Study of Efficacy and Safety of Xolair® (Omalizumab) in Chinese Patients With Chronic Spontaneous Urticaria

Chronic Spontaneous Urticaria Clinical Trial

Official title:

A Phase III Study to Evaluate the Efficacy and Safety of Xolair® (Omalizumab) in Chinese Patients With Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03328897
• Other study ID #: CIGE025E2305
• Status: Completed
• Phase: Phase 3
• Start date: April 26, 2017
• Est. completion date: September 24, 2019

Study information

• Verified date: October 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to demonstrate the efficacy and safety of omalizumab, compared with placebo, as an add-on to H1 antihistamines (H1AH) therapy in adult patients suffering from Chronic Spontaneous Urticaria (CSU) who remained symptomatic despite H1AH therapy.

Description:

This was a randomized, multicenteric, double-blinded, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab as an add-on therapy for the treatment of patients of refractory CSU who remained symptomatic despite approved-dosed H1AH treatment. The study consisted of three distinct epochs over 24 weeks: Screening epoch (Day -28 to Day -1), Randomized treatment epoch (Day 1 to Week 12) and Post-treatment follow-up epoch (Week 12 to Week 20). Patients were randomized into three treatment groups (omalizumab 300 mg s.c. omalizumab 150 mg s.c. and placebo) in a 2:2:1 ratio, stratified by latent tuberculosis (TB) status at Baseline (Yes/No). On Day 1, eligible patients were randomly assigned to receive omalizumab (150 mg or 300 mg) or placebo by subcutaneous (s.c.) injection every 4 weeks (on Day 1, Week 4, and Week 8) during the 12-week double-blind randomized-treatment epoch. Patients visited the study center at 4-week intervals. Patients were instructed to stay on the same CSU H1AH treatment at stable dose that they were using during the pre-randomization period during the randomized treatment epoch. They were allowed to use diphenhydramine as rescue medication during all epochs. The last dose of the study drug during the randomized-treatment epoch was administered at Week 8 study visit, however, the last assessment was done at Week 12. After the completion of the 12-week randomized-treatment epoch, all patients entered an 8-week post-treatment follow-up epoch.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 418
• Est. completion date: September 24, 2019
• Est. primary completion date: July 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Main Inclusion Criteria:

• Symptomatic CSU patients with CSU diagnosis for at least 6 months.
• Patients must have been on an approved dose of an H1AH for CSU for at least the 3 consecutive days immediately prior to the Day -14 screening visit
• Patients must have documented current use on the day of the initial screening visit Main Exclusion Criteria
• Clearly defined underlying etiology for chronic urticarias other than CSU (main manifestation being physical urticaria)
• Other skin disease associated with itch Urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma, leukemia, or generalized cancer

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Urticaria

Intervention

Drug:
• Omalizumab
injection of 150mg or 300 mg
• Placebo
Injection of placebo

Locations

Country	Name	City	State
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Fuzhou	Fujian
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Harbin	Heilongjiang
China	Novartis Investigative Site	Nanjing
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanning	Guangxi
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Urumqi	Xinjiang
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Wuxi	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline of the Itch Severity Score (ISS7) Score After 12 Weeks of Treatment	The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0.; Itch (Pruritus) Severity Score Scale: 0 = None; = Mild (minimal awareness, easily tolerated); = Moderate (definite awareness, bothersome but tolerable); = Severe (difficult to tolerate)	Baseline, Week 12
Secondary	Change From Baseline of Urticaria Activity Score (UAS7) After 12 Weeks of Treatment	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement.	Baseline, Week 12
Secondary	Change From Baseline of Number of Hives Score (NHS7) After 12 Weeks of Treatment	Hives Severity Score (HSS), defined by number of hives, were recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly number of hives score (NHS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21. The complete hives response was defined as NHS7 = 0.; Hives Severity Score scale: 0 - None; Mild (1-6 hives/12 hours); Moderate (7-12 hives/12 hours); Severe (>12 hives/12 hours)	Baseline, Week 12
Secondary	Percentage of Patients With UAS7=6 at Week 12	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Week 12 responders were defined as patients who achieved an absolute UAS7 = 6 at Week 12. A patient with missing data at Week 12 was imputed as a responder if the patient was a responder at Week 10 and Week 11, otherwise as a non-responder.	Week 12
Secondary	Percentage of Complete Responders (UAS7 = 0) at Week 12	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Complete responders are defined as participants who achieved UAS7 = 0.	Week 12
Secondary	Percentage of Patients With ISS7 Minimally Important Difference (MID) at Week 12	The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0.; Itch (Pruritus) Severity Score Scale: 0 = None; = Mild (minimal awareness, easily tolerated); = Moderate (definite awareness, bothersome but tolerable); = Severe (difficult to tolerate); The ISS7 MID response was defined as a reduction from Baseline in ISS7 of = 5 points.	Week 12
Secondary	Change From Baseline of Dermatology Life Quality Index (DLQI) Score After 12 Weeks of Treatment	Dermatology life quality index (DLQI) is a 10-item dermatology- specific health-related quality of life measure. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives. An overall score was calculated as well as separate scores for the following domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, treatment. Each domain had 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment.	Week 12
Secondary	Time to ISS7 MID Response by Week 12	The ISS7 MID response was defined as a reduction from Baseline in ISS7 of = 5 points. Time to ISS7 MID response was the time (in weeks) from the date of the first dose to the date where ISS7 MID response was first achieved during Week 1 to Week 12.	12 weeks