A Proof-of-mechanism Study of Multiple, Oral Doses of Fevipiprant (QAW039) in COPD Patients With Eosinophilia

Clinical Trial ID: NCT03810183

Description

This is an exploratory, randomized, subject- and investigator-blind, placebo-controlled, parallel group, proof-of-mechanism study in approximately 50 COPD patients with eosinophilia.

The study consists of a screening period during which the subject's phenotype and eligibility for the study will be assessed. All subjects will undergo induction of their sputum to examine the baseline sputum cell counts. Subjects will be required to demonstrate both blood and sputum eosinophilia to be eligible for participation in the study. Eligible subjects will be randomized 3:2 to active (QAW039 orally daily) vs. placebo arms. Subjects will continue their standard of care COPD and other medications during the entire course of the study. Subjects will receive multiple doses of fevipiprant for six weeks, with safety, efficacy/pharmacodynamic and pharmacokinetic assessments performed. Sputum induction will be repeated at the end of the treatment period and at the end of the study.


Criteria

Inclusion Criteria: 1. Acceptable and reproducible spirometry with post-bronchodilator FEV1/FVC < 0.7 and post-bronchodilator FEV1≥ 30 and ≤ 80% of predicted at the screening and baseline visits (GOLD stage II or III COPD). 2. Patients with a physician-diagnosed history of COPD for at least 1 year prior to screening visit, and a documented history of at least one COPD exacerbation within the year prior to screening visit and on a stable therapy regimen for COPD for at least 4 weeks prior to screening visit with inhaled glucocorticoid + one or more long acting bronchodilator. 3. Current or ex-smokers who have a smoking history of at least 10 pack-years (10 pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years, or equivalent). 4. Circulating eosinophils ≥ 300 cells/µL blood AND sputum eosinophils ≥ 3% of total cell count during screening period. Exclusion Criteria: 1. Patients with a past or current medical history of asthma. 2. Patients with a past or current medical history of conditions other than COPD or allergic rhinitis that could result in elevated sputum eosinophils (e.g., asthma, hypereosinophilic syndrome, Churg-Strauss Syndrome). Patients with known parasitic infestation within 6 months prior to screening are also excluded. 3. Patients who have had a respiratory tract infection or COPD worsening or systemic steroid use within 4 weeks prior to screening visit or between screening and randomization visits. 4. Patients with history of concomitant chronic or severe pulmonary disease (e.g., sarcoidosis, interstitial lung disease, cystic fibrosis, tuberculosis). Exception: patients with concomitant mild or moderate pulmonary hypertension or bronchiectasis are permitted to participate. 5. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective contraception (also called basic contraception)methods during the study. 6. Patients on any statin therapy with a CK level > 2 X ULN at screening. 7. Patients who have a clinically significant laboratory abnormality at the screening visit including (but not limited to): - Total white blood cell count <2500 cells/uL - AST or ALT > 2.0 X ULN or total bilirubin > 1.3 X ULN - Estimated Glomerular Filtration Rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation or Bedside Schwartz equation <55 mL/minute/1.73 m2. 8. Patients with any of the following cardiac related concerns: - A resting QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female) at screening visit - A history of familial long QT syndrome or known family history of Torsades de Pointe - Receiving any medications or other agents known to prolong the QT interval - patients with a history of moderate or severe uncontrolled tachyarrhythmias - History of a clinically significant cardiovascular event within 1 year prior to the screening visit, such as acute myocardial infarction, congestive heart failure, unstable arrhythmia - Patients who, in the judgment of the investigator have a clinically significant ECG abnormality such as (but not limited to) sustained ventricular tachycardia, or clinically significant second or third degree AV block without a pacemaker

  • Start Date

    2019-05-21

  • Last Updated

    2019-10-17

  • Sponsor

    Novartis Pharmaceuticals

  • Condition Name

    COPD

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