Safety and Immunogenicity of Cat-allergen Intralymphatic Immunotherapy: an Open Label Phase II Study in Patients With Cat Allergy With and Without Asthma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Change of blood tryptase levels at baseline, after first ILIT and in case of systemic allergic reactions
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
ALUTARD SQ® Felis domesticus, Fix dose: 1000 SQ
Patients will get 3 injections of each 1000 SQ contained in each 0.1 mL
干预措施: ALUTARD SQ® Felis domesticus (Drug)
ALUTARD SQ® Felis domesticus, Dose escalation: low dose and volume
Patients will get 3 injections with 100, 1000 and finally 10000 SQ contained in each 0.1 mL
干预措施: ALUTARD SQ® Felis domesticus (Drug)
Dose escalation: high dose and volume
Patients will get 3 injections 200, 2000 and finally 10000 SQ contained in 0.2, 0.2 and finally 0.1 mL
干预措施: ALUTARD SQ® Felis domesticus (Drug)
结局指标
主要结局
Change of blood tryptase levels at baseline, after first ILIT and in case of systemic allergic reactions
时间窗: 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.
The overall objective is to test whether ILIT with a cat hair allergen extract is safe and tolerable in patients with allergy to cat hair allergen. To assess safety, blood tryptase levels (μg/L) are measured at baseline, 2 hours after the first ILIT and within 1 hour in case of systemic allergic reactions in the following ILIT-visits. Tryptase is released during a systemic allergic reaction.
Incidence and severity of adverse events using the WAO rating system 2024
时间窗: From enrollment to the end of treatment at 8 months.
Safety assessment by analyzing allergic reactions and their severity using World Allergy Organization Grading System (WAO 2024). The scale reaches from 0 (no averse events) to 5 (e.g. anaphylaxis or respiratory or cardiac arrest). Higher number indicating higher severity.
次要结局
- Effect on phenotype and reactivity of cat-allergen-specific lymphocytes measuring basophil activation to cat allergen(From enrollment to the end of treatment at 8 months.)
- Change in total IgE concentration from baseline to each injection, 1 and 4 months after the end of treatment(From enrollment to the end of treatment at 8 months.)
- Change in cat allergen-specific IgE from baseline to each injection and 1 and 4 months after the end of treatment(From enrollment to the end of treatment at 8 months.)
- Change in cat allergen-specific IgG4 from baseline to each injection, 1 and 4 months after the end of treatment(From enrollment to the end of treatment at 8 months)
- Change in cat allergen-specific IgG from baseline to each injection, 1 and 4 months after the end of treatment(From enrollment to the end of treatment at ca. 8 months)
- Assessment of treatment benefit by calculating the ratio of cat allergen-specific IgG4 to IgE(From enrollment to the end of treatment at 8 months.)
- Change in skin sensitivity by measuring the diameters in Skin Prick Test (SPT) at baseline and 4 months after treatment(From enrollment to the end of treatment at 8 months. At baseline and at 4 months after end of treatment.)
- Change in spirometry from baseline and 4 months after end of treatment(From enrollment to the end of treatment at 8 months. At baseline and 4 months after end of treatment.)
- Change of Fraction Exspiratory Nitric Oxide (FeNo) from baseline to 4 months after end of treatment(From enrollment to the end of treatment at 8 months. At baseline and at 4 months after treatment.)
- Efficacy assessment using Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)(From enrollment to the end of treatment at 8 months)
- Efficacy assessment using Asthma Quality of Life Questionnaire (AQLQ)(From enrollment to the end of treatment at 8 months)
- Change in leukotriene release of blood cells from baseline to each injection and 1 and 4 months after the end of treatment(From enrollment to the end of treatment at 8 months. At baseline, each ILIT injection, 1 and 4 months after end of treatment.)
- Change of rhinal secretion by using the Schirmer Test after nasal provocation test (NPT) at baseline and 4 months after end of treatment.(From enrollment to the end of treatment at 8 months. At baseline and 4 months after end of treatment.)
- Change of nasal reactivity by rhinoscopic assessment before and after nasal provocation test (NTP) at baseline and 4 months after end of treatment(From enrollment to the end of treatment at 8 months. At baseline and 4 months after end of treatment.)