Immunological Analysis of Lymph Node Tissue After Intralymphatic Immunotherapy: A Prospective Case Control Study

NCT05960266 | Completed Early Phase 1

• 1 other identifier: 2023-00821
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Allergy is a public health problem as more than 20% of western society is affected by it. Symptomatic treatment of allergy suffices with less severe allergy. Patients with more severe allergy should be treated with allergen immunotherapy (AIT). Present options of AIT are efficient but of long duration, associated with side effects and require much time from the patient. With Intralymphatic immunotherapy (ILIT), allergen is injected into the lymph node under ultrasound guidance. ILIT is complete after 3 treatment visits, may be more effective than and may have markedly fewer side effects than presently available methods of AIT. The investigators plan a randomized, parallel group, open-label, prospective case-control study to assess immunological changes in lymph node and peripheral blood after intralymphatic (ILIT) or subcutaneous (SCIT) immunotherapy with POLVAC. The intervention consists of one ultrasound-guided injection of allergen into inguinal lymph node or subcutaneous injection 1 cm next to the lymph node. Intervention quality (accuracy of injection) will be assessed by the administering physician during treatment and via video recording on the ultrasound device. Side effects associated with treatment will be recorded by the patients for 3 days after the injection. The effect of intralymphatic or subcutaneous injection on lymph node tissue and immunoglobulins E and G4 in serum as well as cellular analyses of lymph node tissue and peripheral blood will be determined in samples taken during the trial. The primary effect parameter is the effect of a single intralymphatic allergen injection on immunological parameters as well as allergen delivery to the lymph node as compared with a single subcutaneous injection.

Conditions

Hypersensitivity; Hay Fever; Rhinitis, Allergic, Seasonal; Rhinoconjunctivitis

Outcome Measures

Primary Outcomes (2)

• Frequency of treatment-related immune cells in the FNA sample

  An FNA of an inguinal lymph node will be performed at either 2, 6 or 24 hours after allergen injection depending on the individual randomization. The lymph node tissue will be evaluated for changes in cellular composition by mass cytometry (CyTOF). Multiple measurements (ca. 30) will be aggregated and described in a heat map.

  At 2, 6 or 24 hours post allergen injection.

• Frequency of treatment-related immune cells in the blood samples sample

  Venous blood will be collected at first at baseline (day 0), then 2, 6 or 24 hours after allergen injection depending on the randomization, the on days 7 and 28 post allergen injection. The blood will be analysed by measuring cellular composition in whole blood by mass cytometry (CyTOF). Multiple measurements (ca. 30) will be aggregated and described in a heat map.

  First bleeding on day 0. Second bleeding at 2, 6 or 24 hours post allergen injection. Third and fourth bleeding on days 7 and 28.

Secondary Outcomes (2)

• Concentration of allergen-specific antibodies as a function of treatment

  Day 0, day 7 and day 28.

• Concentration of leucocytes as a function of treatment

  Day 0. Then 2, 4 or 24 hours post allergen injection. Then on days 7 and 28.

Study Arms (2)

Subcutaneous immunotherapy

ACTIVE COMPARATOR

Subcutaneous injection of grass-rye pollen allergen extract and micro-crystalline tyrosine. Single dose of 2000 U allergen in 0.5 ml. Dosage form: aqueous suspension.

Biological: Polvac Grass+Rye

Intralymphatic immunotherapy

EXPERIMENTAL

Subcutaneous injection of grass-rye pollen allergen extract and micro-crystalline tyrosine. Single dose of 400 U allergen in 0.1 ml. Dosage form: aqueous suspension.

Biological: Polvac Grass+Rye

Interventions

Polvac Grass+Rye BIOLOGICAL

Aqueous suspension of a co-precipitate of allergen extract and tyrosine

Intralymphatic immunotherapy; Subcutaneous immunotherapy

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients who have seasonal grass-pollen-induced rhinoconjunctivitis as confirmed by patient history and type-1-sensitization to grass-pollen in skin and/or serum.
• Patients that undergo pre-seasonal short-term scheme with Polvac™ SCIT at the USZ Allergy Unit in autumn and winter 2023 for treatment of allergic rhinoconjunctivitis.
• Informed Consent as documented by signature.
• Patients are between 18 and 55 years of age when they sign the informed consent.

You may not qualify if:

• Known or suspected allergy to additives to the study product
• Known intolerance or allergy to phenol
• Planned depot steroid injection for treatment of allergic rhinoconjunctivitis
• Uncontrolled asthma or severe asthma with post bronchodilator FEV1\<70%, decided by the investigator
• Pulmonary disease with post bronchodilator FEV1 \< 70 % of predicted
• Pulmonary disease, perennial or seasonal, with daily use of more than 800 microgram inhaled budesonide/day (or equivalent)
• Treatment with omalizumab or other biologics for allergy, AD, urticaria or asthma.
• Allergic reaction within the last 4 days or anaphylaxis within last month before planned ILIT or SCIT injection.

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

University Hospital Zurich

Zurich, 8091, Switzerland

Location

Related Publications (9)

• 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 2021 Aug.

  PMID: 34429875 BACKGROUND

• Jiang S, Xie S, Tang Q, Zhang H, Xie Z, Zhang J, Jiang W. Evaluation of Intralymphatic Immunotherapy in Allergic Rhinitis Patients: A Systematic Review and Meta-analysis. Mediators Inflamm. 2023 May 8;2023:9377518. doi: 10.1155/2023/9377518. eCollection 2023.

  PMID: 37197570 BACKGROUND

• 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.

  PMID: 34187620 BACKGROUND

• 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.

  PMID: 33647073 BACKGROUND

• Heath MD, Mohsen MO, de Kam PJ, Carreno Velazquez TL, Hewings SJ, Kramer MF, Kundig TM, Bachmann MF, Skinner MA. Shaping Modern Vaccines: Adjuvant Systems Using MicroCrystalline Tyrosine (MCT(R)). Front Immunol. 2020 Nov 24;11:594911. doi: 10.3389/fimmu.2020.594911. eCollection 2020.

  PMID: 33324411 BACKGROUND

• Senti G, Johansen P, Kundig TM. Intralymphatic immunotherapy: from the rationale to human applications. Curr Top Microbiol Immunol. 2011;352:71-84. doi: 10.1007/82_2011_133.

  PMID: 21725898 BACKGROUND

• 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. Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17908-12. doi: 10.1073/pnas.0803725105. Epub 2008 Nov 10.

  PMID: 19001265 RESULT

• 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.2020.07.002. Epub 2020 Jul 15.

  PMID: 32679209 RESULT

• 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. No abstract available.

  PMID: 33099797 RESULT

MeSH Terms

Conditions

Hypersensitivity; Rhinitis, Allergic, Seasonal

Condition Hierarchy (Ancestors)

Immune System Diseases; Rhinitis, Allergic; Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate

Study Officials

• Peter Schmid-Grendelmeier, Prof. MD

  University Hospital Zurich, Dept. Dermatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: One arm of patients will be treated by subcutaneous immunotherapy (SCIT). A second arm of patients will be treated by intralymphatic immunotherapy (ILIT).

Study Record Dates

• First Submitted: June 23, 2023
• First Posted: July 25, 2023
• Study Start: November 23, 2023
• Primary Completion: April 14, 2024
• Study Completion: June 1, 2024
• Last Updated: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)