Intralymphatic Immunotherapy in Increasing Doses, After Subcutaneous Immunotherapy

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 that have already undergone subcutaneous immunotherapy will be treated with three intralymphatic injections in increasing doses; 1000 SQ-U, 3000 SQ-U and 10 000 SQ-U, or placebo.

Detailed Description
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38 patients with seasonal allergic rhinitis that have recently (within 20 months) ended a full subcutaneous immunotherapy protocol with birch or grass allergen with improvement but not full symptom relief are recruited. Study subjects are randomized to intralymphatic injections with placebo or ALK Alutard 5-grasses or birch.

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

Conditions
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Rhinitis, Allergic

Intervention / Treatment
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* Drug: ALK Alutard birch or 5-grasses
* Drug: ALK diluent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-55 Accepted and signed informed consent. Recently (within 20 months) ended a full 3 year program with subcutaneous immunotherapy (SCIT) with amelioration of symptoms but not full symptom relief. Exclusion Criteria: Previously subcutaneous immunotherapy (SCIT) with total symptom relief. Previously SCIT but no symptom improvement at all. Sensitizations to house dust mite or furry animals, with symptoms. Severe atopic dermatitis. Patients with significant diseases other than allergic rhinitis. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study. Patients with a respiratory tract infection in the past 4 weeks prior to Visit 2. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm, or subdermal implants). Known autoimmune or collagen disease Cardiovascular disease Perennial pulmonary disease including asthma Hepatic disease Known renal insufficiency Cancer Hematologic disease Chronic infectious disease Any medication with a possible side-effect of interfering with the immune response Previous immuno- or chemotherapy, apart from SCIT 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 Obesity with BMI > 30 since subcutaneous fat makes ultrasound imaging of lymph nodes harder which may risk the correct placement of injection. Patients who, in the opinion of the investigator, abuse alcohol or drugs within 2 years prior to Visit 1. Patients who have taken an investigational drug within 1 month or six half lives, whichever is greater, prior to Visit 1. 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: ALK diluent<br>Human albumin | Drug: ALK diluent<br>* 0,3% human albumin<br>* Other names: Human albumin;|
| Active Comparator: ALK Alutard birch or 5-grasses<br>Grass pollen suspension or birch pollen suspension | Drug: ALK Alutard birch or 5-grasses<br>* 3 injections with 4-5 weeks interval.<br>* Other names: ATC-code V01AA, V04CL and V07AB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total daily symptoms and medications score | Difference between active and placebo group in total daily symptoms and medications score during the pollen season. | 5-7 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement on Visual Analogue Scale (VAS) | Difference in improvement on VAS between active and placebo group. | During pollen season and recalled after pollen season, approximately 1 year after the start of treatment. | 
| Change in skin prick test reactivity | Tested with ALK Soluprick. Measured as the wheal area in millimeter for birch- or grass pollen. | 4-8 weeks after treatment, 9-12 months after treatment | 
| Change in symptoms score after nasal allergen challenge | 0,1 ml of ALK Aquagen Birch or Timothy 10 000 SQU/ml is deposited in each nostril and allergy symptoms are recorded. | 4-8 weeks after treatment, 9-12 months after treatment | 
| Difference between active and placebo group in Quality of Life measured with Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) | At peak pollen season after treatment. | Up to 7 months after treatment. | 
| Difference between active and placebo group in Quality of Life measured with Sino Nasal Outcome Test -22 (SNOT-22) | At peak pollen season after treatment. | Up to 7 months after treatment. | 
| Change in allergen specific S- antibody levels. | IgE, IgG, IgG4 | 4-8 weeks after treatment, 9-12 months after treatment | 
| Incidence of adverse events graded as mild-moderate-severe |  | From first injection to 30 days after last injection. |