<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/NCT02193360</url>
  </required_header>
  <id_info>
    <org_study_id>FFP104-001</org_study_id>
    <secondary_id>2014-001638-27</secondary_id>
    <nct_id>NCT02193360</nct_id>
  </id_info>
  <brief_title>Pilot Study of FFP104 Dose Escalation in PBC Subjects</brief_title>
  <official_title>A Phase I/II, Open Label, Multicenter, Pilot Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacodynamics of FFP104 in Subjects Previously Diagnosed With Primary Biliary Cirrhosis (PBC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fast Forward Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fast Forward Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the initial safety, tolerability and&#xD;
      pharmacodynamics of the CD40-antagonist Mab, FFP104, in subjects with PBC&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2015</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">August 2017</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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of FFP104 in PBC subjects following repeat doses of FFP104</measure>
    <time_frame>Days 1, 3, 5 and weeks 2 - 12, 14, 16 and 24</time_frame>
    <description>Safety outcomes include abbreviated physical examination, treatment emergent adverse events (TEAE), clinically significant changes in clinical haematology, clinical chemistry, and urinalysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with a 10% decrease in Alkaline Phosphatase (ALP) from baseline values</measure>
    <time_frame>Week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with a 25 and 40% decrease in ALP from baseline</measure>
    <time_frame>Weeks 4, 8 and 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with ALP&lt;1.67 from upper limit of normal (ULN), an ALP decrease &gt;15% and bilirubin within normal levels</measure>
    <time_frame>Weeks 4, 8, 12 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with a biochemical response according to 'Paris I' criteria: ALP≤ 3x ULN and Aspartate Transaminase (AST) ≤2x ULN and bilirubin ≤1mg/dL</measure>
    <time_frame>Weeks 4, 8, 12 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the individual and mean changes in serum liver biochemistry from baseline</measure>
    <time_frame>Weeks 2, 4, 8, 12, 16 and 24</time_frame>
    <description>Evaluation of individual and mean changes in lab values (serum ALP, AST, bilirubin, albumin and gamma glutamyl transpeptidase (GGT)) over time from baseline values</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate changes from baseline with Mayo Risk Score</measure>
    <time_frame>Weeks 4, 8, 12 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate changes from baseline in the Patient Report Outcome PBC-40 Quality of Life</measure>
    <time_frame>Weeks 12 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate changes from baseline in pruritus using the Visual Analog Scale (VAS)</measure>
    <time_frame>Weeks 12 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate changes from baseline in fatigue using the VAS</measure>
    <time_frame>Weeks 12 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate changes in serum FFP104 levels from baseline</measure>
    <time_frame>over time</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Primary Biliary Cirrhosis</condition>
  <arm_group>
    <arm_group_label>Single arm Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FFP104</intervention_name>
    <description>Cohorts receiving multiple weekly or biweekly i.v. doses of FFP104. FFP104 dose levels: 1.0, 2.5 and 5.0 mg/kg. Subjects will be treated for 12 weeks and then followed for safety and efficacy assessments for an additional 12 weeks.</description>
    <arm_group_label>Single arm Dose Escalation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female Age between 18 and 75 years of age inclusive at the time of signing the&#xD;
             informed consent&#xD;
&#xD;
          -  Established diagnosis of PBC according to the EASL criteria (European Association for&#xD;
             the Study of the Liver 2009): A diagnosis of PBC can be made with confidence in adult&#xD;
             patients with otherwise unexplained elevation of ALP and presence of&#xD;
             anti-mitochondrial antibody (AMA≥1:40), and/or AMA type M2. A liver biopsy is not&#xD;
             essential for the diagnosis of PBC in these patients, but allows activity and stage of&#xD;
             the disease to be assessed.&#xD;
&#xD;
          -  Having a screening ALP serum level between 1.67 and 5x ULN inclusive.&#xD;
&#xD;
          -  Be on a stable dose of ursodeoxycholic acid (UDCA) 12-20 mg/kg/day for at least 3&#xD;
             months prior to Screening or intolerant of UDCA in the opinion of the investigator (no&#xD;
             UDCA for at least 8 weeks prior to Screening).&#xD;
&#xD;
          -  Are not pregnant or breast feeding and do not plan to become pregnant or father a&#xD;
             child during the study. Female subjects (of childbearing potential) must be willing to&#xD;
             use two medically accepted forms of contraception throughout the study and must be&#xD;
             willing to submit to pregnancy test(s). Male subjects must agree to use medically&#xD;
             accepted contraception methods with their partners throughout the study as described&#xD;
             above, unless they have had a prior vasectomy.&#xD;
&#xD;
          -  Has the ability to communicate adequately with the study staff and to comply with the&#xD;
             requirements of the entire study, with the help of a caregiver, if applicable.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Laboratory screening results&#xD;
&#xD;
               -  alanine transaminase (ALT) &gt;5x ULN&#xD;
&#xD;
               -  aspartate transaminase (AST) &gt;5x ULN&#xD;
&#xD;
               -  Total bilirubin &gt;2x ULN. Isolated bilirubin &gt;2x ULN is acceptable if bilirubin is&#xD;
                  fractionated and direct bilirubin &lt;35%&#xD;
&#xD;
               -  Total white blood cells (WBC) &lt;3000 cells/mm3&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &lt;1500 cells/mm3&#xD;
&#xD;
               -  Platelet count &lt;100,000/mm3&#xD;
&#xD;
               -  Prothrombin time (international normalized ratio (INR)&gt; 1.2&#xD;
&#xD;
          -  Body mass index (BMI) ≥35 or suspected to have relevant nonalcoholic fatty liver&#xD;
             disease (NAFLD) as based on the judgment of the Investigator at screening&#xD;
&#xD;
          -  Subject has a history of, or current viral hepatitis B or C (including hepatitis B&#xD;
             surface antigen [HBsAg], hepatitis B core antibody and hepatitis C virus (HCV)&#xD;
             antibody [anti-HCV] positivity), or a positive HIV antibody screen at time of&#xD;
             screening&#xD;
&#xD;
          -  Recipients of liver or other organ transplantation or anticipated need for orthotropic&#xD;
             organ transplantation in one year as determined by the Mayo Risk Score&#xD;
&#xD;
          -  Co-existing liver or biliary diseases, such as primary sclerosing cholangitis,&#xD;
             choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver&#xD;
             disease, nonalcoholic steatohepatitis (NASH), acute infection of bile duct system or&#xD;
             gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension),&#xD;
             cholangiocarcinoma diagnosed or suspected liver cancers&#xD;
&#xD;
          -  Recurrent variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class B/C,&#xD;
             Esophageal Varices, or refractory ascites within the previous 6 months of Screening&#xD;
             (defined as date informed consent signed)&#xD;
&#xD;
          -  Have a family history (more than one first degree relative) of multiple thrombotic&#xD;
             events or a personal history of any venous or arterial thrombotic event including deep&#xD;
             vein thrombosis, stroke, myocardial infarction, pulmonary embolus, or peripheral&#xD;
             arterial thromboembolic events&#xD;
&#xD;
          -  Prohibited medications 6 months prior to Screening: azathioprine, colchicine,&#xD;
             cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; fenofibrate or&#xD;
             other fibrates; budesonide and other systemic corticosteroids; potentially hepatotoxic&#xD;
             drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin)&#xD;
&#xD;
          -  Prohibited medications 12 months prior to Screening: antibodies or immunotherapy&#xD;
             directed against interleukins or other cytokines or chemokines&#xD;
&#xD;
          -  Subjects with recurrent bacterial infections (as judged by the Investigator) within 6&#xD;
             months prior to first dose of FFP104, active bacterial, fungal or mycobacterial&#xD;
             infections observed during screening, or any recent episode of infection requiring&#xD;
             hospitalizations or treatment with antibiotics (within the 3 months prior to first&#xD;
             dose)&#xD;
&#xD;
          -  History of malignancy, with the exception of resected basal cell carcinoma, squamous&#xD;
             cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ&#xD;
&#xD;
          -  Immunization with a live vaccine within 4 weeks of Screening with the exception of&#xD;
             influenza vaccine and no planned immunisations within the period of the study&#xD;
&#xD;
          -  Known clinically significant cardiac disease (e.g., myocardial infarction or stroke,&#xD;
             unstable angina, claudication, etc.), or evidence of a clinically significant&#xD;
             electrocardiogram (ECG) abnormality within the previous 12 months prior to Screening&#xD;
&#xD;
          -  Subjects with evidence of other serious, significant, acute or chronic medical or&#xD;
             psychiatric illness that, in the judgment of the Investigator, could compromise&#xD;
             subject safety, limit the subject's ability to complete the study, and/or compromise&#xD;
             the objectives of the study&#xD;
&#xD;
          -  History of recent (within 12 months of study) alcohol or drug abuse&#xD;
&#xD;
          -  Use of other immunosuppressive medications 4 weeks prior to Screening&#xD;
&#xD;
          -  Active tuberculosis (TB) in the past or currently suspected TB which is presently&#xD;
             receiving treatment or prophylactic therapy, has a positive TB test (as defined by&#xD;
             local biological requirements), or any significant abnormality on chest X-ray within 3&#xD;
             months prior to Screening&#xD;
&#xD;
          -  Subjects who have planned surgery during the study period or have undergone major&#xD;
             surgery within the 3 months prior to Screening&#xD;
&#xD;
          -  Known clinically significant allergy or known hypersensitivity to drugs that, in the&#xD;
             opinion of the Investigator, may affect the patient's safety&#xD;
&#xD;
          -  Known sensitivity to any component of the study drug or previous sensitivity reaction&#xD;
             or other clinically significant reaction to intravenous medications or biologic&#xD;
             therapy&#xD;
&#xD;
          -  Participated to another clinical trial within the past 30 days prior to Screening, or&#xD;
             is still within a washout period of a previous clinical trial or has previously&#xD;
             received FFP104 (PG102) or ch5D12 in this or any study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Amsterdam Medical Center</name>
      <address>
        <city>Amsterdam</city>
        <zip>1100 DD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Erasmus University Medical Center</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>H R van Buuren, MD</last_name>
      <email>mdlpoli@erasmusmc.nl</email>
    </contact>
    <investigator>
      <last_name>H R van Buuren, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Birmingham</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>G Hirschfield, MD</last_name>
      <email>G.Hirschfield@bham.ac.uk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Free Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>D Thorburn, MD</last_name>
      <email>douglas.thorburn@nhs.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Newcastle upon Tyne Hospitals</name>
      <address>
        <city>Newcastle upon Tyne</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>D Jones, MD</last_name>
      <phone>0191 213 7210</phone>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>July 11, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <last_update_submitted>August 23, 2016</last_update_submitted>
  <last_update_submitted_qc>August 23, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 24, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Inflammation</keyword>
  <keyword>PBC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Liver Cirrhosis, Biliary</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02193360
org study id: FFP104-001
secondary id: 2014-001638-27
nct id: NCT02193360
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine the initial safety, tolerability and
      pharmacodynamics of the CD40-antagonist Mab, FFP104, in subjects with PBC
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of FFP104 in PBC subjects following repeat doses of FFP104
time frame: Days 1, 3, 5 and weeks 2 - 12, 14, 16 and 24
description: Safety outcomes include abbreviated physical examination, treatment emergent adverse events (TEAE), clinically significant changes in clinical haematology, clinical chemistry, and urinalysis.
measure: Proportion of subjects with a 10% decrease in Alkaline Phosphatase (ALP) from baseline values
time frame: Week 12
measure: Proportion of subjects with a 25 and 40% decrease in ALP from baseline
time frame: Weeks 4, 8 and 12
measure: Proportion of subjects with ALP<1.67 from upper limit of normal (ULN), an ALP decrease >15% and bilirubin within normal levels
time frame: Weeks 4, 8, 12 and 24
measure: Proportion of subjects with a biochemical response according to 'Paris I' criteria: ALP≤ 3x ULN and Aspartate Transaminase (AST) ≤2x ULN and bilirubin ≤1mg/dL
time frame: Weeks 4, 8, 12 and 24
measure: To evaluate the individual and mean changes in serum liver biochemistry from baseline
time frame: Weeks 2, 4, 8, 12, 16 and 24
description: Evaluation of individual and mean changes in lab values (serum ALP, AST, bilirubin, albumin and gamma glutamyl transpeptidase (GGT)) over time from baseline values
measure: To evaluate changes from baseline with Mayo Risk Score
time frame: Weeks 4, 8, 12 and 24
measure: To evaluate changes from baseline in the Patient Report Outcome PBC-40 Quality of Life
time frame: Weeks 12 and 24
measure: To evaluate changes from baseline in pruritus using the Visual Analog Scale (VAS)
time frame: Weeks 12 and 24
measure: To evaluate changes from baseline in fatigue using the VAS
time frame: Weeks 12 and 24
measure: To evaluate changes in serum FFP104 levels from baseline
time frame: over time
arm group label: Single arm Dose Escalation
arm group type: Experimental
intervention type: Drug
intervention name: FFP104
description: Cohorts receiving multiple weekly or biweekly i.v. doses of FFP104. FFP104 dose levels: 1.0, 2.5 and 5.0 mg/kg. Subjects will be treated for 12 weeks and then followed for safety and efficacy assessments for an additional 12 weeks.
arm group label: Single arm Dose Escalation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Netherlands
country: United Kingdom
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Liver Cirrhosis, Biliary
mesh term: Fibrosis