<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/NCT03269565</url>
  </required_header>
  <id_info>
    <org_study_id>BCD-100-2</org_study_id>
    <nct_id>NCT03269565</nct_id>
  </id_info>
  <brief_title>International Trial of the Efficacy and Safety of BCD-100 in Patients With Melanoma</brief_title>
  <acronym>MIRACULUM</acronym>
  <official_title>An International Multicenter Open-label Randomized Trial of the Efficacy, Pharmacokinetics, Safety, and Immunogenicity of BCD-100 (JSC BIOCAD, Russia) as Monotherapy in Patients With Unresectable/Metastatic Melanoma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biocad</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biocad</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      An International Multicenter Open-label Randomized Trial of the Efficacy, Pharmacokinetics,&#xD;
      Safety, and Immunogenicity of BCD-100 (JSC BIOCAD, Russia) as Monotherapy in Patients with&#xD;
      Unresectable/Metastatic Melanoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This trial has been designed as an international multicenter open-label Phase II trial.&#xD;
&#xD;
      The trial aims to investigate the efficacy, pharmacokinetics, safety, and immunogenicity of&#xD;
      two dosage regimens of BCD-100 (JSC BIOCAD, Russia) as monotherapy in patients with&#xD;
      unresectable/metastatic melanoma.&#xD;
&#xD;
      According to the design, the trial will include two arms of patients. Each of the trial arms&#xD;
      will receive repeated doses of the test drug as monotherapy; BCD-100 will be administered&#xD;
      using one of the following dosage regimens established in a Phase I trial:&#xD;
&#xD;
        -  Monotherapy, BCD-100 1 mg/kg Q2W (IV infusion over 60 minutes; if a 60-minute infusion&#xD;
           is tolerated well, all following doses can be administered over 30 minutes);&#xD;
&#xD;
        -  Monotherapy, BCD-100 3 mg/kg Q3W (IV infusion over 60 minutes; if a 60-minute infusion&#xD;
           is tolerated well, all following doses can be administered over 30 minutes).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">August 31, 2017</start_date>
  <completion_date type="Anticipated">January 2021</completion_date>
  <primary_completion_date type="Actual">August 29, 2018</primary_completion_date>
  <phase>Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>1 year</time_frame>
    <description>Overall response rate (partial response+complete response rates) assessed according to irRECIST in an mITT population during BCD-100 therapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>One-year progression-free survival rate ;</measure>
    <time_frame>1 year</time_frame>
    <description>One-year progression-free survival rate during BCD-100 therapy;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with severe immune-related AEs</measure>
    <time_frame>1 year</time_frame>
    <description>Percentage of patients with severe immune-related AEs (CTCAE 4.03 Grade 3 or greater);</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">126</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BCD-100 1 mg/kg Q2W;</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BCD-100 3 mg/kg Q3W.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BCD-100</intervention_name>
    <description>Anti-PD-1 monoclonal antibody</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed Informed Consent Form and the subject's ability to follow the Protocol&#xD;
             requirements;&#xD;
&#xD;
          2. Age: 18 years and older at the signing of the informed consent;&#xD;
&#xD;
          3. Histologically verified (documented) unresectable/metastatic melanoma;&#xD;
&#xD;
          4. Newly diagnosed advanced/metastatic melanoma or progressive disease during (or after)&#xD;
             systemic chemotherapy ;&#xD;
&#xD;
          5. Available tissue blocks for histological examination or patient's agreement to give&#xD;
             biopsy specimens for PD-L1 expression status ;&#xD;
&#xD;
          6. ECOG performance status of 0 or 1;&#xD;
&#xD;
          7. LDH less than or equal to 2×upper limit of normal;&#xD;
&#xD;
          8. At least one RESICT 1.1-defined measurable target lesion confirmed by an independent&#xD;
             review;&#xD;
&#xD;
          9. All prior treatment-related toxicities/surgery-related adverse events must be less&#xD;
             than or equal to Grade 2 according to CTCAE 4.03, except for chronic/permanent damage&#xD;
             caused by an AE that does not affect the safety profile of the investigational therapy&#xD;
             (e.g., alopecia);&#xD;
&#xD;
         10. Adequate organ system function ;&#xD;
&#xD;
         11. Life expectancy of at least 12 weeks from the screening.&#xD;
&#xD;
         12. Patients with reproductive potential must agree to practice acceptable methods of&#xD;
             birth control throughout the entire trial period, starting from signing the informed&#xD;
             consent and up to 12 weeks after the last dose of BCD-100.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence of severe or concomitant diseases/life-threatening complications of the main&#xD;
             condition (e.g., massive pleural, pericardial, or peritoneal effusion that requires&#xD;
             medical intervention , pulmonary lymphangitis) at the signing of the informed consent;&#xD;
&#xD;
          2. Subjects with progressive/symptomatic brain metastases (e.g., brain edema, spinal cord&#xD;
             compression) or brain metastases that need therapy with corticosteroids and/or&#xD;
             anticonvulsants ;&#xD;
&#xD;
          3. Any concomitant disease observed at the screening that increases the risk of adverse&#xD;
             events during the investigational therapy:&#xD;
&#xD;
               -  Grade III-IV stable angina, unstable angina, or a history of myocardial&#xD;
                  infarction within 6 months prior to signing the informed consent;&#xD;
&#xD;
               -  Class III or IV heart failure as defined by the New York Heart Association (NYHA)&#xD;
                  functional classification system;&#xD;
&#xD;
               -  Severe, resistant hypertension;&#xD;
&#xD;
               -  History of atopic asthma, angioedema;&#xD;
&#xD;
               -  Moderate to severe respiratory failure, Grade 3 to 4 chronic obstructive&#xD;
                  pulmonary disease;&#xD;
&#xD;
               -  Any other concomitant condition (e.g., metabolism, blood, hepatic, renal,&#xD;
                  pulmonary, neurological, endocrine, cardiac, infectious, or gastrointestinal&#xD;
                  disorder) that constitutes an unacceptable risk to the patient's health during&#xD;
                  the investigational therapy;&#xD;
&#xD;
          4. Systemic autoimmune diseases (including but not limited to SLE, Crohn's disease,&#xD;
             ulcerative colitis, systemic scleroderma, inflammatory myopathy, mixed connective&#xD;
             tissue disease, overlap syndrome, etc.) ;&#xD;
&#xD;
          5. Endocrine disorders that cannot be adequately controlled by hormone replacement&#xD;
             therapy without any dose modification within 28 days prior to the start of the&#xD;
             investigational therapy;&#xD;
&#xD;
          6. Patients who need therapy with corticosteroids or other immunosuppressants;&#xD;
&#xD;
          7. Blood disorders :&#xD;
&#xD;
               -  Neutrophils &lt;1.5×109/L;&#xD;
&#xD;
               -  Platelets &lt;100×109/L;&#xD;
&#xD;
               -  Hb &lt;90 g/L;&#xD;
&#xD;
          8. Impaired renal function: creatinine ≥1.5×ULN;&#xD;
&#xD;
          9. Impaired liver function :&#xD;
&#xD;
               -  Bilirubin ≥1.5×ULN (≤50 μmol/L for patients with Gilbert's syndrome);&#xD;
&#xD;
               -  AST/ALT ≥2.5×ULN (5×ULN for patients with liver metastases);&#xD;
&#xD;
               -  ALP ≥5×ULN;&#xD;
&#xD;
         10. LDH &gt;2×ULN;&#xD;
&#xD;
         11. Anti-cancer therapy (surgery, chemotherapy) within 28 days prior to the first dose of&#xD;
             the investigational product; radiotherapy within 14 days prior to the first dose of&#xD;
             the investigational product;&#xD;
&#xD;
         12. Prior treatment with anti-CTLA4 and/or anti-PD-1/PD-L1/PD-L2 agents;&#xD;
&#xD;
         13. Prior targeted therapy ;&#xD;
&#xD;
         14. Patients who have received more than two lines of systemic chemotherapy for&#xD;
             unresectable or metastatic melanoma;&#xD;
&#xD;
         15. Concomitant cancer (except for cervical carcinoma in situ after radical surgery or&#xD;
             basal cell/squamous cell carcinoma after radical surgery);&#xD;
&#xD;
         16. Any condition that prevents a patient from following the Protocol procedures&#xD;
             (dementia, neurological or mental disorders, drug/alcohol abuse, etc.) ;&#xD;
&#xD;
         17. Simultaneous participation in other clinical trials , participation in other clinical&#xD;
             trials within 30 days prior to the first dose of the investigational product;&#xD;
&#xD;
         18. Acute infection or the acute phase of chronic infection within 28 days prior the first&#xD;
             dose of the investigational product;&#xD;
&#xD;
         19. Active HBV/HCV/HIV infection, active syphilis ;&#xD;
&#xD;
         20. Patients unable to receive an IV infusion of BCD-100;&#xD;
&#xD;
         21. Patients unable to receive an IV contrast agent;&#xD;
&#xD;
         22. Hypersensitivity to any of the components of BCD-100;&#xD;
&#xD;
         23. History of hypersensitivity to any therapeutic monoclonal antibody;&#xD;
&#xD;
         24. Pregnant or lactating female.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yulia N Linkova, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Director of Clinical Development Department, BIOCAD</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>State Budgetary Institution of Healthcare of the Arkhangelsk Region &quot;Arkhangelsk Regional Clinical Oncology Dispensary&quot; (SBHI AR ARCOD)</name>
      <address>
        <city>Arkhangel'sk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;N.N. Blokhin Russian Cancer Research Center&quot;</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Healthcare Institution &quot;Moscow Clinical Scientific Center funded by Moscow Health Department&quot; (SBHI MCSC MHD)</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;Pavlov First Saint Petersburg State Medical University&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;Saint Petersburg Clinical Research and Practice Center for Specialized Medical Care (Oncology)&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Institution &quot;N.N. Petrov Research Institute of Oncology&quot; of the Ministry of Healthcare of the Russian Federation (FSBI N.N. Petrov RIO (Chemotherapy Department with Innovative Technologies)</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Institution &quot;N.N. Petrov Research Institute of Oncology&quot; of the Ministry of Healthcare of the Russian Federation, Research Department of the Innovative Methods of Therapeutic Oncology and Rehabilitation (FSBI N.N. Petrov RIO of the</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LLC BioEk</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Institution of Healthcare &quot;Clinical Oncology Dispensary of Chelyabinsk Region&quot; (SBIH CODCR)</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>September 16, 2020</last_update_submitted>
  <last_update_submitted_qc>September 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03269565
org study id: BCD-100-2
nct id: NCT03269565
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
An International Multicenter Open-label Randomized Trial of the Efficacy, Pharmacokinetics,
      Safety, and Immunogenicity of BCD-100 (JSC BIOCAD, Russia) as Monotherapy in Patients with
      Unresectable/Metastatic Melanoma.
This trial has been designed as an international multicenter open-label Phase II trial.

      The trial aims to investigate the efficacy, pharmacokinetics, safety, and immunogenicity of
      two dosage regimens of BCD-100 (JSC BIOCAD, Russia) as monotherapy in patients with
      unresectable/metastatic melanoma.

      According to the design, the trial will include two arms of patients. Each of the trial arms
      will receive repeated doses of the test drug as monotherapy; BCD-100 will be administered
      using one of the following dosage regimens established in a Phase I trial:

        -  Monotherapy, BCD-100 1 mg/kg Q2W (IV infusion over 60 minutes; if a 60-minute infusion
           is tolerated well, all following doses can be administered over 30 minutes);

        -  Monotherapy, BCD-100 3 mg/kg Q3W (IV infusion over 60 minutes; if a 60-minute infusion
           is tolerated well, all following doses can be administered over 30 minutes).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response rate
time frame: 1 year
description: Overall response rate (partial response+complete response rates) assessed according to irRECIST in an mITT population during BCD-100 therapy
measure: One-year progression-free survival rate ;
time frame: 1 year
description: One-year progression-free survival rate during BCD-100 therapy;
measure: Percentage of patients with severe immune-related AEs
time frame: 1 year
description: Percentage of patients with severe immune-related AEs (CTCAE 4.03 Grade 3 or greater);
arm group label: Arm 1
arm group type: Experimental
description: BCD-100 1 mg/kg Q2W;
arm group label: Arm 2
arm group type: Experimental
description: BCD-100 3 mg/kg Q3W.
intervention type: Biological
intervention name: BCD-100
description: Anti-PD-1 monoclonal antibody
arm group label: Arm 1
arm group label: Arm 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yulia N Linkova, MD, PhD
role: Study Director
affiliation: Director of Clinical Development Department, BIOCAD
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Melanoma
sharing ipd: Undecided