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

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

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

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: QBX258; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Frankfurt, Germany, 60596
    • Novartis Investigative Site
  • Wiesbaden, Germany, 65187
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SE11YR
    • Novartis Investigative Site
  • Manchester, United Kingdom, M23 9QZ
    • Novartis Investigative Site
• United States
  • California
    • Anaheim, California, United States, 92801
      • Novartis Investigative Site
    • Riverside, California, United States, 92506
      • Novartis Investigative Site
    • Rolling Hills Estates, California, United States, 90274
      • Novartis Investigative Site
    • San Marino, California, United States, 91108
      • Novartis Investigative Site
  • Colorado
    • Denver, Colorado, United States, 80206
      • Novartis Investigative Site
    • Denver, Colorado, United States, 80230
      • Novartis Investigative Site
  • Florida
    • Aventura, Florida, United States, 33180
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Novartis Investigative Site
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Novartis Investigative Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Novartis Investigative Site
    • Winston-Salem, North Carolina, United States, 27157
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Novartis Investigative Site
  • Oregon
    • Medford, Oregon, United States, 97504-8741
      • Novartis Investigative Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: QBX258; Participants received QBX258 intravenous (iv) infusion every 4 weeks for up to 4 doses total.	Drug: QBX258; 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.
PLACEBO_COMPARATOR: Placebo; Participants received placebo to QBX258 iv infusion every 4 weeks for up to 4 doses total.	Drug: Placebo; The placebo infusion was an equal volume of 5% dextrose for infusion and was provided by the clinical site.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: November 22, 2011
• First Submitted That Met QC Criteria: November 23, 2011
• First Posted (ESTIMATE): November 24, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): August 1, 2016
• Last Update Submitted That Met QC Criteria: June 20, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Asthma; Interleukin; QBX258; VAK694; QAX576
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: CQBX258X2201; 2011-003066-32 (EUDRACT_NUMBER)