E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with severe to moderate Allegic rhinitis. |
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E.1.1.1 | Medical condition in easily understood language |
Patient with severe to moderate allergy that sufferings from stuffy and runny nose. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Both studies are described in the same protocol.
Date 2015-01-15 version 1.0
Titel : Intralymphatic immunotherapy in increasing doses up to 10 000 SQ-U
a human randomized clinical trial (Substudy)
Primary objectives: 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 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
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E.3 | Principal 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.
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E.4 | Principal 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 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
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E.5 End points |
E.5.1 | 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).
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E.5.1.1 | 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 |
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E.5.2 | 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.
Change leucocytes differential count 4-6 weeks after treatment and 7-12 months after treatment.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Total combined daily symptoms and medications score during entire pollen season.
Nasal allergen challenge visit 2,6, 8, 12,13
Change in recalled seasonal symptoms (VAS)?
QoL peak pollen before inj. peak pollen after inj.
Skin prick test at visit 2,6, 8, 12,13
Allergen-specific IgE- and IgG antibodies visit 2,6, 8, 12,13
Cellular and immunological changes at flow cytometry on blood visit 2 and v 8
Substudy also:
Cellular and immunological changes from the lymph nodes visit 2 and 5
Cellular and immunological changes from nasal lavage visit 2, 6, 7, 8
Cellular and immunological changes on biopsies, tonsils and nasal mucosa visit 2 ,7
Safety endpoints:
Incidence of adverse events visit 3,4,5,6,8, 9,10 ,11,12,13
leucocytes differential count visit 2, 6 and 8 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |