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Clinical Trial Results:
A Randomised Controlled Trial of Mepolizumab Initiated During Admission to Hospital for a Severe Exacerbation of Eosinophilic COPD

Summary
EudraCT number	2018-003924-35
Trial protocol	GB
Global end of trial date	14 Mar 2025

Results information
Results version number	v1(current)
This version publication date	30 Jan 2026
First version publication date	30 Jan 2026
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

0690

ISRCTN number

US NCT number

NCT04075331

WHO universal trial number (UTN)

Other trial identifiers

IRAS Number: 255237, REC Reference Number: 19/EE/0286

Sponsor organisation name

University of Leicester

Sponsor organisation address

Research Governance Office, Research & Enterprise Office, University of Leicester, Leicester, United Kingdom,

Public contact

COPD-HELP Trial Manager, Leicester Clinical trials Unit, University of Leicester, 0044 01162297247, mepo@leicester.ac.uk

Scientific contact

Prof Christopher Brightling, Chief Investigator, Department of Respiratory Sciences, University of Leicester, 0044 0116 250 2704, ceb17@leicester.ac.uk

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

09 Aug 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

21 Jun 2024

Global end of trial reached?

Yes

Global end of trial date

14 Mar 2025

Was the trial ended prematurely?

Main objective of the trial

The primary objective: To evaluate the efficacy of mepolizumab initiated during hospitalisation on future hospital readmission or death (all cause) compared with placebo in severe exacerbations of eosinophilic COPD. The secondary objective: To assess the effects of mepolizumab on health status, well-being, exercise capacity, frailty, moderate exacerbations, healthcare usage, and death, compared with placebo in patients admitted to hospital with an eosinophilic exacerbation of COPD.

Protection of trial subjects

Eligibility criteria for this trial were carefully considered to ensure the safety of the participants. Patients with respiratory conditions including active lung cancer, interstitial lung disease, primary pulmonary hypertension or any other conditions that in the view of the investigator will affect the trial were excluded from the trial. Cardiac safety was evaluated with monitoring of clinical assessments and investigations (heart rate, blood pressure, temperature), the collection of relevant AEs, and other assessments described in the protocol. Serious Adverse Events (SAEs), Suspected Unexpected Serious Adverse Reaction (SUSARs) and deaths were subject to expedited reporting by the site to the Sponsor. Leicester CTU and the Sponsor provided safety updates to the Data Safety Monitoring Committee (DSMC) and Trial Steering Committee (TSC), who reviewed the trial data periodically, and GlaxoSmithKline (funder and supplier of the trial drug and placebo).

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Sep 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 238

Worldwide total number of subjects

238

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

160

85 years and over

Subject disposition

Top of page

Recruitment details

Trial participants were recruited from inpatient admissions to the Clinical Decisions Unit (CDU) at Glenfield Hospital, University Hospitals of Leicester NHS Trust.

Screening details

Potential participants were screened against eligibility criteria. Pseudonymised data were recorded in the screening log. Eligible participants provided informed consent and were randomised. Ineligible or non-consenting participants were recorded as screen failures with reasons.

Period 1 title

Baseline

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Participants, investigators, and all involved in trial conduct, sample analysis, or with any other interest in this trial remained blind to the randomised treatment assignments until after final analysis is complete. Unblinded personnel included the trial statistician, the pharmacy team, trial personnel from the Respiratory BRC responsible for reconstituting the IMP/placebo, where applicable, and dosing the participants, and the DMC in order to periodically review trial data.

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Dosing was undertaken every four weeks (+/- 7 days) over 48 weeks (12 doses in total), each consisting of 100mg of mepolizumab administered subcutaneously or for those dosed from 01 March 2024 to June 2024, solution for injection in pre-filled syringe administered.

Number of subjects in period 1	Placebo	Mepolizumab
Started	119	119
Completed	119	119

Period 2 title

Week 4

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 2	Placebo	Mepolizumab
Started	119	119
Completed	114	113
Not completed	5	6
Death	-	1
Lost to follow-up	5	5

Period 3 title

Week 8

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 3	Placebo	Mepolizumab
Started	114	113
Completed	110	109
Not completed	4	4
Death	2	1
Lost to follow-up	2	3

Period 4 title

Week 12

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

The Investigational Medicinal Product (IMP) for this trial was mepolizumab 100mg powder for solution for injection, or for those dosed from 01 March 2024 to June 2024, solution for injection in pre-filled syringe. Dosing was undertaken every four weeks (+/- 7 days) over 48 weeks (12 doses in total), each consisting of 100mg of mepolizumab administered subcutaneously.

Number of subjects in period 4	Placebo	Mepolizumab
Started	110	109
Completed	109	106
Not completed	1	3
Death	-	2
Lost to follow-up	1	1

Period 5 title

Week 16

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 5	Placebo	Mepolizumab
Started	109	106
Completed	106	103
Not completed	3	3
Death	3	2
Lost to follow-up	-	1

Period 6 title

Week 20

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 6	Placebo	Mepolizumab
Started	106	103
Completed	105	102
Not completed	1	1
Lost to follow-up	1	1

Period 7 title

Week 24

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 7	Placebo	Mepolizumab
Started	105	102
Completed	103	98
Not completed	2	4
Consent withdrawn by subject	1	-
Death	1	1
Lost to follow-up	-	3

Period 8 title

Week 28

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 8	Placebo	Mepolizumab
Started	103	98
Completed	101	97
Not completed	2	1
Lost to follow-up	2	1

Period 9 title

Week 32

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 9	Placebo	Mepolizumab
Started	101	97
Completed	100	94
Not completed	1	3
Death	1	1
Lost to follow-up	-	2

Period 10 title

Week 36

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 10	Placebo	Mepolizumab
Started	100	94
Completed	97	92
Not completed	3	2
Death	1	1
Lost to follow-up	2	1

Period 11 title

Week 40

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 11	Placebo	Mepolizumab
Started	97	92
Completed	95	91
Not completed	2	1
Lost to follow-up	2	1

Period 12 title

Week 44

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 12	Placebo	Mepolizumab
Started	95	91
Completed	92	91
Not completed	3	0
Death	1	-
Lost to follow-up	2	-

Period 13 title

Week 48

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants randomised to a matched placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Sterile saline solution was used for the placebo for those dosed before 01 March 2024; from 01 March 2024, a matched placebo in a pre-filled syringe was used.

Mepolizumab

Arm description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 13	Placebo	Mepolizumab
Started	92	91
Completed	88	87
Not completed	4	4
Death	2	-
Lost to follow-up	2	4

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group values	Placebo	Mepolizumab	Total
Number of subjects	119	119	238
Age categorical
Units: Subjects
Adults (18-64 years)	38	33	71
From 65-84 years	78	82	160
85 years and over	3	4	7
Gender categorical
Units: Subjects
Female	60	61	121
Male	59	58	117
eMRC score
eMRC Dyspnea Scale scores category
Units: Subjects
≤3	39	39	78
>3	80	80	160
Past hospitalisation in previous 12 months
Units: Subjects
No hospitalisation	39	40	79
≥1 hospitalised	80	79	159
Ethnicity
Units: Subjects
White	117	119	236
Asian or Asian British	2	0	2
Smoking status
Units: Subjects
Current Smoker	28	24	52
Ex-Smoker	91	95	186
eMRC dyspnoea current score
Units: Subjects
Grade 2	12	8	20
Grade 3	27	31	58
Grade 4	55	50	105
Grade 5A	19	23	42
Grade 5B	6	6	12
Missing	0	1	1
eMRC dyspnoea baseline score (stable state)
Units: Subjects
Grade 2	12	8	20
Grade 3	27	31	58
Grade 4	55	50	105
Grade 5A	19	23	42
Grade 5B	6	6	12
Missing	0	1	1
WHO Highest level of intervention during baseline admission
Units: Subjects
No oxygen therapy	51	47	98
Oxygen by mask or nasal prongs	57	62	119
Oxygen by NIV or high flow	11	10	21
Background inhaled medication
Units: Subjects
Triple therapy	110	113	223
LABA+ICS	9	6	15
Cardiovascular disease
Defined as the presence of any of atrial fibrillation, previous myocardial infarction, ischemic heart disease, heart failure, or valvular heart disease.
Units: Subjects
Yes	37	48	85
No	82	71	153
Diabetes
Units: Subjects
Yes	33	28	61
No	86	91	177
Anxiety or depression
Units: Subjects
Yes	49	41	90
No	70	78	148
Gastroesophageal reflux disease
Units: Subjects
Yes	33	39	72
No	86	80	166
BMI
Units: kg/m2
arithmetic mean (standard deviation)	27.7 ( 7.6 )	27.4 ( 7.2 )	-
Number of cigarettes per day
Units: Cigarettes
arithmetic mean (standard deviation)	21.4 ( 10.0 )	21.0 ( 9.5 )	-
Number of years smoked
Units: Years
arithmetic mean (standard deviation)	41.6 ( 11.5 )	40.5 ( 13.0 )	-
Number of emergency admissions
Number of emergency admissions (all cause) in previous 12 months
Units: Admissions
median (inter-quartile range (Q1-Q3))	1.0 (0.0 to 3.0)	1.0 (0.0 to 3.0)	-
Number of courses of steroids without antibiotics
Number of courses of steroids without antibiotics for your chest (COPD exacerbations) in previous 12 months
Units: Courses
arithmetic mean (standard deviation)	1.0 ( 2.1 )	0.8 ( 2.3 )	-
Number of courses of antibiotics without steroids
Number of courses of antibiotics without steroids for your chest (COPD exacerbations) in previous 12 months
Units: Courses
arithmetic mean (standard deviation)	1.1 ( 1.9 )	0.8 ( 1.7 )	-
Number of courses of both antibiotics and steroids
Number of courses of both antibiotics and steroids for your chest (COPD exacerbations) in previous 12 months
Units: Courses
arithmetic mean (standard deviation)	3.8 ( 2.9 )	3.3 ( 2.7 )	-
Number of courses of either glucocorticoid, antibiotic, or both
Number of courses of either glucocorticoid, antibiotic, or both (COPD exacerbations) in previous 12 months
Units: Courses
arithmetic mean (standard deviation)	5.7 ( 4.8 )	4.9 ( 4.3 )	-
Systolic Blood Pressure Pre Dose
Systolic (mmHg) Pre-Dose
Units: mmHg
arithmetic mean (standard deviation)	128.8 ( 18.5 )	127.2 ( 17.2 )	-
Diastolic Blood Pressure Pre Dose
Diastolic (mmHg) Pre-Dose
Units: mmHg
arithmetic mean (standard deviation)	72.0 ( 12.5 )	72.1 ( 10.6 )	-
Heart rate Pre Dose
Heart rate (bpm) Pre-Dose
Units: bpm
arithmetic mean (standard deviation)	83.9 ( 15.8 )	85.9 ( 13.4 )	-
Temperature Pre Dose
Temperature (oC) Pre-Dose
Units: oC
arithmetic mean (standard deviation)	36.6 ( 0.4 )	36.6 ( 0.3 )	-
SpO2 Pre Dose
SpO2 (%) Pre-Dose
Units: Percent %
arithmetic mean (standard deviation)	93.5 ( 3.2 )	93.6 ( 3.0 )	-
Respiratory rate Pre Dose
Respiratory rate (per min) Pre-Dose
Units: per min
arithmetic mean (standard deviation)	18.8 ( 2.6 )	18.9 ( 3.2 )	-
Systolic Blood pressure Post-Dose
Systolic (mmHg) Post-Dose
Units: mmHg
arithmetic mean (standard deviation)	130.2 ( 17.6 )	129.3 ( 17.3 )	-
Diastolic Blood Pressure Post-Dose
Diastolic (mmHg) Post-Dose
Units: mmHg
arithmetic mean (standard deviation)	74.7 ( 13.9 )	75.0 ( 11.8 )	-
Heart rate Post-Dose
Heart rate (bpm) Post-Dose
Units: bpm
arithmetic mean (standard deviation)	85.8 ( 16.5 )	86.7 ( 15.5 )	-
Temperature Post-Dose
Units: oC
arithmetic mean (standard deviation)	36.6 ( 0.4 )	36.6 ( 0.4 )	-
SpO2 Post-Dose
Units: Percent %
arithmetic mean (standard deviation)	18.6 ( 2.3 )	19.0 ( 3.0 )	-
Respiratory rate Post-Dose
Units: per min
arithmetic mean (standard deviation)	18.6 ( 2.3 )	19.0 ( 3.0 )	-
Length of hospital stay for index admission (days)
Time to discharge from index admission (days)
Units: Days
median (inter-quartile range (Q1-Q3))	4 (2 to 7)	4 (3 to 7)	-
FEV1, litre
Units: litre
arithmetic mean (standard deviation)	1.3 ( 0.5 )	1.3 ( 0.5 )	-
FEV1, %
Units: percent
arithmetic mean (standard deviation)	50.8 ( 21.3 )	51.0 ( 18.2 )	-
FVC, litre
Units: litre
arithmetic mean (standard deviation)	2.6 ( 0.9 )	2.6 ( 0.8 )	-
FVC, %
Units: percent
arithmetic mean (standard deviation)	81.8 ( 22.1 )	82.6 ( 20.1 )	-
FEV1/FVC ratio, %
Units: percent
arithmetic mean (standard deviation)	48.4 ( 13.3 )	48.9 ( 13.4 )	-
Highest eosinophil count
Highest eosinophil count in previous 12 months
Units: cells/μl
arithmetic mean (standard deviation)	570 ( 410 )	570 ( 340 )	-
Length of hospital stay for index admission
Units: Days
median (inter-quartile range (Q1-Q3))	4 (2 to 7)	4 (3 to 7)	-
CAT total score
Units: Score
arithmetic mean (standard deviation)	26.1 ( 6.1 )	25.2 ( 6.2 )	-
SGRQ-C total score
Units: Score
arithmetic mean (standard deviation)	72.0 ( 13.8 )	69.9 ( 15.7 )	-
SGRQ-C domains: Symptoms Score
Units: Score
arithmetic mean (standard deviation)	75.6 ( 16.1 )	78.5 ( 14.3 )	-
SGRQ-C domains: Activity Score
Units: Score
arithmetic mean (standard deviation)	85.2 ( 15.5 )	82.9 ( 17.9 )	-
SGRQ-C domains: Impact Score
Units: Score
arithmetic mean (standard deviation)	62.8 ( 18.2 )	58.6 ( 20.2 )	-

End points

Top of page

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Primary: Time from randomisation to next hospital readmission or death (all cause)

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End point title

Time from randomisation to next hospital readmission or death (all cause)

End point description

The primary outcome of the trial was defined as the time from randomisation to next hospital readmission or death (all cause).

End point type

Primary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Weeks
median (confidence interval 95%)	25.7 (20.1 to 39.0)	24.4 (17.9 to 33.0)

Time to readmission or death Log Rank Test

Statistical analysis description

The analysis took place on the intention to treat population. The Cox proportional hazard model was used for the primary outcome of the time to re-hospitalisation or death (any cause) as the dependent variable. The treatment group served as an explanatory factor, while baseline MRC dyspnoea score (≤3, >3) and past hospitalisation in the previous 12 months (0, ≥1) were included as stratification factors.

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.811

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.32

Secondary: St George’s Respiratory Questionnaire for COPD Patients (SGRQ-C)

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End point title

St George’s Respiratory Questionnaire for COPD Patients (SGRQ-C)

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

End point values	Placebo	Mepolizumab	Placebo	Placebo	Placebo	Placebo	Placebo	Placebo	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab
Number of subjects analysed	117	111	95	84	85	76	67	77	102	86	79	73	60	67
Units: SGRQ-c total score
arithmetic mean (standard deviation)	72 ( 13.8 )	69.8 ( 15.7 )	66.2 ( 16.4 )	64.4 ( 18.1 )	63.3 ( 16.3 )	61.7 ( 18.2 )	60.4 ( 20.0 )	62.4 ( 18.9 )	65.5 ( 16.0 )	64.3 ( 15.9 )	64.3 ( 16.4 )	64.3 ( 18.0 )	61.2 ( 18.1 )	60.7 ( 19.1 )

SGRQ-c total score - mixed effect linear model

Statistical analysis description

A mixed effect linear model with dependent variable of the outcome at baseline and follow-up time points; explanatory variables of treatment arm, baseline MRC dyspnoea score (≤3, >3) and past hospitalisation in the previous 12 months (0, ≥1) (Stratification factors), visit time point (as categorical variable), baseline score; an interaction term between treatment and visit; and patient identification as a random effect was fitted for each outcome.

Comparison groups

Mepolizumab v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.726

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

-2.63

upper limit

3.78

Variability estimate

Standard error of the mean

Secondary: COPD Assessment Tool (CAT)

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End point title

COPD Assessment Tool (CAT)

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

End point values	Placebo	Mepolizumab	Placebo	Placebo	Placebo	Placebo	Placebo	Placebo	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab
Number of subjects analysed	119	117	99	90	95	83	77	82	102	95	88	84	72	81
Units: CAT total score
arithmetic mean (standard deviation)	26.1 ( 6.1 )	25.2 ( 6.2 )	23.9 ( 6.2 )	23.8 ( 7.1 )	23.0 ( 7.7 )	23.4 ( 7.6 )	22.5 ( 8.4 )	24.0 ( 7.4 )	22.3 ( 6.6 )	23.6 ( 6.4 )	23.6 ( 6.6 )	23.5 ( 6.8 )	22.8 ( 7.3 )	22.3 ( 7.3 )

CAT score - mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

236

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.73

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.88

upper limit

1.25

Secondary: Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)

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End point title

Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

End point values	Placebo	Mepolizumab	Placebo	Placebo	Placebo	Placebo	Placebo	Placebo	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab
Number of subjects analysed	119	116	98	85	86	77	68	77	103	90	82	75	59	69
Units: WEMWBS total score
arithmetic mean (standard deviation)	41.2 ( 9.2 )	42.9 ( 10.4 )	43.3 ( 10.0 )	43.2 ( 10.2 )	45.2 ( 10.0 )	45.0 ( 10.8 )	47.0 ( 9.4 )	46.6 ( 9.4 )	44.9 ( 11.7 )	44.7 ( 11.6 )	45.0 ( 11.9 )	44.5 ( 12.3 )	48.4 ( 11.0 )	47.6 ( 11.6 )

WEMWBS total score - mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.789

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-1.34

upper limit

1.79

Secondary: London Chest Activities of Daily Living Questionnaire (LCADL)

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End point title

London Chest Activities of Daily Living Questionnaire (LCADL)

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

End point values	Placebo	Mepolizumab	Placebo	Placebo	Placebo	Placebo	Placebo	Placebo	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab
Number of subjects analysed	119	117	98	86	87	79	68	77	103	90	82	75	60	69
Units: LCADL total score
arithmetic mean (standard deviation)	28.9 ( 10.8 )	27.6 ( 11.3 )	26.5 ( 11.8 )	24.8 ( 12.3 )	26.2 ( 12.3 )	25.2 ( 12.0 )	24.4 ( 12.4 )	26.4 ( 12.9 )	24.7 ( 11.2 )	24.6 ( 10.2 )	24.3 ( 10.7 )	24.6 ( 12.1 )	22.8 ( 12.2 )	23.6 ( 11.4 )

LCADL score-mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

236

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.563

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-2.06

upper limit

1.12

Secondary: Extended MRC Dyspnoea Score (eMRC)

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End point title

Extended MRC Dyspnoea Score (eMRC)

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

Placebo

Mepolizumab

Placebo

Mepolizumab

Number of subjects analysed

109

106

Units: eMRC Dyspnoea Score

median (inter-quartile range (Q1-Q3))

5.0 (4.0 to 5.0)

5.0 (5.0 to 5.0)

4.0 (3.0 to 4.0)

4.0 (3.0 to 4.5)

4.0 (3.0 to 4.0)

4.0 (3.0 to 5.0)

4.0 (3.0 to 4.0)

4.0 (3.0 to 5.0)

4.0 (3.0 to 4.0)

4.0 (3.0 to 5.0)

eMRC dyspnoea score Wilcoxon rank sum test Week 4

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

215

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.87

Method

Wilcoxon (Mann-Whitney)

Confidence interval

eMRC dyspnoea score Wilcoxon rank sum test Week 8

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

215

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8

Method

Wilcoxon (Mann-Whitney)

Confidence interval

eMRC dyspnoea score Wilcoxon rank sum test Week 12

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

215

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.52

Method

Wilcoxon (Mann-Whitney)

Confidence interval

eMRC dyspnoea score Wilcoxon rank sum test Week 24

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

215

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.55

Method

Wilcoxon (Mann-Whitney)

Confidence interval

eMRC dyspnoea score Wilcoxon rank sum test Week 36

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

215

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.77

Method

Wilcoxon (Mann-Whitney)

Confidence interval

eMRC dyspnoea score Wilcoxon rank sum test Week 48

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

215

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.32

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: SGRQ-c domains- Symptoms

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End point title

SGRQ-c domains- Symptoms

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

End point values	Placebo	Mepolizumab	Placebo	Placebo	Placebo	Placebo	Placebo	Placebo	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab
Number of subjects analysed	118	116	97	87	87	80	68	77	103	89	82	75	60	68
Units: Symptoms score
arithmetic mean (standard deviation)	75.6 ( 16.1 )	78.5 ( 14.3 )	74.8 ( 15.7 )	74.6 ( 17.4 )	74.1 ( 15.8 )	72.7 ( 18.2 )	71.8 ( 17.8 )	71.8 ( 19.2 )	73.7 ( 14.7 )	74.3 ( 15.5 )	73.4 ( 14.7 )	73.4 ( 16.6 )	69.3 ( 16.0 )	68.8 ( 18.3 )

SGRQ-c symptoms domain- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

234

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-3.91

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

-0.72

Secondary: SGRQ-c domains- Activity

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End point title

SGRQ-c domains- Activity

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

End point values	Placebo	Mepolizumab	Placebo	Placebo	Placebo	Placebo	Placebo	Placebo	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab
Number of subjects analysed	117	113	96	84	86	77	68	77	102	86	80	74	60	68
Units: Activity score
arithmetic mean (standard deviation)	85.2 ( 15.5 )	82.9 ( 17.9 )	80.8 ( 19.1 )	79.0 ( 22.1 )	79.0 ( 21.3 )	79.8 ( 22.2 )	76.8 ( 23.0 )	80.3 ( 21.5 )	82.4 ( 19.0 )	81.6 ( 20.0 )	82.2 ( 18.2 )	81.6 ( 20.2 )	81.2 ( 20.8 )	80.5 ( 20.0 )

SGRQ-c activity score- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.157

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

2.64

Confidence interval

level

95%

sides

2-sided

lower limit

-1.02

upper limit

6.3

Secondary: SGRQ-c domains- Impacts

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End point title

SGRQ-c domains- Impacts

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

End point values	Placebo	Mepolizumab	Placebo	Placebo	Placebo	Placebo	Placebo	Placebo	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab
Number of subjects analysed	119	115	95	86	86	76	67	77	102	88	79	73	60	68
Units: SGRQ-c impact score
arithmetic mean (standard deviation)	62.8 ( 18.2 )	58.6 ( 20.2 )	54.4 ( 20.5 )	52.4 ( 21.2 )	50.4 ( 18.3 )	47.6 ( 20.4 )	46.8 ( 22.5 )	48.6 ( 22.0 )	52.6 ( 20.3 )	50.5 ( 19.6 )	50.6 ( 21.2 )	50.7 ( 22.5 )	46.6 ( 22.2 )	46.2 ( 22.8 )

SGRQ-c impact score- - mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

234

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.817

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

4.43

Secondary: Short Physical Performance Battery (SPPB)

Top of page

End point title

Short Physical Performance Battery (SPPB)

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

Placebo

Mepolizumab

Placebo

Mepolizumab

Number of subjects analysed

118

117

100

Units: SPPB total score

median (inter-quartile range (Q1-Q3))

7.0 (5.0 to 9.0)

7.0 (6.0 to 9.0)

8.0 (6.0 to 9.0)

8.0 (6.0 to 10.0)

7.5 (6.0 to 10.0)

8.0 (6.0 to 10.0)

8.0 (6.0 to 11.0)

8.5 (6.5 to 10.0)

8.0 (6.0 to 11.0)

9.0 (6.0 to 11.0)

9.0 (6.0 to 10.0)

9.0 (6.0 to 11.0)

9.0 (7.0 to 11.0)

SPPB total score Wilcoxon rank sum test Week 4

Comparison groups

Mepolizumab v Placebo

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03

Method

Wilcoxon (Mann-Whitney)

Confidence interval

SPPB total score Wilcoxon rank sum test Week 8

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.19

Method

Wilcoxon (Mann-Whitney)

Confidence interval

SPPB total score Wilcoxon rank sum test Week 12

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2

Method

Wilcoxon (Mann-Whitney)

Confidence interval

SPPB total score Wilcoxon rank sum test Week 24

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3

Method

Wilcoxon (Mann-Whitney)

Confidence interval

SPPB total score Wilcoxon rank sum test Week 36

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.52

Method

Wilcoxon (Mann-Whitney)

Confidence interval

SPPB total score Wilcoxon rank sum test Week 48

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Secondary: Handgrip Strength

Top of page

End point title

Handgrip Strength

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

End point values	Placebo	Mepolizumab	Placebo	Placebo	Placebo	Placebo	Placebo	Placebo	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab
Number of subjects analysed	114	115	98	85	84	77	66	74	103	90	80	73	58	69
Units: Hand grip strength
arithmetic mean (standard deviation)	24.9 ( 9.3 )	27.3 ( 9.0 )	25.6 ( 9.1 )	25.1 ( 8.9 )	25.0 ( 9.8 )	26.6 ( 9.8 )	26.8 ( 10.1 )	26.7 ( 10.3 )	27.6 ( 9.6 )	27.4 ( 9.6 )	27.8 ( 9.6 )	28.3 ( 10.0 )	28.4 ( 11.0 )	28.4 ( 10.7 )

Hand grip strength- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.913

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.83

upper limit

0.93

Secondary: Sputum Eosinophil Count (percentage)

Top of page

End point title

Sputum Eosinophil Count (percentage)

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

End point values	Placebo	Mepolizumab	Placebo	Placebo	Placebo	Placebo	Placebo	Placebo	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab
Number of subjects analysed	42	38	45	41	43	38	36	34	32	33	28	27	26	28
Units: Sputum Eosinophil Count (%)
geometric mean (standard error)	0.68 ( 0.224 )	0.75 ( 0.235 )	0.84 ( 0.182 )	0.90 ( 0.219 )	0.70 ( 0.198 )	0.91 ( 0.215 )	0.56 ( 0.187 )	0.69 ( 0.210 )	0.47 ( 0.216 )	0.48 ( 0.244 )	0.75 ( 0.245 )	0.45 ( 0.256 )	0.43 ( 0.220 )	0.51 ( 0.231 )

Sputum Eosinophil Count (%) mixed effect model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Geometric mean ratio

Point estimate

0.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

0.77

Secondary: Serum Eosinophil Count

Top of page

End point title

Serum Eosinophil Count

End point description

End point type

Secondary

End point timeframe

(Week 0 and) Week-4, Week-8, Week-12, Week-24, Week-36 & Week-48

End point values	Placebo	Mepolizumab	Placebo	Placebo	Placebo	Placebo	Placebo	Placebo	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab	Mepolizumab
Number of subjects analysed	119	118	100	86	87	81	69	75	99	87	82	76	62	70
Units: 10^9/L
geometric mean (standard error)	0.13 ( 0.102 )	0.15 ( 0.102 )	0.24 ( 0.065 )	0.28 ( 0.067 )	0.27 ( 0.063 )	0.25 ( 0.067 )	0.26 ( 0.062 )	0.24 ( 0.084 )	0.08 ( 0.066 )	0.07 ( 0.066 )	0.07 ( 0.065 )	0.08 ( 0.069 )	0.07 ( 0.065 )	0.07 ( 0.087 )

Serum Eosinophil count mixed effects model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Geometric mean ratio

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

0.34

Secondary: Adverse Event Rate in the 48 Weeks of the Trial From First Dose

Top of page

End point title

Adverse Event Rate in the 48 Weeks of the Trial From First Dose

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week) i.e. at any point during trial post randomisation.

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	118
Units: Individuals at least 1 (nonserious) AE
At least one (non-serious) AE	91	91
No (non-serious) AEs	28	27

Adverse event rate

Statistical analysis description

Calculated using generalized linear model (assuming negative binomial distribution) adjusting for the baseline MRC dyspnoea score (≤3, >3) and past hospitalisation in the previous 12 months (0, ≥1) (stratification factors) and log-time on treatment (in weeks) as an offset.

Comparison groups

Mepolizumab v Placebo

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.07

Method

t-test, 2-sided

Parameter type

Incidence Rate Ratio

Point estimate

1.24

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

1.56

Secondary: Serious adverse Event Rate in the 48 Weeks of the Trial From First Dose

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End point title

Serious adverse Event Rate in the 48 Weeks of the Trial From First Dose

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week) i.e. at any point during trial post randomisation.

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	118
Units: Serious adverse event rate
At least 1 SAE during trial	3	2
No SAEs during trial	116	116

SAEs rate

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.686

Method

t-test, 2-sided

Parameter type

Incidence Rate Ratio

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.12

upper limit

4.14

Secondary: Clinical Assessments- Pre-Dose Systolic BP

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End point title

Clinical Assessments- Pre-Dose Systolic BP

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	117	118
Units: mmHg
arithmetic mean (standard deviation)	130.2 ( 19.4 )	129.7 ( 18.5 )

Pre-Dose Systolic BP- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.585

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-0.87

Confidence interval

level

95%

sides

2-sided

lower limit

-4.02

upper limit

2.27

Secondary: Clinical Assessments- Pre-Dose Diastolic BP

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End point title

Clinical Assessments- Pre-Dose Diastolic BP

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	117	118
Units: mmHg
arithmetic mean (standard deviation)	73.2 ( 13.2 )	73.1 ( 11.8 )

Pre-Dose Diastolic BP- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.506

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-2.61

upper limit

1.29

Secondary: Clinical Assessments- Pre-Dose Heart Rate

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End point title

Clinical Assessments- Pre-Dose Heart Rate

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	117	118
Units: bpm
arithmetic mean (standard deviation)	81.4 ( 14.1 )	81.8 ( 13.5 )

Pre-Dose Heart Rate- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.423

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-0.88

Confidence interval

level

95%

sides

2-sided

lower limit

-3.03

upper limit

1.27

Secondary: Clinical Assessments- Pre-Dose Temperature

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End point title

Clinical Assessments- Pre-Dose Temperature

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	117	118
Units: °C
arithmetic mean (standard deviation)	36.4 ( 0.4 )	36.4 ( 0.4 )

Pre-Dose Temperature- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.981

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.07

Secondary: Clinical Assessments- Post-Dose Systolic BP

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End point title

Clinical Assessments- Post-Dose Systolic BP

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	118	117
Units: mmHg
arithmetic mean (standard deviation)	128.1 ( 19.6 )	127.4 ( 17.6 )

Post-Dose Systolic BP- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.58

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-3.46

upper limit

1.94

Secondary: Clinical Assessments- Post-Dose Diastolic BP

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End point title

Clinical Assessments- Post-Dose Diastolic BP

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	117	117
Units: mmHg
arithmetic mean (standard deviation)	71.9 ( 13.4 )	72.3 ( 11.6 )

Post-Dose Diastolic BP- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

234

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.729

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-1.68

upper limit

2.41

Secondary: Clinical Assessments- Post-Dose Heart Rate

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End point title

Clinical Assessments- Post-Dose Heart Rate

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	117	117
Units: bpm
arithmetic mean (standard deviation)	79.8 ( 14.4 )	79.6 ( 14.1 )

Post-Dose Heart Rate- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

234

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.24

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-1.28

Confidence interval

level

95%

sides

2-sided

lower limit

-3.24

upper limit

0.86

Secondary: Clinical Assessments- Post-Dose Temperature

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End point title

Clinical Assessments- Post-Dose Temperature

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	115	117
Units: °C
arithmetic mean (standard deviation)	36.5 ( 0.4 )	36.5 ( 0.4 )

Post-Dose Temperature- mixed effect linear model

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.946

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

0.002

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.07

Secondary: Moderate exacerbations per participant in 48-weeks

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End point title

Moderate exacerbations per participant in 48-weeks

End point description

End point type

Secondary

End point timeframe

The rate of moderate exacerbations each participant had over the course of observed time period for each participant (maximum trial duration for a patient was 49 weeks (48 weeks + 7 days))

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Moderate exacerbation rate in 48 weeks
arithmetic mean (standard deviation)	2.22 ( 2.24 )	1.83 ( 1.78 )

mITT analysis of moderate exacerbation in 48 week

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.14

Method

t-test, 2-sided

Parameter type

Rate Ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.06

Secondary: Hospital readmissions per participant in 48 weeks

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End point title

Hospital readmissions per participant in 48 weeks

End point description

End point type

Secondary

End point timeframe

The rate of hospital readmissions each participant had over the course of observed time period for each participant (maximum trial duration for a patient was 49 weeks (48 weeks + 7 days))

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Hospital readmission rate in 48 weeks
arithmetic mean (standard deviation)	1.77 ( 2.88 )	1.54 ( 2.18 )

mITT analysis of hospital readmissions in 48 weeks

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.505

Method

t-test, 2-sided

Parameter type

Rate ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

1.25

Secondary: Severe exacerbations per participant in the 48 weeks

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End point title

Severe exacerbations per participant in the 48 weeks

End point description

End point type

Secondary

End point timeframe

The rate of severe exacerbations each participant had over the course of observed time period for each participant (maximum trial duration for a patient was 49 weeks (48 weeks + 7 days))

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Severe exacerbation rate in 48 weeks
arithmetic mean (standard deviation)	1.20 ( 2.36 )	0.91 ( 1.76 )

mITT analysis of severe exacerbation in 48 week

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.263

Method

t-test, 2-sided

Parameter type

Rate ratio

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.2

Secondary: Moderate and/or Severe exacerbations per participant in the 48 weeks

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End point title

Moderate and/or Severe exacerbations per participant in the 48 weeks

End point description

End point type

Secondary

End point timeframe

The rate of exacerbation each participant had over the course of observed time period for each participant (maximum trial duration for a patient was 49 weeks (48 weeks + 7 days))

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Exacerbation rate in 48 weeks
arithmetic mean (standard deviation)	3.42 ( 3.08 )	2.74 ( 2.36 )

mITT analysis of exacerbation frequency in 48 week

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.054

Method

t-test, 2-sided

Parameter type

Rate ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

Secondary: Death (respiratory cause)

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End point title

Death (respiratory cause)

End point description

Respiratory cause death. Number of individuals that died during follow up is reported. Death due to respiratory cause was analysed as a time to event outcome.

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (48 week visit had a window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Number
number (not applicable)	8	5

Time to death (respiratory cause)

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.432

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

1.95

Secondary: Death (all cause)

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End point title

Death (all cause)

End point description

All cause death. Number of individuals that died during follow up is reported. Death due to all cause was analysed as a time to event outcome.

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (48 week visit had a window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Number
number (not applicable)	11	9

Time from randomisation to death (all cause)

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.705

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.35

upper limit

2.04

Secondary: Hospital readmission (respiratory cause)

Top of page

End point title

Hospital readmission (respiratory cause)

End point description

Hospital readmission (respiratory cause). Number of individuals that hospitalised due to respiratory cause during follow up is reported. Hospital readmission due to respiratory cause was analysed as a time to event outcome.

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (48 week visit had a window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Number
number (not applicable)	55	52

Time to next hospital readmission (respiratory)

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.759

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.38

Secondary: Time from randomisation to next hospital readmission or death due to a respiratory cause

Top of page

End point title

Time from randomisation to next hospital readmission or death due to a respiratory cause

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Weeks
median (confidence interval 95%)	25.7 (20.1 to 39.0)	24.4 (17.9 to 33.0)

Time to next hospital readmission or death (resp)

Statistical analysis description

The analysis is the same as for the primary outcome because where the first event is death, this was always due to respiratory causes.

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.811

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.32

Secondary: Time from randomisation to next hospital readmission (all cause)

Top of page

End point title

Time from randomisation to next hospital readmission (all cause)

End point description

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Weeks
median (confidence interval 95%)	27.9 (20.4 to 40.9)	24.4 (17.9 to 33.0)

Time to next hospital readmission (all cause)

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.938

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.36

Secondary: Time from randomisation to treatment failure

Top of page

End point title

Time from randomisation to treatment failure

End point description

Treatment failure is defined as the composite of three endpoints: 1. treatment intensification with systemic corticosteroids and/or antibiotics for respiratory reasons; 2. step-up in hospital care for respiratory reasons including transfer to the intensive care unit or readmission; or 3. all-cause mortality)

End point type

Secondary

End point timeframe

Patients were followed up for up to 48 weeks (an absolute maximum of 49 weeks as the 48 week visit had a visit window of +- 1 week).

End point values	Placebo	Mepolizumab
Number of subjects analysed	119	119
Units: Weeks
median (confidence interval 95%)	10.0 (7.71 to 12.6)	12.9 (10.1 to 15.7)

Time from randomisation to treatment failure

Statistical analysis description

Comparison groups

Placebo v Mepolizumab

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.849

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.28

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse events were collected for the duration of the study until the final trial visit (week 48/Final Follow-up) or 28 days post cessation of trial treatment where this occurs earlier than protocolised.

Adverse event reporting additional description

Participants were asked about AEs at each study visits and they were recorded on a participant specific AE log. SAEs/SUSARs: reported to Sponsor and Leicester CTU within 24 hours of research staff learning of the event.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

Placebo

Reporting group description

Participants randomised to a matched placebo.

Reporting group title

Mepolizumab

Reporting group description

Participants randomised to receive monthly subcutaneous injections of 100 mg mepolizumab.

Serious adverse events	Placebo	Mepolizumab
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 119 (2.52%)	2 / 118 (1.69%)
number of deaths (all causes)	11	9
number of deaths resulting from adverse events	3	2
Vascular disorders
Aortic aneurysm rupture
subjects affected / exposed	0 / 119 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Cardiac disorders
Congestive heart failure
subjects affected / exposed	0 / 119 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
General disorders and administration site conditions
Multiple organ dysfunction syndrome
subjects affected / exposed	1 / 119 (0.84%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Respiratory, thoracic and mediastinal disorders
Death due to COPD
subjects affected / exposed	2 / 119 (1.68%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	Mepolizumab
Total subjects affected by non serious adverse events
subjects affected / exposed	27 / 119 (22.69%)	34 / 118 (28.81%)
Investigations
Liver function test abnormal
subjects affected / exposed	2 / 119 (1.68%)	6 / 118 (5.08%)
occurrences all number	3	6
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	9 / 119 (7.56%)	8 / 118 (6.78%)
occurrences all number	11	10
General disorders and administration site conditions
Chest pain
subjects affected / exposed	5 / 119 (4.20%)	6 / 118 (5.08%)
occurrences all number	5	6
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	9 / 119 (7.56%)	12 / 118 (10.17%)
occurrences all number	11	20
Infections and infestations
COVID-19
subjects affected / exposed	7 / 119 (5.88%)	8 / 118 (6.78%)
occurrences all number	7	8

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

06 Jan 2020

SA01: • Section viii Key Words – correction of Phase III to Phase IIb. • Section 7.7.4 Visit 13 – Reinstated urine pregnancy test that was removed in version 3.0. This is required at end of IMP exposure. • Section 8.11 – Addition to final sentence of 3rd paragraph to clarify requirement for urine pregnancy test at Visit 13. • Appendix 1 – add urine pregnancy test to Visit 13 in schedule procedures. • Appendix 1 – correction to safety & tolerability measures. AE/SAEs were removed in error in previous version with the removal of safety blood samples from visits 5&6, 8&9, 11&12. These have now been reinstated.

06 Mar 2020

SA02: • Section 7.2 Informed Consent – Amendment made to first sentence of second paragraph to include participants that may be admitted and discharged within one week. Wording changed from ‘Due to the nature of the study (acute illness resulting in hospitalisation), the participant can be consented at any point within their inpatient stay, or within one week of their index hospital admission’ to ‘Due to the nature of the study (acute illness resulting in hospitalisation), the participant can be consented at any point within their inpatient stay, or within one week of discharge’. • Section 7.2.1 – Title amended from ‘Additional consent for biological specimens’ to ‘Additional consent for biological specimens and future research’. ‘Anonymised’ changed to ‘pseudonymised’. Additional paragraph included to describe the linking of outcomes of this trial with environmental exposure listed in the optional section of the Informed Consent Form. The PIS has also been amended to reflect this as it was removed in error during the response to the Provisional Opinion. • Appendix 1 Schedule of procedures – reinstatement of safety blood samples from visits 5&6, 8&9, 11&12 that were removed in error in Protocol version 3.0 (17/10/2019) as part of the response to Provisional Opinion. These have been reinstated to correct the inconsistency with the body text (Section 7.7.3).

21 Jun 2021

SA03: • Section 9.2 - SAEs will be reported following first administration of IMP/placebo rather than following consent. Section 9.1 – clarification provided on events that are clinical outcomes. Section 9.3 – the causality and relatedness assessment may be performed by the PI or a suitably trained delegate (does not require an unblinded doctor). Section 9.4 - clarification provided on notification of deaths. • Section 6.1 and trial summary table: > has been changed to ≥ for the following inclusion criterion: '4. Smoking pack years ≥ 10 years'. • Section 7.7.1 & Appendix 1 - the current (exacerbated state) eMRC score is to be collected at visit 1 in addition to their baseline eMRC score (stable state). • Sections 7.7, 7.8 & Appendix 1 – Clarification that trial assessments (e.g. Quality of Life/Symptoms Assessments) may be completed remotely by telephone consultation, where possible, and when necessary. • Section 7.10 – Pandemic guidance section added. • Sections 3.4.3 and 7.9 – corrections confirming DNA for analysis will only be taken from blood samples at week 0; RNA analysis will occur on blood samples taken at weeks 0, 4, 8, 12, 24, 36, 48. • Section 7.9 - correction to confirm blood tests for Trop I and BNP blood are not stored for the purposes of the study and are either used or destroyed during the testing process. • Section 13.5 - protocol deviations are not required for instances where a participant is unable to produce a sample or for assessments omitted due to a pandemic. • Section 7.7.4 - participants that have discontinued treatment early (prior to visit 12) will be invited back to hospital for visit 13 assessments.

04 Jul 2022

SA04: There have been several occasions where participants have missed trial visits without contacting the research team, and the research team has been unable to contact the participant by telephone within the window for their visit, if at all. A number of participants have been discontinued because of this, and the research team suggested if they tried writing to the participant for a response, they could demonstrate that every effort had been made to retain them. Therefore a participant contact letter has been devised for this purpose. It has been made clear within the letter that participants are free to discontinue without giving a reason, and that their decision to discontinue will not affect the standard of medical care they receive.

26 Oct 2022

SA05: • Removal of COVID-19 omitted procedures: o Faecal sample o Post-BD (FEV1/FVC) Spirometry o Oscillometry o Breath volatile organic compounds o Induced sputum samples o Throat swab (viral PCR) o Nasal epithelial sampling • Clarification that only spontaneous sputum samples are collected as part of standard care • Update to study timelines (recruitment, total study duration) in line with funding extension • Update to wording around indemnity (section 13.10) per Sponsor’s request • Update to statistician information

06 Feb 2023

SA06: • Truncated follow-up for participant recruitment from April 2023 added to protocol and all applicable sections (schedule of events, etc.) amended to reflect new follow-up schedule • Visit 13 also named Final Follow-up for those in the truncated follow-up phase of the trial; patients recruited from April 2023 to September 2023 will be consented to a truncated follow-up model, whereby last patient last visit will remain the same. This will result in participants consented in April to have up to the 44-week follow-up, those in May will have up to the 40-week follow-up, and so on. Patients will be dosed for a minimum of 24 weeks, with secondary outcomes measured as per original timelines (baseline, 4 weeks, 8 weeks, etc.) however final outcome measures normally measured at 48 weeks will occur 4 weeks ± 7 days of final dosing visit.

12 Sep 2023

SA07: Change to IMP constitution for participants dosed from 01 March 2024 due to funder stock supplies; IMP changed from mepolizumab powder reconstituted to mepolizumab in a pre-filled syringe. Dosing and regime to remain the same - updated details in protocol and new SmPC for drug constitution.

22 Jan 2024

SA08: Submission for the approval of the new IMP constitution and matched placebo following GNA for SA07 from the MHRA. The change of IMP from a powder reconstituted to a pre-filled syringe, with the placebo changed from saline to a pre-filled syringe matched placebo, was previously submitted and approved by REC via SA07. This SA08 is to re-submit for approval protocol v9.0 12-09-2023, PIS v2.0 12-09-2023 and Nucala 100mg SMPC (23/05/2023), all of which are unchanged from SA07. The newly included documents address the GNA of the MHRA and include the cross-referral letter for placebo IMPD, and labels for new IMP and placebo syringes.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Randomised Controlled Trial of Mepolizumab Initiated During Admission to Hospital for a Severe Exacerbation of Eosinophilic COPD

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Time from randomisation to next hospital readmission or death (all cause)

Primary: Time from randomisation to next hospital readmission or death (all cause)

Secondary: St George’s Respiratory Questionnaire for COPD Patients (SGRQ-C)

Secondary: St George’s Respiratory Questionnaire for COPD Patients (SGRQ-C)

Secondary: COPD Assessment Tool (CAT)

Secondary: COPD Assessment Tool (CAT)

Secondary: Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)

Secondary: Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)

Secondary: London Chest Activities of Daily Living Questionnaire (LCADL)

Secondary: London Chest Activities of Daily Living Questionnaire (LCADL)

Secondary: Extended MRC Dyspnoea Score (eMRC)

Secondary: Extended MRC Dyspnoea Score (eMRC)

Secondary: SGRQ-c domains- Symptoms

Secondary: SGRQ-c domains- Symptoms

Secondary: SGRQ-c domains- Activity

Secondary: SGRQ-c domains- Activity

Secondary: SGRQ-c domains- Impacts

Secondary: SGRQ-c domains- Impacts

Secondary: Short Physical Performance Battery (SPPB)

Secondary: Short Physical Performance Battery (SPPB)

Secondary: Handgrip Strength

Secondary: Handgrip Strength

Secondary: Sputum Eosinophil Count (percentage)

Secondary: Sputum Eosinophil Count (percentage)

Secondary: Serum Eosinophil Count

Secondary: Serum Eosinophil Count

Secondary: Adverse Event Rate in the 48 Weeks of the Trial From First Dose

Secondary: Adverse Event Rate in the 48 Weeks of the Trial From First Dose

Secondary: Serious adverse Event Rate in the 48 Weeks of the Trial From First Dose

Secondary: Serious adverse Event Rate in the 48 Weeks of the Trial From First Dose

Secondary: Clinical Assessments- Pre-Dose Systolic BP

Secondary: Clinical Assessments- Pre-Dose Systolic BP

Secondary: Clinical Assessments- Pre-Dose Diastolic BP

Secondary: Clinical Assessments- Pre-Dose Diastolic BP

Secondary: Clinical Assessments- Pre-Dose Heart Rate

Secondary: Clinical Assessments- Pre-Dose Heart Rate

Secondary: Clinical Assessments- Pre-Dose Temperature

Secondary: Clinical Assessments- Pre-Dose Temperature

Secondary: Clinical Assessments- Post-Dose Systolic BP

Secondary: Clinical Assessments- Post-Dose Systolic BP

Secondary: Clinical Assessments- Post-Dose Diastolic BP

Secondary: Clinical Assessments- Post-Dose Diastolic BP

Secondary: Clinical Assessments- Post-Dose Heart Rate

Secondary: Clinical Assessments- Post-Dose Heart Rate

Secondary: Clinical Assessments- Post-Dose Temperature

Secondary: Clinical Assessments- Post-Dose Temperature

Secondary: Moderate exacerbations per participant in 48-weeks

Secondary: Moderate exacerbations per participant in 48-weeks

Secondary: Hospital readmissions per participant in 48 weeks

Secondary: Hospital readmissions per participant in 48 weeks

Secondary: Severe exacerbations per participant in the 48 weeks

Secondary: Severe exacerbations per participant in the 48 weeks

Secondary: Moderate and/or Severe exacerbations per participant in the 48 weeks

Secondary: Moderate and/or Severe exacerbations per participant in the 48 weeks

Secondary: Death (respiratory cause)

Secondary: Death (respiratory cause)

Secondary: Death (all cause)

Secondary: Death (all cause)

Secondary: Hospital readmission (respiratory cause)

Secondary: Hospital readmission (respiratory cause)

Secondary: Time from randomisation to next hospital readmission or death due to a respiratory cause

Secondary: Time from randomisation to next hospital readmission or death due to a respiratory cause

Secondary: Time from randomisation to next hospital readmission (all cause)

Secondary: Time from randomisation to next hospital readmission (all cause)

Secondary: Time from randomisation to treatment failure

Secondary: Time from randomisation to treatment failure

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Clinical Trial Results:
A Randomised Controlled Trial of Mepolizumab Initiated During Admission to Hospital for a Severe Exacerbation of Eosinophilic COPD