A Study of the Efficacy and Safety of Omalizumab Through 48 Weeks in Participants With Chronic Idiopathic Urticaria

XTEND-CIU (Xolair Treatment Efficacy of Longer Duration in Chronic Idiopathic Urticaria): A Phase IV, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Omalizumab Through 48 Weeks in Patients With Chronic Idiopathic Urticaria

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of subcutaneous (SC) omalizumab (Xolair) as an add-on therapy through 48 weeks for treatment of H1 antihistamine refractory chronic idiopathic urticaria (CIU). After completing an initial 24-week open-label treatment period with omalizumab 300 milligrams (mg) every 4 weeks (Q4W), participants responding to omalizumab will be randomized at a 3:2 ratio (omalizumab:placebo) to either continue omalizumab or be transitioned to placebo for a further 24 weeks.

Study Overview

• Status: Completed
• Conditions: Urticaria
• Intervention / Treatment: Drug: Omalizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Granada Hills, California, United States, 91344
      • Allergy and Asthma Relief Experts
    • Long Beach, California, United States, 90808
      • Allergy & Asthma Care Center of Southern California
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associate
    • Mission Viejo, California, United States, 92691
      • Southern California Research Center
    • Orange, California, United States, 92868
      • Choc Psf, Amc
    • Redwood City, California, United States, 94063
      • Allergy & Asthma Consultants
    • Walnut Creek, California, United States, 94598
      • Allergy and Asthma Clinical Research, Inc.
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe Research Centers
    • Denver, Colorado, United States, 80230
      • Colorado Allergy & Asthma Centers, PC
  • Florida
    • Aventura, Florida, United States, 33180
      • Florida Center for Allergy and Asthma Research
    • Miami, Florida, United States, 33173
      • Florida Ctr-Allergy & Asthma
    • Sarasota, Florida, United States, 34239
      • Sarasota Clinical Research
    • Tampa, Florida, United States, 33613
      • University of South Florida
  • Illinois
    • Shiloh, Illinois, United States, 62269
      • Clinical Research Center of Southern Illinois LLC
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Deaconess Clinic
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Clinical Res LLC
  • Kentucky
    • Fort Mitchell, Kentucky, United States, 41017
      • Abraham Research PLLC
    • Louisville, Kentucky, United States, 40241
      • Dermatology Specialists Research, LLC
    • Owensboro, Kentucky, United States, 42301
      • Allergy & Asthma Specialists, PSC
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • Asthma, Allergy & Sinus Center
    • Chevy Chase, Maryland, United States, 20815
      • Institute For Asthma & Allergy
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
      • Respiratory Medicine Research; Institue of Michigan P.L.C.
  • Nevada
    • Las Vegas, Nevada, United States, 89117
      • James Q. Del Rosso, DO, LLC
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Ocean Allergy & Resp Res Ctr
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Group;Department of Medicine
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • Rochester, New York, United States, 14618
      • AAIR Research Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center; University Dermatology Associates
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Allergy Partners of Western NC
  • Ohio
    • Canton, Ohio, United States, 44718
      • Allergy & Respiratory Center
    • Cincinnati, Ohio, United States, 45231
      • Bernstein Clinical Research Center LLC
    • Toledo, Ohio, United States, 43617
      • Toledo Inst of Clin Research
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Vital Prospects Clin Res Pc
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Asthma, Nasal Disease, and Allergy Research Center of New England
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • National Allergy and Asthma Research
  • Texas
    • Live Oak, Texas, United States, 78233
      • Live Oak Allergy & Asthma Clinic
    • San Antonio, Texas, United States, 78229
      • Allergy & Asthma Research Center
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • Timber Lane Allergy-Asth Res
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • O & O Alpan, LLC
  • Washington
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of CIU refractory to H1 antihistamines at baseline
• Presence of itch and hives for at least 8 consecutive weeks at any time prior to enrollment despite current use of H1 antihistamine treatment (up to four times the approved dose) during this time period
• UAS7 score (range 0-42) ≥ 16 and itch component of UAS7 (range 0-21) ≥ 8 during 7 days prior to baseline
• Participants must have been on a non-sedating H1 antihistamine treatment (up to four times the approved dose) for CIU for at least 3 consecutive days immediately prior to screening visit with continued current use on the day of the initial screening visit
• CIU diagnosis for ≥ 6 months
• Willing and able to complete a daily symptom eDiary for the duration of the study

Exclusion Criteria:

• Treatment with an investigational agent within 30 days of the initial screening visit
• Body weight less than 20 kilograms
• Clearly defined underlying etiology for chronic urticarias other than CIU
• Evidence of a parasitic infection
• Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or other skin disease associated with itch
• Previous treatment with omalizumab within 1 year prior to the initial screening visit
• Participants may not have taken during treatment period or have been taking within 30 days before the initial screening visit any of the following medications or treatments:

regular (daily/every other day during 5 or more consecutive days) systemic corticosteroids, hydroxychloroquine, methotrexate, mycophenolate, cyclosporine, cyclophosphamide, intravenous immunoglobulin G or plasmapheresis

• Regular (daily/every other day) oral doxepin use within 14 days prior to the initial screening visit
• Pregnant or lactating women, or women intending to become pregnant during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omalizumab; Participants will receive open-label omalizumab treatment at 300 mg SC Q4W for 24 weeks. After 24 weeks open-label treatment, eligible participants will be randomized to receive omalizumab treatment at 300 mg SC Q4W for next 24 weeks (up to Week 48). Participants randomized to omalizumab may, at the discretion of the investigator, be transitioned from blinded study drug to open-label omalizumab at 300 mg SC Q4W if they experience clinically significant worsening in their CIU (as judged by the investigator). Participants who are transitioned to open-label omalizumab will continue to receive open-label omalizumab as study drug until Week 48.	Drug: Omalizumab; Omalizumab 300 mg administered SC Q4W.; Other Names: Xolair; RO5489789
Placebo Comparator: Placebo; Participants will receive open-label omalizumab treatment at 300 mg SC Q4W for 24 weeks. After 24 weeks open-label treatment, eligible participants will be randomized to receive placebo SC Q4W for next 24 weeks (up to Week 48). Participants randomized to placebo may, at the discretion of the investigator, be transitioned from blinded study drug to open-label omalizumab at 300 mg SC Q4W if they experience clinically significant worsening in their CIU (as judged by the investigator). Participants who are transitioned to open-label omalizumab will continue to receive open-label omalizumab as study drug until Week 48.	Drug: Omalizumab; Omalizumab 300 mg administered SC Q4W.; Other Names: Xolair; RO5489789; Drug: Placebo; Placebo matched to omalizumab administered SC Q4W.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Clinical Worsening in CIU as Assessed by Urticaria Activity Score Over 7 Days (UAS7) (Clinical Worsening: UAS7 Greater Than or Equal to [>/=] 12, Maintained for At Least 2 Consecutive Weeks)	Urticaria activity score (UAS) is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals (hives) per 24 hours and the intensity of the pruritus (itch). The total UAS score (sum of the wheal and pruritus scores) ranges from 0 to 6. Due to variations in chronic urticaria disease intensity, assessment of disease activity was based on a weekly (7 days) UAS score called UAS7, that is, the sum of the daily average UASs (average of morning and evening scores), ranging from 0 to 42 per week. A higher score indicates worse disease. Clinical worsening in CIU was defined as UAS7 >/=12 for at least 2 consecutive weeks post-randomization between Weeks 24 and 48.	From randomization (Week 24) to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Clinical Worsening in CIU as Assessed by UAS7 (Clinical Worsening: UAS7 >/=12, Maintained for At Least 2 Consecutive Weeks)	The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total UAS score ranges from 0 to 6. UAS7 is the sum of the daily average UASs (average of morning and evening scores), ranging from 0 to 42 per week. A higher score indicates worse disease. Time to clinical worsening in CIU was defined as the number of weeks from the first double-blind treatment to the first two-week interval with UAS7 >/=12 for both weeks. If clinical worsening did not occur, time to clinical worsening was censored at the end of the last week for which the UAS7 score was not missing and less than (<) 12, prior to last randomized dose + 4 weeks, or the first open-label transition dose, whichever was earlier. Median time to clinical worsening was estimated using Kaplan-Meier analysis and corresponding 95% confidence interval (CI) was computed using the method of Brookmeyer and Crowley.	From randomization (Week 24) to Week 48
Percentage of Participants Who Experienced Clinical Worsening in CIU as Assessed by UAS7 (Clinical Worsening: UAS7 Greater Than [>] 6, Maintained for At Least 2 Consecutive Weeks)	The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total UAS score ranges from 0 to 6. UAS7 is the sum of the daily average UASs (average of morning and evening scores), ranging from 0 to 42 per week. A higher score indicates worse disease. Clinical worsening in CIU was defined as UAS7 >6 for at least 2 consecutive weeks post-randomization between weeks 24 and 48.	From randomization (Week 24) to Week 48
Change From Randomization (Week 24) to Week 48 in UAS7 Among Participants Who Received Total 48 Weeks Treatment With Omalizumab	The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total UAS score ranges from 0 to 6. UAS7 is the sum of the daily average UASs (average of morning and evening scores), ranging from 0 to 42 per week. A higher score indicates worse disease. A negative change in score (Week 48 score minus Week 24 score) indicates improvement.	Week 24 (randomization) and Week 48
Retreatment Efficacy: Change From Time of Retreatment to 12 Weeks After Retreatment in UAS7 Among Participants Randomized to Placebo and Who Were Retreated With Open-Label Omalizumab After Randomization	The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total UAS score ranges from 0 to 6. UAS7 is the sum of the daily average UASs (average of morning and evening scores), ranging from 0 to 42 per week. A higher score indicates worse disease. A negative change in score indicates improvement.	At start of retreatment (any time between Weeks 24 and Week 48) and 12 weeks after retreatment (up to Week 60)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• Casale TB, Murphy TR, Holden M, Rajput Y, Yoo B, Bernstein JA. Impact of omalizumab on patient-reported outcomes in chronic idiopathic urticaria: Results from a randomized study (XTEND-CIU). J Allergy Clin Immunol Pract. 2019 Sep-Oct;7(7):2487-2490.e1. doi: 10.1016/j.jaip.2019.04.020. Epub 2019 Apr 26. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2015
• Primary Completion (Actual): March 9, 2017
• Study Completion (Actual): March 9, 2017

Study Registration Dates

• First Submitted: March 13, 2015
• First Submitted That Met QC Criteria: March 13, 2015
• First Posted (Estimate): March 19, 2015

Study Record Updates

• Last Update Posted (Actual): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 26, 2018
• Last Verified: March 1, 2018

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: ML29510