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

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-20
• Last Update Posted: 18 June 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 Screening 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:
• Inhaled corticosteroids/long-acting ß2-agonist combination, longacting
muscarinic antagonist without regular use of any short-acting
bronchodilator (any short-acting bronchodilator allowed if used as
needed [PRN]) or
• Inhaled corticosteroids/long-acting ß2-agonist combination, without
regular use of any short-acting bronchodilator (any short-acting
bronchodilator allowed if used PRN) or
• Inhaled corticosteroids/long-acting muscarinic antagonist
combination, without regular use of any short-acting bronchodilator (any
short-acting bronchodilator allowed if PRN) or
• Inhaled long-acting ß2-agonist and inhaled long-acting muscarinic
antagonist (with any PRN short acting bronchodilator) or
• Subjects under monotherapy with long-acting muscarinic antagonist
(with any PRN short acting bronchodilator).
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 current
exacerbation of COPD
3. Subjects who have been treated with or require the following
medications:
• Systemic steroids for longer than 3days for COPD exacerbation in the
4weeks prior to the current exacerbation
• Antibiotics for COPD exacerbation for longer than 7days in the 4weeks
prior to the current exacerbation
• Phosphodiesterase type 3/4 inhibitors
• Any p38 mitogen-activated protein kinase inhibitor treatment
• Antibiotics for lower respiratory tract infection in the 4weeks prior to
the current exacerbation (except for treatment of the current
exacerbation, but not 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 nonselective
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
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 last 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
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 anti-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 > 2 x upper limit
of normal [ULN], bilirubin > 1.5 ULN)
17. Impairment of renal function (defined as creatinine clearance < 60
mL/min (estimated by Cockcroft-Gault)
18. Concomitant/recent use of the 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 channel blockers verapamil

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).