Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05297760
Other study ID # University Hospital Zurich
Secondary ID
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date February 10, 2022
Est. completion date June 30, 2025

Study information

Verified date May 2024
Source University of Zurich
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary goal is to investigate the efficacy of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis and allergic asthma due to sensitisation to grass pollen allergens. 60 patients with allergic rhinitis will be included and randomized to receive either Polvac (n=30) or placebo (n=30). All patients will receive three injections with 4-8 weeks interval. The injections into a inguinal lymph node is guided by sonography. Patients will record symptoms and medication use in the summer of 2022 and 2023.


Description:

This study is part of a multicenter trial Phase III that takes place also in Denmark and Sweden (EudraCT registration number 2020-001060-28). The primary goal is to investigate the efficacy of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis and allergic asthma due to sensitisation to grass pollen allergens. In the Swiss arm of trial, Polvac (Allergy Therapeutics, United Kingdom) is applied. In Denmark and Sweden, the applied drug is Alutard (ALK, Denmark). The major difference is the excipient adjuvant, which is microcrystallin tyrosine (MCT) in Polvac aluminium in Alutard. The concentration of major allergen 60 phl p5, as the active ingredient, is the same in both products. The active ingredient is a standardised grass pollen allergen extract combined with MCT. The allergen extract has been treated with glutaraldehyd as to reduce allergenicity, i.e., increase the safety. In Switzerland and Germany, Bencard AG is providing the product. Polvac™, is a marketed product that is approved by the Swiss Medical Product Agencies and adheres to GMP. The product consists of needle-like crystalline structures of average 20 micrometer size. Polvac is approved for subcutaneous immunotherapy (SCIT), which consists of 6 pre-seasonal injections with 1-2 week intervals for 3-4 years, adding up to a total of 18 to 24 injections for the treatment to be completed. In the currents study, 60 patients with allergic rhinitis will be included and randomized to receive either Polvac (n=30) or placebo (n=30). Primary screening is done online through questionnaires. Secondary screening and inclusion is done clinical at the University Hospital Zurich. All patients will receive three injections of Polvac or placebo (saline) with 4-8 weeks interval. The injections into a inguinal lymph node is guided by sonography. For three days post each injections, adverse events will be recorded by patients using an on line application. In the summer seasons of 2022 and of 2023, the patients will record daily allergic symptoms and daily medication usage using an online application. These record are the basics for the efficacy analysis. Addition on January 12th 2024: After unblinding of the study in October to December 2023 and after analysis of the primary endpoint, it was decided to prolong the study in a semi-cross over. That means, study participants that received placebo in the original trial (n=30) will receive active treatment in an open label setting. The treatment will be exact similar to that of the active treatment in 2022, i.e., three ILIT injections of the IMD (Polvac Grass+Rye) with 4 weeks intervals and using the same dose as in 2022. The study participants that originally received active treatment (n=30) will not receive further treatment. All patients (n=60), will be invited to enter symptoms and medication usage during the pollen season of 2024, similar to 2022 and 2023. In September to November 2024, the all patients will be invited for a final follow-up visit for clinical and laboratory tests. All patients will concent to the trial extension in writing prior to entering the trial extension.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 60
Est. completion date June 30, 2025
Est. primary completion date December 31, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria: - passed online screening with a Rhinoconjunctivitis Total Symptom Score (RTSS) value of 8 or higher. - sensitisation to grass pollen allergens with a skin prick test reaction to grass pollen allergen of 3 mm or more. - eligible to allergen immunotherapy. - 18 years or older. - comfortable with digital data entry. Exclusion Criteria: - previous grass pollen-specific immunotherapy. - significant allergy to mugwort or pet animal allergens. - uncontrolled asthma. - upper airway disease. - severe pulmonary disease. - recent allergic reactions. - immunosuppression. - cardiovascular disease. - malignant disease. - use of ACE-blockers. - other diseases or conditions rendering the treatment of anaphylactic reactions difficult.

Study Design


Intervention

Biological:
Polvac Grass+Rye
Suspension of micro crystalline tyrosine with grass and rye pollen allergen
Drug:
Saline 0.9%
Physiological saline solution for use as vehicle for the biological drug (Polvac Grass+Rye) or as placebo.

Locations

Country Name City State
Switzerland University Hospital Zurich Zurich

Sponsors (2)

Lead Sponsor Collaborator
University of Zurich University of Aarhus

Country where clinical trial is conducted

Switzerland, 

References & Publications (12)

Aini NR, Mohd Noor N, Md Daud MK, Wise SK, Abdullah B. Efficacy and safety of intralymphatic immunotherapy in allergic rhinitis: A systematic review and meta-analysis. Clin Transl Allergy. 2021 Aug 17;11(6):e12055. doi: 10.1002/clt2.12055. eCollection 202 — View Citation

Freiberger SN, Zehnder M, Gafvelin G, Gronlund H, Kundig TM, Johansen P. IgG4 but no IgG1 antibody production after intralymphatic immunotherapy with recombinant MAT-Feld1 in human. Allergy. 2016 Sep;71(9):1366-70. doi: 10.1111/all.12946. Epub 2016 Jun 17 — View Citation

Hoang MP, Seresirikachorn K, Chitsuthipakorn W, Snidvongs K. Intralymphatic immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis. Rhinology. 2021 Jun 1;59(3):236-244. doi: 10.4193/Rhin20.572. — View Citation

Schmid JM, Nezam H, Madsen HH, Schmitz A, Hoffmann HJ. Intralymphatic immunotherapy induces allergen specific plasmablasts and increases tolerance to skin prick testing in a pilot study. Clin Transl Allergy. 2016 May 25;6:19. doi: 10.1186/s13601-016-0107- — View Citation

Senti G, Crameri R, Kuster D, Johansen P, Martinez-Gomez JM, Graf N, Steiner M, Hothorn LA, Gronlund H, Tivig C, Zaleska A, Soyer O, van Hage M, Akdis CA, Akdis M, Rose H, Kundig TM. Intralymphatic immunotherapy for cat allergy induces tolerance after onl — View Citation

Senti G, Freiburghaus AU, Larenas-Linnemann D, Hoffmann HJ, Patterson AM, Klimek L, Di Bona D, Pfaar O, Ahlbeck L, Akdis M, Weinfeld D, Contreras-Verduzco FA, Pedroza-Melendez A, Skaarup SH, Lee SM, Cardell LO, Schmid JM, Westin U, Dollner R, Kundig TM. I — View Citation

Senti G, Johansen P, Kundig TM. Intralymphatic immunotherapy. Curr Opin Allergy Clin Immunol. 2009 Dec;9(6):537-43. doi: 10.1097/ACI.0b013e3283310ff7. — View Citation

Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R, McCormack SJ, Simard JJ, Wuthrich B, Crameri R, Graf N, Johansen P, Kundig TM. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. — View Citation

Skaarup SH, Graumann O, Schmid J, Bjerrum AS, Skjold T, Hoffmann HJ. The number of successful injections associates with improved clinical effect in intralymphatic immunotherapy. Allergy. 2021 Jun;76(6):1859-1861. doi: 10.1111/all.14642. Epub 2020 Nov 16. — View Citation

Skaarup SH, Schmid JM, Skjold T, Graumann O, Hoffmann HJ. Intralymphatic immunotherapy improves grass pollen allergic rhinoconjunctivitis: A 3-year randomized placebo-controlled trial. J Allergy Clin Immunol. 2021 Mar;147(3):1011-1019. doi: 10.1016/j.jaci — View Citation

Werner MT, Bosso JV. Intralymphatic immunotherapy for allergic rhinitis: A systematic review and meta-analysis. Allergy Asthma Proc. 2021 Jul 1;42(4):283-292. doi: 10.2500/aap.2021.42.210028. — View Citation

Zaleska A, Eiwegger T, Soyer O, van de Veen W, Rhyner C, Soyka MB, Bekpen C, Demiroz D, Treis A, Sollner S, Palomares O, Kwok WW, Rose H, Senti G, Kundig TM, Ozoren N, Jutel M, Akdis CA, Crameri R, Akdis M. Immune regulation by intralymphatic immunotherap — View Citation

* Note: There are 12 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Combined symptom medication score (cSMS) Daily registration of symptoms and medication usage by the study participants and by means of a online application. This is done during the pollen season of 2022 (and possible 2023 if the 2022 season is poor with low amounts of pollen). The assessment is done over a time period, but the records are integrated for the calculation of one single score (cSMS), which is the primary outcome. 3 months (2 minutes per day)
Secondary Rhino conjunctivitis quality of life score (RQLQ) Weekly questionnaire for studying the quality of life of the study participants during the pollen season of 2022 (and possible 2023 if the 2022 season is poor with low amounts of pollen). The RQLQ will assess seven domains on a weekly basis on a scale from 0 (best) to 6 (worst). The assessment is done over a long time period, but the records are integrated for the calculation of one single score (RQLC), which is the secondary outcome. 3 months (10 minutes per week)
Secondary Lower airway disease We will assess spirometry, at each follow-up time point (winter and summer visits) and analyse a time series of the development of each parameter in each treatment group. The assessments will be performed at several time-points and the changes from baseline assessments (before ILIT) is measured. 10 minutes (5 times in two years)
Secondary Asthma We will assess FeNo (Fraction Exspiratory Nitric Oxide) at each follow-up time point (winter and summer visits) and analyse a time series of the development of each parameter in each treatment group. The assessments will be performed at several time-points and the changes from baseline assessments (before ILIT) are measured. 10 minutes (5 times in two years)
Secondary Biomarkers Circulating levels of IgE, IgG1, and IgG4 specific for grass pollen extract and the major allergens Phl p 5 and Phl p 1 will be determined in blood samples before every treatment and at all the follow-up visits, for a total of 7 times per participant. The analysis is done using ImmunoCAP ELISA. In addition, IgE assessment by ISAC (112 allergens in one array) will be performed to analyse if sensitisation to other allergens develops or changes. All assessments will be performed at several time-points and the changes from baseline assessments (before ILIT) are measured. 5 minutes (8 times in two years)
See also
  Status Clinical Trial Phase
Recruiting NCT05080322 - Efficacy and Safety of On-demand and Continuous Administration of Nasal Spray in the Treatment of Allergic Rhinitis Phase 4
Recruiting NCT06028490 - A Study of IL4Rα Monoclonal Antibody in Patients With Uncontrolled Seasonal Allergic Rhinitis. Phase 2
Completed NCT04388358 - Traditional Chinese Medicine for the Treatment of Perennial Allergic Rhinitis on Gut Microbiota and Immune-modulation N/A
Recruiting NCT04202263 - Assessment of Suppression of Cutaneous Allergic Responses and Pruritis by Topical Minocycline Phase 2
Completed NCT04078009 - Standardising Nasal Allergen Challenge in Adult With Hay Fever N/A
Completed NCT03644680 - Changes in Adaptive Immune Responses and Effector Cell Responses Upon Nasal Allergen Exposure - a Pilot Study N/A
Completed NCT04541004 - Adolescent Mite Allergy Safety Evaluation Phase 3
Recruiting NCT05378594 - HDM and Silver Birch NAC Standardisation N/A
Not yet recruiting NCT05684380 - Efficacy and Safety of MAZ-101 in the Treatment of Persistent Allergic Rhinitis (PER) Phase 3
Not yet recruiting NCT01014325 - Safety and Efficacy Study With Allergen Extracts of House Dust Mites for Specific Sublingual Immunotherapy Phase 3
Completed NCT02910401 - Clinical Response to Rhinovirus Challenge Phase 2
Completed NCT02943720 - ATIBAR - Efficacy and Safety of Two Doses of AllerT in Patients Allergic to Birch Pollen Phase 2
Completed NCT02556801 - Efficacy and Safety of SUBLIVAC Phleum for Immunotherapy of Grass Pollen-Allergy Phase 2
Completed NCT02352168 - Airway Inflammation in Children With Allergic Rhinitis and Intervention N/A
Not yet recruiting NCT02233426 - Effect of Hypertonic Solutions on Allergic Rhinitis Patients N/A
Completed NCT01918956 - PURETHAL Birch RUSH Study Phase 4
Completed NCT01946035 - Alpha-Blockers in Allergic Rhinitis (MAN 01) Phase 4
Completed NCT01682070 - SUBLIVAC FIX Phleum Pratense DT/DRF Phase 2
Recruiting NCT01454492 - The Relationship Between Allergic Rhinitis and Geographic Tongue N/A
Completed NCT01438463 - PURETHAL® Mites Dose Range Finding Study in Patients With Persistent Allergic Rhinitis/Rhinoconjunctivitis Phase 2