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

NCT ID: NCT05960266

Last Updated: 2025-05-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-23

Study Completion Date

2024-06-01

Brief Summary

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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.

Detailed Description

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This is a prospective, comparative, clinical open label pilot study. From patients with grass pollen allergy who undergo a pre-seasonal SCIT scheme with Polvac™ Grass+RyeSCIT at the USZ Allergy Unit, 30 patients will be recruited for the study.

Four to six weeks after end of SCIT treatment (at maximal maintenance dose), the patients will be randomized to one out of two treatment groups and receive one additional allergen injection. Both treatment groups receives the same drug, but at different doses and routes of administration. Fifteen patients will be allocated to receive another subcutaneous injection with 0.5 ml (2000 U) Polvac Grass+Rye. The other 15 patients will be allocated to receive an intralymphatic injection of 0.1 ml Polvac Grass+Rye with 400 U allergen. Both SCIT and ILIT injections are performed by ultrasound-guidance as to assure injection into the lymph node (ILIT) or 1 cm next to the lymph node (SCIT).

The FNA of lymph node tissue will be conducted at 2, 6 or 24 hours after allergen injection. At the same time, FNA of a contralateral lymph nodes will be performed as baseline. Venous blood will be sampled at all visits: at baseline as well as after 2, 6 or 24 hours, after 7 days and after 28 days of the allergen ILIT or SCIT. The FNA is performed by ultrasound-guidance.

Drug preparation:

The 1 ml medication vial (4000 U/ml) is shaken for 10 seconds. The head of the vial is disinfected and 0.5 ml (for SCIT) or 0.1 ml (for ILIT) of the medication is drawn into a 1 ml syringe with 23G hypodermic needle assuring no air in the syringe or needle. The medication is used no later than 4 hours after the preparation. Replica of the dose are made if more than one injection is to be performed. The remaining medication is discarded.

Fine needle aspiration (FNA):

The FNA is minimally invasive and performed by an experienced investigator. The skin above the lymph node, will be disinfected and a sterile needle (23-25g), attached to the 5 ml syringe, fixed in a FNA gun, will be inserted into the lymph node cortex under colour Doppler ultrasound guidance while avoiding important tissues and organs, such as large blood vessels and nerves. The syringe plunger is drawn to set the seal at a 2 ml scale in order to maintain negative pressure in the syringe. After rotating and aspirating the syringe 5 times, the needle is rotated to aspirate in a fan shape way at different trajectories in the lymph node. The needle is withdrawn when ca. 0.1 ml tissue is present in the syringe. The puncture site is covered with sterile gauze and pressure is applied with appropriate force for 10 min. Patients are observed for 30 min of observation and released when no adverse reaction. The FNA sample will be rinsed with dimethyl sulfoxide (DMSO)-containing live cell freezing medium (10% DMSO and 90% fetal bovine serum (FBS)), put into a cryotube and frozen in -80°C.

Blood collection and preservation of cells and blood serum:

Venous blood collection is performed just before SCIT/ILIT, at 2, 6 or 24 hours post SCIT/ILIT, and at 7 and 28 post SCIT/SLIT. Each time, 25 ml venous blood is collected for preparation of PBMCs and 5 ml blood is collected for preparation of serum. Both samples are processed by routine in-house methods within 2 hours for preparation of serum and cells. The produced serum is aliquoted in 1 ml samples and frozen at - 20 °C for later analysis. Whole blood is centrifuged on Ficoll and the PBMCs isolated and washed in PBS before re-suspended in DMSO-containing live cell freezing medium. 1 ml aliquots of the cells are slow-frozen in cryotubes and finally stored at -80 °C before further analysis.

Conditions

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Hypersensitivity Hay Fever Rhinitis, Allergic, Seasonal Rhinoconjunctivitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

One arm of patients will be treated by subcutaneous immunotherapy (SCIT). A second arm of patients will be treated by intralymphatic immunotherapy (ILIT).
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Subcutaneous immunotherapy

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.

Group Type ACTIVE_COMPARATOR

Polvac Grass+Rye

Intervention Type BIOLOGICAL

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

Intralymphatic immunotherapy

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.

Group Type EXPERIMENTAL

Polvac Grass+Rye

Intervention Type BIOLOGICAL

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

Interventions

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Polvac Grass+Rye

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Zurich

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Peter Schmid-Grendelmeier, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Zurich, Dept. Dermatology

Locations

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University Hospital Zurich

Zurich, , Switzerland

Site Status

Countries

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Switzerland

References

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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.

Reference Type BACKGROUND
PMID: 34429875 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 37197570 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34187620 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33647073 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33324411 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21725898 (View on PubMed)

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.

Reference Type RESULT
PMID: 19001265 (View on PubMed)

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.

Reference Type RESULT
PMID: 32679209 (View on PubMed)

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.

Reference Type RESULT
PMID: 33099797 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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2023-00821

Identifier Type: -

Identifier Source: org_study_id

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