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/NCT05988203</url>
    </required_header>
    <id_info>
      <org_study_id>BNT166-01</org_study_id>
      <nct_id>NCT05988203</nct_id>
    </id_info>
    <brief_title>A Clinical Study Investigating the Safety and Immune Responses After Immunization With Investigational Monkeypox Vaccines</brief_title>
    <official_title>A Randomized, Partially Observer-blind, Dose-escalation, Phase I/II Trial Evaluating the Safety and Immunogenicity of Investigational RNA-based Mpox Vaccine Candidates</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>BioNTech SE</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>BioNTech SE</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>
        This is a randomized, partially observer-blind, dose-escalation, Phase I/II trial evaluating&#xD;
        the safety, tolerability, reactogenicity and immunogenicity of investigational RNA-based&#xD;
        multivalent vaccine candidates (BNT166a and BNT166c) for active immunization against&#xD;
        monkeypox (mpox).&#xD;
  &#xD;
        This trial will start with the two substudies, i.e., substudy A (SSA) and substudy B (SSB).&#xD;
  &#xD;
        This trial will be initiated with the dose-escalation SSA. In each substudy, dosing will&#xD;
        start with an initial sentinel group, followed by the expansion cohort.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Substudy A is an open-label, dose-escalation, Phase I substudy to assess the reactogenicity,&#xD;
        safety and immunogenicity of up to three dose levels of two multivalent vaccine candidates&#xD;
        (BNT166a and BNT166c) in ~64 healthy participants with no prior history of known or suspected&#xD;
        smallpox vaccination (vaccinia-naïve participants). Two doses will be given ~31 days apart.&#xD;
        The sponsor may decide to not activate the group with BNT166c, in this case there will be no&#xD;
        randomization.&#xD;
  &#xD;
        Substudy B is a randomized, observer-blinded and sponsor-unblinded Phase I substudy to assess&#xD;
        the reactogenicity, safety and immunogenicity of two multivalent vaccine candidates (BNT166a&#xD;
        and BNT166c) in ~32 healthy participants with prior history of smallpox vaccination&#xD;
        (vaccinia-experienced).Two doses will be given ~31 days apart. Participants will be&#xD;
        randomized 1:1. Sponsor may decide to not activate one of the groups, in that case this&#xD;
        substudy will be a one group open-label substudy.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">May 2024</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Prevention</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
      <masking_description>SSA: open-label; SSB: observer-blinded and sponsor-unblinded</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>SSA and SSB - Proportion (%) of subjects reporting solicited local reactions at the injection site up to 7 days after each investigational medicinal product (IMP) dose for each group</measure>
      <time_frame>Up to 7 day after each IMP dose</time_frame>
      <description>For each group</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SSA and SSB - Proportion (%) of subjects reporting solicited systemic events up to 7 days after each IMP dose for each group</measure>
      <time_frame>Up to 7 day after each IMP dose</time_frame>
      <description>For each group</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SSA and SSB - Proportion (%) of subjects with at least one unsolicited adverse event (AE) occurring from Dose 1 to 28 days after the dose</measure>
      <time_frame>From Dose 1 to 28 days after Dose 1</time_frame>
      <description>For each group</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SSA and SSB - Proportion (%) of subjects with at least one unsolicited AE occurring from Dose 2 to 28 days after the dose</measure>
      <time_frame>From Dose 2 to 28 days after Dose 2</time_frame>
      <description>For each group</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SSA and SSB - Proportion (%) of subjects with at least one serious adverse event (SAE) occurring from Dose 1 to 24 weeks after Dose 2</measure>
      <time_frame>From Dose 1 to 24 weeks after Dose 2</time_frame>
      <description>For each group</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SSA and SSB - Proportion (%) of subjects with worsening grading shifts in hematology and chemistry laboratory values between baseline and 1 week after Dose 1, before Dose 2, 1 week and 1 month after Dose 2</measure>
      <time_frame>From baseline to 1 month after Dose 2</time_frame>
      <description>For each group</description>
    </primary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">96</enrollment>
    <condition>Monkeypox</condition>
    <arm_group>
      <arm_group_label>SSA - BNT166a</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Escalating dose levels</description>
    </arm_group>
    <arm_group>
      <arm_group_label>SSA - BNT166c</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>One dose level</description>
    </arm_group>
    <arm_group>
      <arm_group_label>SSB - BNT166a</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>One dose level</description>
    </arm_group>
    <arm_group>
      <arm_group_label>SSB - BNT166c</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>One dose level</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>BNT166a</intervention_name>
      <description>Multivalent ribonucleic acid (RNA)-based vaccine for active immunization against monkeypox administered as intramuscular injection</description>
      <arm_group_label>SSA - BNT166a</arm_group_label>
      <arm_group_label>SSB - BNT166a</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>BNT166c</intervention_name>
      <description>Multivalent RNA-based vaccine for active immunization against monkeypox administered as intramuscular injection</description>
      <arm_group_label>SSA - BNT166c</arm_group_label>
      <arm_group_label>SSB - BNT166c</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Have given informed consent by signing and dating the informed consent form (ICF)&#xD;
               before initiation of any trial-specific procedures.&#xD;
  &#xD;
            -  Are willing and able to comply with scheduled visits, treatment schedule, laboratory&#xD;
               tests, and other requirements of the trial, including the prohibited concomitant&#xD;
               medications. This includes that they are able to understand and follow trial-related&#xD;
               instructions.&#xD;
  &#xD;
            -  SSA only: Are 18 through 45 years of age (inclusive) at the time of informed consent.&#xD;
  &#xD;
            -  SSB only: Are 50 through 65 years of age (inclusive) at the time of informed consent.&#xD;
  &#xD;
            -  Have a body mass index over 18.5 kg/m^2 and under 30 kg/m^2 and weigh at least 50 kg&#xD;
               at Visit 0.&#xD;
  &#xD;
            -  Are healthy, in the clinical judgment of the investigator based on volunteer-reported&#xD;
               medical history data, physical examination, 12-lead electrocardiogram (ECG), vital&#xD;
               signs, and clinical laboratory test results.&#xD;
  &#xD;
            -  SSA only: Have no prior history of known or suspected smallpox vaccination and no&#xD;
               detectable smallpox vaccination characteristic scar (vaccinia-naïve subjects).&#xD;
  &#xD;
            -  SSB only: Have a history of prior smallpox vaccination (i.e., are&#xD;
               vaccinia-experienced), determined based on medical records and/or presence of smallpox&#xD;
               vaccination characteristic scar. The most recent smallpox vaccination should have been&#xD;
               received before 1980.&#xD;
  &#xD;
            -  Agree not to enroll in another trial with an IMP starting from Visit 0 and until the&#xD;
               end of this trial (Visit 12).&#xD;
  &#xD;
            -  Negative human immunodeficiency virus (HIV)-1 and HIV-2 antigen/antibody blood test&#xD;
               result at Visit 0.&#xD;
  &#xD;
            -  Negative Hepatitis B surface antigen test result and negative anti Hepatitis C virus&#xD;
               antibodies (anti-HCV), or negative Hepatitis C virus (HCV) polymerase chain reaction&#xD;
               (PCR) test result if the anti-HCV is positive at Visit 0.&#xD;
  &#xD;
            -  Volunteers of childbearing potential (VOCBP) must not be pregnant. VOCBP and men who&#xD;
               are sexually active with partners of childbearing potential and their sexual partners&#xD;
               born female should use a highly effective form of contraception from at least 28 days&#xD;
               prior to Dose 1 up to at least 90 days after receiving the last dose of trial&#xD;
               treatment, and should agree not to donate eggs (ova, oocytes) or sperm.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of mpox, smallpox or vaccinia infection based on volunteer-reported medical&#xD;
               history.&#xD;
  &#xD;
            -  Pregnant, breastfeeding, planning pregnancy or planning to father children starting&#xD;
               from Visit 0 and continuously until 90 days after receiving Dose 2.&#xD;
  &#xD;
            -  History of known or suspected severe adverse reaction including allergic reaction&#xD;
               (e.g., anaphylaxis) to vaccines or to vaccine components such as lipids.&#xD;
  &#xD;
            -  Current or history of the following medical conditions at Visit 0 or Visit 1:&#xD;
  &#xD;
                 -  Uncontrolled, moderate or severe asthma; asthma severity as defined in the US&#xD;
                    National Asthma Education and Prevention Program Expert Panel report&#xD;
  &#xD;
                 -  Chronic obstructive pulmonary disease.&#xD;
  &#xD;
                 -  Diabetes mellitus type 1 or type 2, including cases controlled with diet alone&#xD;
                    (Not excluded: history of isolated gestational diabetes).&#xD;
  &#xD;
                 -  Hypertension: If a person has hypertension, exclude for blood pressure that is&#xD;
                    not well controlled. Well controlled blood pressure is defined as consistently&#xD;
                    ≤140 mm Hg systolic and ≤90 mm Hg diastolic, with or without medication, with&#xD;
                    only isolated, brief instances of higher readings, which must be &lt;150 mm Hg&#xD;
                    systolic and &lt;100 mm Hg.&#xD;
  &#xD;
                 -  Systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥100 mm Hg.&#xD;
  &#xD;
                 -  Malignancy, excluding localized basal or squamous cell cancer.&#xD;
  &#xD;
                 -  Cardiovascular diseases, (e.g., myocarditis, pericarditis, coronary heart&#xD;
                    disease, myocardial infarction, congestive heart failure, cardiomyopathy or&#xD;
                    clinically significant arrhythmias, stroke or transient ischemic attack).&#xD;
  &#xD;
                 -  Bleeding disorders (e.g., factor deficiency, coagulopathy, or platelet disorder).&#xD;
  &#xD;
                 -  Seizure disorder: History of seizure(s) within past 3 years; use of medications&#xD;
                    in order to prevent or treat seizure(s) at any time within the past 3 years.&#xD;
  &#xD;
                 -  Estimated glomerular filtration rate &lt;60 mL/min/1.73 m^2.&#xD;
  &#xD;
                 -  Chronic liver disease.&#xD;
  &#xD;
            -  Schizophrenia, major depressive disorder, suicidal ideation. Such psychiatric&#xD;
               illnesses, as bipolar disorder, autism and attention deficit-hyperactivity disorder&#xD;
               that at the discretion of the investigator could interfere with participation and&#xD;
               follow-up as outlined by the trial.&#xD;
  &#xD;
            -  Current or history of the following diseases associated with immune dysregulation:&#xD;
  &#xD;
                 -  Known or suspected immunodeficiency.&#xD;
  &#xD;
                 -  History of solid organ or bone marrow transplantation.&#xD;
  &#xD;
                 -  Asplenia: any condition resulting in the absence of a functional spleen.&#xD;
  &#xD;
                 -  Currently existing or history of any autoimmune disease.&#xD;
  &#xD;
            -  At Visit 0, any screening hematology and/or blood chemistry laboratory value that&#xD;
               meets the definition of a Grade ≥1 abnormality (according to the toxicity grading&#xD;
               scale; see separate criteria for indirect bilirubin and troponin I). Individuals with&#xD;
               any stable Grade 1 abnormalities may be considered eligible at the discretion of the&#xD;
               investigator. A stable Grade 1 laboratory abnormality is defined as the value which is&#xD;
               ≤ Grade 1 upon repeated testing on a second sample from this individual during the&#xD;
               screening period (prior to Visit 1). Individuals with abnormal but not clinically&#xD;
               significant parameters not included in the toxicity guidance may be considered&#xD;
               eligible at discretion of investigator.&#xD;
  &#xD;
            -  Abnormal total bilirubin at Visit 0. Note: inclusion of volunteers with bilirubin&#xD;
               ≤1.25 upper limit of normal (ULN) if due to Gilbert's syndrome is allowed.&#xD;
  &#xD;
            -  Any abnormal troponin I value at Visit 0.&#xD;
  &#xD;
            -  A 12-lead ECG at Visit 0 which is consistent with probable or possible&#xD;
               myocarditis/pericarditis or which demonstrates clinically relevant abnormalities that&#xD;
               may affect subject safety or are otherwise clinically significant findings (e.g.,&#xD;
               complete left bundle branch block, AV block, average corrected QT interval by&#xD;
               Fridericia (QTcF interval) &gt;450 msec, signs of myocardial infarction, ST elevation&#xD;
               consistent with myocardial ischemia, or serious brady- or tachyarrhythmias).&#xD;
  &#xD;
            -  Febrile illness (body temperature ≥38.0°C) or other acute illness within 48 hours&#xD;
               prior to Dose 1 and/or current (if presented at Visit 1, temporary deferral is&#xD;
               allowed).&#xD;
  &#xD;
            -  Participation or planned participation in strenuous or endurance exercise within 7&#xD;
               days before or after each IMP administration.&#xD;
  &#xD;
            -  SSA only: Vaccination with any Orthopoxvirus-based vaccine including vaccines for&#xD;
               prevention of smallpox, disease caused by vaccinia virus or mpox, or vector&#xD;
               Orthopoxvirus-based vaccines.&#xD;
  &#xD;
            -  SSB only: Vaccination for prevention of mpox or disease caused by vaccinia virus, or&#xD;
               with vector Orthopoxvirus-based vaccine. Vaccination for prevention of smallpox done&#xD;
               in or after 1980.&#xD;
  &#xD;
            -  Any vaccination within 28 days before Dose 1. Seasonal inactivated influenza vaccine&#xD;
               is allowed, however, it should be administered at least 14 days before IMP&#xD;
               administration.&#xD;
  &#xD;
            -  Any non-trial IMP within 28 days or five half-lives (whichever is longer) before Dose&#xD;
               1.&#xD;
  &#xD;
            -  Blood/plasma products and/or immunoglobulins within 120 days before Dose 1.&#xD;
  &#xD;
            -  Allergy treatment with antigen injections within 14 days before Dose 1.&#xD;
  &#xD;
            -  Immunosuppressive therapy, including corticosteroids, or radiotherapy within 6 months&#xD;
               or five half-lives (whichever is longer) before Dose 1. If systemic corticosteroids&#xD;
               have been administered short term (≤14 days, at a dose of ≤20 mg/day of prednisone or&#xD;
               equivalent) for treatment of an acute illness, individuals should be enrolled in the&#xD;
               trial only after corticosteroid therapy has been discontinued for at least 28 days&#xD;
               before Dose 1. Intraarticular, intrabursal, or topical (skin or eyes) corticosteroids&#xD;
               are permitted.&#xD;
  &#xD;
            -  Have a history of alcohol abuse within 1 year before Visit 0 or have a history of&#xD;
               substance abuse within the past 5 years before Visit 0.&#xD;
  &#xD;
            -  Are vulnerable individuals as per ICH E6 definition, i.e., are individuals whose&#xD;
               willingness to volunteer in a clinical trial may be unduly influenced by the&#xD;
               expectation, whether justified or not, of benefits associated with participation, or&#xD;
               of a retaliatory response from senior members of a hierarchy in case of refusal to&#xD;
               participate.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>BioNTech Responsible Person</last_name>
      <role>Study Director</role>
      <affiliation>BioNTech SE</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>BioNTech clinical trials patient information</last_name>
      <phone>+49 6131 9084</phone>
      <phone_ext>0</phone_ext>
      <email>patients@biontech.de</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 4, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Prevention of monkeypox</keyword>
    <keyword>Monkeypox virus</keyword>
    <keyword>RNA vaccine</keyword>
    <keyword>Vaccine</keyword>
    <keyword>mpox</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Monkeypox</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT05988203
  org study id: BNT166-01
  nct id: NCT05988203
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a randomized, partially observer-blind, dose-escalation, Phase I/II trial evaluating
        the safety, tolerability, reactogenicity and immunogenicity of investigational RNA-based
        multivalent vaccine candidates (BNT166a and BNT166c) for active immunization against
        monkeypox (mpox).
  
        This trial will start with the two substudies, i.e., substudy A (SSA) and substudy B (SSB).
  
        This trial will be initiated with the dose-escalation SSA. In each substudy, dosing will
        start with an initial sentinel group, followed by the expansion cohort.
  Substudy A is an open-label, dose-escalation, Phase I substudy to assess the reactogenicity,
        safety and immunogenicity of up to three dose levels of two multivalent vaccine candidates
        (BNT166a and BNT166c) in ~64 healthy participants with no prior history of known or suspected
        smallpox vaccination (vaccinia-naïve participants). Two doses will be given ~31 days apart.
        The sponsor may decide to not activate the group with BNT166c, in this case there will be no
        randomization.
  
        Substudy B is a randomized, observer-blinded and sponsor-unblinded Phase I substudy to assess
        the reactogenicity, safety and immunogenicity of two multivalent vaccine candidates (BNT166a
        and BNT166c) in ~32 healthy participants with prior history of smallpox vaccination
        (vaccinia-experienced).Two doses will be given ~31 days apart. Participants will be
        randomized 1:1. Sponsor may decide to not activate one of the groups, in that case this
        substudy will be a one group open-label substudy.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Prevention
  masking: Triple (Participant, Care Provider, Investigator)
  masking description: SSA: open-label; SSB: observer-blinded and sponsor-unblinded
  measure: SSA and SSB - Proportion (%) of subjects reporting solicited local reactions at the injection site up to 7 days after each investigational medicinal product (IMP) dose for each group
  time frame: Up to 7 day after each IMP dose
  description: For each group
  measure: SSA and SSB - Proportion (%) of subjects reporting solicited systemic events up to 7 days after each IMP dose for each group
  time frame: Up to 7 day after each IMP dose
  description: For each group
  measure: SSA and SSB - Proportion (%) of subjects with at least one unsolicited adverse event (AE) occurring from Dose 1 to 28 days after the dose
  time frame: From Dose 1 to 28 days after Dose 1
  description: For each group
  measure: SSA and SSB - Proportion (%) of subjects with at least one unsolicited AE occurring from Dose 2 to 28 days after the dose
  time frame: From Dose 2 to 28 days after Dose 2
  description: For each group
  measure: SSA and SSB - Proportion (%) of subjects with at least one serious adverse event (SAE) occurring from Dose 1 to 24 weeks after Dose 2
  time frame: From Dose 1 to 24 weeks after Dose 2
  description: For each group
  measure: SSA and SSB - Proportion (%) of subjects with worsening grading shifts in hematology and chemistry laboratory values between baseline and 1 week after Dose 1, before Dose 2, 1 week and 1 month after Dose 2
  time frame: From baseline to 1 month after Dose 2
  description: For each group
  arm group label: SSA - BNT166a
  arm group type: Experimental
  description: Escalating dose levels
  arm group label: SSA - BNT166c
  arm group type: Experimental
  description: One dose level
  arm group label: SSB - BNT166a
  arm group type: Experimental
  description: One dose level
  arm group label: SSB - BNT166c
  arm group type: Experimental
  description: One dose level
  intervention type: Biological
  intervention name: BNT166a
  description: Multivalent ribonucleic acid (RNA)-based vaccine for active immunization against monkeypox administered as intramuscular injection
  arm group label: SSA - BNT166a
  arm group label: SSB - BNT166a
  intervention type: Biological
  intervention name: BNT166c
  description: Multivalent RNA-based vaccine for active immunization against monkeypox administered as intramuscular injection
  arm group label: SSA - BNT166c
  arm group label: SSB - BNT166c
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: BioNTech Responsible Person
  role: Study Director
  affiliation: BioNTech SE
  last name: BioNTech clinical trials patient information
  phone: +49 6131 9084
  phone ext: 0
  email: patients@biontech.de
  responsible party type: Sponsor
  mesh term: Monkeypox
  sharing ipd: No