Three-month, Single-center Study to Identify Biomarkers/Response to Xolair Therapy in Chronic Idiopathic Urticaria

This is a single center, non-comparative exploratory study, to investigate the effect of
omalizumab over a 3-month treatment period in adult (≥18 years) patients with chronic
idiopathic urticaria who had remained symptomatic despite the use of high dose
H1-antihistamines. After an initial screening visit within two weeks of the Day 1 baseline
visit, patients receive one subcutaneous injection of omalizumab at a dose of 300 mg on Days
1, 30, and 60. Patients will return for clinical assessments and blood draws on Day 3 and Day
30 (study conclusion). Blood will be collected at the screening visit (Day -14), baseline
(Day 1, prior to omalizumab injection), Day 14, Day 30 (prior to omalizumab injection), Day
60 (prior to omalizumab injection), and Day 90 (study completion) for microsomal miRNA
extraction, basophil isolation, and also stored at -70oC for later periostin assays for a
total of 275ml of blood over the course of the study (25ml at screening and 50ml for each of
the 5 subsequent visits (i.e., Days 1, 14, 30, 60, and 90). Plasma exosomal miRNA
bioinformatics analyses will be conducted in early (i.e., Day 14) and later (i.e., Day 30,
60, 90) responder groups. The 2 wk time point will capture the early responders and the 4, 8,
and 12 wk time points will capture the remaining responder groups based on the following: Two
Phase III, global, multicenter, randomized, double-blind, placebo-controlled trials (Appendix
B, CIU Study 1 and CIU Study 2 data) and data of CIU patients with a starting UAS7 score of
25.3 ± 2.0 (mean ± SEM) treated with Xolair® outside of clinical trials (Metz et al., 2014),
where 57% attained complete response within one week of their first treatment and a further
29% within 4 weeks (Metz et al., 2014).

To address the role/mechanism of basophils in the immunopathogenesis of chronic urticaria, we
will do basophil mRNA/miRNA arrays.

Inclusion Criteria:

- • at least 6 weeks of chronic idiopathic urticaria with itching despite current use of
up to x4 H1-antihistamines (Kaplan, 2004)

- an urticaria activity score (UAS) during a 7-day period (UAS7) of 16 or more (on
a scale ranging from 0 to 42, with higher scores indicating greater activity and
a minimally important difference [MID] of 9.5 to 10.5) (Mathias et al., 2012)

- a weekly itch-severity score (ISS) of 8 or more (on a scale ranging from 0 to 21,
with higher scores indicating more severe itching and an MID of ≥5) during the 7
days before first treatment with omalizumab.

- All females of childbearing potential must be either abstinent from sexual
intercourse or using adequate contraception and must also have a negative urine
pregnancy test.*

Exclusion Criteria:

- • a clearly defined underlying cause for chronic urticaria (e.g., physical urticaria)

- routine administration (i.e., daily or every other day for ≥5 consecutive days)
of systemic glucocorticoids, hydroxychloroquine, methotrexate, cyclosporine,
cyclophosphamide, or intravenous immune globulin within the previous 30 days

- the use of any H2-antihistamine or leukotriene-receptor antagonist within 7 days
preceding the screening visit

- a history of cancer

- a known hypersensitivity to omalizumab

- treatment with omalizumab within the previous year, or

- pregnant or nursing females*