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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01479595
First received: November 22, 2011
Last updated: June 20, 2016
Last verified: June 2016
  Purpose
This study is designed to investigate the efficacy and safety of QBX258 in subjects with moderate to severe asthma.

Condition Intervention Phase
Asthma
Drug: QBX258
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Asthma Control Questionnaire (ACQ) Score [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    FEV1 was assessed using central spirometry according to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines.

  • Change in Asthma Quality of Life Questionnaire (AQLQ) Score [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]

    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.


  • Morning and Evening Peak Expiratory Flow (PEF) Rate [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Maximum Expiratory Flow [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Maximum expiratory flow was assessed using central spirometry according to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines.

  • Number of Participants With Anti-QAX576 Antibodies or Anti-VAK694 Antibodies [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Anti-QAX576 and anti-VAK694 antibodies in serum were analyzed.

  • Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of the QAX576 Analyte [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Blood samples were obtained to measure Cmax,ss.

  • Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) of the VAK694 Analyte [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Blood samples were obtained to measure Cmax,ss.

  • Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) of the QAX576 Analyte [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Blood samples were obtained to measure Cmin,ss.

  • Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) of the VAK694 Analyte [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Blood samples were obtained to measure Cmin,ss.

  • Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 65
Study Start Date: February 2012
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01479595

Locations
United States, California
Novartis Investigative Site
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
United States, Colorado
Novartis Investigative Site
Denver, Colorado, United States, 80206
Novartis Investigative Site
Denver, Colorado, United States, 80230
United States, Florida
Novartis Investigative Site
Aventura, Florida, United States, 33180
United States, Massachusetts
Novartis Investigative Site
Boston, Massachusetts, United States, 02115
United States, Minnesota
Novartis Investigative Site
Minneapolis, Minnesota, United States, 55402
United States, Missouri
Novartis Investigative Site
St. Louis, Missouri, United States, 63110
United States, North Carolina
Novartis Investigative Site
Raleigh, North Carolina, United States, 27607
Novartis Investigative Site
Winston-Salem, North Carolina, United States, 27157
United States, Oklahoma
Novartis Investigative Site
Oklahoma City, Oklahoma, United States, 73120
United States, Oregon
Novartis Investigative Site
Medford, Oregon, United States, 97504-8741
United States, South Carolina
Novartis Investigative Site
Spartanburg, South Carolina, United States, 29303
Germany
Novartis Investigative Site
Berlin, Germany, 10117
Novartis Investigative Site
Frankfurt, Germany, 60596
Novartis Investigative Site
Wiesbaden, Germany, 65187
United Kingdom
Novartis Investigative Site
London, United Kingdom, SE11YR
Novartis Investigative Site
Manchester, United Kingdom, M23 9QZ
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01479595     History of Changes
Other Study ID Numbers: CQBX258X2201  2011-003066-32 
Study First Received: November 22, 2011
Results First Received: February 23, 2016
Last Updated: June 20, 2016
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Asthma
Interleukin
QBX258
QAX576
VAK694

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on August 25, 2016