolics, Cytokines, Anti-PIF Antibody, Periodic Physical Examination, Including Vital Signs Measurements and 12-lead ECG</measure>
    <time_frame>29 Day</time_frame>
    <description>Single Ascending Dose (SAD):&#xD;
Adverse events, concomitant medications: Days 1, 2, 3, 5, 8 Vital signs, Physical exams: Days 1, 2, 8 Complete blood counts (CBC), Serum chemistry, Liver function tests, Pharmacokinetics: Days 1, 2, 8 Lipids, Coagulation, Urinalysis, Pregnancy test: Days 1, 8 EKG, chest x-ray (CXR): Days 1 and 8&#xD;
Multiple Ascending Dose (MAD):&#xD;
Adverse events, concomitant medications: Days 1, 2, 3, 4, 5, 8, 15, 29 Vital signs, Physical exams: Days 1, 2, 3, 4, 5, 8, 15, 29 CBC, Serum chemistry, Liver function tests, Pharmacokinetics: Days 1, 3, 5, 8, 15, 29 Lipids, Coagulation, Urinalysis, Pregnancy test, EKG: Days 1, 5, 29 CXR: Days 1, 29</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-sPIF Antibodies and Drug Interactions</measure>
    <time_frame>29 Day</time_frame>
    <description>Following sPIF administration, using a validated assay, serum samples were tested for anti-sPIF antibodies</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Autoimmune Hepatitis</condition>
  <arm_group>
    <arm_group_label>SAD sPIF 0.1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single ascending dose (SAD) 3 patients with normal liver function tests (LFTs) and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single subcutaneous (SQ) dose 0.1 mg/kg sPIF or Placebo Day 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAD sPIF 0.5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: single SQ dose 0.5 mg/kg sPIF or Placebo Day 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAD sPIF 1.0</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Cohort 3: single SQ dose 1.0 mg/kg sPIF or Placebo Day 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MAD sPIF 0.1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ (one time) 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.1 mg/kg sPIF or Placebo Days 1-5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MAD sPIF 0.5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.5 mg/kg sPIF or Placebo Days 1-5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MAD sPIF 1.0</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 1.0 mg/kg sPIF or Placebo Days 1-5</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sPIF</intervention_name>
    <arm_group_label>MAD sPIF 0.1</arm_group_label>
    <arm_group_label>MAD sPIF 0.5</arm_group_label>
    <arm_group_label>MAD sPIF 1.0</arm_group_label>
    <arm_group_label>SAD sPIF 0.1</arm_group_label>
    <arm_group_label>SAD sPIF 0.5</arm_group_label>
    <arm_group_label>SAD sPIF 1.0</arm_group_label>
    <other_name>synthetic PreImplantation Factor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>MAD sPIF 0.1</arm_group_label>
    <arm_group_label>MAD sPIF 0.5</arm_group_label>
    <arm_group_label>MAD sPIF 1.0</arm_group_label>
    <arm_group_label>SAD sPIF 0.1</arm_group_label>
    <arm_group_label>SAD sPIF 0.5</arm_group_label>
    <arm_group_label>SAD sPIF 1.0</arm_group_label>
    <other_name>Ringer's lactated solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female, aged from 18 to 70 years old, of non-child bearing potential (to avoid the&#xD;
             possibility if antibodies are formed to sPIF this could put the patient at risk for&#xD;
             future fertility)&#xD;
&#xD;
          -  Females must be either&#xD;
&#xD;
               -  Postmenopausal for greater than two years,&#xD;
&#xD;
               -  Postmenopausal for less than two years with an follicle stimulating hormone (FSH)&#xD;
                  level greater &gt; 40 million international units per milliliter (mIU/mL )&#xD;
&#xD;
               -  Or documented as surgically sterile (bilateral tubal ligation, bilateral&#xD;
                  oophorectomy or post-hysterectomy) at least three months prior to the screening&#xD;
                  evaluation&#xD;
&#xD;
          -  Autoimmune hepatitis as documented by a:&#xD;
&#xD;
               -  Pretreatment score ≥15&#xD;
&#xD;
               -  Or a post-treatment score of ≥17 on the International Criteria for the Diagnosis&#xD;
                  of Autoimmune Hepatitis (Appendix 2)&#xD;
&#xD;
          -  Treatment with prednisone and/or other oral, immunosuppressive drug(s) must have been&#xD;
             stabilized for at least 6 weeks prior to screening for this study.&#xD;
&#xD;
          -  Stable ALT levels with a fixed dose of their immunosuppressant medications&#xD;
&#xD;
          -  Subjects do not have to have had a documented relapse after completion of an initial&#xD;
             course of therapy&#xD;
&#xD;
          -  Permitted concomitant immunosuppressant medications will include&#xD;
&#xD;
               -  Azathioprine dose equal to/or less 100 mg per day,&#xD;
&#xD;
               -  Budesonide dose equal to/or less 9 mg per day,&#xD;
&#xD;
               -  Mycophenolate mofetil equal to/or less 3000 mg per day,&#xD;
&#xD;
               -  Prednisone equal to/or less than 10 mg per day&#xD;
&#xD;
               -  Ursodeoxycholic acid equal to/or less than 1000 mg per day&#xD;
&#xD;
          -  In the judgment of the Investigator, be in reasonable general health, based on review&#xD;
             of the results of a screening evaluation (to include physical examination, measurement&#xD;
             of vital signs, 12-lead ECG trace and the collection of blood and urine for routine&#xD;
             clinical laboratory testing), performed no more than 30 days prior to Day 1 of study.&#xD;
&#xD;
          -  Patients must agree to abstain from alcohol use during their participation in the&#xD;
             study protocol.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) levels of no more than five times the upper limit of&#xD;
             normal (reference) range (ULN) at the screening evaluation.&#xD;
&#xD;
          -  Normal renal function as determined by a serum creatinine&#xD;
&#xD;
          -  A female of childbearing potential who is documented as either surgically sterile&#xD;
             (bilateral tubal ligation, bilateral oophorectomy or post-hysterectomy at least 3&#xD;
             months prior to the screening evaluation) or post-menopausal for ≥ 2 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any other forms of chronic liver disease.&#xD;
&#xD;
          -  Decompensated liver disease defined on the basis of any one of the following&#xD;
             laboratory parameters at the screening evaluation: total bilirubin &gt; 1.5 × ULN,&#xD;
             prothrombin time &gt; 1.2 × ULN, platelets ≤ 100,000/mm3, or albumin &lt; 3 g/dL OR current&#xD;
             or prior history of clinical hepatic decompensation (e.g., ascites, jaundice,&#xD;
             encephalopathy or variceal hemorrhage).&#xD;
&#xD;
          -  Hemoglobin &lt; 11 g/dL at the screening evaluation.&#xD;
&#xD;
          -  Serological evidence of infection with HIV upon review of the medical record.&#xD;
&#xD;
          -  Evidence of hepatocellular carcinoma (i.e., screening α-fetoprotein &gt; 50 ng/mL or&#xD;
             other standard of care measure).&#xD;
&#xD;
          -  Subjects with, or a history of clinically significant oncologic, pulmonary, hepatic,&#xD;
             gastrointestinal, renal, other cardiovascular, hematologic, metabolic, endocrine,&#xD;
             neurologic, immunologic or hematologic illness or any other major medical disorder&#xD;
             that, in the judgment of the Investigator, would interfere with subject treatment,&#xD;
             assessment or compliance with the protocol or should otherwise preclude their&#xD;
             participation in this trial.&#xD;
&#xD;
          -  Have received therapy with potentially hepatotoxic drugs within 3 months (90 days)&#xD;
             prior to Day 1 or are expected to receive such therapy during the study.&#xD;
&#xD;
          -  Patient who are expected to receive a change in their immunosuppressant therapies&#xD;
             during the protocol.&#xD;
&#xD;
          -  Patients who may receive chemotherapeutic agents (e.g., corticosteroids,&#xD;
             immunoglobulins and other immune- or cytokine-based therapies) during the study for&#xD;
             any other medical condition.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher B. O'Brien, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Liver Diseases; University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chief Scientist, BIOINCEPT, LLC / Chairman, (SIEP) / Director, Ob&amp;Gyn CAMcare Health Center</name>
      <address>
        <city>Cherry Hill</city>
        <state>New Jersey</state>
        <zip>08003-3157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 10, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <results_first_submitted>January 16, 2018</results_first_submitted>
  <results_first_submitted_qc>October 30, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 20, 2019</results_first_posted>
  <last_update_submitted>October 30, 2019</last_update_submitted>
  <last_update_submitted_qc>October 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>Christopher O'Brien, MD</investigator_full_name>
    <investigator_title>Professor of Clinical Medicine</investigator_title>
  </responsible_party>
  <keyword>sPIF</keyword>
  <keyword>synthetic PreImplantation Factor</keyword>
  <keyword>Autoimmune</keyword>
  <keyword>Liver</keyword>
  <keyword>Hepatitis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Autoimmune</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no plan to share with other researchers.</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>sPIF (0.1, 0.5, or 1.0 mg/kg) given single SQ for 5 consecutive days. In SAD, n=18 randomized in a 2:1 sPIF/placebo ratio. 9 patients normal liver function and 9 abnormal liver function. In MAD, n=18 randomized in a 2:1 sPIF/placebo ratio. 9 patients normal liver function and 9 abnormal liver function. N=36 completed the study. total screened 36</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>SAD sPIF 0.1</title>
          <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 0.1 mg/kg sPIF or Placebo Day 1</description>
        </group>
        <group group_id="P2">
          <title>SAD sPIF 0.5</title>
          <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 0.1 mg/kg sPIF or Placebo Day 1</description>
        </group>
        <group group_id="P3">
          <title>SAD sPIF 1.0</title>
          <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 0.1 mg/kg sPIF or Placebo Day 1</description>
        </group>
        <group group_id="P4">
          <title>MAD sPIF 0.1</title>
          <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.1 mg/kg sPIF or Placebo Days 1-5</description>
        </group>
        <group group_id="P5">
          <title>MAD sPIF 0.5</title>
          <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.1 mg/kg sPIF or Placebo Days 1-5</description>
        </group>
        <group group_id="P6">
          <title>MAD sPIF 1.0</title>
          <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.1 mg/kg sPIF or Placebo Days 1-5</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Females only</population>
      <group_list>
        <group group_id="B1">
          <title>SAD sPIF 0.1</title>
          <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 0.1 mg/kg sPIF or Placebo Day 1</description>
        </group>
        <group group_id="B2">
          <title>SAD sPIF 0.5</title>
          <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 0.5 mg/kg sPIF or Placebo Day 1</description>
        </group>
        <group group_id="B3">
          <title>SAD sPIF 1.0</title>
          <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 1.0 mg/kg sPIF or Placebo Day 1</description>
        </group>
        <group group_id="B4">
          <title>MAD sPIF 0.1</title>
          <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug : placebo) to multiple 0.1 mg/kg sPIF doses of sPIF administered subcutaneously once a day for 5 consecutive days (Days 1 to 5)</description>
        </group>
        <group group_id="B5">
          <title>MAD sPIF 0.5</title>
          <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug : placebo) to multiple 0.5 mg/kg sPIF doses of sPIF administered subcutaneously once a day for 5 consecutive days (Days 1 to 5)</description>
        </group>
        <group group_id="B6">
          <title>MAD sPIF 1.0</title>
          <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug : placebo) to multiple 1.0 mg/kg sPIF doses of sPIF administered subcutaneously once a day for 5 consecutive days (Days 1 to 5)</description>
        </group>
        <group group_id="B7">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="6"/>
            <count group_id="B6" value="6"/>
            <count group_id="B7" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="63" spread="10"/>
                    <measurement group_id="B2" value="59" spread="8"/>
                    <measurement group_id="B3" value="59" spread="9"/>
                    <measurement group_id="B4" value="56.75" spread="13.40"/>
                    <measurement group_id="B5" value="58.75" spread="9.43"/>
                    <measurement group_id="B6" value="58.5" spread="7.33"/>
                    <measurement group_id="B7" value="59.25" spread="9.063"/>
                  </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="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" 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="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Safety/Tolerability Measured by Clinical Laboratory Tests, Metabolics, Cytokines, Anti-PIF Antibody, Periodic Physical Examination, Including Vital Signs Measurements and 12-lead ECG</title>
        <description>Single Ascending Dose (SAD):&#xD;
Adverse events, concomitant medications: Days 1, 2, 3, 5, 8 Vital signs, Physical exams: Days 1, 2, 8 Complete blood counts (CBC), Serum chemistry, Liver function tests, Pharmacokinetics: Days 1, 2, 8 Lipids, Coagulation, Urinalysis, Pregnancy test: Days 1, 8 EKG, chest x-ray (CXR): Days 1 and 8&#xD;
Multiple Ascending Dose (MAD):&#xD;
Adverse events, concomitant medications: Days 1, 2, 3, 4, 5, 8, 15, 29 Vital signs, Physical exams: Days 1, 2, 3, 4, 5, 8, 15, 29 CBC, Serum chemistry, Liver function tests, Pharmacokinetics: Days 1, 3, 5, 8, 15, 29 Lipids, Coagulation, Urinalysis, Pregnancy test, EKG: Days 1, 5, 29 CXR: Days 1, 29</description>
        <time_frame>29 Day</time_frame>
        <population>All patients participating in each arm were assessed for adverse events by symptoms, physical examination and laboratory studies.</population>
        <group_list>
          <group group_id="O1">
            <title>SAD sPIF 0.1</title>
            <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 0.1 mg/kg sPIF or Placebo Day 1</description>
          </group>
          <group group_id="O2">
            <title>SAD sPIF 0.5</title>
            <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 0.5 mg/kg sPIF or Placebo Day 1</description>
          </group>
          <group group_id="O3">
            <title>SAD sPIF 1.0</title>
            <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 1.0 mg/kg sPIF or Placebo Day 1</description>
          </group>
          <group group_id="O4">
            <title>MAD sPIF 0.1</title>
            <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.1 mg/kg sPIF or Placebo Days 1-5</description>
          </group>
          <group group_id="O5">
            <title>MAD sPIF 0.5</title>
            <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.5 mg/kg sPIF or Placebo Days 1-5</description>
          </group>
          <group group_id="O6">
            <title>MAD sPIF 1.0</title>
            <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 1.0 mg/kg sPIF or Placebo Days 1-5</description>
          </group>
        </group_list>
        <measure>
          <title>Safety/Tolerability Measured by Clinical Laboratory Tests, Metabolics, Cytokines, Anti-PIF Antibody, Periodic Physical Examination, Including Vital Signs Measurements and 12-lead ECG</title>
          <description>Single Ascending Dose (SAD):&#xD;
Adverse events, concomitant medications: Days 1, 2, 3, 5, 8 Vital signs, Physical exams: Days 1, 2, 8 Complete blood counts (CBC), Serum chemistry, Liver function tests, Pharmacokinetics: Days 1, 2, 8 Lipids, Coagulation, Urinalysis, Pregnancy test: Days 1, 8 EKG, chest x-ray (CXR): Days 1 and 8&#xD;
Multiple Ascending Dose (MAD):&#xD;
Adverse events, concomitant medications: Days 1, 2, 3, 4, 5, 8, 15, 29 Vital signs, Physical exams: Days 1, 2, 3, 4, 5, 8, 15, 29 CBC, Serum chemistry, Liver function tests, Pharmacokinetics: Days 1, 3, 5, 8, 15, 29 Lipids, Coagulation, Urinalysis, Pregnancy test, EKG: Days 1, 5, 29 CXR: Days 1, 29</description>
          <population>All patients participating in each arm were assessed for adverse events by symptoms, physical examination and laboratory studies.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Liver Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skeletal Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Muscular Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nervous Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Endocrine Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cardiovascular Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Digestive Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urinary Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Reproductive Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Liver Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Skeletal Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Muscular Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Nervous Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Endocrine Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Cardiovascular Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Blood Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Skin Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Digestive Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Urinary Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Respiratory Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PE Reproductive Grade 2,3, or 4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Liver Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Skeletal Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Muscular Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Nervous Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Endocrine Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Cardiovascular Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Blood Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Skin Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Digestive Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Urinary Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Respiratory Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lab: Reproductive Grade 2,3,4 Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Anti-sPIF Antibodies and Drug Interactions</title>
        <description>Following sPIF administration, using a validated assay, serum samples were tested for anti-sPIF antibodies</description>
        <time_frame>29 Day</time_frame>
        <group_list>
          <group group_id="O1">
            <title>SAD sPIF 0.1</title>
            <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 0.1 mg/kg sPIF or Placebo Day 1</description>
          </group>
          <group group_id="O2">
            <title>SAD sPIF 0.5</title>
            <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 0.5 mg/kg sPIF or Placebo Day 1</description>
          </group>
          <group group_id="O3">
            <title>SAD sPIF 1.0</title>
            <description>single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single SQ dose 1.0 mg/kg sPIF or Placebo Day 1</description>
          </group>
          <group group_id="O4">
            <title>MAD sPIF 0.1</title>
            <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.1 mg/kg sPIF or Placebo Days 1-5</description>
          </group>
          <group group_id="O5">
            <title>MAD sPIF 0.5</title>
            <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.5 mg/kg sPIF or Placebo Days 1-5</description>
          </group>
          <group group_id="O6">
            <title>MAD sPIF 1.0</title>
            <description>multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 1.0 mg/kg sPIF or Placebo Days 1-5</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Anti-sPIF Antibodies and Drug Interactions</title>
          <description>Following sPIF administration, using a validated assay, serum samples were tested for anti-sPIF antibodies</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of Patients with anti-sPIF Antibody</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Patients with Drug to Drug Interactions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected in the single ascending dose (SAD) until Day 8. Adverse events were collected in the multiple ascending dose (MAD) until Day 29. The total time period for the adverse event data collection was 26 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Single Ascending Dose Placebo</title>
          <description>Single dose of placebo administered subcutaneously (Day 1)</description>
        </group>
        <group group_id="E2">
          <title>Single Ascending Dose 0.1</title>
          <description>Single dose 0.1 mg/kg sPIF administered subcutaneously (Day 1)</description>
        </group>
        <group group_id="E3">
          <title>Single Ascending Dose 0.5</title>
          <description>Single dose 0.5 mg/kg sPIF administered subcutaneously (Day 1)</description>
        </group>
        <group group_id="E4">
          <title>Single Ascending Dose 1.0</title>
          <description>Single dose 1.0 mg/kg sPIF administered subcutaneously (Day 1)</description>
        </group>
        <group group_id="E5">
          <title>Multiple Ascending Placebo</title>
          <description>Placebo administered subcutaneously once a day for 5 consecutive days (Days 1 to 5)</description>
        </group>
        <group group_id="E6">
          <title>Multiple Ascending Dose 0.1</title>
          <description>0.1 mg/kg sPIF administered subcutaneously once a day for 5 consecutive days (Days 1 to 5)</description>
        </group>
        <group group_id="E7">
          <title>Multiple Ascending Dose 0.5</title>
          <description>0.5 mg/kg sPIF administered subcutaneously once a day for 5 consecutive days (Days 1 to 5)</description>
        </group>
        <group group_id="E8">
          <title>Multiple Ascending Dose 1.0</title>
          <description>1.0 mg/kg sPIF administered subcutaneously once a day for 5 consecutive days (Days 1 to 5)</description>
        </group>
      </group_list>
      <serious_events>
        <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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (10.0)</default_vocab>
        <default_assessment>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="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>liver fullness (bloating)</sub_title>
                <description>liver fullness</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>transient skin irritation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <description>transient headache</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to the small number of subjects, formal statistical analysis was not performed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Christopher O'Brien</name_or_title>
      <organization>University of Miami</organization>
      <phone>305-243-2329</phone>
      <email>CObrien@med.miami.edu</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/NCT02239562
org study id: 20140114
secondary id: 119219
nct id: NCT02239562
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to study the safety and tolerability of synthetic
      PreImplantation Factor (sPIF) in female patients with autoimmune hepatitis. Autoimmune
      hepatitis is a disease where the patient's immune system produces an inappropriate immune
      response against their own liver. PreImplantation Factor is a substance that is secreted by
      viable fetuses during pregnancy. PIF apparently initiates both maternal tolerance preventing
      the loss/rejection of the fetus. Synthetic PIF (sPIF) successfully translates PIF endogenous
      properties to pregnant and non-pregnant immune disorders. sPIF was found to be effective in
      preclinical models of autoimmunity and transplantation (published). Specifically sPIF
      protected the liver against immune attack. Toxicity studies (mice, dogs) have shown that
      high-dose sPIF administration for 2 weeks followed by 2 weeks observation period demonstrated
      a high safety profile. This study will evaluate the safety, tolerability and the blood level
      of this synthetic version of this natural compound in the circulation.
Both sPIF as well as natural PIF appears to orchestrate a complex series of cytokine effects
      that overall appear to cause return of proper immune function and regulation rather than a
      nonspecific immune suppression. PIF acts on both the innate and adaptive arms of the immune
      system in a dynamic, diverse and synergetic manner "per need". In the pregnancy setting, PIF
      maintains basal immunity required for embryo and maternal survival, and aids in tolerance for
      self by blocking activated T cells proliferation that would otherwise harm the embryo. The
      activity of PIF appears to have a dual complementary mode of action that is dependent on
      whether the immune system is in the basal or the stimulated immune state. The sPIF
      concentrations that were used are in the same range as those that are present in maternal
      circulation of viable pregnancy. sPIF targets three major intracellular proteins that pivotal
      in autoimmune control.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety/Tolerability Measured by Clinical Laboratory Tests, Metabolics, Cytokines, Anti-PIF Antibody, Periodic Physical Examination, Including Vital Signs Measurements and 12-lead ECG
time frame: 29 Day
description: Single Ascending Dose (SAD):
Adverse events, concomitant medications: Days 1, 2, 3, 5, 8 Vital signs, Physical exams: Days 1, 2, 8 Complete blood counts (CBC), Serum chemistry, Liver function tests, Pharmacokinetics: Days 1, 2, 8 Lipids, Coagulation, Urinalysis, Pregnancy test: Days 1, 8 EKG, chest x-ray (CXR): Days 1 and 8
Multiple Ascending Dose (MAD):
Adverse events, concomitant medications: Days 1, 2, 3, 4, 5, 8, 15, 29 Vital signs, Physical exams: Days 1, 2, 3, 4, 5, 8, 15, 29 CBC, Serum chemistry, Liver function tests, Pharmacokinetics: Days 1, 3, 5, 8, 15, 29 Lipids, Coagulation, Urinalysis, Pregnancy test, EKG: Days 1, 5, 29 CXR: Days 1, 29
measure: Number of Participants With Anti-sPIF Antibodies and Drug Interactions
time frame: 29 Day
description: Following sPIF administration, using a validated assay, serum samples were tested for anti-sPIF antibodies
arm group label: SAD sPIF 0.1
arm group type: Experimental
description: single ascending dose (SAD) 3 patients with normal liver function tests (LFTs) and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single subcutaneous (SQ) dose 0.1 mg/kg sPIF or Placebo Day 1
arm group label: SAD sPIF 0.5
arm group type: Experimental
description: single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: single SQ dose 0.5 mg/kg sPIF or Placebo Day 1
arm group label: SAD sPIF 1.0
arm group type: Experimental
description: single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Cohort 3: single SQ dose 1.0 mg/kg sPIF or Placebo Day 1
arm group label: MAD sPIF 0.1
arm group type: Experimental
description: multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ (one time) 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.1 mg/kg sPIF or Placebo Days 1-5
arm group label: MAD sPIF 0.5
arm group type: Experimental
description: multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.5 mg/kg sPIF or Placebo Days 1-5
arm group label: MAD sPIF 1.0
arm group type: Experimental
description: multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 1.0 mg/kg sPIF or Placebo Days 1-5
intervention type: Drug
intervention name: sPIF
arm group label: MAD sPIF 0.1
arm group label: MAD sPIF 0.5
arm group label: MAD sPIF 1.0
arm group label: SAD sPIF 0.1
arm group label: SAD sPIF 0.5
arm group label: SAD sPIF 1.0
other name: synthetic PreImplantation Factor
intervention type: Drug
intervention name: Placebo
arm group label: MAD sPIF 0.1
arm group label: MAD sPIF 0.5
arm group label: MAD sPIF 1.0
arm group label: SAD sPIF 0.1
arm group label: SAD sPIF 0.5
arm group label: SAD sPIF 1.0
other name: Ringer's lactated solution
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Christopher B. O'Brien, MD
role: Principal Investigator
affiliation: University of Miami
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Miami
investigator full name: Christopher O'Brien, MD
investigator title: Professor of Clinical Medicine
mesh term: Hepatitis A
mesh term: Hepatitis
mesh term: Hepatitis, Autoimmune
sharing ipd: No
ipd description: There is no plan to share with other researchers.
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to the small number of subjects, formal statistical analysis was not performed.
point of contact: 