Efficacy and Safety of BI 655066/ABBV-066 (Risankizumab) in Patients With Severe Persistent Asthma

Phase IIa, Randomized, Double-blind, Placebo Controlled, Parallel Group Study to Assess the Safety and Efficacy of Subcutaneously Administered BI 655066/ABBV-066 (Risankizumab) as add-on Therapy Over 24 Weeks in Patients With Severe Persistent Asthma.

The objectives of this trial are primarily to evaluate the efficacy and safety of BI 655066/ABBV-066 (risankizumab) as compared to placebo over a 24-week treatment period in severe asthma patients. The primary endpoint is time to first asthma worsening during the planned 24 week treatment period for active vs. placebo treated patients on top of standard of care therapy. Upon demonstration of a meaningful clinical response, another important objective is the identification of biomarkers that can be used to target patients who will likely respond to treatment with BI 655066/ABBV-066 (risankizumab).

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: risankizumab; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • ULB Hôpital Erasme
  • Bruxelles, Belgium, 1200
    • Brussels - UNIV St-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • Centre hospitalier universitaire de Liege
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Ontario
    • Burlington, Ontario, Canada, L7N 3V2
      • Burlington Lung Clinic
    • Hamilton, Ontario, Canada, L8N 4A6
      • Airway Inflammometry Laboratory
• France
  • Grenoble, France, 38043
    • HOP CHU de Grenoble
  • Marseille, France, 13915
    • HOP Nord
  • Montpellier, France, 34295
    • HOP Arnaud de Villeneuve
  • Nantes, France, 44093
    • HOP Nord Laennec
  • Paris, France, 75018
    • HOP Bichat
• Germany
  • Berlin, Germany, 12203
    • MECS Research GmbH, Berlin
  • Berlin, Germany, 10717
    • Praxis Dr. Linnhoff, Berlin
  • Bochum, Germany, 44789
    • Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH
  • Frankfurt, Germany, 60596
    • IKF Pneumologie GmbH & Co. KG
  • Frankfurt, Germany, 60596
    • Medaimun GmbH
  • Frankfurt, Germany, 60389
    • Praxis Dr. med. Claus Keller
  • Hamburg, Germany, 20354
    • Hamburger Institut für Therapieforschung GmbH (HIT)
  • Hannover, Germany, 30173
    • Praxis Dr. Hoffmann, Hannover
  • Homburg/Saar, Germany, 66421
    • Universitatsklinikum des Saarlandes
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • Koblenz, Germany, 56068
    • KPPK GmbH, Studienzentrum
  • Lübeck, Germany, 23552
    • KLB Gesundheitsforschung Lubeck GmbH
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Neu-Isenburg, Germany, 63263
    • Institut fur klinische Forschung GmbH
  • Rüdersdorf, Germany, 15562
    • IFG Institut für Gesundheitsförderung GmbH
• Korea, Republic of
  • Cheongju, Korea, Republic of, 361-771
    • Chungbuk National University Hospital
  • Gwangju, Korea, Republic of, 501-757
    • Chonnam National University Hospital
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 130-709
    • The Catholic University of Korea, St.Paul's Hospital
• Netherlands
  • Den Haag, Netherlands, 2545 CH
    • Hagaziekenhuis
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum (LUMC)
• Poland
  • Katowice, Poland, 40-752
    • Gibinski Univ.Clin.Cnter of Silesian Med.Uni.Katowice,Outpat
  • Krakow, Poland, 30033
    • Specjalistyczny Osrodek Alergologiczno-Intern. ALL-MED
  • Krakow, Poland, 31066
    • Univ. Hospital in Krakow,Pulmonology Clinical Dept
  • Lodz, Poland, 90 141
    • Barlicki University Hospital No. 1
  • Lodz, Poland, 90141
    • Barlicki University Hospital No. 1
• Taiwan
  • Keelung, Taiwan, 20401
    • Chang Gung Memorial Hospital Keelung
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
• United Kingdom
  • Belfast, United Kingdom, BT9 6AD
    • Celerion Inc
  • Bradford, United Kingdom, BD9 6RJ
    • Bradford Royal Infirmary
  • Leicester, United Kingdom, LE3 9QP
    • Glenfield Hospital
  • Manchester, United Kingdom, M23 9QZ
    • The Medicines Evaluation Unit
  • Wishaw, United Kingdom, ML2 0DP
    • Wishaw General Hospital
• United States
  • California
    • Costa Mesa, California, United States, 92626
      • WCCT Global, LLC
    • Mountain View, California, United States, 94040
      • El Camino Hospital
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe Research Centers
  • Connecticut
    • New Haven, Connecticut, United States, 06504
      • Yale New Haven Hospital
  • Florida
    • Tampa, Florida, United States, 33607
      • Clinical Research Trials of Florida, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Buffalo, New York, United States, 14215
      • VA WNY Healthcare System
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • American Health Research, Inc.
    • New Bern, North Carolina, United States, 28562
      • Coastal Carolina Health Care, P.A.
    • Winston-Salem, North Carolina, United States, 27104
      • Wake Forest School of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University School of Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • Pittsburgh, Pennsylvania, United States, 15243
      • Research Protocol Mgmt Spc
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Medtrial, LLC
    • Greenville, South Carolina, United States, 29615
      • Vitalink Research
  • Texas
    • The Woodlands, Texas, United States, 77380
      • Respiratory and Sleep Disorders Specialists
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • O and O Alpan, LLC

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

Inclusion criteria:

1. Pre-bronchodilator clinic measured forced expiratory volume (FEV1) of =40% and =85% of predicted normal.
2. One year history of asthma diagnosed by a physician, and have FEV1 reversibility of =12% and an absolute change of at least 200 mL after administration of 400 µg salbutamol.
3. Must be on at least medium dose inhaled corticosteroids and at least one other asthma controller medication for at least one year.
4. Must have documented history of two or more severe asthma exacerbations in the last 12 months.

Exclusion criteria:

1. Patients with a significant disease other than asthma.
2. Patients who are not able to produce sputum or sputum samples of sufficient quality.
3. Patients who had clinically relevant history of intubation for asthma exacerbation in the past year.
4. Patients diagnosed with any concurrent respiratory disease.
5. Recent history (within 6 months) of myocardial infarction or hospitalized for cardiac failure in the past year.
6. Patients who have undergone thoracotomy with pulmonary resection.
7. Patients who have undergone bronchial thermoplasty or radiotherapy procedure in the past year or have planned procedures during the study.
8. Patients taking oral corticosteroids with a total daily dose of more than 20 mg prednisone (or equivalent) in the past 6 weeks.
9. Pregnant or nursing women.
10. Women of childbearing potential that, if sexually active, is unwilling to use a highly effective method of birth control.
11. Clinically relevant acute infections or chronic infections.
12. Have received any live bacterial or live viral vaccination in the last12 weeks.
13. Have received Bacille Calmette-Guerin (BCG) vaccination in the last 12 months.
14. Have received treatment with ustekinumab (Stelara®).
15. Have received treatment with any other biologics in the last 3 months or within 6 times the half-life of the compound.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Risankizumab; Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe with 90 milligram/ milliliter (mg/mL) risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20).	Drug: risankizumab; Monoclonal IgG antibody; Other Names: BI 655066; ABBV-066
Placebo Comparator: Placebo; Patients received subcutaneous injection of 1 milliliter (mL) prefilled syringe consisting of matching placebo to risankizumab once every 4 weeks (weeks 0, 4, 8, 12, 16, 20).	Drug: placebo; Matching placebo for risankizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Asthma Worsening During the Planned 24 Week Treatment Period	Time to first asthma worsening during the planned 24 week treatment period: Asthma worsening was defined as the occurrence of any one of the following four criteria: a) Decrease from baseline of ≥30% in morning peak expiratory flow (PEF) on at least 2 consecutive days. b) Increase from baseline of ≥50% and an increase of least 4 puffs in daily use of rescue medication for at least 2 consecutive days. c) Increase from baseline of ≥0.75 units in ACQ5. d) Severe asthma exacerbations defined as initiation of systemic corticosteroids (prednisone or equivalent) for 3 or more consecutive days for asthma. Additionally, for subjects on maintenance systemic corticosteroids, at least doubling of the maintenance dose resulting in a total daily dose of ≥ 20 mg for three or more consecutive days was considered a severe asthma exacerbation.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Asthma Worsening During the Planned 24 Week Treatment Period According to Alternative Definition	Time to first asthma worsening during the planned 24 week treatment period according to alternative definition: Asthma worsening was defined as the occurrence of any one of the following four criteria: a) Decrease from baseline of ≥30% in morning peak expiratory flow (PEF) on at least 2 consecutive days. b) Increase from baseline of ≥50% and an increase of least 4 puffs in daily use of rescue medication for at least 2 consecutive days. c) Increase from baseline of ≥0.5 units in ACQ5. d) Severe asthma exacerbations defined as initiation of systemic corticosteroids (prednisone or equivalent) for 3 or more consecutive days for asthma. Additionally, for subjects on maintenance systemic corticosteroids, at least doubling of the maintenance dose resulting in a total daily dose of ≥ 20 mg for three or more consecutive days was considered a severe asthma exacerbation.	24 weeks
Annualized Rate of Asthma Worsening During the Planned 24 Week Treatment Period	Annualized rate of asthma worsening during the planned 24 week treatment period. Asthma worsening was defined as the occurrence of any one of the following four criteria: a) Decrease from baseline of ≥30% in morning peak expiratory flow (PEF) on at least 2 consecutive days. b) Increase from baseline of ≥50% and an increase of least 4 puffs in daily use of rescue medication for at least 2 consecutive days. c) Increase from baseline of ≥0.75 units in ACQ5. d) Severe asthma exacerbations defined as initiation of systemic corticosteroids (prednisone or equivalent) for 3 or more consecutive days for asthma. Additionally, for subjects on maintenance systemic corticosteroids, at least doubling of the maintenance dose resulting in a total daily dose of ≥ 20 mg for three or more consecutive days was considered a severe asthma exacerbation. Mean is Annualized rate.	24 weeks
Time to First Severe Asthma Exacerbation During the Planned 24 Week Treatment Period	Time to first severe asthma exacerbation during the planned 24 week treatment period. Severe asthma exacerbation was defined as initiation of systemic corticosteroids (prednisone or equivalent) for 3 or more consecutive days for asthma. Additionally, for subjects on maintenance systemic corticosteroids, at least doubling of the maintenance dose resulting in a total daily dose of ≥ 20 mg for three or more consecutive days was considered a severe asthma exacerbation.	24 weeks
Annualized Rate of Severe Asthma Exacerbation During the Planned 24-week Treatment Period	Annualized rate of severe asthma exacerbation during the planned 24-week treatment period. Severe asthma exacerbation was defined as initiation of systemic corticosteroids (prednisone or equivalent) for 3 or more consecutive days for asthma. Additionally, for subjects on maintenance systemic corticosteroids, at least doubling of the maintenance dose resulting in a total daily dose of ≥ 20 mg for three or more consecutive days was considered a severe asthma exacerbation. Mean is Annualized rate.	24 weeks
Trough Forced Expiratory Volume in 1 Second (FEV1) In-clinic Change From Baseline at Week 24	Trough forced expiratory volume in 1 second (FEV1) in-clinic change from baseline at week 24.	Baseline and 24 weeks
Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) In-clinic Change From Baseline at Week 24	Post-bronchodilator forced expiratory volume in 1 second (FEV1) in-clinic change from baseline at week 24.	Baseline and 24 weeks
Weekly Asthma Control Questionaire Score at Week 24	The score at week 24 is the average of the responses to the five ACQ5 questions for the week preceding the Week 24 visit. The ACQ5 asks patients to rate the severity of their asthma symptoms and the degree to which asthma affected their sleep and other daily activities. The scale for all five ACQ5 questions range from the best possible answer of 0 (No symptoms, None, Never) to the worst possible answer of 6 (very severe, unable to sleep, totally limited). The ACQ5 score can range from 0.0 (best) to 6.0 (worst).	24 weeks

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Boehringer Ingelheim

Publications and helpful links

General Publications

• Brightling CE, Nair P, Cousins DJ, Louis R, Singh D. Risankizumab in Severe Asthma - A Phase 2a, Placebo-Controlled Trial. N Engl J Med. 2021 Oct 28;385(18):1669-1679. doi: 10.1056/NEJMoa2030880.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2015
• Primary Completion (Actual): October 13, 2017
• Study Completion (Actual): February 2, 2018

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: May 11, 2015
• First Posted (Estimate): May 13, 2015

Study Record Updates

• Last Update Posted (Actual): April 10, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• 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: 1311.14; 2014-004932-20 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes