Impact of Omalizumab on Quality of Life Measures and Angioedema Occurrence in Patients With CSU Refractory to Therapy

Chronic Spontaneous Urticaria Clinical Trial

— X-ACT  

Official title:

A Randomized, Double-blind, Placebo-controlled, 28-week Treatment With a 8 Week Follow-up to Investigate the Impact of Omalizumab on Quality of Life Measures and the Incidence and Severity of Angioedema Despite H1-antihistamine Therapy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01723072
• Other study ID #: CIGE025EDE16
• Status: Completed
• Phase: Phase 3
• Start date: January 23, 2013
• Est. completion date: May 9, 2014

Study information

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

Clinical Trial Summary

This study will assess the impact of omalizumab on the quality of life improvement when added to the standard therapy in refractory patients suffering from chronic spontaneous urticaria and angioedema.

Description:

This study will be conducted using a double-blind, placebo-controlled, randomized, multicenter design to investigate the impact of omalizumab on Quality of Life (QoL) in Chronic Spontaneous Urticaria (CSU) and will assess its effectiveness in reducing and/or inhibiting the occurrence, time-course and severity of angioedema episodes.

Omalizumab is administered subcutaneously every 4 weeks as an add-on therapy to the current approved treatment of adult CSU patients. The treatment period is 28 weeks which is followed by an 8-week follow-up. The study aims to enroll approximately 70 patients.

The study is divided into a 2-week screening period, a 28-week double-blind treatment phase with omalizumab or placebo-omalizumab, and an 8-week follow-up phase.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: May 9, 2014
• Est. primary completion date: May 9, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Diagnosis of chronic spontaneous urticaria (CSU) refractory to H1-antihistamine treatment

• Presence of itch an hives for more than 6 weeks

• UAS7 score of more than 14 (range 0-42)

• Patient has history of insufficient response to 4x of the approved dose of H1-antihistamines

• CSU diagnosis for more than 6 months

• Angioedema at least 4x in the last 6 months

Exclusion Criteria:

• Patients with non urticaria associated angioedema

• History of hypersensitivity to omalizumab or the rescue medication or to drugs of similar chemical structure

• Evidence of parasitic infection

• Previous treatment with omalizumab within the last 6 months prior to screening

• History of anaphylactic shock

• Woman who are pregnant or breast feeding

• Other protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Angioedema
• Chronic Spontaneous Urticaria
• Urticaria

Intervention

Biological:
• Omalizumab
Humanized monoclonal antibody against human IgE

Drug:
• Placebo
Placebo to omalizumab

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gera
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mannheim	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Oldenburg
Germany	Novartis Investigative Site	Regensburg	Bavaria
Germany	Novartis Investigative Site	Selters
Germany	Novartis Investigative Site	Wiesbaden

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS)	The CU-Q2oL is a questionnaire that measures the relative burden of chronic urticaria on subjective well-being. It consists of 23 questions in 3 domains (symptoms, general impairment, difficulties and problems due to urticaria). Participants are asked to respond how much they are troubled by each problem on a 5-point Likert scale (1= not at all to 5= very much). An overall score is calculated and normalized to a scale of 1 to 100.	Baseline, 4, 12, 20, 28 and 36 weeks
Secondary	Number of Angioedema Burdened Days by Study Phase (Observed Cases With Imputation)		Baseline, week 28; and the follow-up period (weeks 29-36)
Secondary	Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes		Baseline to week 28
Secondary	Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation)	A cumulative activity score, evaluated in the screening period and throughout the study. The records each evening on a daily basis symptoms of itch and hives into a patient diary. min. score = 0 ; max. score= 100	Baseline to week 28; and follow-up period (to week 36)
Secondary	Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1)	data points per group	week -2 to -1
Secondary	Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28)	data points per group	weeks 25 to 28
Secondary	Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36)	data points per group	weeks 33 to 36
Secondary	Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1)	data points per group	weeks -2 to -1
Secondary	Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28)	data points per group	weeks 25 to 28
Secondary	Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36)	data points per group	weeks 33 to 36
Secondary	Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases)	The AE-Q2oL is a questionnaire for patients suffering from angioedema. It consists of 29 questions relevant to angioedema and its specific impact on quality of life. Patients are asked to respond how much they are troubled be each problem on a 5-point Likert scale (1= does not apply to 5= very much). An overall score is calculated and a higher score indicates lower quality of life. A negative change score (week 28 score minus baseline score) indicates improvement.; Each AE-QoL question has 5 answer options (scored 1-5), with lower and higher scores indicting less and more adverse impact, respectively. The total score is calculated, which is then transformed into a linear scale that ranges from 0 to 100, with a score of 100 indicating the worst possible impairment of HRQoL	baseline to week 28; and then follow-up to week 36
Secondary	Rescue Medication During the Treatment Period		baseline to 28 weeks
Secondary	Days of Rescue Medication During the Treatment Period	data points per group	baseline to 28 weeks
Secondary	Days of Rescue Medication During the Follow-up Period	data points per group	weeks 33 to 36
Secondary	Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases)	The UAS7 is the sum of urticaria activity scores over a seven day period. The possible range of the weekly UAS7 score is 0-42. 0 means complete response and a better outcome and 42 means no response and a worse outcome.; Complete UAS7 response is defined as UAS7=0. The UAS7 is the sum of the Hive Severity Score over seven days (HSS7) and the Itch Severity Score over seven days (ISS7) . The Hive Severity Score has a scale of 0 (none) to 3 (intense/severe). Complete hives response is defined as HSS7=0. The Itch Severity Score has a scale of 0 (None) to 3 (Severe (difficult to tolerate)). Complete itch response is defined as ISS7=0	baseline to week 28; and then follow-up to week 36
Secondary	Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases)	change in Dermatology Quality of Life Index scores; The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 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.	baseline to week 28; and follow-up to week 36