<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/NCT03264989</url>
  </required_header>
  <id_info>
    <org_study_id>CSEG101A2202</org_study_id>
    <nct_id>NCT03264989</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics and Pharmacodynamics Study of SEG101 (Crizanlizumab) in Sickle Cell Disease (SCD) Patients With Vaso- Occlusive Crisis (VOC)</brief_title>
  <official_title>A Phase 2, Multicenter, Open-Label Study to Assess PK/PD of SEG101 (Crizanlizumab), With or Without Hydroxyurea/Hydroxycarbamide, in Sickle Cell Patients With Vaso-Occlusive Crisis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the CSEG101A2202 study was to characterize the PK and PD of&#xD;
      SEG101/crizanlizumab at 5 mg/kg and to evaluate the safety and efficacy of&#xD;
      SEG101/crizanlizumab in SCD patients.&#xD;
&#xD;
      Study CSEG101A2202 was designed as a Phase II, multicenter, open-label study. The first 45&#xD;
      patients (to identify 27 evaluable patients) were enrolled to the treatment group&#xD;
      crizanlizumab 5.0 mg/kg to complete full PK/PD sampling at week 1 and week 15. In all&#xD;
      patients, trough PK/PD samples was collected prior to each dose. In addition, throughout the&#xD;
      study (and when possible), all patients had blood drawn for serum to assess PK and PD drawn&#xD;
      at times of onset and resolution of each VOC event, fever, or infection. Once the up to 45&#xD;
      patients were enrolled, 12 additional patients were enrolled to the exploratory treatment&#xD;
      group and begin at 7.5 mg/kg of crizanlizumab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 19, 2017</start_date>
  <completion_date type="Anticipated">August 11, 2023</completion_date>
  <primary_completion_date type="Anticipated">August 11, 2023</primary_completion_date>
  <phase>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>To characterize PK (AUC) of crizanlizumab at 5.0 mg/kg in SCD patients.</measure>
    <time_frame>Week1 Day 1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; 72hr; Week2 Day 1; Week3 Day 1; Week15 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; 72hr; Week16 Day1; Week17 Day1; Week18 Day1; Week19 Day1</time_frame>
    <description>PK (AUC)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To characterize PK (Ctrough) of crizanlizumab at 5.0 mg/kg in SCD patients.</measure>
    <time_frame>Week 1 Day1; Week3 Day1; Week7 Day1; Week11 Day1; Week15 Day1; Week19 Day1; Week23 Day1; Week27 Day1; Week31 Day1; Week35 Day1; Week39 Day1; Week43 Day1; Week47 Day1; Week51 Day1, W75 Day1, W99 Day 1, W123 Day 1, W147 Day 1, W171 Day 1, Safety FU</time_frame>
    <description>PK (Ctrough)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To characterize PK (Cmax) of crizanlizumab at 5.0 mg/kg in SCD patients.</measure>
    <time_frame>Week1 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; Week15 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr</time_frame>
    <description>PK (Cmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacodynamics (PD): Percentage of P-selectin inhibition and PD-AUC inhibition of crizanlizumab at 5.0 mg/kg in SCD patients</measure>
    <time_frame>Week1 Day1 Pre-dose, 2hr, 24hr; 72hr; Week2 Day1; Week3 Day1; Week15 Day1 Pre-dose, 2hr, 24hr; 72hr; Week16 Day1; Week17 Day1; Week18 Day1; Week19 Day1</time_frame>
    <description>P-selectin inhibition percentage &amp; PD AUC inhibition after the starting dose, after multiple doses and prior to each study drug dose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of VOC events leading to healthcare visit in clinic/ER/hospital over time.</measure>
    <time_frame>Week 1 through end of treatment (approximately 24 months)</time_frame>
    <description>Assess efficacy of crizanlizumab (VOC leading to healthcare visits)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of VOC events treated at home (based on documentation by health care provider following phone contact with patient) over time.</measure>
    <time_frame>Week 1 through end of treatment (approximately 24 months)</time_frame>
    <description>Assess efficacy of crizanlizumab (VOC treated at home)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of VOC events (including both healthcare visit and home treatment).</measure>
    <time_frame>Week 1 through end of treatment (approximately 24 months)</time_frame>
    <description>Assess efficacy of crizanlizumab (VOC events)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of each subcategory of all VOC events (uncomplicated pain crisis, acute chest syndrome, hepatic sequestration, splenic sequestration, priapism) over time.</measure>
    <time_frame>Week 1 through end of treatment (approximately 24 months)</time_frame>
    <description>Assess efficacy of crizanlizumab (subcategory of VOC events)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of hospitalizations and ER visits (both total and VOC-related) over time.</measure>
    <time_frame>Week 1 through end of treatment (approximately 24 months)</time_frame>
    <description>Assess efficacy of crizanlizumab (hospitalizations and ER visits)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized days of ER/hospitalization (both total and VOC-related) over time.</measure>
    <time_frame>Week 1 through end of treatment (approximately 24 months)</time_frame>
    <description>Assess efficacy of crizanlizumab (Days of ER/hospitalizations)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Sickle Cell Disease (SCD)</condition>
  <arm_group>
    <arm_group_label>crizanlizumab 5 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>crizanlizumab</intervention_name>
    <description>SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion</description>
    <arm_group_label>crizanlizumab 5 mg/kg</arm_group_label>
    <other_name>SEG101</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and non-pregnant female patients 16-70 years of age (inclusive)&#xD;
&#xD;
          -  Confirmed diagnosis of sickle cell disease by hemoglobin electrophoresis or&#xD;
             high-performance liquid chromatography (HPLC) [performed locally]. All sickle cell&#xD;
             disease genotypes are eligible.&#xD;
&#xD;
          -  Experienced at least 1 VOC within the preceding 12 months prior to Screening, as&#xD;
             determined by medical history.&#xD;
&#xD;
          -  If receiving HU/HC or erythropoietin stimulating agent, must have been receiving the&#xD;
             drug for at least 6 months prior to Screening&#xD;
&#xD;
          -  Hemoglobin ≥4.0 g/dL. Absolute neutrophil count ≥1.0 x 109/L and platelet count ≥75 x&#xD;
             109/L&#xD;
&#xD;
          -  Adequate renal and hepatic function as defined:&#xD;
&#xD;
          -  GFR ≥45 mL/min/1.73 m2 calculated by CKD-EPI&#xD;
&#xD;
          -  ALT ≤3 x ULN&#xD;
&#xD;
          -  Direct (conjugated) bilirubin ≤2 x ULN&#xD;
&#xD;
          -  ECOG performance status ≤2&#xD;
&#xD;
          -  Written informed consent (or assent/ parental consent for minor subjects) prior to any&#xD;
             screening procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of stem cell transplant.&#xD;
&#xD;
          -  Acute VOC ending 7 days prior to first dosing&#xD;
&#xD;
          -  Ongoing hospitalization prior to Screening&#xD;
&#xD;
          -  Received blood products within 30 days to first dosing&#xD;
&#xD;
          -  Participating in a chronic transfusion program (pre-planned series of transfusions for&#xD;
             prophylactic purposes)&#xD;
&#xD;
          -  History of severe hypersensitivity reactions to other monoclonal antibodies&#xD;
&#xD;
          -  Received a monoclonal antibody or immunoglobulin -based agent within 1 year of&#xD;
             Screening, or has documented immunogenicity to a prior biologic.&#xD;
&#xD;
          -  Received active treatment on another investigational trial within 30 days (or 5&#xD;
             half-lives of that agent, whichever is greater) prior to Screening&#xD;
&#xD;
          -  Significant active infection or immune deficiency (including chronic use of&#xD;
             immunosuppressive drugs)&#xD;
&#xD;
          -  Resting QTcF ≥470 msec at pretreatment (baseline) or other cardiac or cardiac&#xD;
             repolarization abnormality&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Orange</city>
        <state>Florida</state>
        <zip>32763</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27858</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104-4399</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rock Hill</city>
        <state>South Carolina</state>
        <zip>29732</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>June 21, 2023</last_update_submitted>
  <last_update_submitted_qc>June 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sickle cell disease</keyword>
  <keyword>SCD</keyword>
  <keyword>sickle cell anemia</keyword>
  <keyword>vaso-occlusive crisis</keyword>
  <keyword>P-selectin</keyword>
  <keyword>SEG101</keyword>
  <keyword>crizanlizumab</keyword>
  <keyword>monoclonal antibody</keyword>
  <keyword>Anemia, Sickle Cell</keyword>
  <keyword>HbS Disease</keyword>
  <keyword>Hemoglobin SC Disease</keyword>
  <keyword>Sickle Cell Disorders</keyword>
  <keyword>Sickling Disorder Due to Hemoglobin S</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
    <ipd_url>http://www.clinicalstudydatarequest.com</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 4, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT03264989/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT03264989/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03264989
org study id: CSEG101A2202
nct id: NCT03264989
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the CSEG101A2202 study was to characterize the PK and PD of
      SEG101/crizanlizumab at 5 mg/kg and to evaluate the safety and efficacy of
      SEG101/crizanlizumab in SCD patients.

      Study CSEG101A2202 was designed as a Phase II, multicenter, open-label study. The first 45
      patients (to identify 27 evaluable patients) were enrolled to the treatment group
      crizanlizumab 5.0 mg/kg to complete full PK/PD sampling at week 1 and week 15. In all
      patients, trough PK/PD samples was collected prior to each dose. In addition, throughout the
      study (and when possible), all patients had blood drawn for serum to assess PK and PD drawn
      at times of onset and resolution of each VOC event, fever, or infection. Once the up to 45
      patients were enrolled, 12 additional patients were enrolled to the exploratory treatment
      group and begin at 7.5 mg/kg of crizanlizumab.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To characterize PK (AUC) of crizanlizumab at 5.0 mg/kg in SCD patients.
time frame: Week1 Day 1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; 72hr; Week2 Day 1; Week3 Day 1; Week15 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; 72hr; Week16 Day1; Week17 Day1; Week18 Day1; Week19 Day1
description: PK (AUC)
measure: To characterize PK (Ctrough) of crizanlizumab at 5.0 mg/kg in SCD patients.
time frame: Week 1 Day1; Week3 Day1; Week7 Day1; Week11 Day1; Week15 Day1; Week19 Day1; Week23 Day1; Week27 Day1; Week31 Day1; Week35 Day1; Week39 Day1; Week43 Day1; Week47 Day1; Week51 Day1, W75 Day1, W99 Day 1, W123 Day 1, W147 Day 1, W171 Day 1, Safety FU
description: PK (Ctrough)
measure: To characterize PK (Cmax) of crizanlizumab at 5.0 mg/kg in SCD patients.
time frame: Week1 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; Week15 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr
description: PK (Cmax)
measure: Pharmacodynamics (PD): Percentage of P-selectin inhibition and PD-AUC inhibition of crizanlizumab at 5.0 mg/kg in SCD patients
time frame: Week1 Day1 Pre-dose, 2hr, 24hr; 72hr; Week2 Day1; Week3 Day1; Week15 Day1 Pre-dose, 2hr, 24hr; 72hr; Week16 Day1; Week17 Day1; Week18 Day1; Week19 Day1
description: P-selectin inhibition percentage & PD AUC inhibition after the starting dose, after multiple doses and prior to each study drug dose
measure: Annualized rate of VOC events leading to healthcare visit in clinic/ER/hospital over time.
time frame: Week 1 through end of treatment (approximately 24 months)
description: Assess efficacy of crizanlizumab (VOC leading to healthcare visits)
measure: Annualized rate of VOC events treated at home (based on documentation by health care provider following phone contact with patient) over time.
time frame: Week 1 through end of treatment (approximately 24 months)
description: Assess efficacy of crizanlizumab (VOC treated at home)
measure: Annualized rate of VOC events (including both healthcare visit and home treatment).
time frame: Week 1 through end of treatment (approximately 24 months)
description: Assess efficacy of crizanlizumab (VOC events)
measure: Annualized rate of each subcategory of all VOC events (uncomplicated pain crisis, acute chest syndrome, hepatic sequestration, splenic sequestration, priapism) over time.
time frame: Week 1 through end of treatment (approximately 24 months)
description: Assess efficacy of crizanlizumab (subcategory of VOC events)
measure: Annualized rate of hospitalizations and ER visits (both total and VOC-related) over time.
time frame: Week 1 through end of treatment (approximately 24 months)
description: Assess efficacy of crizanlizumab (hospitalizations and ER visits)
measure: Annualized days of ER/hospitalization (both total and VOC-related) over time.
time frame: Week 1 through end of treatment (approximately 24 months)
description: Assess efficacy of crizanlizumab (Days of ER/hospitalizations)
arm group label: crizanlizumab 5 mg/kg
arm group type: Experimental
description: SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion.
intervention type: Drug
intervention name: crizanlizumab
description: SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion
arm group label: crizanlizumab 5 mg/kg
other name: SEG101
criteria: 
gender: All
minimum age: 16 Years
maximum age: 70 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
ipd url: http://www.clinicalstudydatarequest.com
provided document: 
provided document: 