Study of Efficacy and Safety of Omalizumab in Refractory Chronic Spontaneous Urticaria Patients

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Omalizumab in Patients With Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite H1 Antihistamine Therapy

This was a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab administered subcutaneously as an add-on therapy for the treatment of adolescent and adult participants 12 - 75 years who received the diagnosis of refractory chronic spontaneous uriticaria and who remained symptomatic despite standard-dosed non-sedating H1 antihistamine treatment.

Study Overview

• Status: Completed
• Conditions: Chronic Spontaneous Uriticaria
• Intervention / Treatment: Biological: Omalizumab; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Toyoake-city, Aichi, Japan, 470-1192
      • Novartis Investigative Site
  • Hiroshima
    • Hiroshima-city, Hiroshima, Japan, 734-8551
      • Novartis Investigative Site
  • Hyogo
    • Kobe-city, Hyogo, Japan, 650-0017
      • Novartis Investigative Site
    • Nishinomiya-city, Hyogo, Japan, 663-8186
      • Novartis Investigative Site
  • Ibaraki
    • Hitachi-city, Ibaraki, Japan, 317-0077
      • Novartis Investigative Site
  • Kagawa
    • Takamatsu-city, Kagawa, Japan, 760-0017
      • Novartis Investigative Site
  • Kanagawa
    • Kawasaki-city, Kanagawa, Japan, 213-8507
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 236-0004
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 221-0825
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 231-0868
      • Novartis Investigative Site
    • Yokosuka-city, Kanagawa, Japan, 238-8558
      • Novartis Investigative Site
  • Kumamoto
    • Kamimashi-gun, Kumamoto, Japan, 861-3101
      • Novartis Investigative Site
  • Nagano
    • Nagano-city, Nagano, Japan, 381-8551
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 532-0003
      • Novartis Investigative Site
    • Sakai-city, Osaka, Japan, 593-8324
      • Novartis Investigative Site
  • Saitama
    • Saitama-city, Saitama, Japan, 330-0854
      • Novartis Investigative Site
  • Shimane
    • Izumo-city, Shimane, Japan, 693-8501
      • Novartis Investigative Site
  • Tokyo
    • Kodaira-city, Tokyo, Japan, 187-8510
      • Novartis Investigative Site
    • Machida-city, Tokyo, Japan, 194-0013
      • Novartis Investigative Site
    • Meguro-ku, Tokyo, Japan, 153-8515
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 107-6206
      • Novartis Investigative Site
    • Ota-ku, Tokyo, Japan, 143-0023
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 141-8625
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 161-8521
      • Novartis Investigative Site
  • Yamanashi
    • Kofu-city, Yamanashi, Japan, 400-8506
      • Novartis Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • Novartis Investigative Site
  • Daegu, Korea, Republic of, 705-703
    • Novartis Investigative Site
  • Gwangju, Korea, Republic of, 501-757
    • Novartis Investigative Site
  • Incheon, Korea, Republic of, 405-760
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 120-752
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 156-755
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 130-872
    • Novartis Investigative Site
  • Gangwon
    • Wonju, Gangwon, Korea, Republic of, 220-701
      • Novartis Investigative Site
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of, 13620
      • Novartis Investigative Site
  • Gyeonggi-do
    • Hwaseong-si, Gyeonggi-do, Korea, Republic of, 445-170
      • Novartis Investigative Site
    • Suwon, Gyeonggi-do, Korea, Republic of, 443-380
      • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 06591
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 152-703
      • Novartis Investigative Site

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

Key Inclusion Criteria:

• Diagnosis of chronic spontaneous urticaria refractory to H1 antihistamine at the time of randomization
• Chronic spontaneous urticaria diagnosis for 6 months

Key Exclusion Criteria:

• Weight less than 20 kg
• Clearly defined underlying etiology for chronic urticaria other than chronic spontaneous urticaria
• Evidence of parasitic infection
• Any other skin diseases than chronic spontaneous urticaria with chronic itching
• Previous treatment with omalizumab
• Contraindications to diphenhydramine
• History of anaphylactic shock
• History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study
• History of hypersensitivity to omalizumab or to drugs of similar chemical classes
• Pregnant or nursing (lactating) women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omalizumab 300 mg; Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.	Biological: Omalizumab; Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.; Other Names: Xolair
Experimental: Omalizumab 150 mg; Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.	Biological: Omalizumab; Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.; Other Names: Xolair
Placebo Comparator: Placebo; Participants will receive placebo subcutaneously every 4 weeks during the 12 week treatment period.	Other: Placebo; Placebo was supplied as a lyophilized, sterile powder in a single-use vial without study drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Weekly Itch Severity Score at Week 12	The weekly itch severity score is a component of the Urticaria Activity Score 7 (UAS7) composite score. The UAS7 is a composite score of the number of wheals (hives) and the severity of the itch. The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score from baseline indicates improvement.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Week 12	The UAS7 is a composite score of the number of wheals (hives) and the severity of the itch. The UAS7 is determined by the sum of the daily urticaria activity scores over 7 days and ranges from 0 to 42. The daily urticaria activity score is the average of the morning and evening urticaria activity scores and ranges from 0 to 6. The urticaria activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticaria activity scores over the 7 days prior to the first treatment. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement.	Baseline to Week 12
Change From Baseline in the Weekly Number of Hives Score at Week 12	The weekly hives score is the sum of the daily hives scores over 7 days and ranges from 0 to 21. The number of hives is measured twice daily (morning and evening) on a scale of 0 (none) to 3 (> 12 hives per 12 hours). The daily hives score is the average of the morning and evening scores. The Baseline score is the sum of the daily hives scores over the 7 days prior to the first treatment. A higher score indicates more hives. A negative change score indicates improvement.	Baseline to Week 12
Percentage of Participants With a UAS7 Score ≤ 6 at Week 12	The UAS7 is a composite score of the number of wheals (hives) and the severity of the itch. The UAS7 is determined by the sum of the daily urticaria activity scores over 7 days and ranges from 0 to 42. The daily urticaria activity score is the average of the morning and evening urticaria activity scores and ranges from 0 to 6. The urticaria activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticaria activity scores over the 7 days prior to the first treatment. A higher urticaria activity score indicates more severe symptoms.	Week 12
Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12	The weekly size of the largest hive score is the sum of the daily size of the largest hive scores over 7 days and ranges from 0 to 21. The daily size of the largest hive score is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (> 2.5 cm). The daily size of the largest hive score is the average of the morning and evening scores. The Baseline weekly size of the largest hive score is calculated over the 7 days prior to the first treatment. A higher score indicates larger hives. A negative change score from baseline indicates a reduction in hive size.	Baseline to Week 12
Percentage of Weekly Itch Severity Score Minimally Important Difference (MID) Responders at Week 12	Weekly itch severity score MID response is defined as a reduction from baseline in weekly itch severity score of ≥ 5 points.	Week 12
Percentage of Complete Responders (UAS7 = 0) at Week 12	Complete responders are defined as participants who achieved UAS7 = 0.	Week 12
Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12	The DLQI is a 10-item dermatology-specific health-related quality of life measure. Participants rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives on a scale of 0 (Not at all) to 3 (Very much). The overall DLQI is the sum of the responses to the 10 items and ranges from 0 to 30. A lower score indicates a better quality of life. A negative change score from baseline indicates improvement.	Baseline to Week 12
Percentage of Participants With Production of Anti-omalizumab Antibody	Serum samples were collected for anti-omalizumab antibody testing.	Week 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 15, 2014
• First Submitted That Met QC Criteria: December 29, 2014
• First Posted (Estimate): December 31, 2014

Study Record Updates

• Last Update Posted (Estimate): September 21, 2016
• Last Update Submitted That Met QC Criteria: September 20, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Omalizumab; Chronic spontaneous uriticaria
• 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: CIGE025E2306