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

Asthma Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02443298
• Other study ID #: 1311.14
• Secondary ID: 2014-004932-20
• Status: Completed
• Phase: Phase 2
• Start date: June 23, 2015
• Est. completion date: February 2, 2018

Study information

• Verified date: March 2019
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: February 2, 2018
• Est. primary completion date: October 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• placebo
Matching placebo for risankizumab
• risankizumab
Monoclonal IgG antibody

Locations

Country	Name	City	State
Belgium	Brussels - UNIV St-Luc	Bruxelles
Belgium	ULB Hopital Erasme	Bruxelles
Belgium	UZ Leuven	Leuven
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Canada	Burlington Lung Clinic	Burlington	Ontario
Canada	Airway Inflammometry Laboratory	Hamilton	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
France	HOP CHU de Grenoble	Grenoble
France	HOP Nord	Marseille
France	HOP Arnaud de Villeneuve	Montpellier
France	HOP Nord Laënnec	Nantes
France	HOP Bichat	Paris
Germany	MECS Research GmbH, Berlin	Berlin
Germany	Praxis Dr. Linnhoff, Berlin	Berlin
Germany	Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil gGmbH	Bochum
Germany	IKF Pneumologie GmbH & Co. KG	Frankfurt
Germany	Medaimun GmbH	Frankfurt
Germany	Praxis Dr. med. Claus Keller	Frankfurt
Germany	Hamburger Institut für Therapieforschung GmbH (HIT)	Hamburg
Germany	Praxis Dr. Hoffmann, Hannover	Hannover
Germany	Universitätsklinikum des Saarlandes	Homburg/Saar
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	KPPK GmbH, Studienzentrum	Koblenz
Germany	KLB Gesundheitsforschung Lübeck GmbH	Lübeck
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Institut für klinische Forschung GmbH	Neu-Isenburg
Germany	IFG Institut für Gesundheitsförderung GmbH	Rüdersdorf
Korea, Republic of	Chungbuk National University Hospital	Cheongju
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, St.Paul's Hospital	Seoul
Netherlands	HagaZiekenhuis	Den Haag
Netherlands	Leids Universitair Medisch Centrum (LUMC)	Leiden
Poland	Gibinski Univ.Clin.Cnter of Silesian Med.Uni.Katowice,Outpat	Katowice
Poland	Specjalistyczny Osrodek Alergologiczno-Intern. ALL-MED	Krakow
Poland	Univ. Hospital in Krakow,Pulmonology Clinical Dept	Krakow
Poland	Barlicki University Hospital No. 1	Lodz
Poland	Barlicki University Hospital No. 1	Lodz
Taiwan	Chang Gung Memorial Hospital Keelung	Keelung
Taiwan	China Medical University Hospital	Taichung
United Kingdom	Celerion Inc	Belfast
United Kingdom	Bradford Royal Infirmary	Bradford
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	The Medicines Evaluation Unit	Manchester
United Kingdom	Wishaw General Hospital	Wishaw
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	VA WNY Healthcare System	Buffalo	New York
United States	IMMUNOe Research Centers	Centennial	Colorado
United States	American Health Research, Inc.	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	MedTrial, LLC	Columbia	South Carolina
United States	WCCT Global, LLC	Costa Mesa	California
United States	O and O Alpan, LLC	Fairfax	Virginia
United States	VitaLink Research	Greenville	South Carolina
United States	El Camino Hospital	Mountain View	California
United States	Coastal Carolina Health Care, P.A.	New Bern	North Carolina
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Temple University School of Medicine	Philadelphia	Pennsylvania
United States	Research Protocol Mgmt Spc	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Clinical Research Trials of Florida, Inc.	Tampa	Florida
United States	Respiratory and Sleep Disorders Specialists	The Woodlands	Texas
United States	Wake Forest School of Medicine	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Korea, Republic of,  Netherlands,  Poland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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