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

Three-month, Single-center Study to Identify Biomarkers (Plasma Exosomal miRNAs) and Mechanism of Response (Basophil Transcriptome Analysis) to Xolair® (Omalizumab) in Patients With 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.

Study Overview

• Status: Completed
• Conditions: Chronic Idiopathic Urticaria
• Intervention / Treatment: Biological: Xolair

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98115
      • Asthma Inc Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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*

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Open-label Xolair; The patients will receive one subcutaneous injection of omalizumab at a dose of 300 mg on Days 1, 30, and 60. There is no control drug.

Biological: Xolair; The patients will receive one subcutaneous injection of Xolair® (omalizumab) at a dose of 300 mg on Days 1, 30, and 60. This dose is based on the results of the international, multicenter, randomized, double-blind, placebo-controlled study which demonstrated that omalizumab significantly decreased clinical symptoms and signs of chronic idiopathic urticaria in patients who had remained symptomatic despite the use of H1-antihistamines (Maurer et al., 2013); Other Names: Omalizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
miRNAs in the blood differentially expressed after treatment with Xolair® in patients with chronic idiopathic urticaria.	Identification of specific miRNA(s) that are novel biomarker(s) predicting response to Xolair® treatment in 20 patients with chronic idiopathic urticaria.	12 week period of Xolair® treatment

Collaborators and Investigators

• Sponsor: Asthma Inc Clinical Research Center
• Collaborators: University of Washington
• Investigators: Study Director: William Henderson, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): November 2, 2018
• Study Completion (Actual): November 2, 2018

Study Registration Dates

• First Submitted: May 31, 2016
• First Submitted That Met QC Criteria: June 23, 2016
• First Posted (Estimate): June 28, 2016

Study Record Updates

• Last Update Posted (Actual): January 24, 2019
• Last Update Submitted That Met QC Criteria: January 22, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Chronic Urticaria; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: CIGE025EUS44T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: A paper may be written but individual participant data will not be made available