E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039085 |
E.1.2 | Term | Rhinitis allergic |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010744 |
E.1.2 | Term | Conjunctivitis allergic |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 aim of the trial is to provide statistically significant data supporting the safety and clinical efficacy of intralymphatic immunotherapy at three different doses of allergen: 300 SQ-U/injection, 1000 SQ-U/injection or 3000 SQ-U/injection as compared to placebo in relieving medication use and symptoms during the grass pollen seaso |
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E.2.2 | Secondary objectives of the trial |
A second aim is to select the optimal dose of allergen for treatment after one or two allergen seasons and provide a good description of the side effects to be expected during treatment. This will enable health care providers to consider ILIT as a fundamentally new, shortened allergen immunotherapy treatment method with increased appeal to patients. A third aim is to determine whether ILIT limits grass pollen allergic asthma of treated patients by asking asthma related questions and measuring IOS.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients have seasonal grass pollen induced rhino conjunctivitis during the two most recent seasons and a positive skin prick test resulting in a wheal diameter ≥ 3 mm to ALK Soluprick Grass 225. The latter is important as it predicts that the patients IgE recognises allergens found in ALKs preparation for treatment, a crucial condition for treatment success. Patients are adults; more than 18 years old on the day of first treatment, Patients must be comfortable with digital data entry and have accepted and digitally approved the informed consent document. Patient have to have sufficient symptoms during the grass pollen season to allow us to record an effect of the treatment; we will evaluate question 1 – 6 and 18 – 22 of their RHINE III and the sum of the retrospective RTSS questionnaires from the pre-screening tools to assess the severity of grass pollen dependent rhinoconjunctivitis and to identify or predict possible grass pollen dependent asthma affecting patients. For inclusion, patients have to have a retrospective RTSS score >7 on a scale of 0 – 18 (most severe). We will select patients with the highest RTSS score. 90% of patients included for the baseline year will be included in the treatment study. |
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E.4 | Principal exclusion criteria |
pregnancy 1 previous allergen immunotherapy for grass pollen allergy 2 Significant allergic sensitisation to mugwort (Artemisia vulgaris) or sensitisation with persistent exposure to pet animal allergens that results in allergic symptoms 3 Known or suspected allergy to additives to the study product; allergy to aluminium hydroxide or phenol 4 Depot steroid injection for treatment of allergic rhinoconjunctivitis 5 Upper airway disease (non-allergic sinusitis, nasal polyps) 6 uncontrolled asthma or severe asthma with post bronchodilator FEV1<70% of expected, decided by the investigator 7 Pulmonary disease, perennial or seasonal with daily use of more than 800 microgram inhaled budesonide/ day (or equivalent) or treatment with omalizumab or other biologics for allergy or asthma. 8 Pulmonary disease with post bronchodilator FEV1 < 70 % of predicted 9 Allergic reaction within the last 4 days or anaphylaxis last month before ILIT injections
10 severe Autoimmune or collagen disease 11 Disease or conditions rendering the treatment of anaphylactic reactions difficult (symptomatic coronary heart diseases, severe arterial hypertension and treatment with beta-blockers) 12 Known cardiovascular disease, i.e. not even NYHA class I. 13 Use of ACE-blockers. If ACE-blockers are used, they should be withdrawn after discussion with the Principal Investigator 2 weeks before first injection and until after the last injection 14 Recent or on-going hepatic or renal disease 15 All malignant diseases 16 Immuno- or chemotherapy during the last 15 years, 17 Increased bleeding tendency 18 Any other than study medication with an effect of interfering with the immune response 19 Chronic obstructive or restrictive lung disease 20 Skin diseases with barrier defect in the inguinal areas 21 Alcohol or drug abuse 22 Participation in another clinical study from visit 1-8.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is a reduction of more than 20% in the annual median combined symptom medication score (cSMS) on a scale from 0 – 6, suggested by EAACI, over the allergen season defined by EAACI in patients treated with Alutard at 1000 SQU per injection compared with patients treated with placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change in parameters from the pollen season before treatment to the season after treatment and the second season after treatment. Change in parameters between groups in the grass pollen season after treatment, as well as in the second season after treatment. |
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E.5.2 | Secondary end point(s) |
Dose response of allergen dose (300 – 1000 – 3000 SQU/injection) to document clinical effect as cSMS change in specific IgE and IgG4 to Grass and Phl p5 Effect of treatment quality (nr of successful injections) on treatment effect in cSMS the importance of patient engagement for quality of cSMS data cSMS can also be interpreted also as Well days and Hell days , and as response to Log10 of daily grass pollen counts The predictive ability of the skin prick test as a ratio of the histamine positive control (Cha) for cSMS 1 Effect of treatment with ILIT on patients with asthma as assessed with ACT and with IOS In patients without asthma we will monitor small airway changes with IOS
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change in parameters from the pollen season before treatment to the season after treatment and the second season after treatment. Change in parameters between groups in the grass pollen season after treatment, as well as in the second season after treatment. |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
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 | 4 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |