Efficacy and Safety of Healsea® Babykids in the Treatment of Acute Infectious Rhinitis Symptoms in Children
Phase: NA
Conditions: Common Cold, Rhinitis Viral
Sponsor: Lallemand Pharma AG

 
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Study Number: LPH-2202 
 
Efficacy and safety of Healsea® Babykids in the treatment of acute 
infectious rhinitis symptoms in children 
CLINICAL INVESTIGATION PLAN 
 
 
Study Number: LPH-2202 
Short Title: BASICC 
Version 1.1; 2023.02.02 
 
 
This Clinical Investigation is being sponsored by: 
 
Lallemand Pharma AG 
Via Selva 2 
6900 Massagno 
Switzerland 
 
Represented by Dr Frédéric Durmont 
 
 Coordinating Investigator:  
Assoc. Prof. Rada Markova 
Medical Center First 
Pediatric Consultative Clinic Ltd 
51A Bulgaria Blvd.,Triaditsa district, 1404, Sofia, Bulgaria 
 
 
 

 
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Study Number: LPH-2202 
 
 
 
HISTORY OF CLINICAL INVESTIGATION PLAN’S UPDATES 
Version 
Date 
Purpose of Update 
Version 1 
2022-12-14 
Initial version 
Version 1.1 
2023-02-02 
Correction of a typography (7.1.3) & addition of 
two sites 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Study Number: LPH-2202 
STUDY CONTACT LIST 
COORDINATING 
INVESTIGATOR/ 
PRINCIPAL INVESTIGATOR 
(site 01) 
Assoc. Prof. Rada Markova 
Medical Center First Pediatric 
Consultative Clinic Ltd 
51A Bulgaria Blvd.,Triaditsa district, 
1404, Sofia, Bulgaria 
e-mail : rada_markova@yahoo.com 
PRINCIPAL INVESTIGATOR 
(Site 02) 
Dr. Yoan Nikolov 
Multiprofile Hospital for Active 
Treatment Zdraveto 2012 Ltd. 
4 Maestro Kanev Str., 1618, Sofia, 
Bulgaria 
e-mail: dr.yoan.nikolov@abv.bg 
PRINCIPAL INVESTIGATOR 
(Site 03) 
Dr. Emiliya Yancheva 
Medical Center VELACLINIC Ltd. 
2 Lyuben Karavelov Str., floor 2, 4002, 
Plovdiv, Bulgaria 
Phone: +359 888604039 
e-mail: velaclinic@abv.bg 
PRINCIPAL INVESTIGATOR 
(Site 04) 
Prof. Dr. Tonyo Shmilev 
MEDICAL CENTER PLOVDIMED Ltd. 
3 Osvobozhdenie Blvd., floor 1, 4023, 
Plovdiv, Bulgaria 
e-mail: t.shmilev@gmail.com 
PRINCIPAL INVESTIGATOR 
(Site 05) 
Dr. Zheni Varuzhan 
Voskinaryan-Diloyan 
Ambulatory for Outpatient Specialized 
Medical Care - Medical Center 
Polimed AD 
47 Bregalnitsa Str., Vazrazhdane 
district, 1303 Sofia, Bulgaria 
e-mail: drjenivoskinarian@gmail.com 
PRINCIPAL INVESTIGATOR 
(Site 06) 
Dr. Vladislav Ulevinov 
Medical Center VELACLINIC Ltd. 
8 Lale Str.,  Lozenets district, 1421, 
Sofia, Bulgaria 
e-mail: vladi_ulevinoff@yahoo.com 
PRINCIPAL INVESTIGATOR 
(Site 07) 
Dr. Mariana Mandazhieva-
Pepelanova 
Medical Center Iskar Ltd. 
22 Iskar Str., Oborishte district, 1000, 
Sofia, Bulgaria 

 
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PRINCIPAL INVESTIGATOR 
(Site 08) 
Dr. Silviya Hristova 
Medical Center SilviMed Ltd 
78 Vasil Kanchov Str., 3000 Vratsa, 
Bulgaria 
MONITOR 
Marina Bakalova, CRA 
 
 
Ralitsa 
Dimitrova-
Komileva, CRA 
CONVEX Ltd. 
6 Tri Ushi Str., Office 2 
1000 Sofia, Bulgaria 
tel:  + 359 2 9863 109 
fax:+ 359 2 9888  700 
e-mail : 
marina@convex.bg; 
r.dimitrova@convex.bg 
MEDICAL WRITER 
 
Géraldine Julou Schaeffer, 
PharmD, PhD 
 
BIOMEDICAL AND GLOBAL CLINICAL 
SOLUTION 
Parc Technologique du Canal 
26 rue Hermès 
31520 Ramonville-Saint-Agne, France 
Tel: +33 561 531 944 
e-mail : 
g.schaeffer@bgclinicals.com 
 
DATA MANAGEMENT / 
STATISTICS  
Catherine Gentil,  
Statistician 
 
 
AXIODIS CRO 
58, boulevard d’Arcole 
31000 Toulouse, France 
Tel: +33 684 521 611 
e-mail : cgentil@axiodis.com 
 
 
 
 
 

 
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Study Number: LPH-2202 
APPROVAL FORM 
STUDY: LPH-2202 
CLINICAL INVESTIGATION PLAN Version:  
1.1 – 2023-02-02 
 
Sponsor’s representative: 
 
 
Dr Frédéric Durmont 
 
 
 
 
 
 
 
 
Coordinating Investigator: 
 
 
 
Assoc. Prof. Rada Markova 
 
Study’s monitor: 
 
 
Ralitsa Dimitrova-Komileva  
 
 
 
 
Study’s Statistician: 
 
 
Catherine Gentil 
 
 
 
Medical Writer 
 
Géraldine Julou-Schaeffer, PharmD,PhD 
 
 
Date: 
Signature: 
 
Date: 
Signature: 
 
Date: 
Signature: 
 
Date: 
Signature: 
 
Date: 
Signature: 
 

 
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Table of Contents 
1. 
Synopsis ......................................................................................................................................... 13 
2. 
Flow Chart ..................................................................................................................................... 18 
3. 
Identification and description of the investigational device and of the Placebo .......................... 19 
3.1 Summary description ................................................................................................................ 19 
3.1.1 
The investigational device ............................................................................................. 19 
3.1.2 
The comparator ............................................................................................................. 20 
3.2 Manufacturer ............................................................................................................................ 20 
3.3 Name or number of the model to permit full identification ..................................................... 20 
3.4 Traceability ................................................................................................................................ 20 
3.5 Intended purpose of the devices in the clinical investigation ................................................... 20 
3.6 Population and indications for which the device is intended ................................................... 20 
3.7 Devices description ................................................................................................................... 21 
3.7.1 
Investigational device .................................................................................................... 21 
3.7.2 
The comparator ............................................................................................................. 22 
3.7.3 
Primary and secondary packaging and labelling ........................................................... 22 
3.8 Investigation Device training/ experience................................................................................. 23 
3.9 Reference to the IFU ................................................................................................................. 24 
4. 
Justification for the design of the clinical investigation ................................................................ 24 
5. 
Risks and Benefits of the Investigational Device and Clinical Investigation .................................. 26 
5.1 Anticipated clinical benefit ........................................................................................................ 26 
5.2 Anticipated adverse device effects ........................................................................................... 26 
5.3 Risk associated with the participation in the clinical investigation ........................................... 26 
5.4 Possible interaction with concomitant treatments as considered under the risk analysis ...... 26 
5.5 Steps that will be taken to control and mitigate the risks ........................................................ 27 
5.5.1 
Healsea® Babykids ......................................................................................................... 27 
5.5.2 
Placebo .......................................................................................................................... 27 
5.5.3 
Mitigation of risk during the clinical investigation ........................................................ 27 
5.6 Rational for the benefit risk ratio .............................................................................................. 28 
6. 
Objectives and hypotheses of the clinical investigation ............................................................... 29 
6.1 Hypothesis ................................................................................................................................. 29 
6.2 Primary Objective ...................................................................................................................... 29 

 
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6.3 Secondary Objectives ................................................................................................................ 29 
6.4 Scientific justification and clinical relevance for effect sizes, non-inferiority margins or 
equivalence ....................................................................................................................................... 29 
6.5 Risks and anticipated adverse effects that are to be assessed ................................................. 29 
7. 
Design of the clinical investigation ................................................................................................ 30 
7.1 General ...................................................................................................................................... 30 
7.1.1 
Design type of clinical investigation .............................................................................. 30 
7.1.2 
Measures to be taken to minimize or avoid bias .......................................................... 30 
7.1.3 
Primary Endpoint with methods and timing for assessing recording and analysing 
variables 31 
7.1.4 
Secondary Endpoints with methods and timing for assessing, recording and analysing 
variables 31 
7.1.5 
Equipment to be used for assessing the clinical investigation variables ...................... 32 
7.1.6 
Any procedures for the replacement of subjects .......................................................... 32 
7.1.7 
Investigation sites: number, location ............................................................................ 32 
7.1.8 
Definition of the completion of the study ..................................................................... 32 
7.2 Investigational device and comparator ..................................................................................... 33 
7.2.1 
Description of the exposure to the investigational device ........................................... 33 
7.2.2 
Description and justification of the choice of the comparator ..................................... 33 
7.3 Subjects ..................................................................................................................................... 33 
7.3.1 
Eligibility Criteria............................................................................................................ 33 
7.3.2 
Point of enrolment and randomization ......................................................................... 35 
7.3.3 
Total expected duration of the clinical investigation .................................................... 35 
7.3.4 
Expected duration of each subject’s participation ........................................................ 35 
7.3.5 
Number of subjects required to be included in the clinical investigation .................... 35 
7.3.6 
Estimated time needed for the enrolment ................................................................... 35 
7.3.7 
Relationship of investigation population to target population ..................................... 35 
7.3.8 
Vulnerable, pregnant and breastfeeding population .................................................... 36 
7.3.9 
Compensation ............................................................................................................... 36 
7.4 Procedures................................................................................................................................. 36 
7.4.1 
Description of clinical investigation-related procedures .............................................. 36 
7.4.2 
Concomitant Medication ............................................................................................... 38 
7.4.3 
Activities performed by sponsor representatives (excluding monitoring) ................... 38 

 
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7.4.4 
Any known/foreseeable factors that can compromise the outcome of the clinical 
investigation and methods for addressing these factors .............................................................. 38 
7.4.5 
Follow-up and medical care after completion of the study .......................................... 39 
7.4.6 
Potential use of samples obtained from subjects ......................................................... 39 
7.5 Monitoring plan ......................................................................................................................... 39 
7.5.1 
Initiation visit ................................................................................................................. 39 
7.5.2 
Monitoring ..................................................................................................................... 39 
7.5.3 
Routine Close-out .......................................................................................................... 40 
7.5.4 
Retention of Documentation......................................................................................... 40 
8. 
Statistical design and analysis ....................................................................................................... 40 
8.1 Analysis population ................................................................................................................... 40 
8.2 Baseline Characteristics ............................................................................................................. 40 
8.3 Primary endpoint ....................................................................................................................... 41 
8.4 Secondary endpoints ................................................................................................................. 41 
8.5 Sample Size calculation and justification .................................................................................. 41 
8.6 Rationale for the number of procedures to be performed by a single user ............................. 41 
8.7 Interim analysis ......................................................................................................................... 41 
8.8 Management of bias (randomization, blinding) ........................................................................ 42 
8.9 Management, justification, and documentation of missing data, including drop-outs ........... 42 
8.10 Procedures for reporting any deviation(s) from the original statistical analysis plan .............. 42 
9. 
Data Management ......................................................................................................................... 42 
9.1 Source documents ..................................................................................................................... 42 
9.2 Methods for data entry and collection ..................................................................................... 42 
9.3 Procedure used for eCRF tracking, data review, database cleaning and issuing/resolving data 
queries. .............................................................................................................................................. 43 
9.4 Procedures for verification, validation and securing of electronic clinical data system ........... 44 
9.5 Procedures to maintain and protect subject privacy ................................................................ 44 
9.6 Methods for database locking at the start of analysis and storage upon completion of the 
clinical investigation .......................................................................................................................... 44 
9.7 Procedure for data retention .................................................................................................... 44 
10. Amendments to the CIP ................................................................................................................ 45 
11. Deviation from Clinical Investigation Plan..................................................................................... 45 
12. Device accountability .................................................................................................................... 45 
13. Ethical consideration ..................................................................................................................... 46 

 
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13.1 Informed Consent ...................................................................................................................... 46 
13.2 Subject confidentiality ............................................................................................................... 47 
13.3 Insurance policy ......................................................................................................................... 48 
14. Vigilance ........................................................................................................................................ 48 
14.1 General ...................................................................................................................................... 48 
14.2 Definitions ................................................................................................................................. 48 
14.3 Reporting in the eCRF ................................................................................................................ 50 
14.4 Investigator’s responsibilities and processing timelines ........................................................... 50 
14.4.1 
Materiovigilance ............................................................................................................ 50 
14.4.2 
Vigilance reporting according to Article 80 of the MDR ............................................... 50 
14.5 Sponsor responsibilities and processing timelines.................................................................... 51 
14.5.1 
Materiovigilance ............................................................................................................ 51 
14.5.2 
Vigilance according to Article 80 ................................................................................... 52 
15. Suspension, or premature termination of the Clinical Investigation ............................................ 52 
16. Publication policy .......................................................................................................................... 53 
17. References ..................................................................................................................................... 54 
List of Appendix ..................................................................................................................................... 55 
Appendix A: IFU ..................................................................................................................................... 56 
Appendix B: Acute Rhinitis Symptoms Severity Questionnaire (English version) ................................. 58 
Appendix C: Primary Notification Form ................................................................................................ 59 
Appendix D: SAE form ........................................................................................................................... 62 
 
 
 

 
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Study Number: LPH-2202 
PRINCIPAL INVESTIGATOR STUDY APPROVAL PAGE 
STUDY: BASICC-LPH 2202 
CLINICAL INVESTIGATION PLAN Version:  
Version 1.1 – 2023.02.02 
 
By signing the hereinafter form, I hereby confirm that I agree: 
 
To conduct the trial described in the Clinical Investigation Plan (LPH-2202) Version 1 dated 
2022-12-14 in compliance with GCP, with applicable regulatory requirements and with the 
Clinical Investigation Plan agreed upon by the sponsor and given approval/favourable opinion 
by the Ethics Committee; 
 
To document the delegation of significant study related duties and to notify the sponsor of 
changes in site personnel involved in the study; 
 
To comply with procedures for data recording and reporting; 
 
To permit monitoring, auditing and inspection; 
 
To retain the trial-related essential documents until the sponsor informs these documents are 
no longer needed. 
 
Furthermore, I hereby confirm that I will have and will use the availability of adequate resources, 
personnel, and facilities for the conduct of this trial. 
 
 
Principal Investigator’s Name:  __________________________________________________ 
 
Principal Investigator’s Title: 
__________________________________________________ 
 
Principal Investigator’s Address: 
 
__________________________________________________ 
 
__________________________________________________ 
 
 
 
Principal Investigator’s Signature: 
 
 
 
Date of signature: 
 
__________________________________________________
 
 
 

 
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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
ARSSQ 
Acute Rhinitis Symptoms Severity Questionnaire 
CA 
Competent Authority 
CIP 
Clinical Investigation Plan 
CRF 
Case Report Form 
CRO 
Clinical Research Organization 
EEC 
European Economic Community 
EC 
Ethics Committee 
FAS 
Full Analysis Set 
GDPR 
General Data Protection Regulation 
GP 
General Practitioner  
IFU 
Instruction For Use 
LPLV 
Last Patient Last Visit 
MDCG 
Medical Devices Coordination Group 
MDR 
Medical Device Regulation 
MedDRA 
Medical Dictionary for Regulatory Activities 
NSAID 
Non-Steroidal Anti-Inflammatory Drugs 
PI 
Principal Investigator 
PMCF 
Post-Market Clinical Follow-up 
PNF 
Primary Notification Form 
PP 
Per Protocol 
PT 
Preferred Term 
SAE 
Serious Adverse Event 

 
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SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event 
URTI 
Upper Respiratory Tract Infection 
 
 

 
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Study Number: LPH-2202 
1. Synopsis 
Sponsor: LALLEMAND PHARMA AG 
Coordinating 
Investigator: 
Assoc. Prof. Rada Markova 
Title: Efficacy and safety of Healsea® Babykids in the treatment of acute infectious 
rhinitis symptoms in children  
Short Title BASICC (BАbykids Spray In Common Cold) 
CIP version: Version 1-2022-12-14 
Competent Authority:  Bulgarian Drug Agency / Central Ethics Committee 
Rationale: Healsea® Babykids is an isotonic saline solution based nasal spray 
supplemented with a natural Symbiofilm® extract (0.04%) isolated from marine 
bacteria. Symbiofilm® is an exopolymeric composition with emulsifying 
properties, in vitro antibiofilm activity and detachment properties against 
various bacterial pathogens involved in respiratory tract infections. 
Symbiofilm® has no bacteriostatic nor bactericidal activities. Symbiofilm® also 
protects in vitro human nasal epithelial cells viability after Rhinovirus, 
Adenovirus, coronavirus OC43 and flu infection. Healsea® Babykids is a nasal 
spray indicated in children above 2 years to clean and moisten the nose during 
colds and rhinitis.  
The common cold is an acute viral infection of the upper respiratory tract, 
involving, to variable degrees, sneezing, nasal congestion and discharge 
(rhinorrhea), sore throat, cough, low-grade fever, headache, and malaise. It can 
be caused by members of several families of viruses; the most common are the 
more than 100 serotypes of rhinoviruses. Acute viral rhinitis is generally self-
limiting. In children where the illness is not self-limiting and extends beyond 7-
10 days, many agree that a bacterial infection is likely. Bacterial over infections 
and progression to a chronic state are favoured by the formation of biofilms, 
which facilitate bacterial growth and persistence as well as reducing antibiotic 
efficacy.  
The aim of this study is to demonstrate that Healsea® Babykids alleviates 
symptoms of the acute rhinitis phase with better efficacy than isotonic saline 
solution used as Placebo. 
Objectives: Primary Objective: 
- To assess the efficacy of Healsea® Babykids on the overall health status score 
of the Acute Rhinitis Symptoms Severity Questionnaire (ARSSQ) in 2-6 years old 
children during a treatment period of 7 to 10 days as compared to Placebo. 
 
Secondary Objectives: 
- To assess the impact of Healsea® Babykids on the duration of each infectious 
rhinitis symptom and on quality of life as compared to Placebo.  
 

 
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- To assess the impact of Healsea® Babykids on the intake of conventional 
common cold medication (antibiotics, antipyretics, mucolytics, decongestants, 
antitussives, systemic and topical corticosteroids) as compared to Placebo.  
 
- Safety: to assess systemic and local tolerance of Healsea® Babykids over the 
study period. 
Endpoints: Primary Endpoint: 
The primary endpoint is the AUC of the global score of the Acute Rhinitis 
Symptoms Severity Questionnaire (ARSSQ) over the first 11 days of symptoms. 
The ARSSQ will be assessed once daily in the evening from Day 1 to Day 8 and, 
if needed, until complete resolution of all symptoms for 2 consecutive days 
(“not sick” at question 1 of the ARSSQ). Due to the study schema, data may be 
censored at Visit 2 (between Day 15 and Day 18 after inclusion). 
 
Secondary Endpoints: 
- Duration of each cold symptom as reported in questions 2 to 7 of the ARSSQ 
(refer to table 1). For each separate symptom, the duration is defined as the 
number of days between Day 1 and the first day the parent reports the patient 
not having this symptom (“Not present”) for 2 consecutive days. 
As mentioned for primary endpoint, duration may be censored at Visit 2. 
- Duration of quality-of-life impairment as reported in questions 8 to 10 of the 
ARSSQ. For each separate activity, the duration is defined as the number of 
days between Day 1 and the first day the parent reports no impact on the 
patient quality of life (“No impact”) for 2 consecutive days. 
 
As mentioned for primary endpoint, duration may be censored at Visit 2. 
- Frequency and number of days of use of concomitant treatments that may 
affect common cold symptoms (antibiotics, antipyretics, systemic or local 
mucolytics, decongestants, antitussives, systemic and topical corticosteroids). 
- Safety: Assessment of adverse event related to acute rhinitis and incidents 
throughout the study. 
Indication: Treatment of acute rhinitis in children 2-6 years old  
Investigation Design: Prospective, Double-Blind Placebo controlled randomized trial 
The study will comprise 2 parts: 
- Part 1 (D1-D11): treatment of the acute phase 
• 
with Healsea® Babykids, 2 puffs in each nostril 2 times per day with a 
minimum of 7-day-treatment period (14 intakes of Healsea® Babykids) 
up to 10 days (20 intakes of the investigational device).  
or  
• 
with isotonic nasal spray (Placebo), 2 puffs in each nostril 2 times per 
day with a minimum of 7-day-treatment period (14 intakes of Placebo) 
up to 10 days (20 intakes of the investigational device).  
 
- 
Part 2 (up to D15/D18): follow-up phase.  
 
Visit 1 (V1) - (Day 1): Screening/Inclusion/Randomization  

 
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Information and provision of the information sheet to legal guardians/parents 
of participants, consent signature, demographic data and medical history, 
ongoing medication, inclusion/non-inclusion criteria, physical and clinical 
examination, baseline assessment of the ARSSQ, randomization, diary 
presentation, treatment dispensation of Healsea® Babykids Nasal Spray or 
Placebo (Isotonic nasal spray) (according to randomization list).  
 
D1-D8 up to D1-D11 (at home):  
Daily completion of the paper diary (questionnaire, adverse events/incidents 
and concomitant medications), Healsea® Babykids /Placebo nasal spray 
treatment daily administration. 
 
Between D8 and D11 (at home): 
End of Healsea® Babykids/Placebo nasal spray treatment.  
 
Up to D15/D18 (at home): 
Daily completion of the diary (adverse events/incidents, concomitant 
medications, ARSSQ if applicable, until the subject feels not sick for two 
consecutive days).  
Visit 2 (V2) – (Day 15-18): end of study 
Diary review, reporting of adverse event/incidents/, compliance, ARSSQ 
completion if “not sick” is not ticked for 2 consecutive days in the previous days.  
 
Number of Subjects: It is planned to enroll a cohort of 200 subjects. 
 
Target Population: Children with symptoms of acute infectious rhinitis 
Permitted and 
prohibited concomitant 
medication 
Permitted concomitant medications during the study: 
o Antipyretics  
o Systemic and/or local mucolytics  
o Local decongestants (to be taken away from nasal score 
assessment, 2 hours minimum) 
o Systemic antihistamines only if taken for more than 4 weeks at 
screening or started at/after screening 
o Local and systemic corticosteroids 
o Antitussive 
o Antibiotics 
Non-permitted concomitant medications: 
o Saline nasal spray 
 
Inclusion/Exclusion 
criteria: 
Inclusion Criteria: 
Subjects will be enrolled if they meet all of the following criteria: 
1. Male/Female subjects >2 and ≤6-year-old  
2. Acute infectious rhinitis/rhinosinusitis for ≤48h before trial entry 
3. Patient presenting with fever ≥ 37.5 °C at screening 

 
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4. Subjects with nasal congestion (blocked / stuffy nose) rated at least as 
moderate on the Acute Rhinitis Symptoms Severity Questionnaire, 
based on evaluation by the investigator  
5. Subjects showing at least moderate grade for at least one of the 
following additional signs of acute rhinitis: runny nose, nasal crust 
(dry mucus), sneezing and cough 
6. Written consent obtained from parent/legal guardians 
Non-inclusion Criteria: 
Subjects will not be enrolled if one of the following criteria is present:  
1. Known hypersensitivity/allergy to any component of the test device 
2. Medical history that is considered by the investigator as a reason for 
non-inclusion,  
3. Severe nasal septum deviation or other condition that could cause 
nasal obstruction such as the presence of nasal polyps 
4. History of nasal or sinus surgery that in the opinion of the investigator 
may influence symptom scores 
5. Antibiotic intake within 2 weeks before screening 
6. Systemic corticosteroids within 4 weeks before screening 
7. Chronic decongestant use 
8. Recent (within the previous 2 days) intake of a common cold medicine 
that in the opinion of the investigator may influence ARSSQ score at 
screening (NSAID, nasal decongestants, cough medicines) 
Number of sites: 8 sites in Bulgaria 
Test Device: Healsea® Babykids nasal spray, class I 
Comparator Device: Isotonic nasal spray used as Placebo 
Duration of 
investigation: 
Duration of inclusion period: 3 months 
Duration of patient’s participation: up to 18 days 
Total study duration: 4 months 
Study Start Date: February 2023 
Statistical Analysis: Variables will be described according to the appropriate summary statistics, 
e.g.: 
⦁ Number and percentages of subjects in each category for categorical data. 
For tabular summaries of percentages, the denominator (e.g. number of 
subjects with non-missing data) will be displayed. 
⦁ Number of observations, mean, standard deviation, median, and range for 
continuous data. 
⦁ Number of observations, number of events, median time for time to event 
data. 
When calculating treatment effects (e.g. differences, hazard ratios, odds ratios) 
and when using treatment arm as a covariate in regression modelling, the 
Placebo arm will be used as the reference group. 
Details of the statistical analyses, methods and data conventions will be 
described in the Statistical Analysis Plan. 

 
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All statistical tests will be 2-sided and performed using a 0.05 significance level. 
 
A multivariate regression model of the AUC of the global score of the ARSSQ 
during the first 11 days will be used to analyse the primary endpoint.  
A Cox survival regression model will be used to analyse the secondary 
endpoints of duration of cold symptoms and of impact of quality of life. 
 
A multivariate Poisson regression model will be used to analyse the secondary 
endpoint related to the number of days of use of conventional common cold 
medications (overall and by therapeutic class). 
A multivariate logistic regression model will be used to analyse the secondary 
endpoint related to the use (yes/no) of conventional common cold medications 
(overall and by therapeutic class). 
 
 
-Safety: Adverse events/incidents will be summarized by the number of 
occurrences, the number and percentage of patients by treatment group, 
classified by System Organ Class and Preferred Term as defined by MedDRA 
dictionary. Only treatment-emergent events will be analysed.  
 
Expected benefits: Healsea® Babykids nasal spray is expected to reduce the symptoms of acute 
rhinitis without any safety concern. 
 
 

 
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2. Flow Chart 
 
 
Acute phase 
Follow-up phase 
Visit name 
Screening/Inclusion 
At home 
At home 
End of study 
Visit Number 
V1 
 
 
V2 
Days 
D1 
D1 to D11 
D12 to End of study 
D15-D18 
Informed consent 
X 
 
 
 
Eligibility criteria 
X 
 
 
 
Demography and Medical history *** 
X 
 
 
 
Physical and clinical examination 
X 
 
 
X 
Baseline assessment of the Acute Rhinitis Symptoms 
Severity Questionnaire 
X 
 
 
 
Ongoing medication 
X 
 
 
 
Randomization  
X 
 
 
 
Treatment (Healsea® Babykids or Placebo)  
X* 
X# 
 
 
Subject paper diary (Acute Rhinitis Symptoms Severity 
Questionnaire**) 
 
 
 
Adverse events/incidents and concomitant medication 
reporting 
 
Compliance  
 
 
 
X 
* Treatment dispensation 
** ARSSQ to be completed with the investigator on site at screening and at the end of the study if the patient still has symptoms (“not sick” not ticked for 2 consecutive days in the previous 
days). After day 8, until complete resolution of symptoms for 2 consecutive days (question 1 of the questionnaire). 
# Treatment from D1 to D8 and up to D11.  
*** Medical History - Relevant medical history in connection to infectious acute rhinitis, allergic rhinitis, nasal disorders and asthma back to 2 years 
 
 

 
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Study Number: LPH-2202 
3. Identification and description of the investigational device and of the 
Placebo 
3.1 Summary description  
3.1.1 The investigational device 
Healsea® Babykids is a CE marked nasal spray composed with an isotonic saline solution (0.9% NaCl) 
and Symbiofilm® (0.04%) (Table 1). Symbiofilm® is a Lallemand proprietary marine postbiotic 
composition including an exopolysaccharide mainly composed of N-acetyl hexosamines, acidic and 
neutral monosaccharides.  
 
Table 1 : Qualitative and quantitative composition of Healsea® Babykids 
Ingredient 
Concentration (g/L) 
NaCl 
9 g/L 
Symbiofilm® 
0.4 g/L 
Purified Water 
QS 1L 
 
Healsea® Babykids is a class I medical device (in accordance with the rule 5 of the annex IX of European 
Council Directive 93/42/EEC). 
In accordance with annex IX of European Council Directive 93/42/EEC, the medical device classification 
is based on the following characteristics:  
-  Duration of continuous use: Short-term (60 min to 30 days)  
- Type of device: Invasive, with respect to body orifice, non-active, not surgically inserted, no 
implantable device  
- Location of action: Nasal cavity  
 
The primary packaging is a plastic bottle with atmospheric pump in 20 ml format. 
 
Healsea® Babykids is a nasal spray indicated in children above 2 years to clean and moisten the nose 
during colds and rhinitis. Healsea® Babykids shall be administered in children with the help of an adult.  
One-two sprays, twice a day in each nostril during 10 days.  
 
The technical performances are summarised below: 
 
Table 2 : Technical performances of Healsea® Babykids 
Component  
Function(s)  
Isotonic Saline Solution 0,9%  
- Improve nasal mucosa function  
- Clean the nasal cavity and eliminate allergens 
and infectious agents  
Symbiofilm®  
- Enhancing the cleansing efficacy  
- Reducing biofilm formation  
 

 
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3.1.2 The comparator 
The comparator is an isotonic saline nasal spray (same primary and secondary packaging) used as 
Placebo.  
Ingredient 
Concentration (g/L) 
NaCl 
9g/L 
Purified Water 
QS 1L 
 
3.2 Manufacturer 
Healsea® Babykids is a class I Medical Device manufactured by Lallemand Pharma. The device is CE 
marked (17 May 2021). The subcontractor for the manufacturing is C.O.C Farmaceutici Srl, Via Chiesa 
Sud, 156 C/D/E/F/G – 41016 Rovereto s/ Secchia - Novi di Modena (MO) - Italy 
Clinical batches (Healsea® Babykids and Placebo) are manufactured by C.O.C Farmaceutici and the 
blinding of the investigational devices is ensured by Creapharm, ZA Air-Space Avenue de Magudas, CS 
2007, 33185 Le Haillan, Email : contact@creapharm.com. 
The Lallemand AG identifier numbers are the following: 75014DJMM (20/04/2022) for Healsea® 
Babykids and 75014DJMQ (22/07/2022) for the Placebo (Isotonic saline nasal solution). 
 
3.3 Name or number of the model to permit full identification 
Because the Investigational Device and the Placebo will be used in a blinded manner, a single lot 
number will be attributed to the devices.  
3.4 Traceability 
The traceability of the Investigational Device and of the Placebo will be insured during the clinical study 
according to the SOP “Investigational Products Management” of the CRO.  
3.5 Intended purpose of the devices in the clinical investigation 
This is a post market clinical investigation, and the devices will be used in the treatment of acute 
infectious rhinitis. 
 
3.6 Population and indications for which the device is intended 
The target population of the study is children of 2-6 years with acute infectious rhinitis. The only 
contraindication is hypersensitivity to one or several of the components. This is a non-inclusion 
criterion. 
 

 
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Healsea® Babykids will be used within its intended purpose i.e., in children to clean and moisten the 
nose during colds and rhinitis, and to clean the nasal cavity and eliminate allergens and infectious 
agents. 
 
The comparator is a saline isotonic nasal spray considered as inert Placebo i.e., neutral for the nasal 
mucosa. Nevertheless, nasal irrigation with isotonic saline solution is known to have some efficacy in 
reducing common cold symptomatology. 
 
3.7 Devices description 
3.7.1 Investigational device 
Healsea® Babykids is a nasal spray (available in 20mL) using the APF (Advanced Preservative-Free) 
technology. This is a spray pump consisting of a white high density polyethylene bottle and a manual 
polyolefine/homopolymer polypropylene actuator holding the nozzle spraying the solution in the 
nostrils. A single activation propels a volume of 100 ± 20 µliters of solution. 
This is a non-sterile device. The primary packaging is described in Figure 1. 
Figure 1: The spray pump 
 
 
The sponsor certified that the Healsea® Babykids Medical Device:  
● does not contain any human blood derivative,  
● does not contain any medicinal product,  
● is not manufactured using tissues of animal origin.  
 
As summarized below, Healsea® Babykids is intended to be used on nasal mucosa. The duration of use 
is 10 days.  
Table 3: Contact with body and total duration treatment 
Type of contact 
Device in contact with a surface 
Type of tissues 
Mucous membranes  

 
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Total duration treatment 
It can be used for 10 days 
 
Healsea® Babykids and the Placebo need to be indistinguishable in the context of a blinded study. The 
subcontractor in charge of the blinding will stick a black-out label on both primary packagings then 
stick a white label with the mentions requested by the regulation.  
3.7.2 The comparator 
The Placebo is a nasal spray (available in 20mL) using the same technology as those described above 
for the investigational device (Figure 1).  
This is a non-sterile device.  
3.7.3 Primary and secondary packaging and labelling  
The primary packaging is a white vial (Figure 2) 
Figure 2: primary packaging 
 
The secondary packaging is a white cardboard box.  

 
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A white label is sticked on the primary packaging with the following mentions:  
 
 
A white label is sticked on the secondary packaging with the following mentions:  
 
 
3.8 Investigation Device training/ experience 
In real life setting, there is no need for specific training in using Healsea® Babykids.  
A usability engineering process test according to the standard EN ISO 62366-1:2015 was conducted on 
Healsea® Babykids with 10 people representatives of the parents/legal guardians of the target 

 
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population to ensure that the leaflet and the label were well understood, and that the medical device 
was used correctly to ensure its safe understanding and use.  
The analysis of the results demonstrates that:  
- The information provided by the user interface is readable and understandable by participants. The 
information tested was easy to understand, without interpretation.  
- The observations made during the simulations of use of the device have confirmed that all safety-
related handling steps are properly followed, in accordance with the instructions given in the 
instruction for use.  
 
Nevertheless, Healsea® Babykids and the comparator will be specially conditioned for this controlled 
and blinded study. An IFU leaflet is included in each secondary packaging: on one face, the IFU of 
Healsea® Babykids, on the other face, the IFU of Healsea® Placebo (see 3.9). During the site initiation 
visit, the investigator will be briefly trained how to use the study devices. After the enrolment, the 
investigator will instruct each parents/legal guardians on how to use the nasal spray on their child. 
 
3.9 Reference to the IFU 
An IFU leaflet is included in each secondary packaging: on one face, the IFU of Healsea® Babykids, on 
the other face, the IFU of Healsea® Placebo (See appendix A). 
 
4. Justification for the design of the clinical investigation 
The common cold is the most frequent upper respiratory tract infection (URTI), which is the most 
commonly treated acute problem in primary pediatric care (1). The common cold is an acute viral 
infection of the upper respiratory tract, involving, to variable degrees, sneezing, nasal congestion and 
discharge (rhinorrhea), sore throat, cough, low-grade fever, headache, and malaise (2). The common 
cold is caused by a variety of viruses.  Improvements in viral detection techniques during the past two 
decades, including various viral antigen detection methods and particularly the advent of PCR-based 
assays, have substantially increased the rates of viral detection in clinical specimens. The relative 
proportions of different viruses in the cause of the common cold vary depending on several factors, 
such as age, season, and viral sampling and detection methods. However, rhinoviruses have been 
consistently found to be the most common cause in all age groups, irrespective of the viral detection 
techniques used. Yearly, rhinoviruses account for about 30–50% of all respiratory illnesses, but during 
the autumn peak season these viruses can cause up to 80% of all upper respiratory infections. 
Coronaviruses and Influenza viruses account for about 10-15% and for 5-15% of acute infectious 
rhinitis respectively. Other viruses such as Respiratory Syncytial virus, Adenoviruses and Parainfluenza 
viruses are less involved (2).  
Acute viral rhinitis is generally self-limiting. In children where the illness is not self-limiting and extends 
beyond 7-10 days, many agree that a bacterial infection is likely (2,3). Acute bacterial rhinosinusitis is 
diagnosed in a child based on several criteria: persistent upper respiratory tract symptoms more than 

 
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10 days (cough or nasal discharge or both); or recurrence of symptoms after initial improvement: fever, 
worsening cough, or worsening or new purulent rhinorrhea; or severe onset of symptoms like fever or 
purulent nasal discharge lasting more than three consecutive days associated with facial tenderness 
or headache. Bacterial over infections and progression to a chronic condition are favoured by the 
formation of biofilms, which facilitate bacterial growth and persistence as well as reducing antibiotic 
efficacy (4,5). Despite the usually benign nature of the illness, the socioeconomic impact of acute 
rhinitis is well established: visits to GP, additional prescriptions and over prescription of antibiotics, 
absence from work, school or day care (1). 
Although clinical evidence from well-designed trials is scarce (6), European and American guidelines 
for acute rhinosinusitis recommend daily nasal saline irrigation for reduction of the severity of 
symptoms and for speeding recovery (2,7). The exact mechanisms by which nasal irrigation works are 
not fully elucidated. However, most of the experts agree that it is primarily a mechanical intervention 
leading to direct cleansing of the nasal mucosa (8,9). The mucus lining the nasal cavity may be softened 
and dislodged. The increase of mucociliary clearance is associated with a decrease of pathogens 
burden. Moreover, inflammatory mediators such as cytokines, prostaglandins and leukotrienes can be 
removed, favoring the resolution of URTIs. Although the impact of the salt concentration of the saline 
solution on all these parameters is still debated, the efficacy of saline irrigation remains moderate (6).  
 
The Healsea® products are a saline-based nasal spray line supplemented with a natural Symbiofilm™ 
extract (0.02% to 0.04%) isolated from the marine flora of the deep seas of the Panarea Islands, in 
Sicily. Healsea® Babykids is an isotonic saline solution (0.9%) with Symbiofilm™ (0.04%). 
Symbiofilm™ is an exopolysaccharide composition secreted by Bacilllus licheniformis LP-T14, a 
Lallemand Pharma proprietary strain, with in vitro antibiofilm activity and detachment properties 
against various bacterial pathogens involved in respiratory tract infections, i.e Haemophilus influenzae 
type b, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and streptococcus 
pneumoniae. Antibiofilm effects of Symbiofilm™ have been reported in vitro, using microtiter plate-
based model and human nasal epithelial cells. The antibiofilm activity of Symbiofilm™ is likely to rely 
on its emulsifying properties. Symbiofilm™ (400 µg/ml) has also been demonstrated to protect in vitro 
human nasal epithelial cells viability after Adenovirus, Rhinovirus, Coronavirus OC43 and Flu infections. 
The technical performances of Symbiofilm ™ may enhance the benefit of saline nasal irrigation for the 
treatment of acute infectious rhinitis and common cold.  
The aim of this investigation is to demonstrate that thanks to the antibiofilm and antiviral properties 
of Symbiofilm™, isotonic saline solution and Symbiofilm™ alleviate symptoms of the acute rhinitis 
phase with better efficacy than isotonic saline solution without Symbiofilm™. 
To demonstrate the efficacy of Healsea® Babykids in common cold, a Double Blind Randomized 
Controlled Study will be performed. The efficacy of the test product will be assessed by comparison 
with an isotonic saline nasal spray. 

 
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5. Risks and Benefits of the Investigational Device and Clinical Investigation 
5.1 Anticipated clinical benefit  
Healsea® Babykids is an isotonic saline solution (0.9%) with Symbiofilm™ (0.04%). 
Healsea® Babykids is indicated in children above 2 years to clean and moisten the nose during colds 
and rhinitis.  
The exact mechanisms by which classic saline nasal irrigation works are not known. However, most of 
the experts agree that it is primarily a mechanical intervention leading to direct cleaning of the nasal 
mucosa. 
The supplementation of the saline solution with Symbiofilm™ impacts the performance of the device. 
Indeed, Symbiofilm™ has also been demonstrated to protect in vitro human nasal epithelial cells 
viability after Adenovirus, Rhinovirus, Coronavirus OC43 and Flu infection.  
Therefore, isotonic saline solution and Symbiofilm™ may act in a synergistic manner to alleviate 
symptoms of the acute rhinitis phase resulting in better efficacy than isotonic saline solution without 
Symbiofilm™ used as Placebo. As a consequence, patients receiving daily administrations of Healsea® 
Babykids are expected to recover more rapidly from common cold than those receiving the Placebo. 
Subjects who receive Placebo will not benefit from as effective a treatment although nasal 
administrations of isotonic saline are well described as cleansing and hydrating the nasal mucosa. 
Nevertheless, these subjects will receive all concomitant treatments necessary in the context of acute 
rhinitis with the exception of other saline solutions. 
5.2 Anticipated adverse device effects 
There is no expected side effect in using Healsea® Babykids nor the Placebo. 
No adverse effect is expected with the Placebo. 
5.3 Risk associated with the participation in the clinical investigation 
The assessments planned in the clinical investigation are questionnaires with no associated risk. 
5.4 Possible interaction with concomitant treatments as considered under 
the risk analysis 
No interaction is expected. Nevertheless, parents/legal guardians will be instructed to respect a 60-
minute minimum interval after administration of the investigational medical device before 
administration of another local medication e.g., decongestant or mucolytics (if permitted) on their 
child. 

 
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5.5 Steps that will be taken to control and mitigate the risks  
5.5.1 Healsea® Babykids 
In line with NF EN ISO 14971:2019 standard (Medical Devices – Application of risk management to 
medical devices), a risk analysis has been conducted to estimate the risks associated with each step of 
the device lifecycle. Most of the risk has been mitigated through product design and manufacturing.  
The residual risk to patients who are administered this intervention is low. A list of potential risks 
associated with the device, procedures undertaken to minimise them, and methods used for their 
management is described in the device Risk Management Process File.  
 
Considering:  
- the risk analysis (ISO 14 971 activities) that demonstrates: 
• 
There is no longer High-level risk,  
• 
That, the 12 Medium risk level residual risks have an acceptable benefit-risk balance,  
• 
And all the others residual risks (62) are at Low risk.  
• 
Healsea® Babykids can be considered as safe and effective  
 
and regarding the evaluation of benefit/risk profile, as detailed in the Clinical evaluation report, 
considering: 
• 
The clinical data of the equivalent device (Physiomer® Spray Hygiène du nez)  
• 
The currently available data on products use for the treatment of nasal cold and flu symptoms 
and the prevention of upper respiratory tract infections  
 
it can be concluded that the benefit/risk ratio of Healsea® Babykids is acceptable, in compliance with 
essential requirements. 
5.5.2 Placebo 
Isotonic saline nasal solutions are well known for cleansing and hydrating the nasal mucosa without 
any safety concern. No risk analysis has been conducted to estimate the risk associated with each step 
of this device lifecycle. Anyway, the residual risk for the Placebo is expected to be lower than for 
Healsea® Babykids since this latter contains Symbiofilm® and isotonic saline solution and therefore 
represents the worst case. Thus, the Placebo used during this study can also be considered as safe.  
5.5.3 Mitigation of risk during the clinical investigation 
Although no obvious specific risk is identified for subjects participating in the study, and according to 
the requirements of ISO 14155:2020, some specific points have been identified requiring particular 
attention to guarantee the safety and the well-being of the subject. 
As the study will be conducted in a blinded manner in minors, stringent risk acceptability thresholds 
per site are defined in the Study Risk Management Plan. Because of the paediatric population of the 
study, any issue with the informed consent process, any major protocol deviation or any serious 
incident are deemed unacceptable and shall trigger an immediate action plan.  

 
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More generally, the number of unreported incident/serious incident or adverse event per site, the 
timelines for materiovigilance/vigilance reporting to sponsor, the dispensation issues (number of 
devices delivered different from the number reported in the e-CRF), inadequate process to ensure the 
traceability of the investigational product, number of patient diary not collected at V2 shall be tracked 
according to the risk management plan in which risk acceptability thresholds are defined. 
All issues shall be tracked according to the risk management plan and shall trigger an immediate action 
plan if the threshold is reached.  
Should a potential unanticipated risk be detected, an action plan will be implemented with no delay.  
5.6 Rational for the benefit risk ratio 
Although infectious rhinitis is in most cases self-limiting, it impacts the children’s quality of life during 
generally about 7 to 10 days. Furthermore, bacterial over-infections with worsening of symptoms can 
occur requiring antibiotic prescription. Progression to a chronic state, i.e. chronic rhinosinusitis is also 
observed.  
Conventional therapies for infectious rhinitis are symptomatic and are not without side effect. For 
example, decongestant use can increase blood pressure, antihistamine intake is associated with 
drowsiness.  
Healsea® Babykids represents an interesting alternative because this nasal spray could alleviate 
infectious rhinitis symptoms but also limit the complication and progression to chronic state. 
Furthermore, there is no expected side effect. 
 
 
 

 
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6. Objectives and hypotheses of the clinical investigation 
6.1 Hypothesis  
Our hypothesis is that Healsea® Babykids nasal spray can improve the symptomatology of acute rhinitis 
with more efficacy than an isotonic saline nasal spray used as Placebo. 
6.2 Primary Objective 
To assess the efficacy of Healsea® Babykids on the overall health status score of the Acute Rhinitis 
Symptoms Severity Questionnaire (ARSSQ) in 2-6 years old children during a treatment period of 7 to 
10 days as compared to Placebo. 
6.3 Secondary Objectives 
- To assess the impact of Healsea® Babykids on the duration of each infectious rhinitis symptom and 
on quality of life as compared to Placebo.  
- To assess the impact of Healsea® Babykids on the intake of conventional common cold medication 
(antibiotics, antipyretics, mucolytics, decongestants, antitussives, systemic and topical corticosteroids) 
as compared to Placebo.  
- Safety: to assess systemic and local tolerance of Healsea® Babykids over the study period. 
 
6.4 Scientific justification and clinical relevance for effect sizes, non-
inferiority margins or equivalence 
This is a PMCF study. The primary endpoint is a customized symptom and quality of life questionnaire. 
An arbitrary cohort of 200 children has been chosen. A cohort of 100 children in the Healsea® Babykids 
arm and 100 children in the Placebo arm is anticipated to allow to demonstrate the interest of using 
Healsea® Babykids in the acute infectious rhinitis. Indeed, 100 patients by arm are enough to detect a 
Cohen’s effect size of 0.4 with a power of 80% and a type I error of 5%. Cohen’s effect size is defined 
as the standardized difference between AUC in groups. According to Cohen’s methodology, 0.4 is an 
intermediate size between a small effect (0.2) and a medium effect (0.5) and is coherent with the 
expected result. The Placebo arm will be used as the reference group. 
 
The recruitment will be performed using a 1:1 randomization ratio.  
 
6.5 Risks and anticipated adverse effects that are to be assessed 
No specific risk for subject participating in the study is identified, provided that the eligibility criteria 
are fulfilled. The safety and well-being of subjects will be monitored throughout the study and a Risk 
Management Plan has defined stringent risk acceptability thresholds (see 5.5.3).  
 
 

 
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7. Design of the clinical investigation  
7.1 General 
7.1.1 Design type of clinical investigation 
This is a two-arm, double-blind, parallel group, randomized controlled trial (RCT). 
The primary endpoint ARSSQ will be assessed once daily. After D8, the ARSSQ will be assessed once 
daily until the subject feels not sick for two consecutive days.  
7.1.2 Measures to be taken to minimize or avoid bias 
Randomization: 
The random product attribution will be performed after checking that the eligibility criteria are 
fulfilled, thus minimizing the selection bias. Each site will receive several treatment blocks in 
accordance with the randomization table generated by Axiodis (blocks of 4). During the V1 visit, the 
investigator will deliver a product (active or placebo) to the patient in chronological order using the list 
of treatments allocated to the respective site. This method allows to maintain the 1:1 balance in a 
multicentric study. 
Example: the site 01 received 3 treatment blocks, i.e. 12 treatments, number 001 to 012. For the 
patient 01-001, the investigator will deliver the treatment 001. The site 02 received 3 treatments 
blocks, i.e 12 treatments, number 013 to 025. For the patient 02-001, the investigator will deliver the 
treatment 013.  
 
Blinding and unblinding: 
The randomization list will be drawn up using a validated software and before the beginning of the 
study, by a statistician (at Axiodis) not involved in the study. The master randomization list will be 
stored confidentially until the study blind is broken at the end of study. 
The randomization list will be: 
- 
Transmitted by the Axiodis statistician to the person in charge of the product preparation, 
Creapharm 
- 
Uploaded into the patient unblinding module of the eCRF 
 
During the whole study and in the absence of unblinding, neither the investigators nor the subjects 
nor the staff involved (CRO, sponsor…) will be aware whether the product is Healsea® Babykids or the 
Placebo. Every effort will be made to maintain the blind during the study as well as during the follow-
up period. 
Both Medical Devices (Healsea® Babykids and Placebo) will be indistinguishable: same aspect, same 
packaging and same labelling of the vials.  
The unblinding will occur after the database locking, at the end of the study. The statistician 
responsible for the randomization list will be in charge of the unblinding.  
 

 
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Emergency Unblinding:  
In case of a medical emergency where knowledge of the blinded treatment is necessary for the 
treatment of an adverse event/incident, the investigator shall perform the unblinding via the 
unblinding module of the eCRF. The investigator shall send an e-mail informing about the unblinding 
with patient ID, date and reason of unblinding (the name of patient not to be communicated for GDPR 
compliance) to: 
• 
The CRO in charge of the study coordination: etudes@bgclinicals.com 
• 
The sponsor (officelp@lallemand.com and rbelloti@lallemand.com (vigilance manager)) 
• 
The statistician if charge of the randomisation list 
The date and the reason for the unblinding will be indicated in the e-CRF and in the source document 
of the study.  
7.1.3 Primary Endpoint with methods and timing for assessing recording and 
analysing variables 
The AUC of the global score of the Acute Rhinitis Symptoms Severity Questionnaire (ARSSQ) during 
first 11 days of symptoms will be compared between both groups.  
ARSSQ is a non-validated customized questionnaire (Appendice 1). It includes 10 items assessing 
symptoms, functional impairments, and global severity. Each item is scored from 0 (not present/no 
impact/ not sick) to 3 (severe, severe impact and very sick) for symptoms, functional impairment and 
global severity respectively. Parents/legal guardians will respond to questions according to the 
evolution of their child's symptoms. This questionnaire is based on the most common symptoms 
reported for children with common cold and on functional impairments easily evaluable by parents. In 
order to evaluate the time dependent efficacy of active/placebo, an AUC computation will be carried 
out.  
The ARSSQ assessment will be completed in a paper diary once daily in the evening, taking into account 
the symptoms from the morning to the evening, within D2-D8 period. After D8, the ARSSQ will be 
assessed once daily until resolution of all symptoms for 2 consecutive days (question 1 of the 
questionnaire “not sick” ticked). At D1, the ARSSQ will be completed during the screening/inclusion 
visit V1. If the patient still has symptoms at V2, (“not sick” not ticked for 2 consecutive days in the 
previous days), the questionnaire will be also completed during the visit. 
To be noticed that the duration may be censored at the end of study participation (visit V2, between 
day 15 and D18 after inclusion). 
 
7.1.4 Secondary Endpoints with methods and timing for assessing, recording 
and analysing variables 
- Comparison of duration of each cold symptom (questions 2 to 7 of the ARSSQ) in both groups.  

 
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For each separate symptom, the duration is defined as the number of days between Day 1 and the first 
day the parent/legal guardian reports the patient not having this symptom (“Not present”) for 2 
consecutive days. 
As mentioned for primary endpoint, duration may be censored at Visit 2. 
- Comparison of duration of quality-of-life impairment (questions 8 to 10 of the ARSSQ). 
For each separate activity, the duration is defined as the number of days between Day 1 and the first 
day the parent/legal guardian reports no impact on the patient quality of life (“No impact”) for 2 
consecutive days. 
As mentioned for primary endpoint, duration may be censored at Visit 2. 
- Comparison of the frequency and number of days of concomitant treatments use that may affect 
common cold symptoms (antibiotics, antipyretics, systemic or local mucolytics, decongestants, 
antitussives, systemic and topical corticosteroids). 
By reducing duration of the common cold symptoms, Healsea® Babykids will very likely reduce the use 
of common rescue medication. Concomitant treatments use will be reported in the paper diary by 
parents/legal guardians throughout the study, validated by the investigator at the end of the study 
visit before being reported in the e-CRF.  
- Safety: Assessment of adverse event related to acute rhinitis and incidents throughout the study in 
both groups. 
Adverse events/incidents will be reported in the paper diary by the parent , validated by the 
investigator at the end of study visit before being reported in the e-CRF.  
 
7.1.5 Equipment to be used for assessing the clinical investigation variables 
No specific equipment is required for the conduct of the study. 
7.1.6 Any procedures for the replacement of subjects 
Not applicable.  
7.1.7 Investigation sites: number, location 
The clinical investigation will be conducted in 8 sites in Bulgaria. All investigators are familiar with acute 
infectious rhinitis and study procedures.  
7.1.8 Definition of the completion of the study 
This is defined as the date of last patient last visit (LPLV). 
 

 
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7.2 Investigational device and comparator  
7.2.1 Description of the exposure to the investigational device 
The investigational device will be Healsea® Babykids. This is a CE marked Medical Device used for acute 
rhinitis and administered by spraying 2 puffs in each nostril 2 times per day with a minimum of 7-day-
treatment period (14 intakes of the investigational device) up to 10 days (20 intakes of the 
investigational device). The patient should stop taking the investigational device before D11 only if the 
question 1 “not sick” of the ARSSQ is ticked YES for 2 consecutive days. 
7.2.2 Description and justification of the choice of the comparator 
Clinical batches are manufactured by C.O.C Farmaceutici and the blinding of the investigational devices 
is ensured by Creapharm, ZA Air-Space Avenue de Magudas CS 200733185 Le Haillan, Email: 
contact@creapharm.com. 
The comparator is an isotonic saline nasal spray indistinguishable from the Healsea® Babykids product.  
We hypothesize that isotonic saline solution and Symbiofilm™ will be more effective that the isotonic 
saline solution for achieving the principal action, i.e. reduction of the duration of acute rhinitis 
symptoms.  
We have chosen isotonic saline solution as Placebo which can be considered as inert solution; 
nevertheless, nasal irrigation with isotonic saline solution is known to have some efficacy in reducing 
common cold symptomatology. Posology, instructions for use, contraindications, precaution of use 
and labelling are identical to those for Healsea® Babykids. 
 
7.3 Subjects 
The target population is children (>2, ≤6 years) with early symptoms of common cold / acute infectious 
rhinitis. 
7.3.1 Eligibility Criteria 
7.3.1.1 
Inclusion Criteria 
Subjects will be enrolled if they meet all of the following criteria: 
1. Male/Female subjects >2 and ≤6-year-old  
2. Acute infectious rhinitis/rhinosinusitis for ≤48h before trial entry 
3. Patient presenting with fever ≥ 37.5 °C at screening 
4. Subjects with nasal congestion (blocked / stuffy nose) rated at least as moderate on the Acute 
Rhinitis Symptoms Severity Questionnaire, based on evaluation by the investigator  
5. Subjects showing at least moderate grade for at least one of the following additional signs of 
acute rhinitis: runny nose, nasal crust (dry mucus), sneezing and cough 
6. Written consent obtained from parent/legal guardians 

 
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7.3.1.2 
Non-inclusion Criteria 
Subjects will not be enrolled if one of the following criteria is present:  
1. Known hypersensitivity/allergy to any component of the test device 
2. Medical history that is considered by the investigator as a reason for non-inclusion,  
3. Severe nasal septum deviation or other condition that could cause nasal obstruction such as 
the presence of nasal polyps 
4. History of nasal or sinus surgery that in the opinion of the investigator may influence symptom 
scores 
5. Antibiotic intake within 2 weeks before screening 
6. Systemic corticosteroids within 4 weeks before screening 
7. Chronic decongestant use 
8. Recent (within the previous 2 days) intake of a common cold medicine that in the opinion of 
the investigator may influence ARSSQ score at screening (NSAID, nasal decongestants, cough 
medicines) 
 
7.3.1.3 
Withdrawal Criteria and procedures 
The reasons for a subject’s premature withdrawal from the study may be the following: 
• 
A parent/legal guardian can withdraw his/her consent from the study for any reason at any 
time but he/she must inform the investigator. In all cases, whenever possible, the investigator 
should attempt to contact the parent/legal guardian as soon as possible for a final assessment 
in order to: 
o Obtain the reason(s) for withdrawal and report it/them in the Case Report Form,  
o Evaluate the patient’s clinical condition, 
o If necessary, take appropriate therapeutic measures: management of an adverse 
effect or concomitant disease, prescription of another treatment. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
• 
If any clinical adverse event, incident or other medical condition or situation occurs such that 
continued participation in the study would not be in the best interest of the participant 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation. The monitor will be immediately 
informed by phone or e-mail A letter or report explaining the withdrawal will be forwarded to 
the monitor as soon as possible. 
In these cases, a premature end of study visit will be scheduled. Available data will be retained for the 
safety/efficacy analysis.  
It should be noted that COVID-19 is not an exclusion criterion. Nevertheless, the investigator may 
consider on a case-by-case basis that a subject should be withdrawn from the study prematurely.  
7.3.1.4 
Subject lost to follow-up 
If a parent/legal guardian cannot be contacted to collect follow-up information even beyond the 7 days 
from visit 2, the patient will be considered “lost to follow-up”. But before declaring that a patient is 

 
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"lost to follow-up", the Principal Investigator (or his/her team) must do his/her best effort to contact 
parent/legal guardian and attempts should be made via all available routes.  
The methods used to attempt contacting the parent/legal guardian should be noted in the patient 
medical file. 
7.3.1.5 
Subject replacement  
It is not anticipated to replace withdrawal patients.  
7.3.2 Point of enrolment and randomization 
The subjects will be recruited by the sites among outpatients coming in consultation because of early 
symptoms of common cold.  
The study participation can be proposed to parents/legal guardians of children coming for 
consultation.  
In order to facilitate the enrolment, the site may choose to inform parents/legal guardian of this clinical 
investigation before this visit.  
Before performing any study procedure, the investigator will give all the information pertaining to the 
study. Parents/legal guardians will have the opportunity to carefully review the information document 
and ask questions prior to accepting or not to participate in the study. The children will also receive an 
information specific to their age. The subject will be enrolled in the study just after the consent 
signature. 
 
7.3.3 Total expected duration of the clinical investigation  
The total study duration is planned to be 4 months.  
7.3.4 Expected duration of each subject’s participation 
The duration of each patient’s participation is up to 18 days.  
7.3.5 Number of subjects required to be included in the clinical investigation 
A cohort of 200 patients is expected to participate in the study.  
7.3.6 Estimated time needed for the enrolment 
Based on the number of participating sites, an enrolment period of 3 months is considered sufficient 
to enrol the cohort of 200 patients.  
7.3.7 Relationship of investigation population to target population 
Healsea® Babykids will be used within its intended use, in children above 2 years with acute infectious 
rhinitis. This post-market clinical investigations aims to demonstrate that isotonic saline solution and 

 
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Symbiofilm™ act in a synergistic manner to alleviate symptoms of the acute rhinitis phase resulting in 
better efficacy than isotonic saline solution without Symbiofilm™. 
7.3.8 Vulnerable, pregnant and breastfeeding population 
Patient under tutorship or legal guardianship are not eligible.  
Pregnant and breastfeeding women: not applicable because it is a paediatric observational study.   
7.3.9 Compensation 
A compensation of 200 BGN for costs resulting from participation in the clinical investigation 
(transportation, absence of work…) will be paid to the parents of each patient having completed the 
study (diary completion and availability for visits).   
7.4 Procedures  
7.4.1 Description of clinical investigation-related procedures  
The clinical investigation is divided into 2 parts: 
- 
Part 1 (D1-D11): treatment of the acute phase with Healsea® Babykids/Placebo, with a minimum 
of 7-day-treatment period (14 intakes of investigational device) up to 10 days (20 intakes of 
investigational device).  
- 
Part 2 (up to D15/D18): follow-up phase.  
The clinical investigation comprises 2 visits.  
Visit 1 (V1) - (Day 1): Screening/Inclusion/Randomization  
Parents/legal guardians of children with symptoms of acute infectious rhinitis for ≤48h will go to the 
site for the screening/inclusion visit (visit 1). The investigator will give oral information relative to the 
study and will answer all questions relative to the study participation. Appropriate information using 
drawings will be also delivered to the child. If both parents/legal guardians agree that their child 
participate in the study, they will receive the information sheet and will be also asked to give a written 
consent. In case one parent should not be available for the visit; he/she will be asked to confirm in 
writing that he/she agrees with the participation of the child in the study. Each screened subject will 
be assigned a subject identifier number during screening that will be used on all subject 
documentation. The subject identifier number will contain the site number and the subject number 
and will be assigned in numerical order at the screening visit based on chronological order of screening 
dates (e.g., 01-010 for the 10th subject screened at the Site #01). 
The investigator or his/her delegated designee will: 
• 
Record demographic data, medical history and ongoing medication. 
• 
Perform a physical and clinical examination. 
• 
Instruct the parents/legal guardian of the patient to complete the baseline ARSSQ 
questionnaire, The investigator/designee will then rate patient nasal congestion symptoms 
and additional signs of acute rhinitis (runny nose, nasal crust, sneezing, cough) 

 
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• 
Verify that eligibility criteria are fulfilled. 
• 
Explain to the parents/legal guardians how to complete every day the paper diary ARSSQ 
recording, how to report concomitant medications, adverse events/incidents.  
• 
Remind the parents/legal guardians to return the device for assessment of compliance to the 
treatment at V2 and to bring back the paper diary at the study end. 
The investigator will provide the parents/legal guardians with the device according to the site specific 
treatment list, in order to respect the 1:1 randomization (blocks of 4). The investigator will explain how 
to use it.  
NB: The first use of the device will be performed in the evening of the Day 1.  
D1-D8 up to -D11 (at home):  
The Parent/legal guardian will be asked to complete the ARSSQ in the diary, once daily in the evening. 
The symptoms occurring from the morning to the evening should be taken into consideration. The 
ARSSQ shall be scored at least from D1 to D8. Adverse events/incidents and concomitant medications 
are to be reported during the whole period 
Between D8 and D11 (at home): 
End of Healsea® Babykids/Placebo nasal spray. 
 NB: The last study nasal spray intake will be performed between D8 and D11 in the 
morning. The patient should stop taking the investigational device before D11 only if 
the question 1 “not sick” of the ARSSQ is ticked YES for 2 consecutive days. 
Up to D15/D18 (at home): 
Parents/legal guardians will continue to complete the paper diary daily (incidents/adverse 
events/expected undesirable sides effects, concomitant medications). For patients for whom common 
cold symptoms persist, parents/ legal guardians will be instructed to continue to complete the ARSSQ, 
until the subject feels not sick for two consecutive days.  
Visit 2 (V2) – (Day 15-Day 18): end of study 
The investigator or his/her delegated designee will: 
• 
Perform a physical and clinical examination.  
• 
Collect the patient diary. 
• 
Review the paper diary to validate adverse events pertinent in the context of the common 
cold, incidents linked to medical device use and concomitant medications reported by the 
parents/legal guardians. Complete the e-CRF accordingly and report any new relevant safety 
events. 
• 
Ask parents/legal guardians to complete the ARSSQ if the patient still has symptoms. 
• 
Assess the compliance to the treatment by weighing the device bottle returned by the 
parents/legal guardians. If a nasal spray is not returned or lost, the investigator will ask the 

 
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parents/legal guardians to specify the number of missed nasal spray uses and will report the 
data into the e-CRF. 
7.4.2 Concomitant Medication  
7.4.2.1 
Permitted concomitant medications during the study: 
o Antipyretics  
o Systemic and/or local mucolytics  
o Local decongestants (to be taken away from nasal score assessment, 2 hours 
minimum) 
o Systemic antihistamines only if taken for more than 4 weeks at screening 
o Antitussive 
o Antibiotics  
o Local or systemic corticosteroids 
o  
7.4.2.2 
Non-permitted concomitant medications: 
o Saline nasal spray 
 
7.4.3 Activities performed by sponsor representatives (excluding monitoring) 
The sponsor has delegated to the CRO the provision of tasks relative to the project management, 
medical writing, clinical operations, data management and statistics, and site(s) oversight. These 
delegated tasks have been established through a Study Management Plan, signed by both parties.  
The CRO will rely on its in-force Quality Management System to ensure that the clinical investigation 
is conducted and monitored, and that data are generated, documented, recorded, evaluated and 
reported in compliance with the ISO 14155:2020, the CIP, any subsequent amendment(s) and any 
other applicable standards and in accordance with the regulation requirements. The CRO will ensure 
the management of ongoing risk in close collaboration with the sponsor throughout the clinical 
investigation and will take all measures to protect rights, safety and well-being of patients who 
participate in the study.  
Tasks still under sponsor responsibility: 
• 
Reporting of non-compliance trends and safety issues to the Ethics Committee/Competent 
Authorities and investigators. 
• 
Triggering audit to be performed if applicable. 
 
7.4.4 Any known/foreseeable factors that can compromise the outcome of the 
clinical investigation and methods for addressing these factors 
There is no known/foreseeable factor that can compromise the outcome of the clinical investigation. 

 
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7.4.5 Follow-up and medical care after completion of the study 
The patients will receive all treatments needed if the common cold is not cured or in case of 
complication or safety issues. In this case, the patient will be followed until the end of the issue.  
7.4.6 Potential use of samples obtained from subjects 
Not applicable.  
7.5 Monitoring plan  
A risk-based monitoring plan included in a separate document will describe in detail who will conduct 
the monitoring, at what frequency monitoring will be done, at what level of detail monitoring will be 
performed, and the distribution of monitoring reports. Results of the risk assessment will be used to 
develop a risk-based monitoring plan and a supporting rationale. 
7.5.1 Initiation visit  
The study will only start at a site after: 
• 
The Ethics Committee has granted approval and the Competent Authority has been notified 
for the conduct of the study,  
• 
Essential documents are in place, such as CVs of the Investigators and site staff, and the Clinical 
Trial Agreement signed.  
In agreeing to participate, the investigator undertakes to strictly comply with the study protocol, Good 
Clinical Practice, the Bulgarian regulation and to MDR. Investigator also guarantees the authenticity of 
the data collected in the context of the study and agrees to the legal provisions for study sponsor 
quality control.  
7.5.2 Monitoring 
Study monitoring delegated by Lallemand Pharma AG to the CRO will be performed at various stages 
of the study. Monitoring will include on-site visits and centralized data review to ensure that the 
investigation is conducted according to the CIP and comply with applicable regulations and deadlines. 
On-site review of electronic Case Report Form (e-CRFs) will include the review of forms for 
completeness, clarity, and consistency with source documents available for each subject. In case of 
queries, investigators should respond within agreed timelines. 
Investigators must permit study-related monitoring visits, audits review by the Ethics Committee, and 
Competent Authority and allow direct access to source data and source documents provided that 
subject confidentiality is protected. In case of an audit initiated by Lallemand Pharma, the investigator 
will receive written notification in advance.  

 
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7.5.3 Routine Close-out 
Routine close-out procedures will be conducted ensuring that the PIs records are complete, all 
documents needed for the sponsor files are retrieved, remaining clinical investigation materials are 
disposed of, previously identified issues have been resolved. 
7.5.4 Retention of Documentation 
Principal Investigators will retain all copies of the records for a period of 10 years from the completion 
of the clinical investigation. In any circumstances, PIs must contact the sponsor prior to disposing of 
any records related to the clinical investigation. Should the data be no longer required for regulatory 
purposes then the confidential destruction of said documents will be approved.  Should the data be 
maintained for longer, Lallemand Pharma AG will make this information available to all appropriate 
bodies in the same way. A list of essential documents to be maintained will be provided to each site at 
initiation. 
Should a PI have to move/retire, or otherwise leaves his(her) position, he(she) will provide Lallemand 
Pharma AG with the name and address of the person assuming responsibility for records relating to 
this clinical investigation.  
 
8. Statistical design and analysis 
The statistical analysis will be detailed in the Statistical Analysis Plan. This section provides a summary. 
8.1 Analysis population 
The safety population consists in all the patients included in this study who will have used the nasal 
spray at least once. 
Full Analysis Set (FAS): all subjects who will have used the nasal spray at least once and with at least 
one post-baseline efficacy data. 
Safety endpoints will be assessed on the safety population. 
The analysis of primary and secondary endpoints will be performed on the FAS population. 
8.2 Baseline Characteristics 
Variables will be described according to the appropriate summary statistics, e.g.: 
⦁ Number and percentages of subjects in each category for categorical data. For tabular summaries of 
percentages, the denominator (e.g. number of subjects with non-missing data) will be displayed. 
⦁ Number of observations, mean, standard deviation, median, and range for continuous data. 
⦁ Number of observations, number of events, median time for time to event data. 

 
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When calculating treatment effects (e.g. differences, hazard ratios, odds ratios) and when using 
treatment arm as a covariate in regression modelling, the Placebo arm will be used as the reference 
group. 
 
All statistical tests will be 2-sided and performed using a 0.05 significance level. 
8.3 Primary endpoint 
In order to analyze the primary endpoint, a multivariate regression model of the AUC of the global 
score of the ARSSQ during the first 11 days will be used. 
 
 
8.4 Secondary endpoints 
A Cox survival regression model will be used to analyse the secondary endpoints of duration of cold 
symptoms and of impact on quality of life. 
 
A multivariate Poisson regression model will be used to analyse the secondary endpoint related to the 
number of days of use of conventional common cold medications (overall and by therapeutic class). 
 
A multivariate logistic regression model will be used to analyse the secondary endpoint related to the 
use (yes/no) of conventional common cold medications (overall and by therapeutic class). 
 
-Safety: Adverse events/ incidents will be summarized by the number of occurrences, the number 
and percentage of patients by treatment group, classified by System Organ Class and Preferred Term 
as defined by MedDRA dictionary. Only treatment-emergent events will be analysed.  
 
Frequency and percentage of patients with at least one reported adverse event/ incident / expected 
side effects will be tabulated by System Organ Class and by treatment group. 
 
8.5 Sample Size calculation and justification 
See 6.4 
8.6 Rationale for the number of procedures to be performed by a single 
user 
Only non-burdensome and non-invasive procedures are planned in the study investigation, mainly a 
short questionnaire. Two visits are scheduled to assess the study criteria.  
8.7 Interim analysis 
Not applicable.  

 
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8.8 Management of bias (randomization, blinding)  
See section 7.1.2 
8.9 Management, justification, and documentation of missing data, 
including drop-outs 
For subject who stop completing the ARSSQ before D11 (see 7.4), the Last Observation Carried Forward 
(LOCF) imputation will be used. Other missing data for the primary endpoint (ARSSQ) will be estimated 
by interpolation.  
8.10 Procedures for reporting any deviation(s) from the original statistical 
analysis plan 
Any deviation(s) from the original statistical analysis plan will be reported in the final statistical analysis 
plan and in the clinical investigation report.  
9. Data Management 
Subject data will be entered into an electronic case report form (eCRF).  
9.1 Source documents 
The source documents (e.g., medical file, clinical and office charts, study worksheets, log for 
compliance data…) which contain the source of data being recorded in the eCRF should be specified. 
The paper diary will be used as source document for ARSSQ, concomitant treatments and adverse 
events/incidents reported by parents/legal guardians.  
Each subject will be assigned and identified by a unique screening number. Any reference made to an 
individual subject within the study must be done using the unique screening number.  
9.2 Methods for data entry and collection 
A validated electronic case report form (eCRF, 21 CFR Part 11 compliant) will be used to collect clinical 
data for this study. Some of the study data will be recorded in the paper diary by parents/legal 
guardians: 
• 
Daily ARSSQ 
• 
Adverse events/incidents 
• 
Concomitant treatments 
Investigators will validate adverse events pertinent in the context of the common cold, incidents linked 
to medical device use and concomitant medications reported in the paper diary. They will complete 
the e-CRF accordingly. 

 
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The sponsor is responsible for designing the e-CRF. eCRF training will be provided to appropriate 
personnel before/at initiation of the investigation site. Parents/legal guardians will be instructed how 
to complete the paper diary during visit V1.  
9.3 Procedure used for eCRF tracking, data review, database cleaning and 
issuing/resolving data queries.  
The Data Management process includes all activities related to data handling regarding: 
• 
Set-up of eCRF and database 
• 
Specification of on-line checks 
• 
Data entry/Data editing 
• 
Export of data from e-CRF to SAS database 
• 
Creation of post-entry checks and listings 
• 
Clean-file process including execution of post-entry checks and listings 
• 
Post clean-file tasks 
Data entry will be done by investigators and other authorized personnel at the sites. When entering 
data, on-line checks are encoded in the eCRF for consistency and validation. Whenever required, 
queries issued from this review will be submitted to the investigator for resolution and then tracked 
until corrections are entered and validated.  
A data blind review meeting will be held prior to database lock.  
The data review meeting prepared by the project manager, data manager, study monitor, medical 
manager and statistician will be attended by at least the following: 
• 
Coordinating investigator, 
• 
Study monitor, 
• 
Sponsor Vigilance representative, 
• 
Project managers from the sponsor and from the CRO, 
• 
Data manager, 
• 
Statistician. 
The review is also required for defining the analysis populations and validating the statistical analysis 
plan.  
The meeting will be documented by written and signed minutes that will act as the basis for data 
processing by the Biometrics Department. 
All decisions on the evaluability of the data from each individual subject for the statistical analysis must 
be made and documented before locking the database.  
Data will be retained for at least 10 years after investigation closure. All data collected in the electronic 
Case Report Forms will be handled and archived under the responsibility of Lallemand Pharma.  
 

 
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9.4 Procedures for verification, validation and securing of electronic clinical 
data system 
The EXAGIS software is installed on a Linux server (secure Data Center) hosted at the OVH company 
that guarantees the security, maintenance, as well as regular antivirus and firewall updates of this 
dedicated server. Any modification to the data is tracked, i.e. creation and changes are timestamped 
and authors are recorded. Software access is restricted to authorized users using individual encrypted 
passwords. Data processing via SAS software (SAS Institute, Cary, NC, USA) is carried out on a Windows 
2012 R2 production server at OVH, using direct access by SAS or MySQL Workbench. 
9.5 Procedures to maintain and protect subject privacy 
It is the responsibility of the sponsor to maintain a security system that prevents unauthorized access 
to the data, both internally and externally.  
Subject privacy is protected through the EXAGIS system at different levels to preclude unauthorized 
access to data:  
• 
Only authorized persons can access the data: 
Access to the database is restricted to authorized users using individual encrypted passwords. For all 
co-workers (from remote or on-site), an identification via a VPN is mandatory. Then, access to each 
server is always done through an authentication with a login and a personal password.  
• 
The risk of data breaches: 
The risk is minimized by full encryption and controlled access. 
  
• 
External/internal interactions are actively protected:  
A standard operating procedure (SOP) details all processes implemented for ensuring network 
security. This SOP mentioned the following subjects: system update, antivirus, antimalware, VPN 
management, user access accounts, password policy, training and awareness of coworkers, and data 
transfer security with partners/clients.  
 
9.6 Methods for database locking at the start of analysis and storage upon 
completion of the clinical investigation 
The validated database will be locked upon request of the Data Manager following the completion of 
all steps required, i.e. resolution of all queries, validation of the coding, data review meeting. 
 
9.7 Procedure for data retention 
Once the Clinical Investigation Report is signed and validated, the data are archived on a dedicated 
hard disk file with limited access rights. This specific file is mounted on AXIODIS’s OVH server with a 
back-up every two months as well as copied to an external disk that will be stored under seal within 
the premises of AXIODIS. The data are conserved for at least 10 years. 

 
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10. Amendments to the CIP 
Investigators should not implement any changes of the protocol without agreement by the sponsor. 
All changes to the protocol are subject to an amendment which must be dated and signed by the 
sponsor and Principal Investigators and must appear as an amendment to the protocol.  
Substantial amendments are notified to the EC and CA.  
11. Deviation from Clinical Investigation Plan 
A major protocol violation is a deviation that has an impact on subject safety, may substantially alter 
risks to subjects, may have an effect on the integrity of the study data, or may affect the subject's 
willingness to participate in the study. In this PMCF study, the following deviations are considered 
major:  
• 
Non-compliance with the inclusion or exclusion criteria,  
• 
No assessment of the primary efficacy criterion (ARSSQ) at D1, D5±1 and D8-1 during the 
treatment period,  
• 
Intake of wrong treatment, i.e, wrong treatment given to the patient after randomization 
• 
A compliance to study product intake below 80% or greater than 120% 
• 
Intake of forbidden medication, i.e., nasal irrigation  
All other cases will, a priori, be considered as minor deviations. 
All protocol deviations will be managed as per the Standard Operating Procedures of the CRO. 
A deviation log shall be maintained by the study site. 
All deviations will be included, as required in the final study report. 
Any major deviation from the protocol that has not been previously approved by the sponsor must be 
reported to the sponsor within 2 working days of the deviation occurrence. Any deviations from the 
clinical investigation plan that are identified during routine monitoring visits will be reported to the 
sponsor within 24 hours of being identified. 
In case of major deviation, corrective and preventive actions will be implemented as per Study 
Deviation Management plan and Risk management plan.  
12. Device accountability 
The device accountability will be performed all over the study according to the SOP “Investigational 
Product Management” of the CRO. Briefly, sites will complete an accountability log after each receipt 
of the Medical Device and dispensation to parents/legal guardians. The CRA in charge of the site 

 
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monitoring will check the accountability log at each visit. At V2, the compliance will be assessed by 
weighing the device brought back by the parents/legal guardians.  
Return of unused or expired investigational devices to the sponsor will be tracked using a specific 
record. 
 
13. Ethical consideration 
13.1 Informed Consent 
According to Regulation EU 2017/745, ISO 14155:2020 and applicable Bulgarian regulations, the 
Principal Investigator or his/her authorized designee must explain all aspects of the clinical 
investigation that are relevant to the parents/legal guardians’ decision for their child participation 
throughout the clinical investigation before any study procedure.  
In order to ensure that the parents/legal guardians are fully informed the investigator must explain 
the nature of the clinical investigation, including any risks and benefits, its purpose and procedures, 
and expected duration of involvement in the clinical investigation. It must be made clear to the 
parents/legal guardians that participation of their child in the clinical investigation is voluntary and a 
decision not to participate will not affect their child right to the most appropriate treatment/care or 
affect the relationship with the doctor. Patients/legal guardians will have the opportunity to carefully 
review the information document and ask questions prior to accepting or not to participate in the 
study.  
As this investigation is interventional, the consent shall be obtained in writing by both parents (except 
in specific situations as divorce with sole custody, widowhood) and the study participation must be 
documented in the patient medical file. But considering the specifics of the population, the children 
are not chronically ill, and that the screening/inclusion in the study can’t be pre-planned, the written 
consent of only one parent at the screening visit is deemed acceptable with some conditions. Indeed, 
in case one parent would not be available for the visit, an oral consent (phone call) must be collected 
by the investigator during the visit and documented in the patient medical file. The second parent will 
be asked to sign the consent form at the earliest opportunity and to send it by e-mail to the investigator 
or to provide it on the next visit. The original of ICF with the signature of both parents shall be filed in 
the patient medical file. 
In accordance with the “Ethical considerations for clinical trials on medicinal products conducted with 
minors” (Rev.1; 18 Sep 2017), no written assent will be collected for the children, because written 
assent is evaluated not to be obtainable before the school age (6-7 years). But, because children from 
the age of 3-4 years have some capacity of understanding, age- and maturity-appropriate information 
will be delivered by the investigator and the parents. Since textual information is not usable by most 
of these children, visual information using drawings will be used to ensure that the child is properly 
informed. The agreement of a child should be requested systematically, even if the assent is not legally 
required. Their refusal or dissent should be respected.   
Parents/legal guardians reserve the right to withdraw from the clinical investigation at any time, 
irrespective of their initial consent. Objections raised by a child at any time during the trial should also 

 
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be considered. The child’s will should be respected. The child should not be forced to provide reasons. 
The child should be informed of the possibility to freely withdraw from the trial, at any time for any 
reason, without any disadvantage or prejudice. 
 
13.2 Subject confidentiality 
The present study will be conducted under Regulation 2016/679/EU of the European Parliament and 
of the Council of 27 April 2016 on the protection of natural persons about the personal data and free 
movement of such data (GDPR) and PERSONAL DATA PROTECTION ACT, in force as from 1 January 2002. 
In accordance with GDPR, the Sponsor is the “Controller” and the participating sites, monitors, data 
managers and statisticians are “Processors”. Lallemand Pharma AG, sponsor of the study, is 
responsible for the processing of the study data. 
Confidentiality of data shall be observed by all parties throughout the clinical investigation. All data 
will be secured against unauthorized access. Subject names will not be sent to the sponsor. Only the 
patient number will be recorded in the eCRF, and if the patient’s name appears on any document, it 
must be obliterated before a copy of the document is supplied to the sponsor. All subject data that 
appear in reports and publications will be anonymised such that the privacy and confidentiality of each 
subject is maintained. 
No data processing will be performed outside of the European Union. 
To fulfil the requirements of source data verification, the PI will be required to obtain consent from 
each parent/legal guardian stating that they agree for their child’s medical records to be accessed (this 
will form part of the consent process). To comply with GDPR, a specific document explaining the 
lawfulness of personal data processing conditions and patients’ rights will be signed before any study 
procedure by the parents/guardians. 
The patients’ rights are the followings:  
• 
The right to request access to, rectification, deletion or restriction of processing concerning 
personal data collected during the study,  
• 
The right to get back all data linked to the research and to forward them to another data 
processing manager (portability right),  
• 
The right to withdraw consent to data collection at any time and to request a restriction of 
processing concerning personal data as mentioned in GDPR’s article 18. However, the data 
processing manager keeps the ability to reject such request should this right likely make 
impossible or seriously compromise the achievement of the research objectives.  
These rights can be exercised with the investigator or his designated representative or by contacting 
the Data Protection Officer appointed by Lallemand Pharma: Yannick Hervy, yhervy@lallemand.com. 

 
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13.3 Insurance policy 
Lallemand Pharma AG has an insurance policy intended to guarantee against possible damage resulting 
from the investigation. 
It is advisable to underline that non-compliance with the Research Legal Conditions is a cause for 
guarantees exclusion. 
 
14. Vigilance 
14.1 General 
Healsea® Babykids will be used in the intended use covered by the CE mark in this PMCF study. 
Pursuant to (EU)2017/745 Medical Device Regulation, for a post market clinical follow-up investigation 
of a medical device used within the intended use covered by the CE-mark, requirement of MDR articles 
87 to 90 apply (materiovigilance).  
Nevertheless, if a causal relationship between a serious adverse event and an investigational 
procedure has been established, the safety reporting laid down in Article 80 of the MDR. Since the 
electronic system referred to in Article 73 (Eudamed) will not be available and fully functional at the 
date of study start, the procedures for safety reporting will be performed according to modalities 
described in the MDCG 2020-10/1 and -10/2. 
All modalities of safety reporting will be detailed in a Safety Management Plan signed by the sponsor’s 
vigilant, the Principal Investigators, the local CRA in charge of the monitoring and a representant of the 
CRO. 
 
14.2 Definitions  
Incident means any malfunction or deterioration in the characteristics or performance of a device 
made available on the market, including use-error due to ergonomic features, as well as any 
inadequacy in the information supplied by the manufacturer and any undesirable side-effect (MDR 
2017/745).  
Serious incident means any incident that directly or indirectly led, might have led or might lead to any 
of the following: (a) the death of a patient, user or other person, (b) the temporary or permanent 
serious deterioration of a patient's, user's or other person's state of health, (c) a serious public health 
threat (MDR 2017/745).  
Serious public health threat means an event which could result in imminent risk of death, serious 
deterioration in a person's state of health, or serious illness, that may require prompt remedial action, 

 
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and that may cause significant morbidity or mortality in humans, or that is unusual or unexpected for 
the given place and time (MDR 2017/745).  
Expected and foreseeable side effects (MEDDEV 2 12-1 rev. 8) 
They meet all the following criteria:  
• 
Clearly identified in the manufacturer's labelling,  
• 
Clinically well known as being foreseeable and having a certain qualitative and quantitative 
predictability when the device is used and performs as intended,   
• 
Documented in the device master record, with an appropriate risk assessment, prior to the 
occurrence of the incident and,  
• 
Clinically acceptable in terms of the individual patient benefit.  
 
Adverse event means any untoward medical occurrence, unintended disease or injury or any 
untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other persons, 
in the context of a clinical investigation, whether related or not related to the investigational device 
(MDR 2017/745).  
 
Adverse or intercurrent events are graded as follows: 
• 
Mild:  
Awareness of signs or symptoms but easily tolerated. 
• 
Moderate:  Uncomfortable enough to cause interference with usual activity. 
• 
Severe:  
Incapacity with inability to work or do usual activity.  
 
Serious adverse event (SAE) (MDR Article 2(58)): 
Any adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, that resulted in any of the following: 
i. 
life-threatening illness or injury, 
ii. 
permanent impairment of a body structure or a body function, 
iii. 
hospitalisation or prolongation of patient hospitalisation, 
iv. 
medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
v. 
chronic disease, 
c) foetal distress, foetal death or a congenital physical or mental impairment or birth defect  

 
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14.3 Reporting in the eCRF  
At V2, the investigator will validate the adverse events/incidents and concomitant medications 
reported in the paper diary by questioning the parent/legal guardian of the patient.        
All serious and non-serious incidents/serious and non-serious risk of incidents/serious and non-serious 
adverse event (pertinent in the context of the common cold, additional study procedures and of the 
medical device use) occurring during the clinical investigation will be reported in the eCRF.  
 
14.4 Investigator’s responsibilities and processing timelines 
14.4.1 Materiovigilance  
All incidents will be reported to LP vigilance manager according to MDR, MEDDEV 2.12 rev 8 modalities, 
national requirements, ISO 14155:2020 and Lallemand Pharma procedures which are described in the 
safety management plan. This document will be signed by the Principal Investigators of all participating 
sites, representants of the Clinical Research Organization (CRO), CRA in charge of the monitoring and 
the Vigilant Manager, before the study start. 
As soon as the investigator will be informed of the event, he/she will complete a Primary Notification 
Form template (PNF, appendix C) and send it to the sponsor ( officelp@lallemand.com and/or fax +41 
91 980 
4615 
(as 
back-up 
method) 
and 
to 
the 
Vigilance 
manager 
Roberta 
Belotti 
(rbelotti@lallemand.com), to the CRO (etudes@bgclinicals.com and/or fax: +33 561 561 956), to the 
EU 
representative 
Michel 
Huc 
(michel.huc@aspe-conseil.eu), 
and 
to 
the 
local 
CRAs 
(marina@convex.bg and r.dimitrova.convex.bg) with any relevant supportive documentation within 
the same day (<24h) for serious (risk) incident and within two calendar days (<48h) for non-serious 
incidents.  
14.4.2 Vigilance reporting according to Article 80 of the MDR 
Although not expected in this investigation with no invasive procedure, the following events are 
considered reportable events in accordance with MDR Art. 80(2): 
- 
a) Any serious adverse event that has a causal relationship with the investigation procedure or 
where such causal relationship is reasonably possible. 
- 
b) Any new findings in relation to any event referred to in point a) 
 
For the purpose of harmonizing reports, each SAE will be classified according to four different levels of 
causality as per definitions of the MDCG 2020-10/1 rev 1 specified in the safety management plan:  
1. Not related  
2. Possible  
3. Probable  
4. Causal relationship 

 
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Only causality level 1 (i.e. “not related”) is excluded from reporting. 
Any serious adverse event that has a causal relationship with an investigational procedure will be 
reported by the investigator to the sponsor (officelp@lallemand.com and/or fax +41 91 980 4615 (as 
back-up method) and to the Vigilance manager Roberta Belotti (rbelotti@lallemand.com), to the CRO 
(etudes@bgclinicals.com and/or fax: +33 561 561 956), to the EU representative Michel Huc 
(michel.huc@aspe-conseil.eu), and to the local CRA (marina@convex.bg) and r.dimitrova@convex.bg 
immediately, but not later than 3 calendar days after investigation site study personnel’s awareness 
of the event. To this end, the investigator will complete the “SAE form” (appendix D).  
 
14.5 Sponsor responsibilities and processing timelines 
14.5.1 Materiovigilance 
The vigilance manager of Lallemand Pharma is responsible for the reporting to the Bulgarian 
Competent Authority.  
Briefly, for serious incidents or risk of serious incident, the vigilance manager will complete a 
Manufacturer Incident Report. The result of the investigation conducted by the sponsor may lead to 
the implementation of a safety corrective action and completion of a Field Safety Corrective Action 
(FSCA) and of a Field Safety Notice. These documents will be transmitted to the Bulgarian Competent 
Authority and to the Ethics Committee (ekki@bda.bg) in accordance with the timelines provided in the 
table below:  
Serious Public Health Threat 
Report immediately but not more than 2 days 
 
Death or UNANTICIPATED Serious Deterioration 
in status of health 
Report immediately but not more than 10 days 
using electronic Manufacturer Incident Report 
Form (+ paper version for the EC) 
Others (could have led to death or serious 
deterioration in health) 
Report immediately but not more than 15 days 
using electronic Manufacturer Incident Report 
Form (+ paper version for the EC) 
Every FSCA 
Immediately 
before 
the 
measure 
is 
implemented except in case of emergency, when 
the vigilance manager of the sponsor has to 
immediately take a safety corrective action, 
using the electronic FSCA form 
 
Increase rate of non-serious incidents will be reported to the Bulgarian Competent Authority in Trend 
reports as per regulation requirements.  
Responsibilities of sponsor are detailed in the Safety Management Plan. 

 
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14.5.2 Vigilance according to Article 80 
Any serious adverse event that has a causal relationship with an additional procedure or a causal 
relationship reasonably possible, will be reported by the sponsor to the Bulgarian CA and the Ethics 
Committee as follows: 
Any serious adverse event that has a causal 
relationship with the additional procedure or 
a causal relationship reasonably possible, 
will be reported to the Bulgarian CA by the 
sponsor as follows: Imminent risk of death, 
serious injury, or serious illness and that 
requires prompt remedial action for 
patients/subjects or a new finding to it  
Immediately, but not later than 2 calendar days 
after awareness by sponsor of a new reportable 
event or of new information in relation with an 
already reported event. The excel file provided by 
the MDCG 2020-10/2 rev1 is to be used. 
Other reportable events or a new 
finding/update to it  
Immediately, but not later than 7 calendar days 
following the date of awareness by the sponsor of 
the new reportable event or of new information in 
relation with an already reported event. The excel 
file provided by the MDCG 2020-10/2 rev 1 is to be 
used. 
 
15. Suspension, or premature termination of the Clinical Investigation 
Lallemand Pharma AG may suspend or prematurely terminate the clinical investigation. The reasons 
shall be documented.  Reasons for suspension or premature termination at an investigation site may 
include occurrences where monitoring or auditing identifies serious or repeated deviations on the part 
of an investigator. Lallemand Pharma AG will notify the Regulatory Authority as appropriate and 
ensure that the EC is notified of any suspension or early termination of the clinical investigation. 
If suspicion of an unacceptable risk to subjects arises during the clinical investigation, or when so 
instructed by the EC or Regulatory Authority, Lallemand Pharma AG will suspend the clinical 
investigation while the risk is assessed. The sponsor will terminate the clinical investigation if an 
unacceptable risk is confirmed. The decision to maintain or to unblind the study will be taken in 
consultation with the Regulatory Authority.  Should the risk not be confirmed Lallemand Pharma AG 
will, in accordance with regulations, provide relevant persons with justification and data supporting 
the decision to resume the clinical investigation.  
EC or Regulatory Authority may suspend or prematurely terminate participation of one site or of all 
the participating sites. 
The patients will receive all treatments needed in case of complication or safety issues. In this case, 
the patient will be followed until the end of the issue.  
 

 
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16. Publication policy  
The information and data collected during the conduct of this clinical study are considered confidential 
and are used by the sponsor in connection with the development of the study treatment. This 
information will be disclosed by the sponsor depending on current regulations. 
To allow use of the information derived from this clinical study and to ensure compliance with current 
regulations, the investigator must provide the sponsor with complete test results and all data collected 
during the study. 
Only the sponsor may make study information available to physicians and to Regulatory Agencies, 
except as required by current regulations. 
All the results of this study including data and reports are the property of the sponsor. 
In the event that the sponsor chooses to publish study data, the manuscript must be provided to the 
investigator(s) at least 30 days prior to the expected date of submission to the intended publisher. 
The investigator(s) can reserve the right to publish or present study data; if so, the manuscript or 
abstract must be provided to the sponsor for review at least 30 days prior to the expected date of 
submission to the intended publisher or of planned presentation. 
In addition, if necessary, (the) investigator(s) shall withhold publication for an additional 60 days, to 
allow the filing of a patent application, or to allow the sponsor to take any measures he deems 
appropriate to establish and preserve his proprietary rights. 
It is agreed that publication of study results by each site shall be made only as part of a publication of 
the study results obtained by all sites performing the protocol, once the study is completed and 
finalised. 
A description of the clinical investigation is registered in https://www.clinicaltrials.gov/. The content 
will be updated throughout the conduct of the clinical investigation and the results entered at 
completion of the clinical investigation and made publicly available.  
 
 
 
 
 

 
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17. References 
Medical Device Directive 93/42/EEC (MDD) 
“Clinical Investigation of medical devices for human subjects” – Good clinical practice ISO 14155:2020 
Ethical considerations for clinical trials on medicinal products conducted with minors 
Recommendations of the expert group on clinical trials for the implementation of Regulation (EU) No 
536/2014 on clinical trials on medicinal products for human use Revision 1 18 September 2017 
 
1.  
Passioti M, Maggina P, Megremis S, Papadopoulos NG. The common cold: Potential for future 
prevention or cure topical collection on rhinosinusitis. Curr Allergy Asthma Rep [Internet]. 2014 
Feb [cited 2021 Feb 15];14(2). Available from: https://pubmed.ncbi.nlm.nih.gov/24415465/ 
2.  
Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, et al. European Position Paper 
on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020 Feb 20;58:1–464.  
3.  
Heikkinen T, Järvinen A. The common cold. In: Lancet [Internet]. Elsevier Limited; 2003 [cited 
2021 Feb 15]. p. 51–9. Available from: /pmc/articles/PMC7112468/ 
4.  
Yan J, Bassler BL. Surviving as a Community: Antibiotic Tolerance and Persistence in Bacterial 
Biofilms [Internet]. Vol. 26, Cell Host and Microbe. Cell Press; 2019 [cited 2020 Jun 22]. p. 15–
21. Available from: https://pubmed.ncbi.nlm.nih.gov/31295420/ 
5.  
Rabin N, Zheng Y, Opoku-Temeng C, Du Y, Bonsu E, Sintim HO. Biofilm formation mechanisms 
and targets for developing antibiofilm agents [Internet]. Vol. 7, Future Medicinal Chemistry. 
Future 
Science; 
2015 
[cited 
2020 
Jun 
22]. 
p. 
493–512. 
Available 
from: 
https://pubmed.ncbi.nlm.nih.gov/25875875/ 
6.  
King D, Mitchell B, Williams CP, Spurling GK. Saline nasal irrigation for acute upper respiratory 
tract infections. Cochrane Database Syst Rev [Internet]. 2015 Apr 20 [cited 2018 Dec 
5];(4):CD006821. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25892369 
7.  
Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, et al. Clinical 
practice guideline (update): Adult sinusitis. Otolaryngol - Head Neck Surg (United States). 2015 
Apr 6;152:S1–39.  
8.  
Principi N, Esposito S. Nasal irrigation: An imprecisely defined medical procedure. Vol. 14, 
International Journal of Environmental Research and Public Health. MDPI AG; 2017.  
9.  
Talbot AR, Herr TM, Parsons DS. Mucociliary clearance and buffered hypertonic saline solution. 
Laryngoscope. 1997 Apr;107(4):500–3.  
 
 
 

 
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List of Appendix  
Appendix A: Instructions for Use (IFU) 
Appendix B: Acute Rhinitis Symptoms Severity Questionnaire 
Appendix B: Primary Notification Form (PNF) 
Appendix C: Serious Adverse Event (SAE) form 
 
 

 
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Appendix A: IFU 
HEALSEA®BABYKIDS 
MPOSITION 
INDICATION 
Healsea® babykids is a nasal spray indicated in 
children above 2 years to clean and moisten the nose 
during colds and rhinitis  
UNDESIRABLE EFFECTS. 
In case of undesirable effects, contact your doctor. 
COMPOSITION 
Isotonic 
saline 
solution 
(salinity 
0.9%), 
Symbiofilm®. 
 
STORAGE AND WASTE RECOMMENDATION 
Store at room temperature and not above 30°C. 
See the expiry date on the box or the bottle. 
Ask your pharmacist to throw out the bottle after use. 
These 
measures 
contribute 
to 
protect 
the 
environment. 
DIRECTION OF USE 
Healsea® BABYKIDS shall be administered in children 
with the help of an adult. 
One-two sprays twice a day in each nostril for 10 days 
or as recommended by your doctor or pharmacist. 
TECHNOLOGY 
The spray pump APF (Advanced Preservative Free) 
uses a technology that permits to dispense a 
preservative free solution. 
PRECAUTION OF USE 
- Keep out of reach of children. 
-If symptoms persist more than 10 days, ask for 
advices to your doctor or pharmacist. 
-The bottle shall be used by only one person for 
hygiene reason and to avoid the transmission of 
pathogenic agents that could be in contact with the 
nozzle. 
HOW TO USE HEALSEA® BABYKIDS? 
1. Place the nozzle smoothly into the nostril while 
keeping head straight. 
2. Once the nozzle is placed, press on the nozzle in 
each nostril. Let flow the excess of solution and 
wipe. 
3. Clean the nozzle with tissue, soapy water, rinse 
and dry after every use. 
CONTRAINDICATION 
Do not use in children and adolescents under 2 
years. 
Do not use in case of hypersensitivity or allergy to one 
or several components. 
 
 
Healsea® BABYKIDS is a nasal spray containing isotonic saline solution mixed with an innovative extract, 
Symbiofilm®, isolated from the marine biosphere. 
Healsea® BABYKIDS is a natural care preservative free allowing to clean and moisten the nasal mucosa. 
Symbiofilm® is a marine postbiotic, which contains exopolymeric substances, that enhances 
mechanically the cleansing efficiency of isotonic water. 
Symbiofilm® reduces the development of biofilm from respiratory pathogenic microorganisms by 
mechanical action as well as the mucosal adhesion and helps reducing the spreading of viruses in-vitro. 
Healsea® BABYKIDS is the ideal solution for children who suffer from colds or rhinitis by cleaning the 
nasal cavity and eliminating allergens and infectious agents. 
 
 
             Lallemand Pharma AG                                               
               Via Selva 2  
               6900 Massagno  
                             Learn more about                                                          Publication 
Date: Switzerland                                                        biofilms by flashing                                                      2021/12/10_R1                 
                                                                                             this QR code!           
 
 
 
 
 
 
 
 
 
 
                         
    
 
ASPE CONSEIL 
21, chemin de la Favasse 
31140 Aucamville – FRANCE  

 
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PLACEBO 
MPOSITION 
 
INDICATION 
The Medical Device is a nasal spray indicated in 
children above 2 years to clean and moisten the nose 
during colds and rhinitis  
UNDESIRABLE EFFECTS. 
In case of undesirable effects, contact your doctor. 
COMPOSITION 
Isotonic saline solution (salinity 0.9%) 
STORAGE AND WASTE RECOMMENDATION 
Store at room temperature and not above 30°C. 
See the expiry date on the box or the bottle. 
Ask your pharmacist to throw out the bottle after use. 
These 
measures 
contribute 
to 
protect 
the 
environment. 
DIRECTION OF USE 
The Placebo shall be administered in children 
with the help of an adult. 
One-two sprays twice a day in each nostril for 10 days 
or as recommended by your doctor or pharmacist. 
TECHNOLOGY 
The spray pump APF (Advanced Preservative Free) 
uses a technology that permits to dispense a 
preservative free solution. 
PRECAUTION OF USE 
- Keep out of reach of children. 
-If symptoms persist more than 10 days, ask for 
advices to your doctor or pharmacist. 
-The bottle shall be used by only one person for 
hygiene reason and to avoid the transmission of 
pathogenic agents that could be in contact with the 
nozzle. 
HOW TO USE THE PLACEBO? 
1. Place the nozzle smoothly into the nostril while 
keeping head straight. 
2. Once the nozzle is placed, press on the nozzle in 
each nostril. Let flow the excess of solution and 
wipe. 
3. Clean the nozzle with tissue, soapy water, rinse 
and dry after every use. 
CONTRAINDICATION 
Do not use in children and adolescents under 2 
years. 
Do not use in case of hypersensitivity or allergy to one 
or several components. 
 
 
 
 
              Lallemand Pharma AG                                               
                Via Selva 2  
                6900 Massagno  
 
Switzerland 
                                     
 
 
      
 
ASPE CONSEIL 
21, chemin de la Favasse 
31140 Aucamville – FRANCE  
 
 

 
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Appendix B: Acute Rhinitis Symptoms Severity Questionnaire (English 
version) 
Please, tick the box that corresponds to your child's situation 
 
Q1: How sick does your child feel today: 
Not sick  
A little sick  
Sick  
Very sick  
 
Q2-Q7: How do you evaluate the intensity of the following symptoms of your child? 
Symptoms 
Not present 
mild 
moderate 
severe 
Runny nose 
 
 
 
 
Stuffy nose/blocked 
nose 
 
 
 
 
Yellow/green 
discharge 
 
 
 
 
Nasal 
crust 
(dry 
mucus) 
 
 
 
 
Sore throat (hurts to 
swallow) 
 
 
 
 
Sneezing/cough 
 
 
 
 
 
 
Q8-Q10: How do you evaluate the impact of the common cold on your child’s activities? 
Activity 
No impact 
Mild impact 
Moderate 
impact 
Severe impact 
Sleeping 
 
 
 
 
Breathing 
 
 
 
 
Playing/going to the 
nursery or to school 
 
 
 
 
 
 
 
 

 
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Appendix C: Primary Notification Form 
This form is to be completed immediately and no later than 24h (in case of any SERIOUS 
safety issue) or 48h (in case of any NON-SERIOUS safety issue). 
Protocol title:  
Acronym:  
Sponsor code:  
Site number:  
Country:  
 
 
 
 
Competent authority(ies) reference number:  
 
Transmission date:  
 
 
 
  
 
  
 
ddmmyy 
 
1. Date, type and classification of incident report 
Incident codification:  
First notification: 
 
Follow-up: 
 
Final: 
 
Date of the incident 
 
 
 
 
  
 
  
 
ddmmyy 
Reporter awareness date 
 
 
  
 
  
 
ddmmyy 
Classification/type 
of 
the 
incident 
 Serious public health 
threat 
 Death 
Expected 
undesirable 
side effect 
 
Unanticipated 
serious 
deterioration in state of health 
 Non serious incident 
 
2. Patient information 
Birthdate:  
 
Height: 
 
 
 
  
 
 
 
mmyyyy 
   cm 
   cm 
   cm 
   cm 
Gender: Male 
 Female 
 
Unknown 
  
Non applicable 
  
 
Weight:  
 
 
 
 
, 
 
Kg 
List any of the patient’s prior condition of medication that may be relevant to this incident: 
 
3. Medical Device information 

 
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UDI device identifier / 
Eudamed ID: 
 not applicable 
Basic UDI-DI/Eudamed-DI: 
 not applicable 
UDI production identifier: 
 not applicable 
Medical device name (brand, trade, 
proprietary or common name) & SKU: 
 
Class of risk: 
 
Batch number 
 
Expiry date (yyyy/mm): 
 
/  
 
 
Other details: 
 
4. Incident information 
Intended use of the medical device: 
 
Date of first use:  
 
Date of last use:  
 
Frequency of use:________________________ 
 
Description of the incident: Provide a comprehensive description of the incident, including (1) what 
went wrong with device (if applicable) and (2) a description of health effects (if applicable), i.e. 
clinical signs, symptoms …): 
 
 
 
 
 
 
 
 
 
Outcome & Health Impact: 
 
 death 
 life threatening 
 hospitalization (initial or prolonged)  
 required intervention to prevent permanent damage 
 disability or permanent damage 
 congenital abnormality/birth defect  
 
 no serious outcome 
 
 other, please specify:  
 
 
 
 
 
 
  
 
  
 
ddmmyy 
 
 
  
 
  
 
ddmmyy 
Remedial actions taken by investigator, patient, or user subsequent:  
 
 
 
 

 
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5. Reporter information 
 Distributor 
 Patient  
 Healthcare professional: ___________________ 
 Investigator (in case of the safety issue has been occurred during a clinical investigation) 
 Other, please specify: _______________________________ 
 
 
For any follow-up please kindly indicate the contact details: 
 
Name and Surname: ___________________ 
 
Email: ___________________ 
 
Phone number:___________________ 
 
Fax: ___________________ 
 
 
Date:                                                                                          Signature: 
 
 
 
___________________________                                         ___________________________ 
 
 
 
 

 
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Appendix D: SAE form  
This form is to be used when a causal relationship between the serious adverse event and the additional 
investigational procedure is suspected (art 80.5 and 80.6).  
This form is to be completed immediately and no later than 3 days after the investigation site personnel 
have been made aware of the event and sent immediately to the Clinical Study Monitor by mail 
marina@convex.bg and r.dimitrova.convex.bg , to BG ClinicalS etudes@bgclinicals.com, FAX: no 
+33 561 531 956 and to the sponsor officelp@lallemand.com and/or fax: +41 91 980 4615 (as back-up 
method) and to the Vigilance Manager Roberta Belotti (rbelotti@lallemand.com) and the EU 
representative (michel.huc@aspe-conseil.eu).  
Protocol title: 
Efficacy and safety of Healsea® Babykids in the 
treatment of acute infectious rhinitis symptoms in 
children 
 
Acronym: BASICC 
Sponsor code: LPH-2202 
Competent Authority(ies) reference 
number:  
 
 
Transmission date:  
 
 
 
  
 
  
 
ddmmyy 
Site number:  
Country:Bulgaria 
 
 
 
 
 
SAE# 
(to be completed by the 
sponsor) 
 
 
First notification: 
 
Follow-up: 
 
Final: 
 
 
1. Subject information 
 
Birthdate:  
 
Height:  
 
 
 
  
 
 
 
mmyyyy 
 
 
 
cm 
 
Gender: Male 
 Female 
 Other 
 
 
Weight:  
 
 
 
 
,  
Kg 
Investigational arm: 
test group 
comparison group 
blinded 
 
2. Description of the SAE 
The serious adverse event resulted in: 
 Death (whatever may be the cause) 
Serious deterioration in the health of the 
subject, that resulted in any of the following: 
 In-patient hospitalisation or prolongation of  
existing hospitalisation (*) 
 Life threatening illness or injury 
 Permanent impairment to a body structure 
or a body function 
 Medical or surgical intervention to prevent 
life threatening illness or injury or permanent 
impairment to a body structure or a body 
function 
 Chronic disease 
 Foetal distress, foetal death or congenital 
physical or mental impairment or birth defect 
 
Description of the SAE: (if clinical nature, indicate the diagnosis or the major symptoms) 
 
 

 
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Study Number: LPH-2202 
 
 
 
Date of the procedure leading to the SAE:  
 
 
 
  
 
  
 
ddmmyy 
SAE onset date:  
 
 
 
  
 
  
 
ddmmyy 
 
 not capture 
 
SAE stop date: 
 
 
 
  
 
  
 
ddmmyy 
 
 on going 
Or date of death if SAE “fatal” 
 
 
 
  
 
  
 
ddmmyy 
 
Summary description (study procedure, significant medical history, progression of event, available 
laboratory results, study procedure): 
 
 
 
 
 
 
(*) Except hospitalisations with durations and goal planned in the protocol or scheduled before 
study participation 
 
3. Mesures taken following the SAE 
The event led to: 
 Prescription of corrective or symptomatic medication / medical device (specify name, dosage): 
………………………………………………………………………………………………………………….. 
 Other,specify: 
.............................................................................................................................................. 
………………………………………………………………………………………………………………………………………... 
 
 
4. Outcome 
 
 
 Not recovered/Not resolved 
 Recovering/Resolving 
 Recovered/Resolved 
 Recovered/Resolved with 
sequelae 
 Unknown 
 
 Fatal: in case of death, has an autopsy been conducted? 
 Yes 
 No 
 
5. Investigator causality assessment with the study procedure (investigator’s assessment to 
be done as soon as possible) 
 Not related 
 Possible 
 Probable 
 Causal relationship 
 
Comments: 
………………………………………………………………………………………………………. 
 
Enclose in the notification the results of carried out examination, reports of hospitalisation, etc… 
 

 
Strictly Confidential 
 
 
 
Version 1.1 –2023.02.02 
 
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Study Number: LPH-2202 
 
6. Submitter information 
 Investigator 
 Other, please specify: _______________________________ 
 
Name: _____________________________ 
 
e-mail: _____________________________ 
 
Phone number: _______________________________________ 
 
Fax: _________________________________________________ 
 
Date:  
 
Signature: 
 
 
  
 
  
 
ddmmyy