Symbiofilm Trial in Allergic Kids (SYMBIOFILM-TAK)

• ClinicalTrials.gov Identifier: NCT05034328
• Recruitment Status: Completed
• First Posted: September 5, 2021
• Last Update Posted: March 10, 2023
• Sponsor: Lallemand Pharma AG
• Information provided by (Responsible Party): Lallemand Pharma AG

Study Description

Brief Summary:

Healsea® Children is a seawater-based nasal spray supplemented with a natural Symbiofilm® extract (0.02%) isolated from marine bacteria. Symbiofilm has antibiofilm activity against various bacterial pathogens involved in respiratory tract infections.Healsea® Children is indicated in the cleaning and moistening of nasal mucosa during common cold and rhinitis for children above 6 years.

This non interventional post-market clinical investigation aimed to confirm the benefit of Healsea® Children in real life setting in children with perennial allergy who are more prone to common cold.

Condition or disease	Intervention/treatment
Common Cold; Allergy	Device: Healsea® Children; Other: Conventional therapies for common cold

Detailed Description:

Healsea® Children is a seawater-based nasal spray supplemented with a natural Symbiofilm® extract (0.02%) 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. Healsea® Children is indicated in the cleaning and moistening of nasal mucosa during common cold 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 (1). It can be caused by members of several families of viruses; the most common are 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 (1). 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 (2-3).

Allergic diseases may play a particular role in promoting the respiratory infection recurrences (4). The physiological immune response is impaired in allergic subjects and allergic inflammation favours predisposition to respiratory infections. Subjects with allergic disorders may have functional defect of type 1 immune response that is relevant in fighting infections (5-6).

Allergic rhinitis (AR) may affect up to 40% of the paediatric population. Nasal symptoms are caused by exposure to an allergen to which a patient is sensitized.

AR is characterized by typical nasal symptoms and immunoglobulin E (IgE) -mediated inflammation. The allergic inflammatory process releases many cytokines and other proinflammatory proteins. Inflammation caused by nasal allergy leads to obstruction, fluid accumulation and acute disease. If these diseases are unsuccessfully treated, a chronic state of inflammation, obstruction, and infection develops that can cause mucosal damage and, ultimately, chronic disease (7).

For these reasons, the paediatric IgE-dependent allergic population that is more prone to common cold represents a suitable target for Healsea® Children (8-9).

During this prospective post-market clinical investigation, IgE-dependent allergic children with early symptoms of infectious rhinitis will be followed, children being treated with Healsea® Children on top of common cold conventional therapies or with conventional therapies only (excluded nasal irrigation).

Conventional therapies for non-complicated infectious rhinitis are symptomatic but are not without side effects. For example, decongestant use can increase blood pressure, antihistamine intake is associated with drowsiness.

Healsea® Children represents an interesting alternative that can not only improve acute infectious rhinitis symptomatology but could also limit the complication and progression to chronic state.

This non interventional post-market clinical investigation aimed to confirm the benefit of Healsea® Children in a real life setting in children with perennial allergy.

Study Design

• Study Type: Observational
• Actual Enrollment: 186 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Impact of Adding Healsea® Isotonic Nasal Spray to Conventional Therapies for the Care of Children With Allergic Rhinitis Presenting With Symptoms of Acute Infectious Rhinitis: an Observational Study
• Actual Study Start Date: February 14, 2022
• Actual Primary Completion Date: November 3, 2022
• Actual Study Completion Date: November 3, 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
Healsea® Children: isotonic seawater based nasal spray supplemented with natural Symbiofilm® extract; Children will receive Healsea® Children nasal spray on top of conventional therapies for common cold, as needed.	Device: Healsea® Children; Children will be administered Healsea Children , one puff (1-2 sec) in each nostril twice a day for 10 days on top of conventional therapies, as needed; Other Name: Conventional therapies for common cold; Other: Conventional therapies for common cold; Children will receive conventional therapies for common cold, nasal irrigation excluded (antipyretics, mucolytics, decongestants, antitussives, systemic and topical corticosteroids, antibiotics)
Conventional therapies; Children will receive conventional therapies for common cold as needed, nasal irrigation excluded	Other: Conventional therapies for common cold; Children will receive conventional therapies for common cold, nasal irrigation excluded (antipyretics, mucolytics, decongestants, antitussives, systemic and topical corticosteroids, antibiotics)

Outcome Measures

Primary Outcome Measures :

1. AUC (Area Under Curve) of the Wisconsin Upper Respiratory Symptoms Survey for Kids (WURSS-K) during the 10-day treatment period [ Time Frame: Cumulative AUC of the WURSS score assessed from Day 1 to Day 10 ]
   The WURSS-K will be assessed once daily, in the evening, considering the symptoms from the morning to the evening, from Day1 to Day10 (treatment period)

Secondary Outcome Measures :

1. Duration of common cold symptoms during the whole study: items 2 to 7 of WURSS-K [ Time Frame: Number of days with cold symptoms during the intervention period (10-day treatment) and up to 30 days ]
   During the treatment period, the WURSS-K will be assessed once daily. After D10, the WURSS-K will be assessed once daily until the subject feels not sick for two consecutive days. Items 2 to 7 will be used to assess the duration of common cold symptoms in both groups.
2. Respiratory complication requiring antibiotic prescription after the10-day treatment period [ Time Frame: Number of subjects with respiratory complications during the 20-day follow-up period ]
   The number of subjects who develop respiratory complication requiring antibiotic prescription during a 20-day follow-up period after the treatment period will be assessed in both groups and compared
3. Use of concomitant treatments [ Time Frame: During the intervention, up to 30 days ]
   Frequency and number of days of use of concomitant treatments (conventional therapies) that may affect common cold symptoms (antibiotics, antipyretics, systemic or local mucolytics, decongestants, antitussives, systemic and topical corticosteroids) will be assessed in both groups and compared
4. Spread of the common cold [ Time Frame: During the intervention, up to 30 days ]
   The number of family members in close contact developing common cold symptoms after the patient all over the study period
5. Reporting of incidents, undesirable expected side effects and adverse events [ Time Frame: During the intervention, up to 30 days ]
   Assessment of adverse events, incidents, undesirable expected side effects during the intervention up to 30 in both groups

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 10 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

The study population comprises children 6 to10 years old with perennial allergy and early symptoms of common cold.

The recruitment will be competitive in both group, exposed to Healsea® Children or not exposed to Healsea® Children. However, when 100 patients will be recruited in one group, the recruitment will be stopped in this group but will continue in the other group until 100 patients to be enrolled.

Criteria

Inclusion Criteria:

1. Male/Female subjects ≥6 and ≤10-year-old
2. AsIgE (Allergy specific IgE) ≥ class 2 (RAST) or positive prick test for at least one perennial allergen
3. Acute infectious rhinitis/rhinosinusitis for ≤48h before trial entry
4. Patient presenting with fever ≥ 37.5 °C at screening
5. Symptoms of headache, muscle ache, chilliness, sore throat, blocked nose, runny nose, cough, sneezing with a total score ≤9 (according to a physician-rated symptom score; scale: 0 to 3 [0: no symptom to 3: severe intensity])
6. At least one of these symptoms: sore throat, runny nose or blocked nose (i.e., with a score ≥1)
7. Written consent obtained from parent/legal guardians
8. Written assent obtained from patient

Exclusion Criteria:

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. Antihistamines intake for allergy when treatment was started from less than 4 weeks
8. Bacterial lysate intake within 6 months before screening
9. Chronic decongestant use
10. Recent (within the previous 2 days) intake of a common cold medicine that in the opinion of the investigator may influence symptom score at screening (NSAID, nasal decongestants, cough medicines)

Contacts and Locations

Locations

Poland

Research Site

Białystok, Poland, 15-010

Research Site

Białystok, Poland, 15-430

Research Site

Bydgoszcz, Poland, 85-048

Research Site

Dys, Poland, 21-003

Research Site

Głowno, Poland, 95-015

Research Site

Kraków, Poland, 30-644

Research Site

Lublin, Poland, 20-093

Research Site

Lublin, Poland, 20-141

Research Site

Lublin, Poland, 20-552

Research Site

Lublin, Poland, 20-803

Research Site

Lublin, Poland, 20-865

Research Site

Rzeszów, Poland, 35-061

Research Site

Tarnów, Poland, 33-100

Research Site

Warszawa, Poland, 04-314

Research Site

Łomża, Poland, 18-402

Sponsors and Collaborators

Lallemand Pharma AG

Investigators

• Principal Investigator: Andrzej EMERYK, MD, PhD; University Children Hospital, Lublin, Poland

More Information

Publications:

Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, Toppila-Salmi S, Bernal-Sprekelsen M, Mullol J, Alobid I, Terezinha Anselmo-Lima W, Bachert C, Baroody F, von Buchwald C, Cervin A, Cohen N, Constantinidis J, De Gabory L, Desrosiers M, Diamant Z, Douglas RG, Gevaert PH, Hafner A, Harvey RJ, Joos GF, Kalogjera L, Knill A, Kocks JH, Landis BN, Limpens J, Lebeer S, Lourenco O, Meco C, Matricardi PM, O'Mahony L, Philpott CM, Ryan D, Schlosser R, Senior B, Smith TL, Teeling T, Tomazic PV, Wang DY, Wang D, Zhang L, Agius AM, Ahlstrom-Emanuelsson C, Alabri R, Albu S, Alhabash S, Aleksic A, Aloulah M, Al-Qudah M, Alsaleh S, Baban MA, Baudoin T, Balvers T, Battaglia P, Bedoya JD, Beule A, Bofares KM, Braverman I, Brozek-Madry E, Richard B, Callejas C, Carrie S, Caulley L, Chussi D, de Corso E, Coste A, El Hadi U, Elfarouk A, Eloy PH, Farrokhi S, Felisati G, Ferrari MD, Fishchuk R, Grayson W, Goncalves PM, Grdinic B, Grgic V, Hamizan AW, Heinichen JV, Husain S, Ping TI, Ivaska J, Jakimovska F, Jovancevic L, Kakande E, Kamel R, Karpischenko S, Kariyawasam HH, Kawauchi H, Kjeldsen A, Klimek L, Krzeski A, Kopacheva Barsova G, Kim SW, Lal D, Letort JJ, Lopatin A, Mahdjoubi A, Mesbahi A, Netkovski J, Nyenbue Tshipukane D, Obando-Valverde A, Okano M, Onerci M, Ong YK, Orlandi R, Otori N, Ouennoughy K, Ozkan M, Peric A, Plzak J, Prokopakis E, Prepageran N, Psaltis A, Pugin B, Raftopulos M, Rombaux P, Riechelmann H, Sahtout S, Sarafoleanu CC, Searyoh K, Rhee CS, Shi J, Shkoukani M, Shukuryan AK, Sicak M, Smyth D, Sindvongs K, Soklic Kosak T, Stjarne P, Sutikno B, Steinsvag S, Tantilipikorn P, Thanaviratananich S, Tran T, Urbancic J, Valiulius A, Vasquez de Aparicio C, Vicheva D, Virkkula PM, Vicente G, Voegels R, Wagenmann MM, Wardani RS, Welge-Lussen A, Witterick I, Wright E, Zabolotniy D, Zsolt B, Zwetsloot CP. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020 Feb 20;58(Suppl S29):1-464. doi: 10.4193/Rhin20.600.

Yan J, Bassler BL. Surviving as a Community: Antibiotic Tolerance and Persistence in Bacterial Biofilms. Cell Host Microbe. 2019 Jul 10;26(1):15-21. doi: 10.1016/j.chom.2019.06.002.

Rabin N, Zheng Y, Opoku-Temeng C, Du Y, Bonsu E, Sintim HO. Biofilm formation mechanisms and targets for developing antibiofilm agents. Future Med Chem. 2015;7(4):493-512. doi: 10.4155/fmc.15.6. Erratum In: Future Med Chem. 2015;7(10):1362.

Varricchio A, La Mantia I, Brunese FP, Ciprandi G. Inflammation, infection, and allergy of upper airways: new insights from national and real-world studies. Ital J Pediatr. 2020 Feb 10;46(1):18. doi: 10.1186/s13052-020-0782-z.

Ciprandi G, Tosca MA, Fasce L. Allergic children have more numerous and severe respiratory infections than non-allergic children. Pediatr Allergy Immunol. 2006 Aug;17(5):389-91. doi: 10.1111/j.1399-3038.2006.00413.x.

Cirillo I, Marseglia G, Klersy C, Ciprandi G. Allergic patients have more numerous and prolonged respiratory infections than nonallergic subjects. Allergy. 2007 Sep;62(9):1087-90. doi: 10.1111/j.1398-9995.2007.01401.x. Epub 2007 Jun 18.

Eifan AO, Durham SR. Pathogenesis of rhinitis. Clin Exp Allergy. 2016 Sep;46(9):1139-51. doi: 10.1111/cea.12780.

De Corso E, Lucidi D, Cantone E, Ottaviano G, Di Cesare T, Seccia V, Paludetti G, Galli J. Clinical Evidence and Biomarkers Linking Allergy and Acute or Chronic Rhinosinusitis in Children: a Systematic Review. Curr Allergy Asthma Rep. 2020 Sep 5;20(11):68. doi: 10.1007/s11882-020-00967-9.

Lin SW, Wang SK, Lu MC, Wang CL, Koo M. Acute rhinosinusitis among pediatric patients with allergic rhinitis: A nationwide, population-based cohort study. PLoS One. 2019 Feb 12;14(2):e0211547. doi: 10.1371/journal.pone.0211547. eCollection 2019.

• Responsible Party: Lallemand Pharma AG
• ClinicalTrials.gov Identifier: NCT05034328
• Other Study ID Numbers: LPH-2101
• First Posted: September 5, 2021
• Last Update Posted: March 10, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lallemand Pharma AG:

Infectious rhinitis, nasal irrigation, perennial allergy

Additional relevant MeSH terms:

Common Cold; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Picornaviridae Infections; RNA Virus Infections; Virus Diseases