A study to compare the efficacy and safety of BCT197 when it is used together with current treatments for acute respiratory exacerbations of chronic obstructive pulmonary disease (COPD) that result in hospitalisation in adults

Phase 1

• Conditions: Acute exacerbations of chronic obstructive pulmonary disease; MedDRA version: 20.0Level: LLTClassification code 10010953Term: COPD exacerbationSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2015-004631-13-IT
• Lead Sponsor: MEREO BIOPHARMA GROUP LTD

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-02-22
• Last Update Posted: 26 February 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

1. Male and female adults aged = 40 years
2. Written informed consent obtained prior to any study-related procedure
3. Presence of an active exacerbation of the ongoing COPD requiring hospitalisation for treatment:
A sustained worsening of the patient’s condition (dyspnoea, cough and/or sputum production/purulence), from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication in a patient with underlying COPD that includes prescriptions of systemic corticosteroids and/or antibiotics and need for hospitalisation”
4. Subjects with a documented diagnosis of COPD category C or D (post-bronchodilator [BD] FEV1< 50%) at least 12 months prior to the Screening Visit (according to GOLD document updated 2015)
o At least one documented pulmonary function test (PFT) in the last 12 months (the most recent PFT performed in the last 12 months outside an exacerbation and results with curves should be recorded in the case report form (CRF) and filed as source document)
5. Current smokers or ex-smokers who stopped smoking at least 6 months prior to the Screening Visit, with a smoking history of at least 10 pack-years (pack-years = [number of cigarettes per day x number of years/20])
6. A post-BD FEV1 < 50% of the predicted normal value and a post-BD FEV1/forced vital capacity (FVC) < 0.7 at least 10 to 15 min after four puffs (4 x 100 µg) of salbutamol pressurised metered dose inhaler (pMDI)
7. Subjects will need to perform the post-BD spirometry at Baseline on presentation at Visit 1. Subjects who cannot perform the Baseline spirometry will be randomised into the study as long as their prior spirometry (the most recent PFT performed in the last 12 months outside an exacerbation) has a post-BD FEV1 <50% and a FEV1/FVC <0.7
8. A documented history of at least one moderate or severe COPD exacerbation in the 12 months preceding the Screening Visit that required antibiotics and/or systemic corticosteroid (addition or increment on subject current use) as defined below:
o A sustained worsening of the patient’s condition (dyspnoea, cough and/or sputum production/purulence), from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication in a patient with underlying COPD that includes prescriptions of systemic corticosteroids and/or antibiotics or need for hospitalisation”
o Also, documented visits to an emergency department due to COPD exacerbation are considered acceptable to fulfil this criterion.
9. Current regular treatment for COPD (categories C and D according to GOLD guidelines, updated 2015) for at least 2 months prior to the Screening Visit with either:
o Inhaled corticosteroids/long-acting ß2-agonist combination, long-acting muscarinic antagonist without regular use of short-acting muscarinic antagonist (short-acting muscarinic antagonist allowed if used as needed [PRN]) or
o Inhaled corticosteroids/long-acting ß2-agonist combination, without regular use of short-acting muscarinic antagonist (short-acting muscarinic antagonist allowed if used PRN) or
o Inhaled corticosteroids/long-acting muscarinic antagonist combination, without regular use of shortacting ß2-agonist (SABA) (short-acting ß2-agonist allowed if PRN) or
o Inhaled long-acting ß2-agonist and inhaled long-acting muscarinic antagonist or
o Subjects under monotherapy with long-acting muscarinic antagonist.
10. Ideally subjects should be screened, r

Exclusion Criteria

1. Current diagnosis of asthma, history of allergic rhinitis or atopic disease
2. Subjects who have already completed treatment for the current exacerbation of COPD.
3. Subjects who have been treated with or require use of the following medications (Refer to Table 10-1 in protocol).
4. Subjects currently requiring intensive care unit (ICU) and/or mechanical ventilation
5. Subjects treated with non-cardioselective ß-blockers in the 10 days preceding the Screening Visit. Those subjects may enter the study after non-selective ß-blockers withdrawal and/or cardioselective ß-blockers
intake for at least 10 days before Randomisation
6. Subjects treated with long-acting anti-histamines unless taken at stable regimen at least 2 months prior to Screening and to be maintained constant during the study, or if taken as PRN
7. Subjects requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
8. Known respiratory disorders other than COPD which may impact the efficacy of the study drug according to the investigator’s judgement. This can include but is not limited to a-1 antitrypsin deficiency, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial
lung disease
9. Subjects who have had pulmonary lobectomy or lung volume reduction surgery or lung transplantation
10. Subjects who have had a vaccination in the last 30 days prior to study start
11. Subjects who have a clinically significant cardiovascular condition (including, but not limited to, unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV, left ventricular failure, acute myocardial infarction); or the current exacerbation is due to a cardiovascular condition
12. An abnormal and clinically significant 12-lead ECG which may impact the safety of the subject according to the investigator’s judgement at Screening or Baseline
13. Subjects whose 12-lead ECG shows QTcF > 450 msec at Screening and at Randomisation visits; ECG does not need to be repeated if Screening and Randomisation visit are on the same day
14. Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anti-cholinergic agents
15. History of hypersensitivity to anti-cholinergics, ß2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the study which may raise contra-indications or impact the efficacy of the study drug according to the investigator’s clinical judgement
16. Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug according to the investigator’s clinical judgement
17. Subjects with liver enzyme alterations (serum alanine aminotransferase and/or aspartate aminotransferase > 2 x upper limit of normal [ULN], bilirubin > 1.5 ULN)
18. Impairment of renal function (defined as creatinine clearance (CrCL) < 60 mL/min (estimated by Cockcroft-Gault)
19. Concomitant use of the CYP3A inhibitors including, but not limited to macrolide antibiotics and of the calcium channel blockers verapamil and diltiazem; consumption of grapefruit will also be excluded

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of two different dosing regimens of BCT197 added to standard of care (SoC) versus placebo added to SoC in the treatment of acute respiratory exacerbations of COPD that required hospitalisation by comparison of change in forced expiratory volume in 1 second (FEV1) from Baseline (pre-dose) to Day 7.;Secondary Objective: - To evaluate the efficacy and tolerability of two different dosing regimens of BCT197 added to SoC versus placebo added to SoC in treatment of an acute exacerbation of COPD.<br><br>- Safety and tolerability of BCT197<br>- Please see protocol for exploratory objectives;Primary end point(s): Change in FEV1 from Baseline (pre-dose) at Day 7.;Timepoint(s) of evaluation of this end point: Please refer to protocol (Table 9-1 Schedule of Assessments).