E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Food Allergy with Anaphylaxis |
Fødevareallergi med anafylaksi |
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E.1.1.1 | Medical condition in easily understood language |
Food Allergy with severe symptoms |
Fødevareallergi med alvorlige symptomer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014315 |
E.1.2 | Term | Egg allergy |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016709 |
E.1.2 | Term | Fish allergy |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040539 |
E.1.2 | Term | Shellfish allergy |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001745 |
E.1.2 | Term | Allergy to cow's milk |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034202 |
E.1.2 | Term | Peanut allergy |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027024 |
E.1.2 | Term | Meat allergy |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011240 |
E.1.2 | Term | Cow's milk allergy |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054957 |
E.1.2 | Term | Allergy to grains |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054959 |
E.1.2 | Term | Allergy to nuts |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064075 |
E.1.2 | Term | Seafood allergy |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076438 |
E.1.2 | Term | Milk protein allergy |
E.1.2 | System Organ Class | 100000004870 |
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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 will be to investigate if the combination of initial IgE-specific immunoadsorption and subsequent therapy with Omalizumab will increase the clinical threshold to the culprit food and thus prevent medical emergencies in patients with food anaphylaxis. |
At undersøge om en kombination af fjernelse af specifikt IgE ved immunabsorption og efterfølgende behandling med lægemidlet Omalizumab (Xolair) vil øge den kliniske tærskelværdi for en ikke-tålt fødevare hos patienter med fødevareudløst anafylaksi. |
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E.2.2 | Secondary objectives of the trial |
Not applicable |
Ikke relevant |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 10 male or female subjects, age 18 - 70 years with verified allergy to a food allergen, where validated methods for determination of specific IgE to the food and to the major allergens (Component Resolved Diagnostics) are available. The foods include, but will not be confined to milk, egg, peanut, hazelnut, sesame, wheat, cod and shrimp. Patients with/without elevated levels of total IgE (> 1000 kIU/l) will be included. Minimum level of specific IgE to the major allergen component in the food in question will be 10 kIU/l. No control group will be included. |
•10 mænd eller kvinder i alderen fra 18 år til 70 år
•Diagnostiseret allergi overfor en fødevare, fx mælk, æg, peanut, hasselnød, sesam, hvede, torsk, reje, hvor specifik IgE bestemmes ved valideret analysemetode. Patienter med/uden forhøjet niveau af total IgE (> 1000 kIU/l), vil kunne inkluderes, hvis minimumniveauet af specifik IgE for det ikke-tålte allergen er større eller lig med 10 kIU/l. Der er ingen kontrolgruppe.
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E.4 | Principal exclusion criteria |
•Ischemic heart disease or other significant co-morbidity (e.g. uncontrolled asthma) that might compromise the patient’s safety or study outcomes.
•Infection on the day of study
•Pregnancy or nursing
•Ongoing treatment with antihistamine or drugs with antihistaminic properties that cannot be paused three days prior to the tests
•Ongoing treatment with β-blockers that cannot be paused one day prior to the tests
•Ongoing treatment with oral glucocorticoids (>10 mg daily)
•Alcohol abuse, abuse of opioids or other drugs
•Occurrence of unexpected side effects
•Patients who are not supposed to be able to meet the requirements in the protocol
•Patients who are physically or mentally unable to consent
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•Iskæmisk hjertesygdom eller anden alvorlig sygdom (fx ukontrolleret astma)
•Infektion på forsøgsdagene
•Gravide eller ammende. Kvinder i den fødedygtige alder skal anvende sikker prævention
•Misbrug af alkohol, lægemidler, narkotika inden for det sidste år
•Blodprøver, der ligger uden for normalværdien på screeningstidspunktet
•Må ikke samtidig indtage:
oBehandling med antihistamin, som ikke kan pauseres i 3 dage før testning
være i behandling med ß-blokerende lægemidler, som ikke kan pauseres 1 dag før testning i systemisk steroidbehandling (>10 mg daglig)
•Ved forekomst af uventede bivirkninger
•Patienter, der ikke er i stand til at overholde krav i protokollen (fx glemmer at møde til aftalt tid)
•Patienter, der ikke er fysisk eller psykisk i stand til samarbejde
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary parameters: Clinical thresholds before, during and after therapy (Tr0, TrP, TrX and TrW) will be determined for each patient as described. Serum levels of total and specific IgE together with skin prick test and basophil histamine release test will be determined at the time points described.
Since clinical threshold values may fluctuate spontaneously over time, only a change exceeding 1 challenge step will be considered clinically significant. Since the theoretical maximal efficacy of the combined therapy is a forty fold increase in threshold (a factor of 10 by plasmapheresis and a factor of at least 4 by Omalizumab 300 mg) the expected change from Tr0 to TrX will be at least a factor of 10, corresponding to at least two dose steps. No difference between Tr0 (before therapy) and TrW (four weeks after cessation of therapy is expected, although an effect on lymphocytic B-cells after repeated immunoadsorption has been suggested.
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Det forventes at se en øgning på ca. 40 gange af tærskelværdien for, hvor meget patienten kan spise af den ikke-tålte fødevare, før allergiske symptomer viser sig, fra udgangspunkt (Tr0) til tærskelværdien efter begge behandlinger (faktor 10 efter immunadsorption og faktor 4 efter Omalizumab). Derimod forventes ingen forskel i tærskelværdierne fra Tr0 til 4 uger efter afsluttede behandlinger (TrW), hvor IgE mængden er gendannet.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
not applicable |
ikke relevant |
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E.5.2 | Secondary end point(s) |
The reduction in total IgE as well as the reduction of the levels of specific IgE to the major components of the allergen will be correlated to the corresponding thresholds. An inverse correlation is expected. Reduction in SPT size and a shift to the right of basophil histamine release is also expected. |
Tilsvarende med hensyn til de øvrige test, blodprøvemålinger for total og specifik IgE og histaminfrigørelse og hudpriktest.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
not applicable |
ikke relevant |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 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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LVLS |
sidste besøg, sidste patient |
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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 | |
E.8.9.1 | In the Member State concerned days | |