<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/NCT03831763</url>
  </required_header>
  <id_info>
    <org_study_id>016317</org_study_id>
    <nct_id>NCT03831763</nct_id>
  </id_info>
  <brief_title>Evaluation of the Use of Various Assessments of Common Cold Symptoms for Proof of Efficacy of ColdZyme Mouth Spray</brief_title>
  <official_title>Single (Investigator)-Blind, Randomized, Parallel-group Study to Evaluate the Use of Various Assessments of Common Cold Symptoms for Proof of Efficacy of CMS016317</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Enzymatica AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Analyze &amp; Realize</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Enzymatica AB</source>
  <oversight_info>
    <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 evaluates the use of various assessments of common cold symptoms for proof of&#xD;
      efficacy of ColdZyme Mouth Spray on naturally acquired common colds. Half of the participants&#xD;
      will receive ColdZyme® Mouth Spray while the other half may use optional care as needed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 25, 2018</start_date>
  <completion_date type="Actual">June 5, 2018</completion_date>
  <primary_completion_date type="Actual">June 5, 2018</primary_completion_date>
  <phase>N/A</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>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in the Jackson scale between the study groups</measure>
    <time_frame>16+/-4 days from start of common cold symptoms</time_frame>
    <description>Jackson scale - total score, local symptoms, systemic symptoms, 2-item score (sore throat &amp; malaise) as recorded in subject diary twice daily, morning and evening). The Jackson score is calculated by summing the following 8 symptom scores: sore throat, blocked nose, runny nose, cough and sneezing (local symptoms) as well as headache, malaise, and chilliness (systemic symptoms). Symptoms are assessed on a 4-point scale: 0 = none (symptom not present), 1 = mild (sensible, but not disturbing or irritating), 2 = moderate (symptoms sometimes disturbing/irritating), 3 = severe (symptoms disturbing/ irritating most of the time).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in WURSS-21 Quality of Life sub score between the study groups</measure>
    <time_frame>16+/-4 days from start of common cold symptoms</time_frame>
    <description>WURSS-21 Quality of Life (QoL) recorded in subject diary once daily, in the evening. WURSS-21 is an evaluative illness-specific quality of life instrument with 21 items, designed to assess the negative impact of acute upper respiratory infection, presumed viral (the common cold). In this study, the QoL part of the WURSS-21 will be applied, from item 12 (&quot;think clearly&quot;) to item 20 (&quot;live your personal life&quot;).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in the Sore Throat Scale between the study groups</measure>
    <time_frame>16+/-4 days from start of common cold symptoms</time_frame>
    <description>The Sore Throat Scale is a 0-10 Likert scale where 0=not sore and 10=very sore. Recorded in subject diary twice daily, morning and evening.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in the Irritated Throat Scale between the study groups</measure>
    <time_frame>16+/-4 days from start of common cold symptoms</time_frame>
    <description>Irritated Throat Scale is a 0-10 Likert scale where 0=not irritated and 10=very irritated. Recorded in subject diary twice daily, morning and evening.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects with prevention of cold outburst</measure>
    <time_frame>Within 3 days from symptom start</time_frame>
    <description>Based on the assessment of the symptoms recorded in the diary by means of the specified criteria for a common cold episode, as well as the evaluation of any symptoms by the investigator at V2 (whether they are attributable to common cold), the percentage of subjects with prevention of common cold outburst (upon originally having experienced initial symptoms) will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in number of findings during physical examination compared between the study groups</measure>
    <time_frame>From randomisation through study completion, maximum 16 weeks</time_frame>
    <description>Physical examination will be performed using standard products and procedures at all study visits. Physical examination by standard clinical examination of the gastrointestinal tract, cardiovascular system, eyes, respiratory tract, lymph nodes, musculoskeletal system, neurological functions, urogenital tract, thyroid gland and skin.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood pressure (mmHg) compared between the study groups</measure>
    <time_frame>From randomisation through study completion, maximum 16 weeks</time_frame>
    <description>Sitting blood pressure (mmHg), systolic and diastolic, will be measured using standard products and procedures at all study visits.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pulse rate (bpm) compared between the study groups</measure>
    <time_frame>From randomisation through study completion, maximum 16 weeks</time_frame>
    <description>Pulse rate (bpm) will be measured using standard products and procedures at all study visits.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>From randomisation through study completion, maximum 16 weeks</time_frame>
    <description>Any AE that occurs during the course of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of device deficiencies</measure>
    <time_frame>During IP use, maximum 12 days from symptom start</time_frame>
    <description>Device deficiencies occurring in the active group (verum)</description>
  </primary_outcome>
  <other_outcome>
    <measure>Duration of common cold symptoms</measure>
    <time_frame>16+/-4 days from start of common cold symptoms</time_frame>
    <description>Number of days since start of cold symptoms until the end of the symptoms (defined as the last day with one or more symptoms followed by at least two symptom-free days (subjects have to answer &quot;No&quot; to the question &quot;Do you think that you are still sick with this respiratory infection?&quot; for 2 days in a row)).</description>
  </other_outcome>
  <other_outcome>
    <measure>Use of concomitant treatment/remedies</measure>
    <time_frame>16+/-4 days from start of common cold symptoms</time_frame>
    <description>Use of any concomitant treatment/remedies, reported in subject diary once daily, in the evening</description>
  </other_outcome>
  <other_outcome>
    <measure>Global evaluation of efficacy by subjects at study end</measure>
    <time_frame>16+/-4 days from start of common cold symptoms</time_frame>
    <description>The subjects in the verum group will evaluate the efficacy of the IP (global scaled evaluation with &quot;very good&quot;, &quot;good&quot;, &quot;moderate&quot; and &quot;poor&quot;) at study end.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">400</enrollment>
  <condition>Common Cold</condition>
  <arm_group>
    <arm_group_label>ColdZyme</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Optional care only</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ColdZyme</intervention_name>
    <description>ColdZyme® Mouth Spray is a CE-marked medical device with the following composition: glycerol, water, cod trypsin, ethanol (&lt;1 %), calcium chloride, trometamol and menthol.&#xD;
ColdZyme® Mouth Spray consists of a 20 ml bottle, pump, spray nozzle and protective cap.</description>
    <arm_group_label>ColdZyme</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men and women&#xD;
&#xD;
          2. Age 18 to 70 years old&#xD;
&#xD;
          3. Increased risk for common cold (at least 3 self-reported occurences of common cold&#xD;
             within the last 12 months prior to V1) but generally in good health&#xD;
&#xD;
          4. Readiness to comply with trial procedures:&#xD;
&#xD;
               -  Use of IP as recommended (verum group)&#xD;
&#xD;
               -  Filling in diary&#xD;
&#xD;
               -  Keeping habitual diet and physical activity level&#xD;
&#xD;
          5. Women of child-bearing potential:&#xD;
&#xD;
               -  Have to agree to use appropriate contraception methods&#xD;
&#xD;
               -  Negative pregnancy testing (beta human chorionic gonadotropin test in urine) at&#xD;
                  V1&#xD;
&#xD;
        Participation is based upon written informed consent by the participant following written&#xD;
        and oral information by the investigator regarding nature, purpose, consequences and&#xD;
        possible risks of the clinical study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known allergy or hypersensitivity to the components of the investigational product&#xD;
&#xD;
          2. History and/or presence of clinically significant condition/ disorder (self-reported),&#xD;
             which per investigator's judgement could interfere with the results of the study or&#xD;
             the safety of the subject, e.g.:&#xD;
&#xD;
               -  Nasal disorder (e.g. polyposis, relevant septal deviation, ulcer etc.) and/or&#xD;
                  reconstructive surgery&#xD;
&#xD;
               -  Acute/chronic airways disease/disorder (e.g. chronic obstructive lung disease,&#xD;
                  asthma, chronic cough of any origin)&#xD;
&#xD;
               -  Acute psychiatric disorders&#xD;
&#xD;
               -  Any other acute/chronic serious organ or systemic diseases&#xD;
&#xD;
          3. Influenza vaccination within the last 3 months prior to V1 and during the study&#xD;
&#xD;
          4. Regular use of products that may influence the study outcome (e.g. immune&#xD;
             suppressants/immune stimulants including natural health products,&#xD;
             analgesics/antirheumatics, anti-phlogistics, antitussives/expectorants, mouth or&#xD;
             throat therapeutics, decongestants, antibiotics, anti-histaminergic drugs, nasal&#xD;
             drops/spray) within the last 4 weeks prior to V1 and during the study (except for the&#xD;
             defined optional care)&#xD;
&#xD;
          5. Pregnancy or nursing&#xD;
&#xD;
          6. History of (in the past 12 months prior to V1) or current abuse of drugs, alcohol or&#xD;
             medication&#xD;
&#xD;
          7. Participation in the present study of a person living in the same household as the&#xD;
             subject&#xD;
&#xD;
          8. Inability to comply with study requirements according to investigator's judgement&#xD;
&#xD;
          9. Participation in another clinical study in the 30 days prior to V1 and during the&#xD;
             study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ralf Uebelhack, Prof. MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>analyze &amp; realize GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>analyze &amp; realize GmbH</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Grube</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr. med. Petra Sandow and Eugenia Fischkina</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr. med. Ruhland</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinische Forschung Berlin</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>POLIKUM Institut GmbH</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Wünsche</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 21, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>August 19, 2019</last_update_submitted>
  <last_update_submitted_qc>August 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2019</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>Common Cold</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie the results reported, after deidentification (text, tables, figures and appendices) will be shared with researchers who provide a methodologically sound proposal, to achieve aims in hte approved proposal.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Beginning 3 months and ending 5 years following article publication.</ipd_time_frame>
    <ipd_access_criteria>Individual participant data that underlie the results reported, after deidentification (text, tables, figures and appendices) will be shared with researchers who provide a methodologically sound proposal, to achieve aims in hte approved proposal. Proposals should be directed to fredrik.lindberg@enzymatica.com. To gain access, data requestors will need to signa data access agreement.</ipd_access_criteria>
  </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/NCT03831763
org study id: 016317
nct id: NCT03831763
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This study evaluates the use of various assessments of common cold symptoms for proof of
      efficacy of ColdZyme Mouth Spray on naturally acquired common colds. Half of the participants
      will receive ColdZyme® Mouth Spray while the other half may use optional care as needed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Difference in the Jackson scale between the study groups
time frame: 16+/-4 days from start of common cold symptoms
description: Jackson scale - total score, local symptoms, systemic symptoms, 2-item score (sore throat & malaise) as recorded in subject diary twice daily, morning and evening). The Jackson score is calculated by summing the following 8 symptom scores: sore throat, blocked nose, runny nose, cough and sneezing (local symptoms) as well as headache, malaise, and chilliness (systemic symptoms). Symptoms are assessed on a 4-point scale: 0 = none (symptom not present), 1 = mild (sensible, but not disturbing or irritating), 2 = moderate (symptoms sometimes disturbing/irritating), 3 = severe (symptoms disturbing/ irritating most of the time).
measure: Difference in WURSS-21 Quality of Life sub score between the study groups
time frame: 16+/-4 days from start of common cold symptoms
description: WURSS-21 Quality of Life (QoL) recorded in subject diary once daily, in the evening. WURSS-21 is an evaluative illness-specific quality of life instrument with 21 items, designed to assess the negative impact of acute upper respiratory infection, presumed viral (the common cold). In this study, the QoL part of the WURSS-21 will be applied, from item 12 ("think clearly") to item 20 ("live your personal life").
measure: Difference in the Sore Throat Scale between the study groups
time frame: 16+/-4 days from start of common cold symptoms
description: The Sore Throat Scale is a 0-10 Likert scale where 0=not sore and 10=very sore. Recorded in subject diary twice daily, morning and evening.
measure: Difference in the Irritated Throat Scale between the study groups
time frame: 16+/-4 days from start of common cold symptoms
description: Irritated Throat Scale is a 0-10 Likert scale where 0=not irritated and 10=very irritated. Recorded in subject diary twice daily, morning and evening.
measure: Percentage of subjects with prevention of cold outburst
time frame: Within 3 days from symptom start
description: Based on the assessment of the symptoms recorded in the diary by means of the specified criteria for a common cold episode, as well as the evaluation of any symptoms by the investigator at V2 (whether they are attributable to common cold), the percentage of subjects with prevention of common cold outburst (upon originally having experienced initial symptoms) will be assessed.
measure: Difference in number of findings during physical examination compared between the study groups
time frame: From randomisation through study completion, maximum 16 weeks
description: Physical examination will be performed using standard products and procedures at all study visits. Physical examination by standard clinical examination of the gastrointestinal tract, cardiovascular system, eyes, respiratory tract, lymph nodes, musculoskeletal system, neurological functions, urogenital tract, thyroid gland and skin.
measure: Blood pressure (mmHg) compared between the study groups
time frame: From randomisation through study completion, maximum 16 weeks
description: Sitting blood pressure (mmHg), systolic and diastolic, will be measured using standard products and procedures at all study visits.
measure: Pulse rate (bpm) compared between the study groups
time frame: From randomisation through study completion, maximum 16 weeks
description: Pulse rate (bpm) will be measured using standard products and procedures at all study visits.
measure: Number of subjects with adverse events
time frame: From randomisation through study completion, maximum 16 weeks
description: Any AE that occurs during the course of the study.
measure: Number of device deficiencies
time frame: During IP use, maximum 12 days from symptom start
description: Device deficiencies occurring in the active group (verum)
measure: Duration of common cold symptoms
time frame: 16+/-4 days from start of common cold symptoms
description: Number of days since start of cold symptoms until the end of the symptoms (defined as the last day with one or more symptoms followed by at least two symptom-free days (subjects have to answer "No" to the question "Do you think that you are still sick with this respiratory infection?" for 2 days in a row)).
measure: Use of concomitant treatment/remedies
time frame: 16+/-4 days from start of common cold symptoms
description: Use of any concomitant treatment/remedies, reported in subject diary once daily, in the evening
measure: Global evaluation of efficacy by subjects at study end
time frame: 16+/-4 days from start of common cold symptoms
description: The subjects in the verum group will evaluate the efficacy of the IP (global scaled evaluation with "very good", "good", "moderate" and "poor") at study end.
arm group label: ColdZyme
arm group type: Active Comparator
arm group label: Optional care only
arm group type: No Intervention
intervention type: Device
intervention name: ColdZyme
description: ColdZyme® Mouth Spray is a CE-marked medical device with the following composition: glycerol, water, cod trypsin, ethanol (<1 %), calcium chloride, trometamol and menthol.
ColdZyme® Mouth Spray consists of a 20 ml bottle, pump, spray nozzle and protective cap.
arm group label: ColdZyme
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ralf Uebelhack, Prof. MD
role: Principal Investigator
affiliation: analyze & realize GmbH
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Common Cold
sharing ipd: Yes
ipd description: Individual participant data that underlie the results reported, after deidentification (text, tables, figures and appendices) will be shared with researchers who provide a methodologically sound proposal, to achieve aims in hte approved proposal.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Beginning 3 months and ending 5 years following article publication.
ipd access criteria: Individual participant data that underlie the results reported, after deidentification (text, tables, figures and appendices) will be shared with researchers who provide a methodologically sound proposal, to achieve aims in hte approved proposal. Proposals should be directed to fredrik.lindberg@enzymatica.com. To gain access, data requestors will need to signa data access agreement.