Intralymphatic Immunotherapy in Increasing Doses, Substudy

Study Overview
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Brief Summary
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The study evaluates the safety and effect of intralymphatic allergen specific immunotherapy in increasing doses. Patients with allergy to grass or birch will be treated with three intralymphatic injections in an up-dosing protocol; 1000 SQ-U, 3000 SQ-U and 10 000 SQ-U, or placebo. ***IMPORTANT INFORMATION!*** The up-dosing protocol is changed due to adverse events at 5000 SQ-U. One patient had general utricaria 15 minutes after injection (moderate reaction). One patient had a serious adverse event with anaphylactic reaction 6 minutes after intralymphatic injection. (1000 SQ-U and 3000 SQ-U have been given with no serious adverse events.) New regimen: 1000 SQ-U, 3000 SQ-U, 3000 SQ-U.

Detailed Description
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40 patients with seasonal allergic rhinitis will be recruited. Study subjects are randomized to intralymphatic injections with placebo or ALK Alutard 5-grasses or birch. Injections are given with 4-5 (-7) weeks interval.

Official Title
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Intralymphatic Immunotherapy in Increasing Doses up to 10 000 SQ-U - a Human Randomized Clinical Trial. Substudy.

Conditions
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Rhinitis, Allergic, Seasonal

Intervention / Treatment
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* Drug: ALK Diluent
* Drug: ALK Alutard SQ 5-grasses or ALK Alutard Birch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Seasonal allergic symptoms for birch and/or grass verified by skin prick test, Accepted informed consent Exclusion Criteria: Pregnancy or nursing Autoimmune or collagen disease (known) Cardiovascular disease Perennial pulmonary disease Hepatic disease Renal disease Cancer Any medication with a possible side-effect of interfering with the immune response Previous immuno- or chemotherapy Chronic diseases Other upper airway disease (non-allergic sinusitis, nasal polyps, chronic obstructive and restrictive lung disease) Disease or conditions rendering the treatment of anaphylactic reactions difficult (symptomatic coronary heart diseases, severe arterial hypertension and treatment with β-blockers) Major metabolic disease Known or suspected allergy to the study product Alcohol or drug abuse Mental incapability of coping with the study Withdrawal of informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Intralymphatic placebo injections<br>ALK Diluent, ATC-code V07AB. 3 injections with 4-7 weeks interval. | Drug: ALK Diluent<br> <br> * Other names: 0,3% human albumin. ATC-code V07AB;|
| Active Comparator: Intralymphatic active injections<br>ATC-code V01AA02. 3 injections with 4-7 weeks interval in an up-dosing protocol; 1000 SQ-U, 3000 SQ-U, 10000 SQ-U. ***IMPORTANT INFORMATION! The up-dosing protocol is changed due to an adverse event at the last injection. New regimen: 1000 SQ-U, 3000 SQ-U, 3000 SQ-U. *** | Drug: ALK Alutard SQ 5-grasses or ALK Alutard Birch<br>* Depot formulation of relevant allergen adsorbed to aluminium hydroxide in a suspension.<br>* Other names: Allergen, grass pollen. ATC-code V01AA02 or V01AA05;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean combined daily symptoms-and-medications-score | Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale) and medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids). | Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean total daily symptoms score | Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale) | Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment). | 
| Mean total daily medications score | Daily scoring of medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids). | Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment). | 
| Change in subjective allergic symptoms following nasal allergen provocation | The study subjects will be intranasally challenged with allergen and symptom score questionnaires are filled out pre-provocation and 5, 10 and 30 min post-provocation. | Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment. | 
| Effects on quality of life | Juniper Rhinitis quality of life questionnaire (RQLQ) questionnaires | During peak pollen season which will be up to 6 months after completed treatment. | 
| Short term change of skin reactivity | Skin prick test | Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment. | 
| S-IgE Grass or Birch |  | Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment | 
| S-IgG4 Grass or Birch |  | Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment | 
| Registration of adverse event |  | From the first injection to 30 days after the last injections has been given | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hay fever, Pollen allergy, Allergic rhinitis