A Study to Evaluate the Efficacy and Safety Study of Povorcitinib in Participants With Inadequately Controlled Moderate to Severe Asthma

Study Overview
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Brief Summary
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The study is being conducted to evaluate the effect of 3 dosing regimens of povorcitinib on pulmonary function

Official Title
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A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging, Efficacy and Safety Study of Povorcitinib in Participants With Inadequately Controlled Moderate to Severe Asthma

Conditions
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Moderate to Severe Asthma

Intervention / Treatment
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* Drug: povorcitinib
* Other: placebo
* Drug: ICS-LABA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physician-diagnosed asthma requiring treatment with medium- to high-dose ICS-LABA for at least 12 months prior to screening. Pre-BD FEV1 < 80% predicted according to central over read value at Visit 2. Documented historical post-BD reversibility of FEV1 ≥ 12% and ≥ 200 mL in FEV1 within 12 months prior to screening OR Post-BD reversibility of FEV1 ≥ 12% and ≥ 200 mL in FEV1 according to central over read value at Visit 2. At least 2 documented asthma exacerbations (requiring treatment with systemic CS, hospitalization, or emergency department visit) within 12 months prior to screening but not within the past 4 weeks prior to screening ACQ-6 ≥ 1.5 at screening. Exclusion Criteria: Maintenance use of asthma controllers other than ICS-LABA. Have undergone bronchial thermoplasty. Current smokers or participants with a smoking history of ≥ 10 pack-years and participants using vaping products, including electronic cigarettes. Women who are pregnant (or who are considering pregnancy) or breastfeeding. Current conditions or history of other diseases, as follows: Clinically important pulmonary disease other than asthma ,Thrombocytopenia, coagulopathy, or platelet dysfunction. Venous and arterial thrombosis, deep vein thrombosis, pulmonary embolism, moderate to severe heart failure (NYHA Class III or IV), cerebrovascular accident, myocardial infarction, coronary stenting, or CABG surgery. Diagnosis of other significant cardiovascular diseases, including but not limited to angina, peripheral arterial disease, or uncontrolled arrhythmias such as atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, and forms of carditis. Recipient of an organ transplant that requires continued immunosuppression. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich syndrome). Any malignancies or history of malignancies. Note: Participants with cured nonmetastatic basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive malignancy or cancers from which the participant has been disease-free for > 1 year after treatment with curative intent are eligible. Chronic or recurrent infectious disease. Receipt of any biologic drugs used for asthma < 12 weeks or 5 half-lives (if known), whichever is longer, prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Placebo Comparator: Inhaled Corticoseroid Long Acting Beta-Agonist(ICS-LABA) + placebo<br>Participants will receive stable background therapy with ICS-LABA in combination with placebo once daily (QD) for 24 weeks during the placebo-controlled period. Participants will be allocated to 1 of 3 doses of povorcitinib during the extension period of 28 weeks | Other: placebo<br>* placebo<br>Drug: ICS-LABA<br>* Background Therapy<br>|
| Experimental: ICS-LABA + povorcitinib Dose 1<br>Participants will receive stable background therapy with ICS-LABA in combination with povorcitinib dose 1 once daily (QD) for 24 weeks during the placebo-controlled period, and Participants will continue to take the same dose of povorcitinib during the extension period of 28 weeks | Drug: povorcitinib<br>* povorcitinib<br>* Other names: INCB54707;Drug: ICS-LABA<br>* Background Therapy<br>|
| Experimental: ICS-LABA + povorcitinib Dose 2<br>Participants will receive stable background therapy with ICS-LABA in combination with povorcitinib dose 2 once daily (QD) for 24 weeks during the placebo-controlled period, and Participants will continue to take the same dose of povorcitinib during the extension period of 28 weeks | Drug: povorcitinib<br>* povorcitinib<br>* Other names: INCB54707;Drug: ICS-LABA<br>* Background Therapy<br>|
| Experimental: ICS-LABA + povorcitinib Dose 3<br>Participants will receive stable background therapy with ICS-LABA in combination with povorcitinib dose 3 once daily (QD) for 24 weeks during the placebo-controlled period, and Participants will continue to take the same dose of povorcitinib during the extension period of 28 weeks | Drug: povorcitinib<br>* povorcitinib<br>* Other names: INCB54707;Drug: ICS-LABA<br>* Background Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in pre-bronchodilator forced expiratory volume in the first 1 second (pre-BD FEV1) | To assess the effect of povorcitinib on lung function (pre-BD FEV1) between baseline and week 24 | Baseline ; Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of asthma exacerbations during the Placebo Controlled (PC) period | Defined as a worsening of asthma | Up to 28 weeks | 
| Absolute change from baseline in pre-BD FEV1 at each visit |  | Up to 14 months | 
| Percent change from baseline in pre-BD FEV1 at each visit |  | Up to 14 months | 
| Absolute change from baseline in post-BD FEV1 at week 24 |  | Baseline; Week 24 | 
| Percent change from baseline in post-BD FEV1 at week 24 |  | Baseline; Week 24 | 
| Absolute change from baseline in pre-BD FVC at each visit |  | Up to 14 months | 
| Percent change from baseline in pre-BD FVC at each visit |  | Up to 14 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Moderate to Severe, INCB54707, Povorcitinib, ICS-LABA