Chronic Idiopathic Urticaria MedDRA version: 14.1 Level: LLT Classification code 10009159 Term: Chronic urticaria System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Conditions
Interventions
Trade Name: Xolair 150 mg powder and solvent for solution for injection
Product Name: Xolair 150 mg powder and solvent for solution for injection
Product Code: IGE025
Pharmaceutical Form: Powder and s
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether treatment with omalizumab in patients with CIU results in a reduction of the high affinity IgE receptor (FceRI) and/or IgE positive skin cells following 12 weeks of treatment (Day 85).;Secondary Objective: Cellular /Sub Cellular Endpoint Objectives • correlation of reduction of FceRI 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).;Primary end point(s): The primary variable is the relative change from baseline in the high affinity IgE receptor (FceRI) and/or IgE positive skin cells, based on skin biopsies collected from patients with CIU after 12 weeks of treatment.;Timepoint(s) of evaluation of this end point: see E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Cellular /Sub Cellular Endpoint Objectives • correlation of the potential reduction of the high affinity IgE receptor (FceRI) 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).;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. | — |
Countries
Germany
Contacts
Public ContactMedizinischer Infoservice
Novartis Pharma GmbH
Outcome results
None listed