E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Idiopathic Urticaria |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009159 |
E.1.2 | Term | Chronic urticaria |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue 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 |
To determine whether treatment with omalizumab in patients with CIU results in a reduction of the high affinity IgE receptor (FcεRI) and/or IgE positive skin cells following 12 weeks of treatment (Day 85). |
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E.2.2 | Secondary objectives of the trial |
Cellular /Sub Cellular Endpoint Objectives
• correlation of reduction of FcεRI and/or IgE on positive skin cells and clinical response
• effect of omalizumab vs placebo on skin cells.
• effect of omalizumab vs placebo on peripheral blood cells.
• differences in skin samples in CIU patients vs healthy volunteers at baseline.
PK/PD Endpoint Objectives
• effect of omalizumab vs placebo in patients with CIU on PK/PD measures:
• trough serum levels of omalizumab,
• total and free IgE levels,
• Specific IgE
Clinical Endpoint Objectives
• safety
• clinical effect of omalizumab vs placebo
• Change from baseline
• Change from baseline vs placebo
the following efficacy outcome measures:
• UAS7,
• global assessment of symptoms (hives and pruritus)
• angioedema,
• Dermatology Life Quality Index (DLQI),
• Skindex-29,
• Chronic Urticaria Quality of Life Questionnaire (Cu-Q2OL). |
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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 |
This study includes an optional exploratory biomarker component which requires a separate signature if the patient agrees to participate. It is required as part of this protocol that the Investigator presents these options to the patient.
This search for biomarkers of disease and drug response will involve an integrated molecular approach examining genetic and genomic profiles. |
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E.3 | Principal inclusion criteria |
Diagnosis of chronic spontaneous urticaria refractory to H1 antihistamines at Baseline (Day -14), as defined by all of the following:
• The presence of itch and hives for > 6 weeks prior to Baseline (Day –14),
• UAS7 score (range 0−42) ≥ 16 and itch component of UAS7 (range 0−21) ≥ 8 during 14 days prior to randomization (pre-dose Day 1). To avoid influences of antihistamines on the outcome of the UAS7, the score will be calculated as follows:
• Patients must have been on an approved dose of an H1 antihistamine for CIU prior to entering the study, and agree to a washout of 3 consecutive days prior to Day -14 which is required in order for the Day -14 Baseline visit to be performed. Patients must agree to switching their current H1 antihistamine to Loratadine, 10 mg, at Baseline (Day -14) that will be used as their rescue medication during the study,
• CIU diagnosis for ≥ 6 months. |
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E.4 | Principal exclusion criteria |
Clearly defined underlying etiology for chronic urticarias other than CIU (main manifestation being physical urticaria). This includes the following urticarias: Acute, solar, cholinergic, heat, cold, aquagenic, delayed pressure or contact, as well as the following diseases as these diseases may have symptoms of urticaria or angioedema: Urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma, leukemia, or generalized cancer.
• Previous treatment with omalizumab.
• A history or presence of atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or other skin disease associated with itch.
• Routine doses of the following medications:
• Systemic or cutaneous (topical) corticosteroids (prescription or over the counter),
hydroxychloroquine, methotrexate, cyclosporine, cyclophosphamide or any other
immunomodulating drug (e.g. interferons) that may alter the response to omalizumab
treatment 30 days prior to Day −14,
• IV immunoglobulin G (IVIG), or plasmapheresis within 30 days prior to Day −14,
• Regular (daily/every other day) doxepin (oral) use within 6 weeks prior to Day −14,
• Any H2 antihistamine use within 7 days prior to Day −14,
• Any leukotriene receptor antagonists (LTRA) (montelukast or zafirlukast) or H2 blockers within 7 days prior to Day −14,
• Any H1 antihistamines at greater than approved doses within 3 days prior to Day −14,
• Patients taking either LTRAs or H2 blockers for diseases other than CIU (e.g., asthma or GERD, respectively) will be permitted to continue their use during the study. Inhaled asthma controllers, including corticosteroids, are also permitted during the study. Patients need to on stable doses for 4 weeks prior to randomization (Day 1).
• History of anaphylactic shock. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable is the relative change from baseline in the high affinity IgE receptor (FcεRI) and/or IgE positive skin cells, based on skin biopsies collected from patients with CIU after 12 weeks of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Cellular /Sub Cellular Endpoint Objectives
• correlation of the potential reduction of the high affinity IgE receptor (FcεRI) and/or IgE on positive skin cells and clinical response as assessed by UAS7 score at week 12 (Day 85).
• investigate the effect of omalizumab compared to placebo on skin cells in patients with CIU.
• investigate the effect of omalizumab compared to placebo on peripheral blood cells.
• To investigate differences in skin samples in CIU patients (affected and unaffected skin) compared to healthy volunteers at baseline.
PK/PD Endpoint Objectives
• To investigate the effect of omalizumab compared to placebo in patients with CIU on the following PK and PD measures at specified time points:
• Summary trough serum levels of omalizumab,
• Serum total and free IgE levels,
• Specific IgE against common allergens and bacterial antigens,
Clinical Endpoint Objectives
• To evaluate the safety of omalizumab in patients with CIU.
• To investigate the clinical effect of omalizumab compared to placebo in patients with CIU as
• Change from baseline
• Change from baseline compared to placebo
• by assessing the following efficacy outcome measures:
• Urticaria activity score (UAS7),
• Patient’s and investigator’s global assessment of symptoms (hives and pruritus) using a graded Likert scale,
• Assessment of angioedema,
• Dermatology Life Quality Index (DLQI),
• Skindex-29,
• Chronic Urticaria Quality of Life Questionnaire (Cu-Q2OL). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Due to the large number of different tests all timepoints of evaluation cannot be captured here, please refer to the assessment schedule page 14 of the protocol. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 2 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |