A proof-of-mechanism study of multiple, oral doses of fevipiprant (QAW039) in COPD patients with eosinophilia

Phase 1

Conditions: MedDRA version: 21.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Chronic obstructive pulmonary disease with eosinophilia
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2018-004267-32-ES

Lead Sponsor: ovartis Farmaceutica, S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 50

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: 6 weeks;Main Objective: The primary objective of this study is to assess the change from baseline in sputum eosinophil levels (% of total count) in COPD patients with eosinophilia after multiple oral doses of fevipiprant when compared to placebo.;Secondary Objective: To assess the safety and tolerability of fevipiprant in COPD patients with eosinophilia.;Primary end point(s): Change from baseline in sputum eosinophil % of total cell count in COPD patients with eosinophilia after multiple oral doses of fevipiprant when compared to placebo

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Physical examination, ECG intervals, vital signs, standard clinical laboratory evaluations (hematology, blood chemistry, and urinalysis), adverse events including COPD exacerbations.;Timepoint(s) of evaluation of this end point: 6 weeks

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