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

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02443298
• Collaborator: Boehringer Ingelheim (Industry)
• Enrollment: 214
• Locations: 65
• Arms: 2
• Actual Duration (Months): 31.4
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: placebo; Drug: risankizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 214 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: Jun 23, 2015
• Actual Primary Completion Date: Oct 13, 2017
• Actual Study Completion Date: Feb 2, 2018

Arms and Interventions

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: ABBV-066 BI 655066
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

Outcome Measures

Primary Outcome Measures

1. Time to First Asthma Worsening During the Planned 24 Week Treatment Period [24 weeks]

   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.

Secondary Outcome Measures

1. Time to First Asthma Worsening During the Planned 24 Week Treatment Period According to Alternative Definition [24 weeks]

   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.

2. Annualized Rate of Asthma Worsening During the Planned 24 Week Treatment Period [24 weeks]

   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.

3. Time to First Severe Asthma Exacerbation During the Planned 24 Week Treatment Period [24 weeks]

   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.

4. Annualized Rate of Severe Asthma Exacerbation During the Planned 24-week Treatment Period [24 weeks]

   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.

5. Trough Forced Expiratory Volume in 1 Second (FEV1) In-clinic Change From Baseline at Week 24 [Baseline and 24 weeks]

   Trough forced expiratory volume in 1 second (FEV1) in-clinic change from baseline at week 24.

6. Post-bronchodilator 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.

7. Weekly Asthma Control Questionaire Score at Week 24 [24 weeks]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• AbbVie
• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Study Protocol - Aug 17, 2017
• Statistical Analysis Plan - Oct 26, 2017

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02443298
• Other Study ID Numbers: 1311.14; 2014-004932-20
• First Posted: May 13, 2015
• Last Update Posted: Apr 10, 2019
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Recruitment Details	This was a randomized, double-blind, placebo-controlled, parallel-group multicenter study to assess the efficacy and safety of risankizumab, an IL-23p19 monoclonal antibody, compared to placebo in patients with severe persistent asthma.
Pre-assignment Detail	All patients were screened for eligibility to participate in the trial. Patients attended a specialist sites which ensured that they (the patients) met all strictly implemented inclusion/exclusion criteria. Patients were not to be randomized to trial treatment if any one of the specific entry criteria was violated.

Arm/Group Title	Risankizumab	Placebo
Arm/Group Description	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)	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)
Period Title: Overall Study
STARTED	105	109
COMPLETED	101	104
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Risankizumab	Placebo	Total
Arm/Group Description	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)	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)	Total of all reporting groups
Overall Participants	105	109	214
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.1 (11.3)	52.3 (12.5)	53.2 (11.9)
Sex: Female, Male (Count of Participants)
Female	69 65.7%	64 58.7%	133 62.1%
Male	36 34.3%	45 41.3%	81 37.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 2.9%	3 2.8%	6 2.8%
Not Hispanic or Latino	102 97.1%	106 97.2%	208 97.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.9%	1 0.5%
Asian	11 10.5%	11 10.1%	22 10.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	9 8.6%	8 7.3%	17 7.9%
White	84 80%	88 80.7%	172 80.4%
More than one race	1 1%	1 0.9%	2 0.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Oral corticosteroid (OCS) use at baseline (Count of Participants)
Yes	15 14.3%	17 15.6%	32 15%
No	90 85.7%	92 84.4%	182 85%
Baseline Morning peak expiratory flow (PEF) (Liter/Minute (L/min)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liter/Minute (L/min)]	299.34 (110.50)	309.56 (115.34)	304.54 (112.84)
Baseline 24 Hour Rescue Medication Use (Puff) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Puff]	3.17 (3.81)	3.89 (4.78)	3.53 (4.34)
Baseline First 5 questions of the Asthma Control Questionnaire (ACQ5) Score (Unit on scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Unit on scale]	2.15 (1.15)	2.39 (1.17)	2.27 (1.17)

Outcome Measures

1. Primary Outcome

Title	Time to First Asthma Worsening During the Planned 24 Week Treatment Period
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment.

Arm/Group Title	Risankizumab	Placebo
Arm/Group Description	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)	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)
Measure Participants	105	109
Median (80% Confidence Interval) [Days]	40.00	85.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risankizumab, Placebo
	Comments	This was analyzed by using a Cox proportional hazards model that included treatment and the stratification factor of OCS use at baseline as fixed effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0255
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 80%; 1.18 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison of Risankizumab to Placebo

2. Secondary Outcome

Title	Time to First Asthma Worsening During the Planned 24 Week Treatment Period According to Alternative Definition
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment.

Arm/Group Title	Risankizumab	Placebo
Arm/Group Description	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)	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)
Measure Participants	105	109
Median (80% Confidence Interval) [Days]	20.00	37.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risankizumab, Placebo
	Comments	This was analyzed by using a Cox proportional hazards model that included treatment and the stratification factor of OCS use at baseline as fixed effects.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0131
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.47
	Confidence Interval	(2-Sided) 80%; 1.20 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison of Risankizumab to Placebo

3. Secondary Outcome

Title	Annualized Rate of Asthma Worsening During the Planned 24 Week Treatment Period
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment.

Arm/Group Title	Risankizumab	Placebo
Arm/Group Description	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)	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)
Measure Participants	105	109
Mean (Standard Error) [Events per patient year]	4.8412 (0.577)	3.2410 (0.401)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risankizumab, Placebo
	Comments	Annualized rate is obtained from fitting a negative binomial regression including logarithm of the exposure as an offset, treatment, and OCS use at baseline as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0065
	Comments
	Method	Negative binomial regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.4937
	Confidence Interval	(2-Sided) 80%; 1.2366 to 1.8044
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.220
	Estimation Comments	Comparison of Risankizumab to Placebo

4. Secondary Outcome

Title	Time to First Severe Asthma Exacerbation During the Planned 24 Week Treatment Period
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment. NA = not estimable due to an insufficient numbers of patient with an event

Arm/Group Title	Risankizumab	Placebo
Arm/Group Description	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)	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)
Measure Participants	105	109
Median (80% Confidence Interval) [Days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risankizumab, Placebo
	Comments	Time to first event is obtained from fitting a Cox proportional-hazards model including treatment, and OCS use at baseline as covariate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4619
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 80%; 0.88 to 1.57
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison of Risankizumab to Placebo

5. Secondary Outcome

Title	Annualized Rate of Severe Asthma Exacerbation During the Planned 24-week Treatment Period
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment.

Arm/Group Title	Risankizumab	Placebo
Arm/Group Description	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)	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)
Measure Participants	105	109
Mean (Standard Error) [Events per patient year]	1.5901 (0.257)	1.4051 (0.228)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risankizumab, Placebo
	Comments	Annualized rate is obtained from fitting a negative binomial regression including logarithm of the exposure as an offset, treatment, and OCS use at baseline as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5550
	Comments
	Method	Negative binomial regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.1317
	Confidence Interval	(2-Sided) 80%; 0.8652 to 1.4803
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.237
	Estimation Comments	Comparison of Risankizumab to Placebo

6. Secondary Outcome

Title	Trough Forced Expiratory Volume in 1 Second (FEV1) In-clinic Change From Baseline at Week 24
Description	Trough forced expiratory volume in 1 second (FEV1) in-clinic change from baseline at week 24.
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment. One patient not included in the analysis due to missing baseline value. Number of patients with either baseline or on-treatment data at the respective week and does not require having both.

Arm/Group Title	Risankizumab	Placebo
Arm/Group Description	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)	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)
Measure Participants	105	109
Least Squares Mean (Standard Error) [Liter (L)]	-0.052 (0.036)	-0.013 (0.035)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risankizumab, Placebo
	Comments	The adjusted mean (SE) are obtained from fitting a mixed effect repeated measures (MMRM) model including treatment, OCS use at baseline, test day, treatment-by-test day interaction, baseline, and baseline-by-test day interaction as covariates patient as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4423
	Comments
	Method	Mixed Models Analysis
	Comments	Unstructured covariance structure for within-patient variation
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.039
	Confidence Interval	(2-Sided) 80%; -0.104 to 0.026
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.051
	Estimation Comments	Comparison of Risankizumab to Placebo

7. Secondary Outcome

Title	Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) In-clinic Change From Baseline at Week 24
Description	Post-bronchodilator forced expiratory volume in 1 second (FEV1) in-clinic change from baseline at week 24.
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

FAS: All randomized patients who received at least one dose of treatment. One patient not included in the analysis due to missing baseline value and one patient not included in the analysis due to missing on-treatment data. Number of patients with either baseline or on-treatment data at the respective week and does not require having both.

Arm/Group Title	Risankizumab	Placebo
Arm/Group Description	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)	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)
Measure Participants	105	109
Least Squares Mean (Standard Error) [Liter (L)]	-0.097 (0.032)	-0.030 (0.032)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risankizumab, Placebo
	Comments	The adjusted mean (SE) are obtained from fitting a mixed effect repeated measures (MMRM) model including treatment, OCS use at baseline, test day, treatment-by-test day interaction, baseline, and baseline-by-test day interaction as covariates patient as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1377
	Comments
	Method	Mixed Models Analysis
	Comments	Unstructured covariance structure for within-patient variation
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.068
	Confidence Interval	(2-Sided) 80%; -0.126 to -0.009
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.045
	Estimation Comments	Comparison of Risankizumab to Placebo

8. Secondary Outcome

Title	Weekly Asthma Control Questionaire Score at Week 24
Description	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).
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment. Ten patients excluded from the analysis due to missing data at week 24.

Arm/Group Title	Risankizumab	Placebo
Arm/Group Description	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)	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)
Measure Participants	105	109
Least Squares Mean (Standard Error) [Unit on Scale]	1.857 (0.099)	1.708 (0.099)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risankizumab, Placebo
	Comments	The adjusted mean (SE) are obtained from fitting an analysis of covariance (ANCOVA) model separately for each week including treatment, OCS use at baseline, and baseline as covariates. The weekly averages of daily measurements are calculated before fitting the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1985
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.149
	Confidence Interval	(2-Sided) 80%; 0.000 to 0.297
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.115
	Estimation Comments	Comparison of Risankizumab to Placebo

Adverse Events

Time Frame	From the administration of first dose of study medication until 16 weeks after last dose of study medication, up to 40 weeks.
Arm/Group Title	Risankizumab		Placebo
Arm/Group Description	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)		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)
All Cause Mortality
	Risankizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/105 (0%)		0/109 (0%)
Serious Adverse Events
	Risankizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/105 (13.3%)		21/109 (19.3%)
Ear and labyrinth disorders
Sudden hearing loss	1/105 (1%)		0/109 (0%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/105 (0%)		1/109 (0.9%)
Immune system disorders
Anaphylactic reaction	0/105 (0%)		1/109 (0.9%)
Infections and infestations
Appendicitis	0/105 (0%)		1/109 (0.9%)
Arthritis bacterial	0/105 (0%)		1/109 (0.9%)
Chronic sinusitis	0/105 (0%)		1/109 (0.9%)
Epstein-Barr virus infection	1/105 (1%)		0/109 (0%)
Localised infection	0/105 (0%)		1/109 (0.9%)
Pneumonia	1/105 (1%)		2/109 (1.8%)
Respiratory syncytial virus infection	1/105 (1%)		0/109 (0%)
Urosepsis	0/105 (0%)		1/109 (0.9%)
Injury, poisoning and procedural complications
Ankle fracture	0/105 (0%)		1/109 (0.9%)
Radius fracture	0/105 (0%)		1/109 (0.9%)
Investigations
Electrocardiogram T wave abnormal	0/105 (0%)		1/109 (0.9%)
Metabolism and nutrition disorders
Hypoglycaemia	0/105 (0%)		1/109 (0.9%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/105 (1%)		1/109 (0.9%)
Lumbar spinal stenosis	0/105 (0%)		1/109 (0.9%)
Rhabdomyolysis	0/105 (0%)		1/109 (0.9%)
Rotator cuff syndrome	1/105 (1%)		0/109 (0%)
Nervous system disorders
Dyskinesia	0/105 (0%)		1/109 (0.9%)
Multiple sclerosis	1/105 (1%)		0/109 (0%)
Transient ischaemic attack	0/105 (0%)		1/109 (0.9%)
Psychiatric disorders
Anxiety	1/105 (1%)		0/109 (0%)
Depression	0/105 (0%)		1/109 (0.9%)
Renal and urinary disorders
Hydronephrosis	0/105 (0%)		1/109 (0.9%)
Nephrolithiasis	0/105 (0%)		1/109 (0.9%)
Respiratory, thoracic and mediastinal disorders
Asthma	6/105 (5.7%)		5/109 (4.6%)
Asthmatic crisis	1/105 (1%)		1/109 (0.9%)
Dyspnoea	1/105 (1%)		0/109 (0%)
Nasal polyps	0/105 (0%)		1/109 (0.9%)
Other (Not Including Serious) Adverse Events
	Risankizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/105 (80%)		80/109 (73.4%)
Infections and infestations
Bronchitis	11/105 (10.5%)		9/109 (8.3%)
Nasopharyngitis	11/105 (10.5%)		22/109 (20.2%)
Sinusitis	6/105 (5.7%)		3/109 (2.8%)
Upper respiratory tract infection	9/105 (8.6%)		10/109 (9.2%)
Urinary tract infection	5/105 (4.8%)		6/109 (5.5%)
Investigations
Blood creatine phosphokinase increased	9/105 (8.6%)		3/109 (2.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/105 (0%)		6/109 (5.5%)
Nervous system disorders
Headache	7/105 (6.7%)		6/109 (5.5%)
Respiratory, thoracic and mediastinal disorders
Asthma	65/105 (61.9%)		58/109 (53.2%)
Dyspnoea	6/105 (5.7%)		7/109 (6.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.