Clinical trial NCT06960382: Safety and Immunogenicity of Cat-allergen Intralymphatic Immunotherapy in Patients With Cat Allergy With and Without Asthma
Official title: Safety and Immunogenicity of Cat-allergen Intralymphatic Immunotherapy: an Open Label Phase II Study in Patients With Cat Allergy With and Without Asthma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Allergic Rhinitis
Allergic Asthma
Keywords: cat allergy
asthma
rhinitis
immunotherapy
intralymphatic injection
ILIT
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2025-05-07
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate the safety and tolerability of intralymphatic immunotherapy (ILIT) with ALUTARD SQ Felis domesticus in patients with cat allergy-induced allergic rhinitis and asthma. The main questions it aims to answer are:

Is ILIT with ALUTARD SQ Felis domesticus safe and well tolerated?

What immunological responses play a role in ILIT?

Researchers will compare the effects of ILIT to existing subcutaneous immunotherapy (SCIT) approaches to assess safety, tolerability, immunogenicity, and efficacy.

Participants will:

Receive 3-4 ILIT injections of ALUTARD SQ Felis domesticus into an inguinal lymph node, guided by ultrasound.

Undergo safety monitoring, including WAO guidelines for systemic allergic reactions and tryptase measurement.

Complete lung function tests, questionnaires, and a modified nasal provocation test to evaluate asthma effects and treatment efficacy.

Provide blood samples for ImmunoCAP and basophil activation testing using CAST ELISA.

Inclusion criteria: Adults aged 18-65 with cat-dander-induced allergic rhinitis and asthma.

Exclusion criteria: Hypersensitivity to treatment components, systemic steroid use, uncontrolled asthma (FEV1 \< 70%), recent severe asthma exacerbations, or serious comorbidities.

The study aims to generate data to inform future efficacy trials.

Detailed description: Patients with allergic rhinitis and asthma due to sensitisation to cat allergens are seldom offered allergen immunotherapy (AIT) due to risk of systemic allergic adverse events such as asthma exacerbations and anaphylaxis. In Switzerland, ALUTARD SQ Felis domesticus is approved for subcutaneous immunotherapy (SCIT). The treatment comprises nearly 50 injections over 3 years. In contrast, intralymphatic immunotherapy (ILIT) is an experimental treatment option that has been suggested to be effective after only 3-4 injections using much lower doses as for SCIT. Since the lymph nodes do not contains mast cells, and due to the lower doses and less injections, ILIT is expected to be a safer alternative to SCIT. This study in patient with cat allergy therefore tests the safety and tolerability of ALUTARD SQ Felis domesticus in ILIT.

The objective is to test if ILIT is safe and tolerable in patients with allergy to cat hair allergen and to determine which immunological responses play a role in ILIT.

The main outcome measures on the safety, tolerability, immunogenicity and efficacy. The data will be used to design later efficacy studies.

Safety is measured using a World Allergy Organization (WAO) guideline for systemic allergic reactions and by tryptase measurement in blood serum. Effects on asthma is measured using lung functions tests and questionnaires. Immunogenicity is measured by ImmunoCAP and basophil activation is measured using CAST ELISA. Treatment effect is measured using a modified nasal provocation test and quality of life questionnaires.

Inclusion: Informed consent, cat-dander-induced ARC, age 18-65 years, any sex and gender.

Exclusion: Hypersensitivity to aluminium hydroxide or phenol. Systemic steroid treatment. Uncontrolled asthma or FEV1 \< 70%. Severe asthma exacerbation last 3 months. Emphysema, bronchiectasis. Serious comorbidities as judged by the recruiting physician.

The study drug is administered by injection into an inguinal lymph node. The targeting of the lymph node is supported by simultaneous sonography.

"ALUTARD SQ Felis domesticus" is administered intralymphatically. The injection volume is 50-200 mcl and the dose is between 10 SQ units and 10,000 SQ units. The injections will be performed three to four times with 4 weeks or more interval between each injection.

The procedures last for 5-10 minutes, but various tests and are performed prior to and after the ILIT injection. The visits therefore last for 2-3 hours, including the safety follow up.

Eligibility criteria: Inclusion Criteria:

* Informed consent as documented by signature.
* Cat-dander-induced ARC as confirmed by patient history and type-1-sensitization to cat dander in skin and/or serum.

Exclusion Criteria:

* Hypersensitivity to phenol.
* Planned depot steroid injection for treatment of ARC
* Patients with uncontrolled asthma or FEV1 \< 70% of the predicted value in adults (after adequate pharmacological therapy).
* Patients with a severe asthma exacerbation in the past 3 months.
* Irreversible secondary changes in the affected organ (e.g., emphysema, bronchiectasis).
* Chronic obstructive or restrictive lung disease.
* Patients with active systemic autoimmune diseases and patients with immune deficiencies or immune weaknesses.
* Severe chronic inflammatory diseases.
* Concomitant infection with fever or other signs/symptoms of an acute or chronic infection at treatment visit.
* Chronic obstructive or restrictive lung disease
* Patients with malignant tumours that currently have clinical significance.
* Disease or conditions rendering the treatment of anaphylactic reactions difficult (symptomatic coronary heart diseases, severe arterial hypertension, and treatment with beta-blockers).
* Known cardiovascular disease, i.e., not even NYHA class I.
* Use of ACE-blockers.
* Recent or on-going hepatic or renal disease.
* Severe chronic renal insufficiency (due to aluminium burden).
* Alcohol or drug abuse
* Women who are pregnant and breast feeding
* Women of childbearing age who wish to become pregnant or do not use contraception.
* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.
* Participation in another study with investigational drug within the 30 days preceding and during the present study.

Primary outcomes:
measure: Change of blood tryptase levels at baseline, after first ILIT and in case of systemic allergic reactions
timeFrame: From enrollment to the end of treatment at 8 monts. At Baseline, 2 hours after the first Injection and within 1 hour in case of systemic allergic reactions.
measure: Incidence and severity of adverse events using the WAO rating system 2024
timeFrame: From enrollment to the end of treatment at 8 months.
Secondary outcomes:
measure: Effect on phenotype and reactivity of cat-allergen-specific lymphocytes measuring basophil activation to cat allergen
timeFrame: From enrollment to the end of treatment at 8 months.
measure: Change in total IgE concentration from baseline to each injection, 1 and 4 months after the end of treatment
timeFrame: From enrollment to the end of treatment at 8 months.
measure: Change in cat allergen-specific IgE from baseline to each injection and 1 and 4 months after the end of treatment
timeFrame: From enrollment to the end of treatment at 8 months.
measure: Change in cat allergen-specific IgG4 from baseline to each injection, 1 and 4 months after the end of treatment
timeFrame: From enrollment to the end of treatment at 8 months
measure: Change in cat allergen-specific IgG from baseline to each injection, 1 and 4 months after the end of treatment
timeFrame: From enrollment to the end of treatment at ca. 8 months
measure: Assessment of treatment benefit by calculating the ratio of cat allergen-specific IgG4 to IgE
timeFrame: From enrollment to the end of treatment at 8 months.
measure: Change in skin sensitivity by measuring the diameters in Skin Prick Test (SPT) at baseline and 4 months after treatment
timeFrame: From enrollment to the end of treatment at 8 months. At baseline and at 4 months after end of treatment.
measure: Change in spirometry from baseline and 4 months after end of treatment
timeFrame: From enrollment to the end of treatment at 8 months. At baseline and 4 months after end of treatment.
measure: Change of Fraction Exspiratory Nitric Oxide (FeNo) from baseline to 4 months after end of treatment
timeFrame: From enrollment to the end of treatment at 8 months. At baseline and at 4 months after treatment.
measure: Efficacy assessment using Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
timeFrame: From enrollment to the end of treatment at 8 months
measure: Efficacy assessment using Asthma Quality of Life Questionnaire (AQLQ)
timeFrame: From enrollment to the end of treatment at 8 months
measure: Change in leukotriene release of blood cells from baseline to each injection and 1 and 4 months after the end of treatment
timeFrame: From enrollment to the end of treatment at 8 months. At baseline, each ILIT injection, 1 and 4 months after end of treatment.
measure: Change of rhinal secretion by using the Schirmer Test after nasal provocation test (NPT) at baseline and 4 months after end of treatment.
timeFrame: From enrollment to the end of treatment at 8 months. At baseline and 4 months after end of treatment.
measure: Change of nasal reactivity by rhinoscopic assessment before and after nasal provocation test (NTP) at baseline and 4 months after end of treatment
timeFrame: From enrollment to the end of treatment at 8 months. At baseline and 4 months after end of treatment.
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
References: