<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/NCT03814746</url>
  </required_header>
  <id_info>
    <org_study_id>CSEG101A2301</org_study_id>
    <secondary_id>2017-001746-10</secondary_id>
    <nct_id>NCT03814746</nct_id>
  </id_info>
  <brief_title>Study of Two Doses of Crizanlizumab Versus Placebo in Adolescent and Adult Sickle Cell Disease Patients</brief_title>
  <acronym>STAND</acronym>
  <official_title>A Phase III, Multicenter, Randomized, Double-blind Study to Assess Efficacy and Safety of Two Doses of Crizanlizumab Versus Placebo, With or Without Hydroxyurea/ Hydroxycarbamide Therapy, in Adolescent and Adult Sickle Cell Disease Patients With Vaso-Occlusive Crises (STAND)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the efficacy and safety of 2 doses of crizanlizumab&#xD;
      (5.0 mg/kg and 7.5 mg/kg) versus placebo in adolescent and adult sickle cell disease (SCD)&#xD;
      patients with history of vaso-occlusive crisis (VOC) leading to healthcare visit.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study CSEG101A2301 (STAND) is an ongoing Phase III, multicenter, randomized, double-blind&#xD;
      study to assess efficacy and safety of two doses of crizanlizumab (5 mg/kg and 7.5 mg/kg)&#xD;
      versus placebo, with or without hydroxyurea/ hydroxycarbamide therapy (HU/HC), in adolescent&#xD;
      and adult patients with SCD and history of VOC leading to healthcare visit.&#xD;
&#xD;
      240 participants (including 48 adolescents) were planned to be randomized in a 1:1:1 ratio to&#xD;
      either 5 mg/kg, 7.5 mg/kg of crizanlizumab or placebo. Randomized participants were&#xD;
      stratified by concomitant HU/HC usage (yes/no) and baseline rate of VOCs leading to a&#xD;
      healthcare visit in 12 months prior to screening visit (2-4 vs. ≥ 5 VOCs) at the time of&#xD;
      enrollment. In November 2020, a capping of 90 adult participants per strata was implemented&#xD;
      to ensure adequate opportunity for enrollment into each of the 4 strata.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 26, 2019</start_date>
  <completion_date type="Anticipated">December 14, 2026</completion_date>
  <primary_completion_date type="Actual">August 31, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</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>
    <masking_description>Double-blind Study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Annualized rate of vaso-occlusive crisis (VOC) events leading to healthcare visit</measure>
    <time_frame>1 year</time_frame>
    <description>To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo in addition to standard of care.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of all VOCs leading to healthcare visit and treated at home (Key Secondary)</measure>
    <time_frame>1 year, 5 years</time_frame>
    <description>To compare the efficacy of 7.5 mg/kg versus placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit), based on documentation by health care provider following contact with participant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of VOCs leading to healthcare visit</measure>
    <time_frame>1 year</time_frame>
    <description>To assess the duration of VOCs leading to a healthcare visit in each group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects free from VOCs leading to healthcare visit</measure>
    <time_frame>1 year</time_frame>
    <description>To assess number of participants free from VOC leading to a healthcare visit in each group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects free from VOCs leading to healthcare visit</measure>
    <time_frame>1 year</time_frame>
    <description>To assess rate of participants free from VOC leading to a healthcare visit in each group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first and second VOC leading to healthcare visit</measure>
    <time_frame>1 year</time_frame>
    <description>To assess the time to first and second VOC leading to healthcare visit in each group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of visits to clinic, Emergency room (ER) and hospitalizations, both overall and VOC-related</measure>
    <time_frame>1 year</time_frame>
    <description>To assess Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC- related</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of albuminuria and albumin creatinine ratio (ACR)</measure>
    <time_frame>1 year</time_frame>
    <description>To assess (sickle cell disease) SCD-related renal damage in each group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) profile of crizanlizumab: AUC</measure>
    <time_frame>after the first and fifth dose</time_frame>
    <description>To characterize the Pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg using AUC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK profile of crizanlizumab: Cmax</measure>
    <time_frame>after the first and fifth dose</time_frame>
    <description>To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK profile of crizanlizumab: Tmax</measure>
    <time_frame>after the first and fifth dose</time_frame>
    <description>To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using Tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK profile of crizanlizumab: half-life</measure>
    <time_frame>after the first and fifth dose</time_frame>
    <description>To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using half-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD parameter (P-selectin inhibition)</measure>
    <time_frame>after the first and fifth dose</time_frame>
    <description>To characterize the pharmacodynamic (PD) (P-selectin inhibition) of crizanlizumab at 5.0 and 7.5 mg/kg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of subtypes of VOCs leading to a healthcare visit</measure>
    <time_frame>1 year, 5 years</time_frame>
    <description>To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs leading to healthcare visit by subtypes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of all VOCs leading to a healthcare visit and treated at home</measure>
    <time_frame>1 year, 5 years</time_frame>
    <description>To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of VOCs managed at home</measure>
    <time_frame>1 year, 5 years</time_frame>
    <description>To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs managed at home.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute change from baseline in hemoglobin</measure>
    <time_frame>5 years</time_frame>
    <description>To assess safety of crizanlizumab over the study period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Growth and sexual maturity assessment in adolescents (Tanner stage)</measure>
    <time_frame>5 years</time_frame>
    <description>To assess safety of crizanlizumab over the study period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of anti-drug antibodies (ADA) to crizanlizumab</measure>
    <time_frame>5 years</time_frame>
    <description>To assess immunogenicity of crizanlizumab over the study period.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">252</enrollment>
  <condition>Sickle Cell Disease (SCD)</condition>
  <arm_group>
    <arm_group_label>Crizanlizumab (SEG101) at 5.0 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received Crizanlizumab (SEG101) at 5.0 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Crizanlizumab (SEG101) at 7.5 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received Crizanlizumab (SEG101) at 7.5 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received the placebo drug.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Crizanlizumab (SEG101)</intervention_name>
    <description>Crizanlizumab was supplied in single use 10 mL glass vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab. This is a concentrate for solution for infusion.&#xD;
IV.</description>
    <arm_group_label>Crizanlizumab (SEG101) at 5.0 mg/kg</arm_group_label>
    <arm_group_label>Crizanlizumab (SEG101) at 7.5 mg/kg</arm_group_label>
    <other_name>SEG101</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo was supplied in single use 10 mL glass vials at a concentration of 0 mg/mL. This is a concentrate for solution for infusion IV.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent must be obtained prior to any screening procedures&#xD;
&#xD;
          2. Male or female patients aged 12 years and older on the day of signing informed&#xD;
             consent. Adolescent include patients aged 12 to 17 years old and adults ≥ 18 years&#xD;
&#xD;
          3. Confirmed diagnosis of SCD by hemoglobin electrophoresis or high performance liquid&#xD;
             chromatography (HPLC) [performed locally]. All SCD genotypes are eligible, genotyping&#xD;
             is not required for study entry&#xD;
&#xD;
          4. Experienced at least 2 VOCs leading to healthcare visit within the 12 months prior to&#xD;
             screening visit as determined by medical history. Prior VOC leading to healthcare&#xD;
             visit must resolve at least 7 days prior to Week 1 Day 1 and must include:&#xD;
&#xD;
               1. Pain crisis defined as an acute onset of pain for which there is no other&#xD;
                  medically determined explanation other than vaso- occlusion -&#xD;
&#xD;
               2. which requires a visit to a medical facility and/or healthcare professional,&#xD;
&#xD;
               3. and receipt of oral/parenteral opioids or parenteral nonsteroidal&#xD;
                  anti-inflammatory drug (NSAID) analgesia Acute chest syndrome (ACS), priapism and&#xD;
                  hepatic or splenic sequestration will be considered VOC in this study&#xD;
&#xD;
          5. If receiving HU/HC or L-glutamine (local HA approved medicinal product), must have&#xD;
             been receiving the drug for at least 6 months and at a stable dose for at least 3&#xD;
             months prior to Screening visit and plan to continue taking it at the same dose and&#xD;
             schedule until the subject has reached one year of study treatment. Patients who have&#xD;
             not been receiving such drug must not have received it for at least 6 months prior to&#xD;
             Screening visit to be included. Patients must have evidence of insufficient control of&#xD;
             acute pain, such as at least one VOC leading to healthcare visit while on HU/HC or&#xD;
             L-Glutamine treatment. If receiving erythropoietin stimulating agent, must have been&#xD;
             receiving the drug for at least 6 months prior to Screening visit and plan to continue&#xD;
             taking the treatment to maintain stable Hb levels at least until the subject has&#xD;
             reached one year of study treatment&#xD;
&#xD;
          6. Patients must meet the following central laboratory values prior to Week 1 Day 1:&#xD;
&#xD;
               -  Absolute Neutrophil Count ≥1.0 x 109/L&#xD;
&#xD;
               -  Platelet count ≥75 x 109/L&#xD;
&#xD;
               -  Hemoglobin: for adults (Hb) ≥4.0 g/dL and for adolescents (Hb) ≥5.5 g/dL&#xD;
&#xD;
               -  Glomerular filtration rate ≥ 45 mL/min/1.73 m2 using CKD-EPI formula in adults,&#xD;
                  and Shwartz formula in adolescents&#xD;
&#xD;
               -  Direct (conjugated) bilirubin &lt; 2.0 x ULN&#xD;
&#xD;
               -  Alanine transaminase (ALT) &lt; 3.0 x ULN&#xD;
&#xD;
          7. ECOG performance status ≤2.0 for adults and Karnofsky ≥ 50% for adolescents&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of stem cell transplant.&#xD;
&#xD;
          2. Participating in a chronic transfusion program (pre-planned series of transfusions for&#xD;
             prophylactic purposes) and/or planning on undergoing an exchange transfusion during&#xD;
             the duration of the study; episodic transfusion in response to worsened anemia or VOC&#xD;
             is permitted.&#xD;
&#xD;
          3. Contraindication or hypersensitivity to any drug or metabolites from similar class as&#xD;
             study drug or to any excipients of the study drug formulation. History of severe&#xD;
             hypersensitivity reaction to other monoclonal antibodies, which in the opinion of the&#xD;
             investigator may pose an increased risk of serious infusion reaction.&#xD;
&#xD;
          4. Received active treatment on another investigational trial within 30 days (or 5&#xD;
             half-lives of that agent, whichever is greater) prior to Screening visit or plans to&#xD;
             participate in another investigational drug trial.&#xD;
&#xD;
          5. Women of child-bearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant unless they are using highly effective methods of contraception&#xD;
             during dosing and for 15 weeks after stopping treatment.&#xD;
&#xD;
          6. Concurrent severe and/or uncontrolled medical conditions which, in the opinion of the&#xD;
             Investigator, could cause unacceptable safety risks or compromise participation in the&#xD;
             study.&#xD;
&#xD;
          7. History or current diagnosis of ECG abnormalities indicating significant risk of&#xD;
             safety such as:&#xD;
&#xD;
               -  Concomitant clinically significant cardiac arrhythmias (e.g ventricular&#xD;
                  tachycardia), and clinically significant second or third degree AV block without&#xD;
                  a pacemaker&#xD;
&#xD;
               -  History of familial long QT syndrome or know family history of Torsades de&#xD;
                  Pointes&#xD;
&#xD;
          8. Not able to understand and to comply with study instructions and requirements.&#xD;
&#xD;
          9. Received prior treatment with crizanlizumab or other selectin targeting agent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</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>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38163</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Edegem</city>
        <state>Antwerpen</state>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brussel</city>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bruxelles</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Salvador</city>
        <state>Bahia</state>
        <zip>41253-190</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Belem</city>
        <state>PA</state>
        <zip>66033 000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Recife</city>
        <state>Pernambuco</state>
        <zip>50070-170</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rio de Janeiro</city>
        <state>RJ</state>
        <zip>20.211-030</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ribeirao Preto</city>
        <state>SP</state>
        <zip>14048-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>05403 000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>08270-070</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>01232-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90035-003</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 1R9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valledupar</city>
        <state>Cesar</state>
        <zip>5602310</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barranquilla</city>
        <zip>080020</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Monteria</city>
        <zip>230004</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Helsinki</city>
        <zip>FIN 00290</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Creteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Marseille Cedex 05</city>
        <zip>13885</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Koeln</city>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stuttgart</city>
        <zip>70376</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Accra</city>
        <zip>0437-0594</zip>
        <country>Ghana</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Athens</city>
        <zip>115 27</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
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        <zip>500082</zip>
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        <state>GE</state>
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  <location>
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        <state>MI</state>
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        <country>Italy</country>
      </address>
    </facility>
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  <location>
    <facility>
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        <city>Verona</city>
        <state>VR</state>
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        <state>Republica De Panama</state>
        <zip>0801</zip>
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      <name>Novartis Investigative Site</name>
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        <zip>0801</zip>
        <country>Panama</country>
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      <address>
        <city>Soweto</city>
        <state>Gauteng</state>
        <zip>2013</zip>
        <country>South Africa</country>
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      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08035</zip>
        <country>Spain</country>
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    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
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      <name>Novartis Investigative Site</name>
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        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
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        <zip>01330</zip>
        <country>Turkey</country>
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        <zip>31100</zip>
        <country>Turkey</country>
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        <state>South Yorkshire</state>
        <zip>S10 2JF</zip>
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        <zip>CB2 0QQ</zip>
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        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
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      <address>
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        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
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      <address>
        <city>Sheffield</city>
        <zip>S10 2TH</zip>
        <country>United Kingdom</country>
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  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Colombia</country>
    <country>Finland</country>
    <country>France</country>
    <country>Germany</country>
    <country>Ghana</country>
    <country>Greece</country>
    <country>India</country>
    <country>Italy</country>
    <country>Jordan</country>
    <country>Lebanon</country>
    <country>Netherlands</country>
    <country>Oman</country>
    <country>Panama</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Kenya</country>
    <country>United Arab Emirates</country>
  </removed_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 21, 2019</study_first_submitted>
  <study_first_submitted_qc>January 21, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <disposition_first_submitted>August 30, 2023</disposition_first_submitted>
  <disposition_first_submitted_qc>August 30, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 1, 2023</disposition_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sickle Cell Disease</keyword>
  <keyword>SCD</keyword>
  <keyword>SEG101</keyword>
  <keyword>Crizanlizumab</keyword>
  <keyword>Hydroxyurea/ Hydroxycarbamide Therapy</keyword>
  <keyword>Vaso-Occlusive Crises</keyword>
  <keyword>SCA</keyword>
  <keyword>blood disorders</keyword>
  <keyword>hemoglobin</keyword>
  <keyword>red blood cells</keyword>
  <keyword>sickle-like shape</keyword>
  <keyword>mutation in hemoglobin gene</keyword>
  <keyword>sickle-cell trait</keyword>
  <keyword>sickle-cell crisis</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>https://www.clinicalstudydatarequest.com</ipd_url>
  </patient_data>
  <pending_results>
    <submitted>August 31, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT03814746
org study id: CSEG101A2301
secondary id: 2017-001746-10
nct id: NCT03814746
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to compare the efficacy and safety of 2 doses of crizanlizumab
      (5.0 mg/kg and 7.5 mg/kg) versus placebo in adolescent and adult sickle cell disease (SCD)
      patients with history of vaso-occlusive crisis (VOC) leading to healthcare visit.
Study CSEG101A2301 (STAND) is an ongoing Phase III, multicenter, randomized, double-blind
      study to assess efficacy and safety of two doses of crizanlizumab (5 mg/kg and 7.5 mg/kg)
      versus placebo, with or without hydroxyurea/ hydroxycarbamide therapy (HU/HC), in adolescent
      and adult patients with SCD and history of VOC leading to healthcare visit.

      240 participants (including 48 adolescents) were planned to be randomized in a 1:1:1 ratio to
      either 5 mg/kg, 7.5 mg/kg of crizanlizumab or placebo. Randomized participants were
      stratified by concomitant HU/HC usage (yes/no) and baseline rate of VOCs leading to a
      healthcare visit in 12 months prior to screening visit (2-4 vs. ≥ 5 VOCs) at the time of
      enrollment. In November 2020, a capping of 90 adult participants per strata was implemented
      to ensure adequate opportunity for enrollment into each of the 4 strata.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blind Study
measure: Annualized rate of vaso-occlusive crisis (VOC) events leading to healthcare visit
time frame: 1 year
description: To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo in addition to standard of care.
measure: Annualized rate of all VOCs leading to healthcare visit and treated at home (Key Secondary)
time frame: 1 year, 5 years
description: To compare the efficacy of 7.5 mg/kg versus placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit), based on documentation by health care provider following contact with participant.
measure: Duration of VOCs leading to healthcare visit
time frame: 1 year
description: To assess the duration of VOCs leading to a healthcare visit in each group
measure: Number of subjects free from VOCs leading to healthcare visit
time frame: 1 year
description: To assess number of participants free from VOC leading to a healthcare visit in each group
measure: Percentage of subjects free from VOCs leading to healthcare visit
time frame: 1 year
description: To assess rate of participants free from VOC leading to a healthcare visit in each group
measure: Time to first and second VOC leading to healthcare visit
time frame: 1 year
description: To assess the time to first and second VOC leading to healthcare visit in each group
measure: Annualized rate of visits to clinic, Emergency room (ER) and hospitalizations, both overall and VOC-related
time frame: 1 year
description: To assess Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC- related
measure: Evolution of albuminuria and albumin creatinine ratio (ACR)
time frame: 1 year
description: To assess (sickle cell disease) SCD-related renal damage in each group.
measure: Pharmacokinetic (PK) profile of crizanlizumab: AUC
time frame: after the first and fifth dose
description: To characterize the Pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg using AUC
measure: PK profile of crizanlizumab: Cmax
time frame: after the first and fifth dose
description: To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using Cmax
measure: PK profile of crizanlizumab: Tmax
time frame: after the first and fifth dose
description: To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using Tmax
measure: PK profile of crizanlizumab: half-life
time frame: after the first and fifth dose
description: To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using half-life
measure: PD parameter (P-selectin inhibition)
time frame: after the first and fifth dose
description: To characterize the pharmacodynamic (PD) (P-selectin inhibition) of crizanlizumab at 5.0 and 7.5 mg/kg
measure: Annualized rate of subtypes of VOCs leading to a healthcare visit
time frame: 1 year, 5 years
description: To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs leading to healthcare visit by subtypes.
measure: Annualized rate of all VOCs leading to a healthcare visit and treated at home
time frame: 1 year, 5 years
description: To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit).
measure: Annualized rate of VOCs managed at home
time frame: 1 year, 5 years
description: To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs managed at home.
measure: Absolute change from baseline in hemoglobin
time frame: 5 years
description: To assess safety of crizanlizumab over the study period.
measure: Growth and sexual maturity assessment in adolescents (Tanner stage)
time frame: 5 years
description: To assess safety of crizanlizumab over the study period.
measure: Measurement of anti-drug antibodies (ADA) to crizanlizumab
time frame: 5 years
description: To assess immunogenicity of crizanlizumab over the study period.
arm group label: Crizanlizumab (SEG101) at 5.0 mg/kg
arm group type: Experimental
description: Participants received Crizanlizumab (SEG101) at 5.0 mg/kg
arm group label: Crizanlizumab (SEG101) at 7.5 mg/kg
arm group type: Experimental
description: Participants received Crizanlizumab (SEG101) at 7.5 mg/kg
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received the placebo drug.
intervention type: Drug
intervention name: Crizanlizumab (SEG101)
description: Crizanlizumab was supplied in single use 10 mL glass vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab. This is a concentrate for solution for infusion.
IV.
arm group label: Crizanlizumab (SEG101) at 5.0 mg/kg
arm group label: Crizanlizumab (SEG101) at 7.5 mg/kg
other name: SEG101
intervention type: Drug
intervention name: Placebo
description: Placebo was supplied in single use 10 mL glass vials at a concentration of 0 mg/mL. This is a concentrate for solution for infusion IV.
arm group label: Placebo
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Belgium
country: Brazil
country: Canada
country: Colombia
country: Finland
country: France
country: Germany
country: Ghana
country: Greece
country: India
country: Italy
country: Jordan
country: Lebanon
country: Netherlands
country: Oman
country: Panama
country: South Africa
country: Spain
country: Turkey
country: United Kingdom
country: United States
country: Kenya
country: United Arab Emirates
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: https://www.clinicalstudydatarequest.com
submitted: August 31, 2023