<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/NCT02241135</url>
  </required_header>
  <id_info>
    <org_study_id>CV-7201-102</org_study_id>
    <secondary_id>2013-002171-17</secondary_id>
    <nct_id>NCT02241135</nct_id>
  </id_info>
  <brief_title>RNActive® Rabies Vaccine (CV7201) in Healthy Adults</brief_title>
  <official_title>Phase I Safety and Immunogenicity Trial of an Investigational RNActive® Rabies Vaccine (CV7201) in Healthy Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CureVac</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CureVac</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this trial is to assess the safety and immunogenicity of an investigational&#xD;
      RNActive® rabies vaccine (CV7201) in healthy adults.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2013</start_date>
  <completion_date type="Actual">February 8, 2018</completion_date>
  <primary_completion_date type="Actual">February 8, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and severity of serious adverse events (SAEs)/adverse events (AEs) and local tolerability assessment of the vaccination site</measure>
    <time_frame>up to 64 days after the last vaccination</time_frame>
    <description>The occurrence of AEs will be assessed by non-directive questioning of the subject at each visit. Further, AEs volunteered by the subject during or between visits - as subject diary card entries - or detected through observation, physical examination, laboratory test, or other assessments during the entire observation period, will be documented. Subjects will be instructed that they must immediately report any AEs, subjective complaints or objective changes in their well-being to the Investigator or the clinic personnel, regardless of the perceived relationship between the event and the test product. The Investigator is responsible for reporting all AEs in the eCRF that are observed or described by the subject, regardless of their relationship to the trial vaccine or their clinical significance.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The lowest CV7201 dose to elicit rabies VNTs ≥ 0.5 IE/ml</measure>
    <time_frame>Rabies VNTs measured 14 days after the 3rd vaccination (Visit 8)</time_frame>
    <description>Rabies virus neutralizing titers (VNTs) measured in serum blood samples taken 14 days after the the last vaccination (Visit 8).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of treatment discontinuation due to IMP-related AEs/SAEs</measure>
    <time_frame>up to 64 days after the last vaccination</time_frame>
    <description>Number of subjects discontinued from treatment after the first or second vaccination due to vaccination-related reactions or AEs/SAEs.&#xD;
Period for observation in order to decide on withdrawal of subjects from next vaccination starts with Visit 1 (day 0, first vaccination) and lasts until the day of the third scheduled vaccination (pre-vaccination examination).</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">101</enrollment>
  <condition>Rabies</condition>
  <arm_group>
    <arm_group_label>80 µg CV7201 mRNA short</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccination by injection on days 0, 7, 28.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>160µg CV7201 mRNA short</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccination by injection on days 0, 7, 28.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>80 µg CV7201 mRNA long</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccination by injection on days 0, 28, 56.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>160 µg CV7201 mRNA long</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccination by injection on days 0, 28, 56.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>320 µg CV7201 mRNA long</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccination by injection on days 0, 28, 56.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>640 µg CV7201 mRNA long</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccination by injection on days 0, 28.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200 µg CV7201 mRNA long</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccination by injection on days 0, 28, 56.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>400 µg CV7201 mRNA long</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaccination by injection on days 0, 28, 56.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CV7201 mRNA</intervention_name>
    <description>CV7201 is composed of 1 RNActive® mRNA that encodes the rabies virus glycoprotein.</description>
    <arm_group_label>160 µg CV7201 mRNA long</arm_group_label>
    <arm_group_label>160µg CV7201 mRNA short</arm_group_label>
    <arm_group_label>200 µg CV7201 mRNA long</arm_group_label>
    <arm_group_label>320 µg CV7201 mRNA long</arm_group_label>
    <arm_group_label>400 µg CV7201 mRNA long</arm_group_label>
    <arm_group_label>640 µg CV7201 mRNA long</arm_group_label>
    <arm_group_label>80 µg CV7201 mRNA long</arm_group_label>
    <arm_group_label>80 µg CV7201 mRNA short</arm_group_label>
    <other_name>CV7201 messenger RNA</other_name>
    <other_name>CV7201 RNActive®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male and female volunteers aged 18 to 40 years inclusive&#xD;
&#xD;
          2. Compliant with protocol procedures and available for clinical follow-up through the&#xD;
             last planned visit (V9)&#xD;
&#xD;
          3. Physical examination and laboratory results without clinically significant findings&#xD;
&#xD;
          4. Body Mass Index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2&#xD;
&#xD;
          5. Females: Negative human chorionic gonadotropin (HCG) pregnancy test (serum) for women&#xD;
             presumed to be of reproductive potential on the day of enrolment&#xD;
&#xD;
          6. Females of childbearing potential must use acceptable methods of birth control during&#xD;
             the trial and Follow-up period (from 6 weeks before the first administration of the&#xD;
             test vaccine for the duration of the trial i.e., until the last planned visit (V9)).&#xD;
             The following methods of birth control are acceptable when used consistently and&#xD;
             correctly: established use of oral, injected or implanted hormonal methods of&#xD;
             contraception; intrauterine devices (IUDs) or intrauterine systems (IUSs) with the&#xD;
             exception of steel or copper wire; barrier methods of contraception (condom or&#xD;
             occlusive cap [diaphragm or cervical/vault caps] with spermicidal&#xD;
             foam/gel/film/cream/suppository); true abstinence (periodic abstinence [e.g.,&#xD;
             calendar, ovulation, symptothermal and postovulation methods] and withdrawal are not&#xD;
             acceptable).&#xD;
&#xD;
          7. Males must use reliable forms of contraception (barrier method with spermicidal agent&#xD;
             or true abstinence) and must refrain from sperm donation during the trial and&#xD;
             Follow-up period i.e., until the last planned visit (V9).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of any investigational or non-registered product (drug or vaccine) other than the&#xD;
             trial vaccine within 4 weeks preceding the administration of the trial vaccine, or&#xD;
             planned use during the trial period&#xD;
&#xD;
          2. Subject has received any other licensed vaccines within 4 weeks prior to the&#xD;
             administration of the trial vaccine&#xD;
&#xD;
          3. Subject has received any investigational or licensed rabies vaccine previously&#xD;
&#xD;
          4. Intending to travel to regions/countries for which rabies vaccinations are recommended&#xD;
             or where high risk of infections exists according to travel recommendations by the&#xD;
             German Society of Tropical Medicine and International Health (DTG) during the trial&#xD;
             and up to V9 (Day 91/120) Follow-up&#xD;
&#xD;
          5. Any treatment with immunosuppressants or other immune-modifying drugs within 6 months&#xD;
             prior to the administration of the trial vaccine. The use of inhaled and nasal&#xD;
             steroids, as well as topical steroids outside the vaccination area, will be permitted&#xD;
&#xD;
          6. Any medically diagnosed or suspected immunodeficient condition based on medical&#xD;
             history and physical examination&#xD;
&#xD;
          7. History of autoimmune disease&#xD;
&#xD;
          8. Administration of immunoglobulins (Igs) and/or any blood products within the 3 months&#xD;
             preceding the administration of the trial vaccine&#xD;
&#xD;
          9. Subject is taking chloroquine for malaria treatment or prophylaxis&#xD;
&#xD;
         10. Acute disease at the time of enrolment. Acute disease is defined as the presence of a&#xD;
             moderate or severe illness or fever ≥ 38 °C measured orally&#xD;
&#xD;
         11. Presence or evidence of significant acute or chronic, uncontrolled medical or&#xD;
             psychiatric illness (subjects with uncomplicated chronic diagnoses stable and treated&#xD;
             for ≥ 3 months e.g., mild hypertension well-controlled with medication, may be&#xD;
             enrolled - provided the condition and its therapy are known not to be associated with&#xD;
             an immunocompromised state or an autoimmune disease&#xD;
&#xD;
         12. Major congenital defects&#xD;
&#xD;
         13. Known allergy to any component of the trial product i.e., protamine. This includes&#xD;
             subjects with allergy to fish protein, diabetics with allergy to protamine-containing&#xD;
             insulin, or post-vasectomy males&#xD;
&#xD;
         14. Known type I allergy to beta lactam antibiotics&#xD;
&#xD;
         15. Evidence of current alcohol or drug abuse&#xD;
&#xD;
         16. History of any neurological disorders or seizures, with the exception of febrile&#xD;
             seizures during childhood&#xD;
&#xD;
         17. Seropositivity for human immunodeficiency virus (HIV), hepatitis B virus (HBV) (except&#xD;
             in subjects previously vaccinated against HBV) or hepatitis C virus (HCV)&#xD;
&#xD;
         18. Foreseeable non-compliance with protocol as judged by the Investigator&#xD;
&#xD;
         19. For females: Pregnancy or lactation&#xD;
&#xD;
         20. History of any life-threatening anaphylactic reactions.&#xD;
&#xD;
         21. Subjects with impaired coagulation in whom an IM injection is contraindicated.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Franz-Josef Falkner von Sonnenburg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ludwig-Maximilians - University of Munich</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Abteilung für Infektions- und Tropenmedizin der Ludwig-Maximilians-Universität</name>
      <address>
        <city>Munich</city>
        <zip>80802</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>August 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>October 25, 2018</last_update_submitted>
  <last_update_submitted_qc>October 25, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rav G protein</keyword>
  <keyword>rabies</keyword>
  <keyword>VNT</keyword>
  <keyword>immunogenicity</keyword>
  <keyword>PrEP vaccination</keyword>
  <keyword>mRNA</keyword>
  <keyword>CV7201</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rabies</mesh_term>
  </condition_browse>
  <!-- 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/NCT02241135
org study id: CV-7201-102
secondary id: 2013-002171-17
nct id: NCT02241135
lead sponsor: 
has dmc: Yes
The purpose of this trial is to assess the safety and immunogenicity of an investigational
      RNActive® rabies vaccine (CV7201) in healthy adults.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Incidence and severity of serious adverse events (SAEs)/adverse events (AEs) and local tolerability assessment of the vaccination site
time frame: up to 64 days after the last vaccination
description: The occurrence of AEs will be assessed by non-directive questioning of the subject at each visit. Further, AEs volunteered by the subject during or between visits - as subject diary card entries - or detected through observation, physical examination, laboratory test, or other assessments during the entire observation period, will be documented. Subjects will be instructed that they must immediately report any AEs, subjective complaints or objective changes in their well-being to the Investigator or the clinic personnel, regardless of the perceived relationship between the event and the test product. The Investigator is responsible for reporting all AEs in the eCRF that are observed or described by the subject, regardless of their relationship to the trial vaccine or their clinical significance.
measure: The lowest CV7201 dose to elicit rabies VNTs ≥ 0.5 IE/ml
time frame: Rabies VNTs measured 14 days after the 3rd vaccination (Visit 8)
description: Rabies virus neutralizing titers (VNTs) measured in serum blood samples taken 14 days after the the last vaccination (Visit 8).
measure: Number of treatment discontinuation due to IMP-related AEs/SAEs
time frame: up to 64 days after the last vaccination
description: Number of subjects discontinued from treatment after the first or second vaccination due to vaccination-related reactions or AEs/SAEs.
Period for observation in order to decide on withdrawal of subjects from next vaccination starts with Visit 1 (day 0, first vaccination) and lasts until the day of the third scheduled vaccination (pre-vaccination examination).
arm group label: 80 µg CV7201 mRNA short
arm group type: Experimental
description: Vaccination by injection on days 0, 7, 28.
arm group label: 160µg CV7201 mRNA short
arm group type: Experimental
description: Vaccination by injection on days 0, 7, 28.
arm group label: 80 µg CV7201 mRNA long
arm group type: Experimental
description: Vaccination by injection on days 0, 28, 56.
arm group label: 160 µg CV7201 mRNA long
arm group type: Experimental
description: Vaccination by injection on days 0, 28, 56.
arm group label: 320 µg CV7201 mRNA long
arm group type: Experimental
description: Vaccination by injection on days 0, 28, 56.
arm group label: 640 µg CV7201 mRNA long
arm group type: Experimental
description: Vaccination by injection on days 0, 28.
arm group label: 200 µg CV7201 mRNA long
arm group type: Experimental
description: Vaccination by injection on days 0, 28, 56.
arm group label: 400 µg CV7201 mRNA long
arm group type: Experimental
description: Vaccination by injection on days 0, 28, 56.
intervention type: Biological
intervention name: CV7201 mRNA
description: CV7201 is composed of 1 RNActive® mRNA that encodes the rabies virus glycoprotein.
arm group label: 160 µg CV7201 mRNA long
arm group label: 160µg CV7201 mRNA short
arm group label: 200 µg CV7201 mRNA long
arm group label: 320 µg CV7201 mRNA long
arm group label: 400 µg CV7201 mRNA long
arm group label: 640 µg CV7201 mRNA long
arm group label: 80 µg CV7201 mRNA long
arm group label: 80 µg CV7201 mRNA short
other name: CV7201 messenger RNA
other name: CV7201 RNActive®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Franz-Josef Falkner von Sonnenburg, MD
role: Principal Investigator
affiliation: Ludwig-Maximilians - University of Munich
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Rabies