A Study to Establish the Efficacy of QBX258 in Patients With Moderate to Severe Asthma

Study Overview
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Brief Summary
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This study is designed to investigate the efficacy and safety of QBX258 in subjects with moderate to severe asthma.

Official Title
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A Randomized Double-blind Multiple-dose Placebo-controlled Trial to Establish the Efficacy of QBX258 (Combination of VAK694 and QAX576) in Asthma That is Inadequately Controlled With Inhaled Corticosteroids and Long Acting Beta Agonists

Conditions
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Asthma

Intervention / Treatment
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* Drug: QBX258
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with atopic asthma >1 year duration diagnosed according to the GINA guidelines. Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 39 kg/m2. Asthma which is not adequately controlled on current treatment, as demonstrated by an Asthma Control Questionnaire (ACQ) score of > 1.5. FEV1 40 to 90% of predicted. Exclusion Criteria: Diagnosed with COPD as defined by the GOLD guidelines Subjects who have had a respiratory tract infection within 4 weeks prior to screening. Women of child-bearing potential must use highly effective methods of contraception during dosing and for at least 18 weeks after last study drug administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QBX258<br>Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total. | Drug: QBX258<br>* QBX258 infusion, a combination of VAK694 and QAX576, was supplied to the Investigator as open label bulk medication. The planned dose of VAK694 (lyophilisate in vial, 150 mg/vial), was 3 mg/kg. The planned dose of QAX576 (lyophilisate in vial, 150 mg/vial), was 6 mg/kg.<br>|
| Placebo Comparator: Placebo<br>Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total. | Drug: Placebo<br>* The placebo infusion was an equal volume of 5% dextrose for infusion and was provided by the clinical site.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Asthma Control Questionnaire (ACQ) Score | The ACQ consists of 7 questions assessing symptoms, rescue medication use and lung function. Except for lung function (FEV1), each question was scored on a 7-point scale where 0 = no impairment and 6 = maximum impairment. Scores ranged between 0 totally controlled to 6 (severely uncontrolled). Participants with a score below 1.0 are considered to have adequately controlled asthma. Participants with a score above 1.0 were considered not to be well controlled. A negative change from baseline indicates improvement. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Forced Expiratory Volume in One Second (FEV1) | FEV1 was assessed using central spirometry according to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. | Baseline and 12 weeks | 
| Change in Asthma Quality of Life Questionnaire (AQLQ) Score | The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments that are most important to patients with asthma. It consists of 4 domains: symptoms, emotions., exposure to environmental stimuli and activity limitation. Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale. The scale ranges from 1 to 7. The overall AQLQ score was the mean response to all 32 questions. Higher scores represent better outcomes. | Baseline and 12 weeks | 
| Morning and Evening Peak Expiratory Flow (PEF) Rate | Morning and evening PEFs were recorded on an electronic diary (e-diary). PEF was assessed twice daily approximately 12 hours apart and the measurements were recorded in the e-diary. | Baseline and 12 weeks | 
| Change From Baseline in Maximum Expiratory Flow | Maximum expiratory flow was assessed using central spirometry according to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. | Baseline and 12 weeks | 
| Number of Participants With Anti-QAX576 Antibodies or Anti-VAK694 Antibodies | Anti-QAX576 and anti-VAK694 antibodies in serum were analyzed. | 12 weeks | 
| Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of the QAX576 Analyte | Blood samples were obtained to measure Cmax,ss. | days 1 (pre-dose and 2 hours post-dose), 15, 29 (pre-dose and 2 hours post-dose), 43, 57 (pre-dose and 2 hours post-dose), 71, 85 (pre-dose and 2 hours post-dose), 99, 113, 141, 183 | 
| Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of the VAK694 Analyte | Blood samples were obtained to measure Cmax,ss. | days 1 (pre-dose and 2 hours post-dose), 15, 29 (pre-dose and 2 hours post-dose), 43, 57 (pre-dose and 2 hours post-dose), 71, 85 (pre-dose and 2 hours post-dose), 99, 113, 141, 183 | 
| Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) of the QAX576 Analyte | Blood samples were obtained to measure Cmin,ss. | days 1 (pre-dose and 2 hours post-dose), 15, 29 (pre-dose and 2 hours post-dose), 43, 57 (pre-dose and 2 hours post-dose), 71, 85 (pre-dose and 2 hours post-dose), 99, 113, 141, 183 | 
| Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) of the VAK694 Analyte | Blood samples were obtained to measure Cmin,ss. | days 1 (pre-dose and 2 hours post-dose), 15, 29 (pre-dose and 2 hours post-dose), 43, 57 (pre-dose and 2 hours post-dose), 71, 85 (pre-dose and 2 hours post-dose), 99, 113, 141, 183 | 
| Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | FeNO was assessed as a measure of airway inflammation. An FeNO machine was used to obtain the FeNO measurements. FeNO measurements were obtained prior to the spirometry assessments. | baseline, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Interleukin, QBX258, QAX576, VAK694