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; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]; MedDRA version: 19.0Level: LLTClassification code 10010953Term: COPD exacerbationSystem Organ Class: 100000004855

• Registration Number: EUCTR2015-004631-13-DE
• Lead Sponsor: Mereo BioPharma 1 Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-15
• Last Update Posted: 29 January 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 diagnosis of COPD with spirometry performed outside an exacerbation within the last 12 months prior to the Screeening Visit.
5. Current smokers or ex-smokers with a smoking history of at least 10 pack-years (pack-years = [number of cigarettes per day x number of years/20])
6. A FEV1 < 65% of the predicted normal value
7. 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.
8. 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.
9. Ideally subjects should be screened, randomised and dosed on the same day. Where information is not available, the Screening period can be extended to a maximum of 24 hours before Randomisation and dosing.
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 108
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 162

Exclusion Criteria

1. Current diagnosis of asthma
2. Subjects who have already completed treatment for the current exacerbation of COPD.
3. Subjects who have been treated with or require the following medications:
o Systemic steroids for longer than 3days for COPD exacerbation in the 4weeks prior to the current exacerbation
o Antibiotics for COPD exacerbation for longer than 7days in the 4weeks prior to the current exacerbation
o Phosphodiesterase type 3/4 inhibitors
o Any p38 mitogen-activated protein kinase inhibitor treatment
o Antibiotics for lower respiratory tract infection in the 4weeks prior to the current exacerbation (except for treatment of the current exacerbation, but no longer than 2days)
4. Subjects currently requiring intensive care unit and/or mechanical ventilation
5. Subjects treated with non-cardioselective ß-blockers in the 10days preceding Screening Visit. Those subjects may enter the study after non-selective ß-blockers withdrawal and/or cardioselective ß-blockers intake for at least 10days before Randomisation
6. Subjects treated with long-acting anti-histamines unless taken at stable regimen at least 2months prior to Screening and to be maintained constant during the study, or if taken as PRN
7. Known respiratory disorders other than COPD which may impact the efficacy of 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
8. Subjects who have had pulmonary lobectomy or lung volume reduction surgery or lung transplantation
9. Subjects who have had a live vaccination in the 30 days prior to study start
10. Subjects who have a clinically significant cardiovascular condition (including, but not limited to, unstable ischemic heart disease, NYHA Class III/IV, left ventricular failure, acute myocardial infarction); or the current exacerbation is due to a cardiovascular condition
11. An abnormal and clinically significant 12-lead ECG which may impact safety of the subject according to the investigator’s judgement at Screening or Baseline
12. 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
13. Current diagnosis of pneumonia, pulmonary embolus or pneumothorax
14. History of hypersensitivity to anto-cholinergics, ß2-agonist, corticosteroids or any excipients contained in 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
15. 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
16. Subjects with liver enzyme alterations (serum alanine aminotransferase and/or aspartate aminotransferase >2x upper limit of normal [ULN], bilirubin >1.5 ULN)
17. Impairment of renal function (defined as creatinine clearance <60mL/min (estimated by Cockcroft-Gault)
18. Concomitant / recent use of CYP3A inhibitors or P-gp inhibitors including, but not limited to macrolide antibiotics troleandomycin, erythromycin, clarithromycin, roxithromycin and chloramphenicol (with the exception of azithromycin, which is not prohibited), and of the calcium chan

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: Please refer to protocol (Table 9-1 Schedule of Assessments).;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.;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.