Safety and Immunogenicity of Cat-allergen Intralymphatic Immunotherapy in Patients With Cat Allergy With and Without Asthma

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.

• Effect on phenotype and reactivity of cat-allergen-specific lymphocytes measuring basophil activation to cat allergen [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: From enrollment to the end of treatment at 8 months]
• Efficacy assessment using Asthma Quality of Life Questionnaire (AQLQ) [Срок оценки: 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 [Срок оценки: From enrollment to the end of treatment at 8 months. At baseline, each ILIT injection, 1 and 4 months after end of treatment.]