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 | Not possible to specify |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of a SCIT (subcutaneous immunotherapy)-treatment with a mutant recombinant fish-parvalbumin (mCyp c1, carp parvalbumin) quantified in mass units and formulated in a solution with alum, in subjects with fish-allergy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of SCIT treatment with mCyp c 1 and determine any possible changes in the severity of the reaction during the pre- and post-treatment DBPCFC (double blind placebo controled food challenge) with fish, in the SPT (skin prick test) reactivity to fish, in specific IgE, IgA, IgG, IgG4 antibodies against fish and rCyp c 1 (recombinant carp parvalbumin) and in the biological activity of IgE, between the active and placebo study groups. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject having given a written informed consent before completing any study related procedure. Male or female subject from 18 to 65 years old and in general good health as determined by past medical history and physical examination. For woman of child bearing potential: -a negative urine pregnancy test at screening visit, -the subject must receive/ use a medically effective contraceptive method during the study. Convincing case history of allergy (immediate allergic reaction ≤ 2 hours) to fish ingestion. Specific IgE to fish by both a positive (3mm mean wheal diameter over negative control) SPT to cod extract and an ImmunoCAP ≥ class 2 (0.70 kUA/L) for cod (f3) and rCyp c 1 at screening. Positive DBPCFC with cod at screening visits. Spirometry FEV1 ≥ 80% of predicted values at screening. Subject accepting to comply fully with the protocol.
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E.4 | Principal exclusion criteria |
Placebo-reaction in DBPCFC. Reaction in the last (7th) dose of the DBPCFC. Food anaphylaxis: anaphylactic shock (a score of 2 or 3 on cardiovascular/ neurologic symptoms according to PRACTALL (1): score 2 = drop in blood pressure and/or >20% from baseline, or significant change in mental status- score 3 = cardiovascular collapse, signs of impaired circulation/ unconscious) due to fish intake, both during the past and at screening DBPCFC. Ongoing immunotherapy (IT) with any kind of allergen. Ongoing or previous treatment with omalizumab. Any clinical condition that contraindicates IT (EAACI guidelines) (8): serious immunological diseases, major cardiovascular disease, cancer, chronic infections, lack of compliance and severe psychological disorders. Any significant clinical condition that the investigators judged might hamper the patient’s safety or the study outcomes. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, mental disease, immunological and endocrine disease. Chronic urticaria. Severe atopic dermatitis or non-controlled atopic dermatitis. Ongoing treatment with betablockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor II antagonists (ARA II). Pregnancy or nursing. Uncontrolled asthma (asthma, if present, should be well controlled according to GINA guidelines using any kind of drugs except oral corticosteroids and omalizumab). An FEV1<80% of predicted value during screening spirometry. Subject who has participated in a clinical trial within 3 months prior to this one. Subject with a history of drug or alcohol abuse. Investigators, co-investigators, as well as their children or spouses and all the study collaborators should not be enrolled in the study. Patients with concurrent allergy symptoms can be included if patients can manage without antihistamines and/or leukotriene receptor antagonists five days prior each screening and treatment visit.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study will be efficacy as determined by the change from baseline in the threshold of fish protein that induces an allergic reaction. This threshold will be assessed by means of a standardized DBPCFC (double blind placebo controlled food challenge) with cod-fish after completion of six months of immunotherapy (SCIT). Success is defined as a statistically significant change in the threshold dose of protein that provokes a reaction in DBPCFC. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The time point for each patient will be 2 weeks after the last maintenance dose of the SCIT. At that time point each patient will be subjected to a post-treatment DBPCFC. |
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E.5.2 | Secondary end point(s) |
The fundamental secondary endpoint will be safety as indicated by clinical safety and tolerability and by the careful recording of adverse events; other surrogates of safety will be: physical examination, vital signs, 12-Lead ECG and laboratory evaluations (complete blood count, biochemical tests, urine analysis and urine pregnancy test). Secondary outcomes of efficacy are the changes from baseline in the severity of the reaction in the post DBPCFC (as compared with pre-treatment), in SPT reactivity against fish and mCyp c 1 (titrated), in serum specific IgE, IgG, IgG4 and IgA antibodies against rCyp c 1 (CAP) and in the biological activity of IgE (stripped basophil histamine release test).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety will be monitored throughout the study. For efficacy, the time point for each patient will be 2 weeks after the last maintenance dose of the SCIT. At that time point each patient will be subjected to a DBPCFC. Before the food challenge patients will be subjected to blood withrawl, urine sample and skin prick tests to assess the secondary end points (both in terms of safety and efficacy). |
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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 | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 | Yes |
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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Last visit of the last patient. The end of the trial is defined as the time at which the last (96th) subject of the study will end treatment and 2 weeks after that will be subjected to the post-treatment evaluation (blood withdrawal, SPTs) and post-treatment DBPCFC (at two visits, visit 15A and 15B). |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |