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A prospective, randomized, double-blind placebo-controlled dose-finding study of different regimens of mannan-conjugated allergoids of birch pollen allergens administered subcutaneously to patients suffering from birch pollen-induced hay fever

Phase 1
Conditions
Therapeutic area: Diseases [C] - Ear, nose and throat diseases [C09]
Treatment of birch pollen-induced allergic rhinitis or rhinoconjunctivitis
MedDRA version: 20.0Level: LLTClassification code 10001728Term: Allergic rhinoconjunctivitisSystem Organ Class: 100000004853
Registration Number
EUCTR2018-002522-23-DE
Lead Sponsor
Inmunotek S.L.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
200
Inclusion Criteria

Patients must meet all of the following inclusion criteria in order to participate in this study:
•Signed and dated Informed Consent Form by a legally competent patient,
•Female or male patients aged 18–64 years,
•Being in good physical and mental health,
•Confirmed normal renal and liver function (including non-clinically significant deviations as defined per laboratory ranges),
•For females: non-pregnant, non-lactating with adequate contraception or females unable to bear children (i.e. tubal ligation, hysterectomy, or post-menopausal (defined as a minimum of one year since the last menstrual period)). Adequate contraception comprises
-Intake of oral contraceptive + condom
-Intrauterine device + hormone addistive or depot-hormone preparation (injection)
-Condom with or without spermicide + diaphragm with spermicide
-Vaginal ring + condom
-Hormone patch + condom
-Sterisilsation + condom or spermicide
•Having the diagnosis of allergy based on all the following criteria:
-A medical history of moderate to severe allergic rhinoconjunctivitis for birch pollen allergens for at least 2 previous seasons (definition of allergy severity according to ARIA [1]),
-A positive skin prick test (SPT - wheal diameter = 3 mm) to birch pollen allergens, positive control (histamine) wheal = 3 mm, negative control (NaCl) wheal < 2 mm,
-Specific IgE against birch pollen allergens (minimum CAP class 3 or higher, = 3.5 kU/L),
-Positive response to a titrated Nasal Provocation Test (TNPT) with 1/10 or 1/100 dilution from a birch allergen provocation test stock solution
•Being treated with anti-allergic medication for at least 2 seasons prior to enrollment,
•For asthmatic patients: confirmed diagnosis of controlled asthma according to Global Initiative for Asthma (GINA) guidelines (steps 1-3, GINA 2014), FEV1 = 80% of the patient’s reference value or Peak Expiratory Flow (PEF) = 80% of the patients´ individual optimal value.
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 200
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients must not meet any of the following non-inclusion criteria in order to participate in this study:
•Simultaneous participation in other clinical trials or previous participation within 30 days before inclusion,
•Previous immunotherapy with birch pollen allergens within the last 5 years,
•Ongoing immunotherapy with birch pollen allergens or any other allergens,
•Being in any relationship or dependence with the Sponsor, CRO and/or Investigator,
•Inability to understand instructions/study documents,
•Patients who do not have Access to a Smartphone (iOS or Android)
• History of severe systemic reactions and/or anaphylaxis, including to food (e.g. peanut, marine animals) or to Hymenoptera venom (e.g. bee, wasp stings) or to medication (e.g. penicillin), etc.,
•History of hypersensitivity to the excipients of the investigational product or placebo,
•Mild persistent to severe persistent asthma, partly controlled or uncontrolled asthma according to GINA guidelines (GINA 2014),
•Chronic asthma or emphysema, particularly with a forced expiratory volume in 1 second (FEV1) < 80% of the patient’s reference value (ECSC) or Peak Expiratory Flow (PEF) < 80% of the patients´ individual optimal value,
•History of a respiratory tract infection and/or exacerbation of asthma within 4 weeks before the screening,
•Patients with acute allergic rhinoconjunctivitis due to other environmental allergens during the study period,
•History of significant renal disease or chronic hepatic disease,
•Malignant active disease (ongoing or within the five past years),
•Severe autoimmune disease,
•Immune defects including immunosuppression, immunopathies,
•Vaccination during the entire study period (e.g. against flu, pneumococae, etc) – see Chapter XII.2 Non-allowed drugs and procedures”,
•Use of systemic immunosuppressive medications (e.g. methotrexate or cyclosporine A) or blood transfusion one month before screening,
•General inflammatory, severe acute or chronic inflammatory diseases
•Other chronic diseases such as severe congestive heart failure, cardiovascular insufficiency, active gastric ulcer, inflammatory bowl disease, uncontrolled diabetes mellitus, etc.
•Intake of antidepressant drugs with potent antihistamine properties suh as tricyclic antidepressants (e.g. doxepin, amitriptyline, desipramine, imipramine, etc.),
•Administration or planned administration of anti-IgE antibodies, mast cell stabilizers or anti-leukotriene agents,
•Intake of beta-blockers/ACE inhibitor medication (angiotensin-converting enzyme inhibitor),
•Active tuberculosis
•Having any contraindication for the use of adrenaline (including hyperthyroidism),
•Having any contraindication for NPT testing – see Section VIII.9.3 Nasal Provocation Test”,
•Known positive serology to Human Immunodeficiency Virus-1/2, Hepatitis B Virus or Hepatitis C Virus,
•Females who are pregnant, lactating, or of child-bearing potential and not using an adequate contraceptive method which is defined in chapter VI.1 Inclusion Criteria”,
•Administration of corticosteroids (oral, topic or nasal) or of anti-histaminic drugs within time period preceding the trial (screening visit), as defined in the protocol, exception made for routine (previously prescribed) control medication for asthmatic patients,
•Clinically relevant laboratory values, i.e. grade = 2 according to the FDA Guidance for Industry for preventive Vaccine Trials (FDA 2007) at screening visit,
•Patients

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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