Omalizumab in Patients With Moderate to Severe Persistent Allergic Asthma Not Adequately Controlled Despite GINA (2009) Step 4 Therapy

Persistent Allergic Asthma Clinical Trial

Official title:

A 24-week, Phase III Randomized, Double-blind, Placebocontrolled, Parallel-group, Multicenter Study of Xolair® (Omalizumab) in Patients With Moderate to Severe Persistent Allergic Asthma Who Remain Not Adequately Controlled Despite GINA (2009) Step 4 Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01202903
• Other study ID #: CIGE025A2313
• Status: Completed
• Phase: Phase 3
• First received: September 14, 2010
• Last updated: March 16, 2015
• Start date: September 2010
• Est. completion date: October 2013

Study information

• Verified date: March 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee (central and local)China: Food and Drug AdministrationChina: Human Genetic Resource Administration of China
• Study type: Interventional

Clinical Trial Summary

This study will assess the efficacy, safety and tolerability of omalizumab, compared to placebo in 18 to 75 year old Chinese patients with moderate to severe persistent allergic asthma who have inadequate asthma control despite treatment according to GINA (2009) Step 4 therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 616
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Met study drug-dosing table eligibility criteria (serum baseline total IgE level = 30 to = 700 IU/mL and body weight > 20 kg and = 150 kg)

• Diagnosed with asthma = 1 year duration at Screening, and a history of asthma that is not adequately controlled with GINA (2009) Step 4 therapy

• Received medium-to-high dose inhaled corticosteroid > 500 µg Beclomethasone Diproprionate (BDP), or equivalent plus regularly inhaled LABA, either separately or in combination, for at least 8 weeks prior to screening

• Met specific asthma exacerbations eligibility criteria prior to the screening period

• Exhibited inadequate symptom control as demonstrated by specific criteria (in keeping with GINA 2009 guidelines)

• Positive skin prick test to at least one perennial aeroallergen documented by a historical test within 12 months prior to screening, or at Visit 1

• FEV1 = 40% and < 80% of the predicted normal value for the patient (using local standards), after withholding bronchodilators at Visit 2

Exclusion Criteria:

• Used other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer. For biological agent-based investigational drugs, such as monoclonal antibodies, at least six months will need to have passed between the last administration of the drug and the patient's Screening Visit.

• History of malignancy

• History of allergies and diseases that could interfere with the analyses

• Clinically significant abnormality on a 12-lead ECG recorded at Visit 1

• Elevated IgE levels for reasons other than allergy

• Current smokers, or a former smoker with a smoking history of > 10 pack-years. A former smoker must have abstained for a minimum of 12 months before randomization

• Receiving specific medications

• Clinically significant laboratory abnormalities (not associated with the study indication) at Visit 1

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma
• Persistent Allergic Asthma

Intervention

Drug:
• Omalizumab
The minimum dose of 0.016 mg/kg/IgE (IU/mL) omalizumab was administered every 4 weeks by subcutaneous injection.
• Placebo
The minimum dose of 0.016 mg/kg/IgE (IU/mL) placebo was administered every 4 weeks by subcutaneous injection.

Locations

Country	Name	City	State
China	Novartis Investigative Site	Beijing	Beijing
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	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changchun	Jilin
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Changsha City	Hunan
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Guang zhou
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Nanchang	Jiangxi
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanjing
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	Shanghai
China	Novartis Investigative Site	Shanghai	Shanghai
China	Novartis Investigative Site	Shengyang	Liaoning
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Shijiazhuang	Hebei
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Xi'an	Shanxi
China	Novartis Investigative Site	Xi'an	Shanxi
China	Novartis Investigative Site	Xian	Shanxi

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Genentech, Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Mean Morning Peak Expiratory Flow (PEF) Following the 24-week Treatment Period	A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits LS Mean of change from baseline in mean morning PEF is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates.	Baseline, 24 weeks	No
Secondary	Change From Baseline in Mean Evening PEF (L/Min) Following 24-week Treatment	A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits. LS Mean of change from baseline in mean morning PEF is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates.	Baseline, 24 weeks	No
Secondary	Change From Baseline in % Predicted FEV1 Following 24-week Treatment	Spirometry was used at defined time points throughout the study to assess the clinical status of patients and to capture the following variables: forced expiratory volume in one second (FEV1), FEV1 percent predicted, forced vital capacity (FVC) and the FEV1/FVC ratio. During the Screening assessment, spirometry was performed pre- and post-bronchodilator administration to assess reversibility. During the treatment period (including prerandomization assessments on Day 1), spirometry was performed after withholding bronchodilators. The results of spirometry were required to meet the ATS/ERS criteria for acceptability and repeatability. Acceptability criteria were applied before repeatability was determined. LS Mean of change from baseline in % predicted FEV1 is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline % predicted FEV1 as covariates.	Baseline, 24 weeks	No
Secondary	Change From Baseline in AQLQ Score Following 24-week Treatment	The standardized version of the Asthma Quality of Life Questionnaire (AQLQs)), was used to assess the patients' asthma-related quality of life. There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental exposure). Each question was answered on a 7 point scale (1-totally limited/problems all the time, 7-not at all limited/no problems). The overall AQLQ score is the mean of all 32 responses, and the individual domain scores are the means of the items in those domains (a minimum domain / overall score of 1 = Severely impaired whereas a maximum domain / overall score of 7 = not impaired at all). A positive change from baseline score indicates improvement.	24 weeks	No
Secondary	Percentage of Patients Achieving at Least a 0.5, 1.0 or 1.5 Point Improvement From Baseline in AQLQ Overall Score Following 24-week Treatment	The standardized version of the Asthma Quality of Life Questionnaire (AQLQs)), was used to assess the patients' asthma-related quality of life. There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental exposure). Each question was answered on a 7 point scale (1-totally limited/problems all the time, 7-not at all limited/no problems). The overall AQLQ score is the mean of all 32 responses, and the individual domain scores are the means of the items in those domains (a minimum domain / overall score of 1 = Severely impaired whereas a maximum domain / overall score of 7 = not impaired at all). A positive change from baseline score indicates improvement.	24 weeks	No
Secondary	Change From Baseline in ACQ Score Following 24-week Treatment	The Asthma Control Questionnaire (ACQ) is a questionnaire consisting of 7 questions assessing symptoms, airway caliber and rescue ß2-agonist use. One value representing overall asthma control on that occasion was calculated. Decrease in scores of 0.5 or higher between ACQ assessments are considered clinically meaningful. The ACQ was completed by the patient at the Investigator's site at Visit 2 (Week 1, pre-dose), Visit 6 (after completion of 16 weeks of treatment) and at the End of Study/Early Termination visit. LS Mean of change from baseline in ACQ score is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, center grouping, smoking status, and baseline ACQ score as covariates. Score 0= totally controlled, 6= extremely poorly controlled	24 weeks	No
Secondary	Percentage of Patients With at Least a 0.5 or 0.75 Point Improvement in the ACQ Score at Week 24	The Asthma Control Questionnaire (ACQ) is a questionnaire consisting of 7 questions assessing symptoms, airway caliber and rescue ß2-agonist use. One value representing overall asthma control on that occasion was calculated. Decrease in scores of 0.5 or higher between ACQ assessments are considered clinically meaningful. The ACQ was completed by the patient at the Investigator's site at Visit 2 (Week 1, pre-dose), Visit 6 (after completion of 16 weeks of treatment) and at the End of Study/Early Termination visit. Only patients with no more than 1 item missing are included, and the missing item was imputed by interpolation	24 weeks	No
Secondary	Change From Baseline in Asthma Symptom Scores Following 24-week Treatment	Total asthma symptom score was derived for each day as the total of the morning (scale 0-1), daytime (scale 0-4) and nocturnal (scale 0-4) scores with a max score of 9. The mean score across the 28 days prior to the week 24 assessment visit was used to calculate a change from baseline. Analysis of total asthma symptom score was performed using ANCOVA model and Van-Elteren test. LS Mean of change from baseline in mean asthma symptom score is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, smoking status, center grouping, and baseline mean asthma symptom scores as covariates. Decrease of score on change from baseline means improvement of asthma symptom control.	24 weeks	No
Secondary	Percentage of Participants With Investigator and Patient Global Evaluation of Treatment Effectiveness (GETE) at Weeks 16 and 24	The global evaluation of treatment effectiveness (GETE) is an assessment of asthma symptom control and overall response to asthma treatment. The evaluation was performed by both investigator and patient, each using the same 5 point scale. The GETE scale ranges were as follows: excellent, good, moderate, poor and worsening. A good or excellent response on the 5 point scale indicated that a patient had responded to treatment. 1=excellent 2=good 3=moderate 4=poor 5= worsening. Responder is defined as the patient who achieved an excellent or good response. Non-responder isdefined as the patient who achieved a moderate or poor or worsening response.	16 and 24 weeks	No
Secondary	Change From Baseline in Number of Puffs of Asthma Rescue Medication Following 24-week Treatment	Analysis of rescue medication use followed a similar method to that employed for total asthma symptom score. The mean number of puffs across the 28 days prior to the Week 24 assessment visit was used to calculate a change from baseline. LS Mean of change from baseline in mean number of puffs of asthma rescue medication is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, smoking status, center grouping, and baseline mean number of puffs of asthma rescue medication as covariates.	24 weeks	No