Double-blind, Randomized, Parallel-group, Placebo-controlled Study to Evaluate Efficacy of CMS008618 for Common Cold

This study evaluates the impact of ColdZyme® Mouth Spray on quality of life during common cold. Half of the participants will receive ColdZyme® Mouth Spray, half will receive a placebo device.

Study Overview

• Status: Completed
• Conditions: Common Cold
• Intervention / Treatment: Device: ColdZyme; Device: ColdZyme Placebo

• Study Type: Interventional
• Enrollment (Actual): 701
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Analyze & Realize GmbH
  • Berlin, Germany
    • emovis GmbH
  • Berlin, Germany
    • Klinische Forschung Berlin-Mitte GmbH
  • Berlin, Germany
    • Klinische Forschung Berlin
  • Berlin, Germany
    • POLIKUM Institut GmbH
  • Berlin, Germany
    • Praxis Frau Barbara Grube
  • Berlin, Germany
    • Thomas Wünsche
  • Esslingen, Germany
    • BioTeSys GmbH
  • Koßdorf, Germany
    • Praxis Dr. med. Gudrun Ruhland
  • Leipzig, Germany
    • SIBAmed Studienzentrum GmbH und Co. KG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women
2. Age 18 to 70 years old
3. Increased risk for common cold (at least 3 self-reported occurences of common cold within the last 12 months prior to V1) but generally in good health

4. Readiness to comply with trial procedures, including in particular:

   • Use of IP as recommended
   • Filling in diary
   • Keeping habitual life-style, including diet and physical activity level
   • No use of products that may influence the study outcome (e.g. immune suppressants/immune stimulants including natural health products, analgesics/anti-rheumatics, anti-phlogistics, anti-tussives/expectorants, mouth or throat therapeutics, decongestants, antibiotics, anti-histaminergic drugs, nasal drops/spray) during the study (except for the defined "rescue" treatment)

5. Women of child-bearing potential:

   • Have to agree to use appropriate contraception methods
   • Negative pregnancy testing (beta human chorionic gonadotropin test in urine) at V1

Participation is based upon written informed consent by the participant following written and oral information by the investigator regarding nature,

Exclusion Criteria:

1. Known allergy or hypersensitivity to the components of the investigational product

2. History and/or presence of clinically significant condition/ disorder (self-reported), which per investigator's judgement could interfere with the results of the study or the safety of the subject, e.g.:

   • Nasal disorder (e.g. polyposis, relevant septal deviation, ulcer etc.) and/or reconstructive surgery
   • Asthma, chronic obstructive lung disease or any other acute/chronic airways disease/disorder (e.g. chronic cough of any origin)
   • Acute psychiatric disorders
   • Any other acute/chronic serious organ or systemic diseases
3. Influenza vaccination within the last 3 months prior to V1 and during the study
4. Regular use of products that may influence the study outcome (e.g. immune suppressants/immune stimulants including natural health products, analgesics/anti-rheumatics, anti-phlogistics, antitussives/ expectorants, mouth or throat therapeutics, decongestants, antibiotics, anti-histaminergic drugs, nasal drops/spray) within the last 4 weeks prior to V1
5. Pregnancy or nursing
6. History of (in the past 12 months prior to V1) or current abuse of drugs, alcohol or medication
7. Participation in the present study of a person living in the same household as the subject
8. Inability to comply with study requirements according to investigator's judgement
9. Participation in another clinical study in the 30 days prior to V1 and during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ColdZyme; ColdZyme® Mouth Spray. The IP should be applied every second hour up to 6 times, with each time 2 sprays (1 dose) per occasion. The IP use should start when following conditions have been fulfilled: Answering "Yes" to either of the questions in the subject daily diary: "Do you think/feel you have a cold?" or "Do you think/feel you are coming down with a cold (might be having the first signs of cold)?" AND; A Jackson score of at least 1 in the subject's cold diary (mild = present, but not disturbing or irritating) for any symptom except headache The IP should be used until 2 days after the subject is symptom free (=answering "No" to the question "Do you think that you are still sick with this respiratory infection?" for 2 days in a row), but not longer than 10 days in total.	Device: ColdZyme; ColdZyme® Mouth Spray, a CE -marked device with the following composition of the spray solution: glycerol, purified water, cod trypsin, ethanol (<1 %), calcium chloride, trometamol and menthol. ColdZyme is a non-sterile mouth spray packaged in a primary container consisting of a 20 ml semi-transparent plastic bottle, pump, actuator (spray nozzle) and an actuator terminal cap.
Placebo Comparator: Placebo; Water based mouth spray manufactured to be similar to ColdZyme® Mouth Spray. The IP should be applied every second hour up to 6 times, with each time 2 sprays (1 dose) per occasion. The IP use should start when following conditions have been fulfilled: Answering "Yes" to either of the questions in the subject daily diary: "Do you think/feel you have a cold?" or "Do you think/feel you are coming down with a cold (might be having the first signs of cold)?" AND; A Jackson score of at least 1 in the subject's cold diary (mild = present, but not disturbing or irritating) for any symptom except headache The IP should be used until 2 days after the subject is symptom free (=answering "No" to the question "Do you think that you are still sick with this respiratory infection?" for 2 days in a row), but not longer than 10 days in total.	Device: ColdZyme Placebo; The placebo mouth spray solution has the following composition: ethanol (<1 %), menthol and water. The placebo mouth spray is packaged in a primary container consisting of a 20 ml semitransparent plastic bottle, pump, actuator (spray nozzle) and an actuator terminal cap.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WURSS-21 QoL sub score	The primary endpoint is the AUC of Wisconsin Upper Respiratory Symptom Survey (WURSS-21) Quality of Life composite subscore during first 8 days of symptoms, to be assessed in comparison between verum and placebo.	Days 1-8 (day 1 is the first day of symptoms)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Composite daily severity of all symptoms within the Jackson score	The first major secondary endpoint: AUC days 1-8 composite daily severity of all symptoms within the Jackson score (mean of morning and evening) (day 1 is the first day of symptom recording)	Days 1-8 (day 1 is the first day of symptoms)
2. Exposure to any concomitant treatment (including natural health products) that may affect common cold symptoms	The second major secondary endpoint: Exposure to any concomitant treatment (including natural health products) that may affect common cold symptoms - immune suppressants/immune stimulants, analgesics/ anti-rheumatics, anti-phlogistics, antitussives/ expectorants, mouth or throat therapeutics, decongestants, antibiotics, anti-histaminergic drugs, nasal drops/spray or any medication/treatment known to affect common cold symptoms - at any dose, expressed as number of days with concomitant treatment during the first 4 days for each subject (based on diary data).	Days 1-4 (day 1 is the first day of symptoms)
Other secondary endpoints: AUC days 1-8 for each single WURSS-21 QoL subscore item	AUC days 1-8 for each single WURSS-21 QoL subscore item	Days 1-8 (day 1 is the first day of symptoms)
AUC days 1-8 composite daily severity of all local symptoms within the Jackson score (mean of morning and evening)	AUC days 1-8 composite daily severity of all local symptoms within the Jackson score (mean of morning and evening) item	Days 1-8 (day 1 is the first day of symptoms)
AUC days 1-8 composite daily severity of each individual symptom of the Jackson score (mean of morning and evening)	AUC days 1-8 composite daily severity of all local symptoms within the Jackson score (mean of morning and evening) item	Days 1-8 (day 1 is the first day of symptoms)
Frequency of subjects with use of concomitant treatment that may affect common cold symptoms or any medication/treatment known to affect common cold symptoms - at any dose	Frequency of subjects with use of concomitant treatment (including natural health products) that may affect common cold symptoms - immune suppressants/immune stimulants, analgesics/anti-rheumatics, anti-phlogistics, antitussives/expectorants, mouth or throat therapeutics, decongestants, antibiotics, anti-histaminergic drugs, nasal drops/spray or any medication/treatment known to affect common cold symptoms - at any dose	Days 1-4
Assessment of duration of first intense phase	Assessment of duration of first intense phase, expressed as number of days from start of treatment until scoring <5 in total Jackson score	From enrolment through study completion, maximum 16 weeks
Assessment of symptom intensity	Assessment of symptom intensity, expressed as mean total Jackson score days 1-4	Days 1-4
Assessment of symptom sore throat per Sore Throat Scale	Assessment of symptom sore throat per Sore Throat Scale, expressed as AUC days 1-8	Days 1-8
Percentage of subjects with confirmed common cold at Visit 2	Percentage of subjects with confirmed common cold at Visit 2 (from all subjects with V2), which should take place within 1-3 days after symptom start	1-3 days after symptom start
Global evaluation of efficacy by subjects and investigators at study end	Global evaluation of efficacy by subjects and investigators at study end, 4-point categorical scale: "very good", "good", "moderate" and "poor"	From enrolment through study completion, maximum 16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoint: Physical examination	Physical examination: standard clinical examination of the gastrointestinal tract, cardiovascular system, eyes, respiratory tract, lymph nodes, musculoskeletal system, neurological functions, urogenital tract, thyroid gland and skin.	From enrolment through study completion, maximum 16 weeks
Safety endpoint: Vital signs	Vital signs: blood pressure (mmHg)	From enrolment through study completion, maximum 16 weeks
Safety endpoint: Vital signs	Vital signs: pulse rate (bpm)	From enrolment through study completion, maximum 16 weeks
Safety endpoint: Global evaluation of tolerability by subjects and investigators	Global evaluation of tolerability by subjects and investigators at study end, 4-point categorical scale: "very good", "good", "moderate" and "poor"	From enrolment through study completion, maximum 16 weeks
Safety endpoint: Assessment of adverse events	Assessment of adverse events throughout the study	From enrolment through study completion, maximum 16 weeks
Safety endpoint: Assessment of device deficiencies	Assessment of device deficiencies at V2 and V3	From enrolment through study completion, maximum 16 weeks

Collaborators and Investigators

• Sponsor: Enzymatica AB
• Collaborators: Analyze & Realize
• Investigators: Principal Investigator: Ralf Uebelhack, Prof. Dr. med., Analyze & Realize GmbH

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2019
• Primary Completion (Actual): June 26, 2019
• Study Completion (Actual): June 26, 2019

Study Registration Dates

• First Submitted: January 3, 2019
• First Submitted That Met QC Criteria: January 4, 2019
• First Posted (Actual): January 7, 2019

Study Record Updates

• Last Update Posted (Actual): August 22, 2019
• Last Update Submitted That Met QC Criteria: August 20, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Picornaviridae Infections; Common Cold
• Other Study ID Numbers: 008618

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan 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 the approved proposal.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication.
• IPD Sharing 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 the approved proposal. Proposals should be directed to fredrik.lindberg@enzymatica.com. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No