Efficacy and Safety of QGE031versus Placebo and Omalizumab in Patients Aged 18-75 Years With Asthma

A Multi-center, Randomized, Double-blind, Placebo and Active-controlled Study With Exploratory Dose-ranging to Investigate the Efficacy and Safety of 16 Weeks Treatment With Subcutaneous (s.c.) QGE031 in Asthma Patients Not Adequately Controlled With High-dose Inhaled Corticosteroids and Long Acting β2-agonists

This study assessed the effect on asthma control of different dose levels and regimens of QGE031 in asthma patients that are inadequately controlled with inhaled steroid and beta-2 agonist medication. Safety was assessed also. Comparison was to placebo and omalizumab. Information from this study was planned to support the design of future studies.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: QGE031; Drug: Omalizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 471
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, B1842DID
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1125ABE
    • Novartis Investigative Site
  • Mendoza, Argentina, M5500CBA
    • Novartis Investigative Site
  • Mendoza, Argentina, M5500FIK
    • Novartis Investigative Site
  • Santa Fe, Argentina, S3000FIL
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1122AAK
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1426ABP
      • Novartis Investigative Site
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • Novartis Investigative Site
  • Capital Federal
    • Caba, Capital Federal, Argentina, C1430CKE
      • Novartis Investigative Site
  • Rosario
    • Santa Fe, Rosario, Argentina, S2000DBS
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000CXH
      • Novartis Investigative Site
    • Rosario, Santa Fe, Argentina, S2000AII
      • Novartis Investigative Site
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, 4000
      • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1V 4W2
    • Novartis Investigative Site
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4G2
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H3G 1L5
      • Novartis Investigative Site
    • St-Charles-Borromée, Quebec, Canada, J6E 2B4
      • Novartis Investigative Site
• Czechia
  • Breclav, Czechia, 690 02
    • Novartis Investigative Site
  • Brno, Czechia, 615 00
    • Novartis Investigative Site
  • Tabor, Czechia, 390 01
    • Novartis Investigative Site
  • CZE
    • Teplice, CZE, Czechia, 415 01
      • Novartis Investigative Site
  • Czech Republic
    • Brno, Czech Republic, Czechia, 639 00
      • Novartis Investigative Site
    • Trutnov, Czech Republic, Czechia, 541 01
      • Novartis Investigative Site
• Finland
  • Helsinki, Finland, 00290
    • Novartis Investigative Site
  • Tampere, Finland, 33520
    • Novartis Investigative Site
  • Turku, Finland, 20521
    • Novartis Investigative Site
• France
  • Le Kremlin Bicetre, France, 94275
    • Novartis Investigative Site
  • Marseille, France, 13915
    • Novartis Investigative Site
  • Montpellier, France, 34059
    • Novartis Investigative Site
  • Strasbourg, France, 67091
    • Novartis Investigative Site
• Germany
  • Frankfurt, Germany, 60596
    • Novartis Investigative Site
  • Hamburg, Germany, 20354
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Leipzig, Germany, 04275
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Roth, Germany, 91154
    • Novartis Investigative Site
  • Rüdersdorf, Germany, 15562
    • Novartis Investigative Site
• Guatemala
  • Guatemala City, Guatemala, 01011
    • Novartis Investigative Site
  • GTM
    • Guatemala City, GTM, Guatemala, 01010
      • Novartis Investigative Site
    • Guatemala City, GTM, Guatemala, 01011
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1121
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Pecs, Hungary, 7635
    • Novartis Investigative Site
  • Torokbalint, Hungary, 2045
    • Novartis Investigative Site
• India
  • Goa
    • Panjim, Goa, India, 403 002
      • Novartis Investigative Site
  • Gujrat
    • Karamsad, Gujrat, India, 388325
      • Novartis Investigative Site
  • Nagpur
    • Dhantoli, Nagpur, India, 12
      • Novartis Investigative Site
• Israel
  • Haifa, Israel, 3436212
    • Novartis Investigative Site
  • Jerusalem, Israel, 91031
    • Novartis Investigative Site
  • Jerusalem, Israel, 9112001
    • Novartis Investigative Site
  • Kfar-Saba, Israel, 4428164
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Rehovot, Israel, 7610001
    • Novartis Investigative Site
• Italy
  • ME
    • Messina, ME, Italy, 98125
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20123
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56124
      • Novartis Investigative Site
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site
• Korea, Republic of
  • Gwangju, Korea, Republic of, 501-757
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 120-752
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 156-755
    • Novartis Investigative Site
  • Chungcheongbuk-do
    • Cheongju-si, Chungcheongbuk-do, Korea, Republic of, 28644
      • Novartis Investigative Site
  • Gyeonggi-Do
    • Bucheon-Si, Gyeonggi-Do, Korea, Republic of, 14584
      • Novartis Investigative Site
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, Korea, Republic of, 16499
      • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 08308
      • Novartis Investigative Site
• Mexico
  • Distrito Federal
    • México, D.F., Distrito Federal, Mexico, 06700
      • Novartis Investigative Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44130
      • Novartis Investigative Site
• Panama
  • Panama City, Panama
    • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15-276
    • Novartis Investigative Site
  • Lodz, Poland, 90-153
    • Novartis Investigative Site
• Portugal
  • Coimbra, Portugal, 3041-853
    • Novartis Investigative Site
  • Lisboa, Portugal, 1749-035
    • Novartis Investigative Site
  • Lisboa, Portugal, 1169-024
    • Novartis Investigative Site
  • Porto, Portugal, 4100-180
    • Novartis Investigative Site
  • Vila Nova de Gaia, Portugal, 4434-502
    • Novartis Investigative Site
• Romania
  • Brasov, Romania, 500112
    • Novartis Investigative Site
  • Brasov, Romania, 500281
    • Novartis Investigative Site
  • Brasov, Romania, 500086
    • Novartis Investigative Site
  • Bucuresti, Romania, 011461
    • Novartis Investigative Site
  • Bucuresti, Romania, 050159
    • Novartis Investigative Site
  • Cluj Napoca, Romania, 400139
    • Novartis Investigative Site
  • Cluj-Napoca, Romania, 400371
    • Novartis Investigative Site
  • Pitesti, Romania, 110114
    • Novartis Investigative Site
  • District 1
    • Bucuresti, District 1, Romania, 10457
      • Novartis Investigative Site
  • District 3
    • Bucharest, District 3, Romania, 030303
      • Novartis Investigative Site
    • Bucharest, District 3, Romania, 030317
      • Novartis Investigative Site
  • Jud. Constanta
    • Constanta, Jud. Constanta, Romania, 900002
      • Novartis Investigative Site
  • ROM
    • Bucharest, ROM, Romania, 12071
      • Novartis Investigative Site
• Russian Federation
  • Barnaul, Russian Federation, 656045
    • Novartis Investigative Site
  • Chelyabinsk, Russian Federation, 454021
    • Novartis Investigative Site
  • Chelyabinsk, Russian Federation, 454000
    • Novartis Investigative Site
  • Moscow, Russian Federation, 127018
    • Novartis Investigative Site
  • Moscow, Russian Federation, 119992
    • Novartis Investigative Site
  • Moscow, Russian Federation, 125315
    • Novartis Investigative Site
  • N.Novgorod, Russian Federation, 603126
    • Novartis Investigative Site
  • Nizhny Novgorod, Russian Federation, 603018
    • Novartis Investigative Site
  • Penza, Russian Federation, 440026
    • Novartis Investigative Site
  • Ryazan, Russian Federation, 390026
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410012
    • Novartis Investigative Site
  • St-Petersburg, Russian Federation, 193312
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 194354
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150003
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
  • Singapore, Singapore, 308433
    • Novartis Investigative Site
• Slovakia
  • Bardejov, Slovakia, 085 01
    • Novartis Investigative Site
  • Bratislava, Slovakia, 826 06
    • Novartis Investigative Site
  • Kosice, Slovakia, 04001
    • Novartis Investigative Site
  • Prievidza, Slovakia, 97101
    • Novartis Investigative Site
  • Ruzomberok, Slovakia, 034 26
    • Novartis Investigative Site
  • Trencin, Slovakia, 91101
    • Novartis Investigative Site
  • Slovak Republic
    • Bratislava, Slovak Republic, Slovakia, 831 03
      • Novartis Investigative Site
    • Nitra, Slovak Republic, Slovakia, 949 01
      • Novartis Investigative Site
• South Africa
  • Cape Town, South Africa, 7531
    • Novartis Investigative Site
  • Cape Town, South Africa, 7505
    • Novartis Investigative Site
  • Durban, South Africa, 4001
    • Novartis Investigative Site
• Turkey
  • Aydin, Turkey, 09100
    • Novartis Investigative Site
  • Fatih / Istanbul, Turkey, 34098
    • Novartis Investigative Site
  • Istanbul, Turkey, 34093
    • Novartis Investigative Site
  • Istanbul, Turkey, 34854
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
  • Mersin, Turkey, 33079
    • Novartis Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Novartis Investigative Site
  • East Yorkshire, United Kingdom, HU16 5JQ
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO16 6YD
    • Novartis Investigative Site
  • West Yorkshire
    • Bradford, West Yorkshire, United Kingdom, BD9 6RJ
      • Novartis Investigative Site
• United States
  • California
    • Fresno, California, United States, 93720
      • Novartis Investigative Site
    • Hawaiian Gardens, California, United States, 90716
      • Novartis Investigative Site
    • Riverside, California, United States, 92506
      • Novartis Investigative Site
    • San Jose, California, United States, 95117
      • Novartis Investigative Site
    • Vista, California, United States, 92083
      • Novartis Investigative Site
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Novartis Investigative Site
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Novartis Investigative Site
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Novartis Investigative Site
    • Waldorf, Maryland, United States, 20602
      • Novartis Investigative Site
  • Michigan
    • Novi, Michigan, United States, 48375
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Novartis Investigative Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Novartis Investigative Site
    • Papillion, Nebraska, United States, 68046
      • Novartis Investigative Site
  • New York
    • Brooklyn, New York, United States, 11229
      • Novartis Investigative Site
    • Mineola, New York, United States, 11501
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Novartis Investigative Site
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Novartis Investigative Site
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Novartis Investigative Site
    • Summerville, South Carolina, United States, 29485
      • Novartis Investigative Site
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Novartis Investigative Site
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Novartis Investigative Site
  • Washington
    • Everett, Washington, United States, 98208
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• A diagnosis of allergic asthma , uncontrolled on current medication.
• History of at least 1 asthma exacerbation during the last 1 year
• Forced Expiratory Volume in one second (FEV1) of ≥ 40% and ≤ 80% of the predicted normal value; reversibility following administration of bronchodilator must also be demonstrated (historical positive reversibility or bronchoprovocation result can be used).

Key Exclusion Criteria:

• Baseline IgE levels or body weight outside the omalizumab dosing table.
• Use of tobacco products within the previous 6 months (Social occasional smokers may be included).
• Recent asthma attack/exacerbation or asthma worsening/ respiratory infection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: QGE031 240 mg every 2 weeks (q2w); Participants received QGE031 240 mg subcutaneously (s.c.) q2w for 16 weeks.	Drug: QGE031; QGE031 was supplied as 120 mg liquid in vial per 1 mL
EXPERIMENTAL: QGE031 240 mg q4w; Participants received QGE031 240 mg s.c. q4w for 16 weeks.	Drug: QGE031; QGE031 was supplied as 120 mg liquid in vial per 1 mL
EXPERIMENTAL: QGE031 180 mg q2w; Participants received QGE031 180 mg s.c. q2w for 16 weeks.	Drug: QGE031; QGE031 was supplied as 120 mg liquid in vial per 1 mL
EXPERIMENTAL: QGE031 120 mg q2w; Participants received QGE031 120 mg s.c. q2w for 16 weeks.	Drug: QGE031; QGE031 was supplied as 120 mg liquid in vial per 1 mL
EXPERIMENTAL: QGE031 36 mg q2w; Participants received QGE031 36 mg s.c. q2w for 16 weeks.	Drug: QGE031; QGE031 was supplied as 120 mg liquid in vial per 1 mL
EXPERIMENTAL: QGE031 12 mg q2w; Participants received QGE031 12 mg s.c. q2w for 16 weeks.	Drug: QGE031; QGE031 was supplied as 120 mg liquid in vial per 1 mL
ACTIVE_COMPARATOR: Omalizumab (as per locally approved dosing table); Participants received omalizumab as per locally approved dosing table s.c. q2w or q4w for 16 weeks.	Drug: Omalizumab; Omalizumab was supplied as 150 mg lyophilisate in vial; Other Names: Xolair
PLACEBO_COMPARATOR: Placebo to QGE031 240 mg q2w; Participants received matching placebo to QGE031 240 mg s.c. q2w for 16 weeks.	Drug: Placebo; Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL
PLACEBO_COMPARATOR: Placebo to QGE031 240 mg q4w; Participants received placebo to QGE031 240 mg s.c. q2w for 16 weeks.	Drug: Placebo; Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL
PLACEBO_COMPARATOR: Placebo to QGE031 180 mg q2w; Participants received QGE031 180 mg s.c. q2w for 16 weeks.	Drug: Placebo; Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL
PLACEBO_COMPARATOR: Placebo to QGE031 120 mg q2w; Participants received QGE031 120 mg s.c. q2w for 16 weeks.	Drug: Placebo; Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL
PLACEBO_COMPARATOR: Placebo to QGE031 36 mg q2w; Participants received QGE031 36 mg s.c. q2w for 16 weeks.	Drug: Placebo; Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL
PLACEBO_COMPARATOR: Placebo to QGE031 12 mg q2w; Participants received QGE031 12 mg s.c. q2w for 16 weeks.	Drug: Placebo; Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL
PLACEBO_COMPARATOR: Placebo to omalizumab; Participants received placebo to omalizumab s.c. q2w or q4w for 16 weeks.	Drug: Placebo; Placebo to QGE031 and Omalizumab was supplied as QGE031 0 mg in vial per 1 mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of QGE031 Participants With Clinically Important Improvement of <= -0.5 in the Asthma Control Questionnaire 7 (ACQ-7) Score Compared to Placebo	The ACQ-7 measures asthma symptom control and consisted of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway caliber (FEV1 % predicted). All 7 questions of the ACQ were equally weighted. Items 1-6 scored along a 7-point response scale, where 0 = good controlled and 6 = poor controlled. The 7th item on % predicted FEV1 (pre-bronchodilator) was scored by clinic staff on a 7-point scale (0 - > 95%; 1 - 90-95%; 2 - 80-89%; 3 - 70-79%; 4 - 60-69%; 5 - 50-59%; 6 - < 50%). The average score of the 7 questions was calculated as the sum of scores divided by the number of questions that were answered by the participants, as long as there were at least 6 questions answered and the missing items were neither question 1 nor question 7.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in ACQ-7 Score	The ACQ-7 measures asthma symptom control and consisted of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway caliber (FEV1 % predicted). All 7 questions of the ACQ were equally weighted. Items 1-6 scored along a 7-point response scale, where 0 = good controlled and 6 = poor controlled. The 7th item on % predicted FEV1 (pre-bronchodilator) was scored by clinic staff on a 7-point scale (0 - > 95%; 1 - 90-95%; 2 - 80-89%; 3 - 70-79%; 4 - 60-69%; 5 - 50-59%; 6 - < 50%). The average score of the 7 questions was calculated as the sum of scores divided by the number of questions that were answered by the participants, as long as there were at least 6 questions answered and the missing items were neither question 1 nor question 7. A negative change from baseline indicates improvement.	Baseline, Weeks 4, 8, 12, 16 and 28
Percentage of Participants With a Change From Baseline in ACQ-7 Score Less Than -1.1	The ACQ-7 measures asthma symptom control and consisted of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway caliber (FEV1 % predicted). All 7 questions of the ACQ were equally weighted. Items 1-6 scored along a 7-point response scale, where 0 = good controlled and 6 = poor controlled. The 7th item on % predicted FEV1 (pre-bronchodilator) was scored by clinic staff on a 7-point scale (0 - > 95%; 1 - 90-95%; 2 - 80-89%; 3 - 70-79%; 4 - 60-69%; 5 - 50-59%; 6 - < 50%). The average score of the 7 questions was calculated as the sum of scores divided by the number of questions that were answered by the participants, as long as there were at least 6 questions answered and the missing items were neither question 1 nor question 7.	Week 16
Change From Baseline 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 participants with asthma. The 32 items in the AQLQ were divided into four domain-specific scores and a total score as follows: Activity limitations = Mean of Items 1, 2, 3, 4, 5, 11, 19, 25, 28, 31, 32 (11 items); Symptoms = Mean of Items 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 29, 30 (12 items); Emotional function = Mean of Items 7, 13, 15, 21, 27 (5 items); Environmental stimuli = Mean of Items 9, 17, 23, 26 (4 items); and Overall Score = Mean of Items 1 to 32 (32 items). Each item of the AQLQ was equally weighted and scored along a 7-point scale, where 1 indicates maximal impairment and 7 indicates no impairment. Thus, higher scores indicate better asthma-related quality of life. The mean overall score ranged from 1 to 7. A positive change from baseline indicates improvement.	Baseline, Week 16, Week 28
Change From Baseline in Mean Number of Puffs of Morning, Evening and Total Daily Asthma Rescue Medication	Participants recorded their use of rescue medication into an electronic diary (eDiary). A negative change from baseline indicates improvement.	Baseline, Week 16

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): January 1, 2016

Study Registration Dates

• First Submitted: October 19, 2012
• First Submitted That Met QC Criteria: October 25, 2012
• First Posted (ESTIMATE): October 30, 2012

Study Record Updates

• Last Update Posted (ACTUAL): August 11, 2017
• Last Update Submitted That Met QC Criteria: August 7, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: asthma; placebo; asthma control; omalizumab; double-blind; allergy; IgE; atopic
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: CQGE031B2201; 2012-002298-69 (EUDRACT_NUMBER)