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

Study Overview
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Brief Summary
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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).

Official Title
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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.

Conditions
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Asthma

Intervention / Treatment
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* Drug: placebo
* Drug: risankizumab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Pre-bronchodilator clinic measured forced expiratory volume (FEV1) of =40% and =85% of predicted normal. 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. Must be on at least medium dose inhaled corticosteroids and at least one other asthma controller medication for at least one year. Must have documented history of two or more severe asthma exacerbations in the last 12 months. Exclusion criteria: Patients with a significant disease other than asthma. Patients who are not able to produce sputum or sputum samples of sufficient quality. Patients who had clinically relevant history of intubation for asthma exacerbation in the past year. Patients diagnosed with any concurrent respiratory disease. Recent history (within 6 months) of myocardial infarction or hospitalized for cardiac failure in the past year. Patients who have undergone thoracotomy with pulmonary resection. Patients who have undergone bronchial thermoplasty or radiotherapy procedure in the past year or have planned procedures during the study. Patients taking oral corticosteroids with a total daily dose of more than 20 mg prednisone (or equivalent) in the past 6 weeks. Pregnant or nursing women. Women of childbearing potential that, if sexually active, is unwilling to use a highly effective method of birth control. Clinically relevant acute infections or chronic infections. Have received any live bacterial or live viral vaccination in the last12 weeks. Have received Bacille Calmette-Guerin (BCG) vaccination in the last 12 months. Have received treatment with ustekinumab (Stelara®). Have received treatment with any other biologics in the last 3 months or within 6 times the half-life of the compound.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Risankizumab<br>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<br>* Monoclonal IgG antibody<br>* Other names: BI 655066;|
| Placebo Comparator: Placebo<br>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<br>* Matching placebo for risankizumab<br>|

What is the study measuring?
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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 |