xml: <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/NCT05974267</url>
    </required_header>
    <id_info>
      <org_study_id>MS201618_0034</org_study_id>
      <nct_id>NCT05974267</nct_id>
    </id_info>
    <brief_title>Efficacy, Safety, and PK of M5717 in Combination With Pyronaridine as Chemoprevention in Adults and Adolescents With Asymptomatic Plasmodium Falciparum Infection (CAPTURE-2)</brief_title>
    <official_title>Phase 2a Proof-of-Concept, Multicenter, Randomized, Open Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of a Single Dose of the Combination M5717-pyronaridine as Chemoprevention in Asymptomatic Adults and Adolescents With Plasmodium Falciparum Malaria Infection (CAPTURE-2)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany</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>
        This study will evaluate the efficacy and safety of a single dose of M5717 plus pyronaridine&#xD;
        tetraphosphate in clearing current Plasmodium falciparum infection and protecting against&#xD;
        recurrent infections in asymptomatic adults and adolescents. The study will also assess the&#xD;
        duration of protection provided by different doses of M5717 plus pyronaridine and the&#xD;
        additional contribution of M5717 to the duration of protection using external study data.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 25, 2023</start_date>
    <completion_date type="Anticipated">April 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2024</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>
      <intervention_model_description>Open Label</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Time to Parasitemia Since Negative Blood Smear after Treatment</measure>
      <time_frame>From Study Start Day 1 up to End of Study (approximately 12 weeks)</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Percentage of Participants with Parasitemia (positive blood smear).</measure>
      <time_frame>From Study Start Day 1 up to End of Study (approximately 12 week)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of Participants with Polymerase Chain Reaction (PCR)-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to new Infections as determined by Genotyping using PCR Techniques)</measure>
      <time_frame>From Study Start Day 1 up to End of Study (approximately 12 weeks)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of Participants with PCR-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to Recrudescence as determined by Genotyping using PCR Techniques)</measure>
      <time_frame>From Study Start Day 1 up to End of Study (approximately 12 weeks)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Parasite Clearance Time</measure>
      <time_frame>Time from dosing to the first negative (no parasites) blood film (microscopy) , assessed up to 12 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs</measure>
      <time_frame>From Study Start Day 1 up to End of Study (approximately 12 Weeks)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic (PK) Plasma Concentrations of M5717 and Pyronaridine</measure>
      <time_frame>Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and (24 hours) on Day 2</time_frame>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">192</enrollment>
    <condition>Malaria Infection</condition>
    <arm_group>
      <arm_group_label>Cohort 1: M5717 (60 mg) + Pyronaridine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive single oral dose of M5717 60 milligram (mg) plus pyronaridine tetraphosphate (pyronaridine) 720 mg (Participants &gt;= 65 kilogram [kg]) or pyronaridine 540 mg (Participants &gt;= 45 to &lt; 65 kg) once daily in a single day treatment regimen.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort 2: M5717 (200 mg) + Pyronaridine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive single oral dose of M5717 200 mg plus pyronaridine 720 mg (Participants &gt;= 65 kg) or pyronaridine 540 mg (Participants &gt;= 45 to &lt; 65 kg) once daily in a single day treatment regimen.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort 3: M5717 (660 mg)+ Pyronaridine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive single oral dose of M5717 660 mg plus pyronaridine 720 mg (Participants &gt;= 65 kg) or pyronaridine 540 mg (Participants &gt;= 45 to &lt; 65 kg) once daily in a single day treatment regimen.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort 4: Atovaquone-proguanil</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive orally 3 doses of Malarone (fixed-dose combination of atovaquone-proguanil) once daily in a 3-day treatment regimen.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>M5717 60 mg</intervention_name>
      <description>Participants will receive single oral dose (Capsules) of 60 mg M5717 on Day 1 under fasting condition</description>
      <arm_group_label>Cohort 1: M5717 (60 mg) + Pyronaridine</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pyronaridine</intervention_name>
      <description>Participants will receive Pyronaridine tablets orally single dose of 720 (Participants &gt;= 65 kg) and 540 mg (Participants &gt;= 45 to &lt; 65 kg) on Study Day 1 under fasting condition</description>
      <arm_group_label>Cohort 1: M5717 (60 mg) + Pyronaridine</arm_group_label>
      <arm_group_label>Cohort 2: M5717 (200 mg) + Pyronaridine</arm_group_label>
      <arm_group_label>Cohort 3: M5717 (660 mg)+ Pyronaridine</arm_group_label>
      <other_name>Pyronaridine tetraphosphate</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Atovaquone-Proguanil</intervention_name>
      <description>Participants will Receive Atovaquone-Proguanil tablets 1000/400 mg once daily in a 3-day treatment regimen.</description>
      <arm_group_label>Cohort 4: Atovaquone-proguanil</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>M5717 200 mg</intervention_name>
      <description>Participants will receive single oral dose (Capsules) of 200 mg M5717 on Day 1 under fasting condition</description>
      <arm_group_label>Cohort 2: M5717 (200 mg) + Pyronaridine</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>M5717 660mg</intervention_name>
      <description>Participants will receive single oral dose (Capsules) of 660 mg M5717 on Day 1 under fasting condition</description>
      <arm_group_label>Cohort 3: M5717 (660 mg)+ Pyronaridine</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Participants with Asymptomatic Plasmodium falciparum Malaria with no Fever or other&#xD;
               sign of Acute Uncomplicated Malaria and, with Microscopic confirmation using&#xD;
               Giemsa-stained thick film, and a Parasitemia of &gt;= 40 to &lt;= 10,000 Asexual&#xD;
               Parasites/Microliter (μL) of Blood.&#xD;
  &#xD;
            -  Axillary Temperature &lt; 37.0 degree Celcius (ºC) or oral/Tympanic/rectal Temperature&lt;&#xD;
               37.5ºC; without history of fever during the previous 48 hours.&#xD;
  &#xD;
            -  Have a body weight &gt;= 45 kilogram (kg)&#xD;
  &#xD;
            -  Participants capable of giving Signed Informed consent which includes Compliance with&#xD;
               the requirements and restriction listed in the Informed consent form&#xD;
  &#xD;
            -  Other Protocol defined Inclusion Criteria could apply&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Participants with any disease requiring Chronic Treatment&#xD;
  &#xD;
            -  Participants with any Preplanned surgery during the study&#xD;
  &#xD;
            -  Participants with any previous Treatment with pyronaridine as part of a combination&#xD;
               therapy during the last 3 months&#xD;
  &#xD;
            -  Participants with any adequate Hematological, Hepatic, and renal function as defined&#xD;
               in the Protocol&#xD;
  &#xD;
            -  Other protocol defined Exclusion Criteria could apply&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>12 Years</minimum_age>
      <maximum_age>55 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Medical Responsible</last_name>
      <role>Study Director</role>
      <affiliation>Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Communication Center</last_name>
      <phone>+49 6151 72 5200</phone>
      <email>service@emdgroup.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Research Site</name>
        <address>
          <city>Darmstadt</city>
          <country>Germany</country>
        </address>
      </facility>
      <contact>
        <last_name>Please Contact the Communication Center</last_name>
        <phone>+49 6151 72 5200</phone>
        <email>service@emdgroup.com</email>
      </contact>
    </location>
    <location_countries>
      <country>Germany</country>
    </location_countries>
    <link>
      <url>https://clinicaltrials.emdgroup.com/en</url>
      <description>Trial Awareness and Transparency website</description>
    </link>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>August 2, 2023</last_update_submitted>
    <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 3, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Plasmodium falciparum</keyword>
    <keyword>Chemoprevention</keyword>
    <keyword>Malaria</keyword>
    <keyword>Plasmodium eukaryotic translation elongation factor 2 (PeEF2)</keyword>
    <keyword>Exposure response</keyword>
    <keyword>Adults</keyword>
    <keyword>Adolescents</keyword>
    <keyword>Asymptomatic Infection</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Infections</mesh_term>
      <mesh_term>Communicable Diseases</mesh_term>
      <mesh_term>Malaria</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Atovaquone</mesh_term>
      <mesh_term>Pyronaridine</mesh_term>
      <mesh_term>Proguanil</mesh_term>
      <mesh_term>Atovaquone, proguanil drug combination</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union</ipd_time_frame>
      <ipd_access_criteria>Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.</ipd_access_criteria>
      <ipd_url>http://bit.ly/IPD21</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05974267
  org study id: MS201618_0034
  nct id: NCT05974267
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This study will evaluate the efficacy and safety of a single dose of M5717 plus pyronaridine
        tetraphosphate in clearing current Plasmodium falciparum infection and protecting against
        recurrent infections in asymptomatic adults and adolescents. The study will also assess the
        duration of protection provided by different doses of M5717 plus pyronaridine and the
        additional contribution of M5717 to the duration of protection using external study data.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Open Label
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Time to Parasitemia Since Negative Blood Smear after Treatment
  time frame: From Study Start Day 1 up to End of Study (approximately 12 weeks)
  measure: Percentage of Participants with Parasitemia (positive blood smear).
  time frame: From Study Start Day 1 up to End of Study (approximately 12 week)
  measure: Percentage of Participants with Polymerase Chain Reaction (PCR)-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to new Infections as determined by Genotyping using PCR Techniques)
  time frame: From Study Start Day 1 up to End of Study (approximately 12 weeks)
  measure: Percentage of Participants with PCR-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to Recrudescence as determined by Genotyping using PCR Techniques)
  time frame: From Study Start Day 1 up to End of Study (approximately 12 weeks)
  measure: Parasite Clearance Time
  time frame: Time from dosing to the first negative (no parasites) blood film (microscopy) , assessed up to 12 weeks
  measure: Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs
  time frame: From Study Start Day 1 up to End of Study (approximately 12 Weeks)
  measure: Pharmacokinetic (PK) Plasma Concentrations of M5717 and Pyronaridine
  time frame: Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and (24 hours) on Day 2
  arm group label: Cohort 1: M5717 (60 mg) + Pyronaridine
  arm group type: Experimental
  description: Participants will receive single oral dose of M5717 60 milligram (mg) plus pyronaridine tetraphosphate (pyronaridine) 720 mg (Participants >= 65 kilogram [kg]) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.
  arm group label: Cohort 2: M5717 (200 mg) + Pyronaridine
  arm group type: Experimental
  description: Participants will receive single oral dose of M5717 200 mg plus pyronaridine 720 mg (Participants >= 65 kg) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.
  arm group label: Cohort 3: M5717 (660 mg)+ Pyronaridine
  arm group type: Experimental
  description: Participants will receive single oral dose of M5717 660 mg plus pyronaridine 720 mg (Participants >= 65 kg) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.
  arm group label: Cohort 4: Atovaquone-proguanil
  arm group type: Experimental
  description: Participants will receive orally 3 doses of Malarone (fixed-dose combination of atovaquone-proguanil) once daily in a 3-day treatment regimen.
  intervention type: Drug
  intervention name: M5717 60 mg
  description: Participants will receive single oral dose (Capsules) of 60 mg M5717 on Day 1 under fasting condition
  arm group label: Cohort 1: M5717 (60 mg) + Pyronaridine
  intervention type: Drug
  intervention name: Pyronaridine
  description: Participants will receive Pyronaridine tablets orally single dose of 720 (Participants >= 65 kg) and 540 mg (Participants >= 45 to < 65 kg) on Study Day 1 under fasting condition
  arm group label: Cohort 1: M5717 (60 mg) + Pyronaridine
  arm group label: Cohort 2: M5717 (200 mg) + Pyronaridine
  arm group label: Cohort 3: M5717 (660 mg)+ Pyronaridine
  other name: Pyronaridine tetraphosphate
  intervention type: Drug
  intervention name: Atovaquone-Proguanil
  description: Participants will Receive Atovaquone-Proguanil tablets 1000/400 mg once daily in a 3-day treatment regimen.
  arm group label: Cohort 4: Atovaquone-proguanil
  intervention type: Drug
  intervention name: M5717 200 mg
  description: Participants will receive single oral dose (Capsules) of 200 mg M5717 on Day 1 under fasting condition
  arm group label: Cohort 2: M5717 (200 mg) + Pyronaridine
  intervention type: Drug
  intervention name: M5717 660mg
  description: Participants will receive single oral dose (Capsules) of 660 mg M5717 on Day 1 under fasting condition
  arm group label: Cohort 3: M5717 (660 mg)+ Pyronaridine
  criteria: 
  gender: All
  minimum age: 12 Years
  maximum age: 55 Years
  healthy volunteers: No
  last name: Medical Responsible
  role: Study Director
  affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
  last name: Communication Center
  phone: +49 6151 72 5200
  email: service@emdgroup.com
  facility: 
  contact: 
  country: Germany
  url: https://clinicaltrials.emdgroup.com/en
  description: Trial Awareness and Transparency website
  responsible party type: Sponsor
  mesh term: Infections
  mesh term: Communicable Diseases
  mesh term: Malaria
  mesh term: Atovaquone
  mesh term: Pyronaridine
  mesh term: Proguanil
  mesh term: Atovaquone, proguanil drug combination
  sharing ipd: Yes
  ipd description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Clinical Study Report (CSR)
  ipd info type: Analytic Code
  ipd time frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
  ipd access criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
  ipd url: http://bit.ly/IPD21