A Phase II, Multi-centre, Randomized, Double Blind, Placebo-controlled Study to Determine the Mode of Action of Omalizumab in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic With Antihistamine Treatment (H1)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Observed Values and Absolute Change From Baseline in FceRI Positive Skin Cells: Dermis, Lesional and Non Lesional Skin
Study Overview
Brief Summary
The study is designed to explore the mode of action for omalizumab therapy in patients with chronic idiopathic urticaria.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of chronic spontaneous urticaria refractory to H1 antihistamines at Baseline
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.
- •Other protocol-defined inclusion/exclusion criteria may apply.
Arms & Interventions
IGE025
Patients will receive omalizumab administered subcutaneously every 4 weeks at the study center.
Intervention: IGE025 (Drug)
Placebo to IGE025
Placebo administered subcutaneously every 4 weeks at the study center.
Intervention: placebo (Drug)
Outcomes
Primary Outcomes
Observed Values and Absolute Change From Baseline in FceRI Positive Skin Cells: Dermis, Lesional and Non Lesional Skin
Time Frame: Baseline through Day 85 post-treatment
Observed values and absolute change in FcεRI positive skin cells: dermis non-lesional and lesional. The primary variable for this study was the relative change from baseline in the high affinity IgE receptor (FcεRI) positive skin cells, based on skin biopsies collected from patients with CIU after 12 weeks of treatment.The values are average of cell numbers derived from counting 5 consecutive microscopic fields. Area counted is 5x 0.196 mm2
Observed Values and Absolute Change From Baseline in IgE Positive Skin Cells: Dermis, Lesional and Non Lesional Skin
Time Frame: Baseline through Day 85 post-treatment
Observed values and absolute change in IgE positive skin cells: dermis non-lesional and lesional The primary variable for this study was the relative change from baseline in IgE positive skin cells, based on skin biopsies collected from patients with CIU after 12 weeks of treatment. The values are average of cell numbers derived from counting 5 consecutive microscopic fields. Area counted is 5x 0.196 mm2
Secondary Outcomes
- Correlation of Change From Baseline in IgE on Positive Skin Cells With Change From Baseline in UAS7 at Week 12 by Treatment, Skin Layer and Lesion Status(Baseline through Day 85)
- Observed Values and Absolute Change From Baseline in Skin Cell Subsets (CD3, CD4, CD8, Eosinophils, DCs, and Mast Cells) by Parameter, Skin Layer, Lesion Status, Treatment and Visit(Baseline to Day 85)
- Observed Values From Baseline Through End of Study of Serum Chemkines or Histamine in Peripheral Blood Cells by Parameter, Treatment and Visit(Baseline through Day 85)
- Serum Levels of Omalizumab(Baseline through Day 85)
- Correlation of Change From Baseline in IgE Receptor FceRI With Change From Baseline in UAS7 at Week 12 by Treatment, Skin Layer and Lesion Status(Baseline through Day 85)
- Chronic Urticaria Quality of Life Questionnaire (Cu-Q2OL) by Treatment(Baseline and Day 85)
- Mean (SD) Serum Total IgE Concentration From Baseline by Visit(Baseline through Day 85)
- Mean (SD) Serum Total IgE % Change From Baseline by Visit(Baseline through Day 85)
- Mean (SD) Serum Free IgE % Change From Baseline by Visit(Baseline through Day 85)
- Observed Values and Change From Baseline in Peripheral Blood Cell Subsets (FACS Parameters) at Week 12 (Day 85) by Treatment (PD Analysis Set) Measured as % Out of Leukocytes.(Baseline through Day 85)
- Observed Values and Change From Baseline in Peripheral Blood Cell Subsets (FACS Parameters) at Week 12 (Day 85) by Treatment (PD Analysis Set) Measured in Fluorescence Units.(Baseline through Day 85)
- Mean (SD) Serum Free IgE Concentration From Baseline by Visit(Baseline through Day 85)
- Change From Baseline in Urticaria Activity Score (UAS7)(Baseline, Day 85)
- Likert Scale-Physician's and Patients In-clinic Global Assessment by Treatment(Baseline, Day 85)
- Comparison of Baseline PD Parameters Between Healthy Volunteers and Urticaria Patients by Skin Layer Pharmacodynamic Analysis Set(Baseline)
- Skindex-29 by Treatment(Baseline and Day 85)
- Summary Statistics of Observed Values and Absolute Change From Baseline in Specific IgE Against Allergens and Bacterial Antigens by Parameter, Treatment and Visit(Baseline through Day 140)
- Percentage of Angioedema-free Days Weeks 4 Through 12 by Treatment(Day 29 to Day 85)
- Change From Baseline in Dermatology Life Quality Index (DLQI) by Treatment(Baseline through Day 85)