A Proof-of-mechanism Study of Multiple, Oral Doses of Fevipiprant (QAW039) in COPD Patients With Eosinophilia
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Eosinophilia
Intervention: QAW039; Placebo
Intervention description: QAW039 (fevipiprant) 450 mg once daily for 6 weeks administered orally as a tablet + Standard of Care; Placebo once daily for 6 weeks administered orally as a tablet + Standard of Care
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: This was a subject and investigator-blinded study. Subjects, investigators and all site staff remained blinded to study treatment throughout the study.
The identity of the treatments was concealed by the use of study drugs that were all identical in packaging, labeling, schedule of administration, appearance, and odor.
The sponsor could be unblinded to the study treatment at any time, especially in case of a safety concern.
Enrollment: 9.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: QAW039; Chronic obstructive pulmonary disease; COPD; sputum; eosinophillic; eosinophilia; prostaglandin D2 receptor; DP2; CRTh2; fevipiprant

Summary:

      This was an exploratory, randomized, subject- and investigator-blind, placebo-controlled,
      parallel group, proof-of-mechanism study of multiple oral doses of fevipiprant (QAW039) in
      chronic obstructive pulmonary disease (COPD) patients with eosinophilia.
    

Eligibility 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