A phase IIa, randomized, double-blind, placebo controlled, parallel group study to assess the safety and efficacy of subcutaneously administered BI 655066 (risankizumab) as add-on therapy over 24 weeks in patients with severe persistent asthma.

Phase 2

Completed

Conditions: Severe asthma
10038716

Registration Number: NL-OMON45129

Lead Sponsor: Boehringer Ingelheim

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 3

Inclusion Criteria

1. Male or female patients aged at least 18 years but not more than 75 years.
2. Pre-bronchodilator clinic measured FEV1 of >=40% and <=85% of predicted normal at the screening visit.
3. A minimum of one year history of asthma diagnosed by a physician, and have FEV1 reversibility as defined by an improvement in FEV1 >=12% and an absolute change of at least 200 ml starting within 15 to 30 minutes after administration of 400 µg salbutamol (albuterol) via MDI. Reversibility testing is performed at the screening visit (visit 1B). If reversibility criteria are not met, the patient may still be randomized if there is:
- documented evidence of reversibility with improvement in FEV1 >=12% above baseline and an absolute increase of at least 200 ml in the 2 years prior to visit 2 (randomization visit) or
- documented evidence of airway hyperresponsiveness (methacholine: PC20 of <8 mg/ml) in the 2 years prior to visit 2 (randomization visit) or
- documented evidence of airflow variability in clinic FEV1 >=20% between two clinic visits documented in the 12 months prior to visit 2 (randomization visit)
If reversibility criteria are not met at visit 1B and if any of the above historic data are not available, reversibility testing can be repeated up to twice during screening period at seperate visits. For the first retest, 400 µg salbutamol via MDI should be used, and for the second retest, up to 800 µg salbutamol via MDI or 2.5 mg nebulized albuterol should be used. Reversibility testing must not occur on the day of randomization. Additional guidelines for reversibility testing can be found in Appendix 10.1.
4. Patients must be on at least medium dose inhaled corticosteroids and at least one other asthma controller medication for at least one year prior to the date of screening. Asthma therapy must have been documented and must be stable for at least 4 weeks prior to the date of screening.
5. Patients must have documented history of at least one of the following criteria:
a) two or more severe asthma exacerbations in the last 12 months, or
b) one severe asthma exacerbation in the last 12 months requiring hospitalization or emergency room visit, or
c) one severe asthma exacerbation in the last 6 months not requiring hospitalization or emergency room visit, prior to the date of screening visit (visit 1B). Patients must not have a severe asthma exacerbation in the 6 weeks prior to screening visit. Patients with only one severe asthma exacerbation in the last 6 months (category c, but not a or b) will be limited to approximately 25% of the total patient population.
6. Patients should be a non-smoker or ex-smoker who stopped smoking at least one year prior to screening. Ex-smokers must have a smoking history of less than 10-pack years.

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.
16. History of allergy or hypersensitivity to biologic agents or its excipients, or hypersensitivity to beta-adrenergic medications.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Time to first asthma worsening during the planned 24 week treatment period.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. Annualized rate of asthma worsening during the planned 24-week treatment<br /><br>period<br /><br>2. Annualized rate of severe asthma exacerbation during the planned 24-week<br /><br>treatment period<br /><br>3. Weekly ACQ5 score at week 24<br /><br>4. Trough FEV1 in-clinic change from baseline at week 24<br /><br>5. Post-bronchodilator FEV1 in-clinic change from baseline at week 24<br /><br>6. Time to first severe asthma exacerbation during the planned 24-week<br /><br>treatment period<br /><br>7. Time to first asthma worsening during the planned 24-week treatment period</p><br>