Patients with severe to moderate Allegic rhinitis.
Conditions
Interventions
Trade Name: ALK, Alutard SQ Betula verrucosa
Pharmaceutical Form: Suspension for injection
Pharmaceutical form of the placebo: Suspension for injection
Route of administration of the placebo: Intralym
Sponsors
Department of Clinical Science, Intervention and Technology, Karolinska Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main study Age 18-50 Accepted and signed informed consent. Recently (within 12 months) ended a full 3 year SCIT-program with amelioration of symptoms but not full symptom relief. Substudy : Age 18-50 Accepted and signed informed consent. Moderate to severe seasonal allergic symptoms for grass or birch. Severity levels are assessed by weighing together patient’s medical history, allergen specific S-IgE and skin-prick test reaction. The patient’s subjective description of symptom load during pollen season is most important. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Previously SCIT with total symptom relief. Previously SCIT but no symptom improvement at all. Sensitizations to house dust mite or fur 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 Hyper-IgE-syndrome 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 ß-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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary study objective is to evaluate the clinical effect of ILIT, with birch or grass in increasing doses according to the specified protocol, in patients with moderate to severe seasonal allergic rhinitis. ;Secondary Objective: Secondary study objectives are to evaluate if ILIT in increasing doses according to the specified protocol can be given without unacceptable side effects reduces symptom score and nasal obstruction after nasal allergen provocation improves quality of life during peak pollen season. reduces skin prick reactions changes levels of allergen specific antibodies in blood changes the cellular and immunological patterns in blood and within the lymph nodes, tonsils and nasal mucosa ;Primary end point(s): The primary efficacy parameter is defined as the total combined daily symptoms and medications score during peak pollen season. It is measured as the sum of the daily score and is compared to baseline and compared to placebo. Baseline is defined as peak pollen season prior to treatment. (The study participants will be scoring the daily symptoms and medications in a questionnaire in a mobile phone app or by e-mail). ;Timepoint(s) of evaluation of this end point: peak pollen season before study drug injections and next coming peak pollen season after study drug injections | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy end points: Total combined daily symptoms and medications score during entire pollen season. Nasal allergen challenge 4-6 weeks and 7-12 months after treatment. Change in recalled seasonal symptoms scored on a visual analogue scale (VAS) after the pollen season. Change in health related quality of life during peak pollen season compared to placebo and the pollen season prior to treatment. Quality of life is measured with Juniper Rhinitis Quality of Life Health Survey and Sinonasal Outcome test -22. The questionnaires are also completed before treatment off pollen season and after treatment to determine baseline quality of life. Change in skin prick test reaction. Change in allergen-specific IgE- and IgG antibodies 4-6 weeks after treatment and 7-12 months after treatment. Cellular and immunological changes at flow cytometry on blood 4-6 weeks after the treatment compared to before treatment. For substudy also: Cellular and immunological changes at flow cytometry on fine needle aspirate from the lymph nodes 4-6 weeks after the treatment compared to before treatment. Cellular and immunological changes at flow cytometry on fluid from nasal lavage after the treatment, during pollen season (3-7 months after treatment) and after pollen season (7-12 months after treatment). Cellular and immunological changes at flow cytometry on biopsies from tonsils and nasal mucosa at pollen season (3-7 months after treatment) compared to before treatment. Nasal allergen challenge at an open follow-up visit 3 years after treatment. Subjective symptom score and objective nasal obstruction at rinomanometry is measured. Change in recalled seasonal symptoms scored on a visual analogue scale (VAS) after the pollen season at an open follow-up visit three years after treatment. Quality of life during peak pollen season as an open follow up 3 years after treatment. Safety endpoints: Incidence of adverse events graded as mild, moderate, severe | — |
Countries
Sweden
Contacts
Public ContactÖNH-mottagningen, B51
Karolinska University Hospital, Huddinge
Outcome results
None listed