Trial Outcomes & Findings for Extension Study of Zemaira® i.v. Administration in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency. (NCT NCT00670007)

NCT ID: NCT00670007

Last Updated: 2016-08-15

Results Overview

As measured by centralized, standardized computer tomographic (CT) lung densitometry. CT scans were acquired at 2 inspiration states: TLC (Total Lung Capacity; ie, full inspiration) and FRC (Functional Residual Capacity; ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average rate of decline in the early start and delayed start subgroups from a linear random regression model with country, inspiration state (only for 'TLC and FRC state'), time (time elapsed since Day 1 \[CE1226\_4001\]), treatment and treatment by time interaction as fixed effects and subject and subject by time interaction as random coefficients.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 140 participants
• Primary outcome timeframe: Up to 2 years
• Results posted on: 2016-08-15

Participant Flow

This multicenter study was conducted at 22 centers in Europe, Canada, and Australia. Alpha1-proteinase inhibitor (A1-PI) deficient individuals with emphysema, who had completed the 2-year treatment and observation periods in study CE1226_4001, except those participating in the USA, were invited to participate in study CE1226_3001.

Subjects who had participated in the CE1226_4001 study, met the inclusion and exclusion criteria, and signed the informed consent were included in study CE1226_3001.

Participant milestones

Measure	Zemaira® Alpha1- proteinase inhibitor \[human\]: Lyophilized preparation of 60 mg/kg body weight administered intravenously once per week
Overall Study STARTED	140
Overall Study COMPLETED	131
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Measure	Zemaira® Alpha1- proteinase inhibitor \[human\]: Lyophilized preparation of 60 mg/kg body weight administered intravenously once per week
Overall Study Drug abuse	1
Overall Study Lung transplant	1
Overall Study Travel/Vacation	1
Overall Study Adverse event, serious fatal	1
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	4

Baseline Characteristics

Extension Study of Zemaira® i.v. Administration in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency.

Baseline characteristics by cohort

Measure	Zemaira® n=140 Participants Alpha1- proteinase inhibitor \[human\]: Lyophilized preparation of 60 mg/kg body weight intravenously once per week
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	130 Participants n=93 Participants
Age, Categorical >=65 years	10 Participants n=93 Participants
Sex: Female, Male Female	61 Participants n=93 Participants
Sex: Female, Male Male	79 Participants n=93 Participants
Region of Enrollment Canada	25 participants n=93 Participants
Region of Enrollment Sweden	17 participants n=93 Participants
Region of Enrollment Czech Republic	2 participants n=93 Participants
Region of Enrollment Romania	1 participants n=93 Participants
Region of Enrollment Ireland	19 participants n=93 Participants
Region of Enrollment Finland	3 participants n=93 Participants
Region of Enrollment Poland	4 participants n=93 Participants
Region of Enrollment Denmark	35 participants n=93 Participants
Region of Enrollment Australia	17 participants n=93 Participants
Region of Enrollment Germany	15 participants n=93 Participants
Region of Enrollment Estonia	2 participants n=93 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: Intention-to-treat (ITT) population. Subjects may not have been included in all efficacy analyses because of missing efficacy assessments.

As measured by centralized, standardized computer tomographic (CT) lung densitometry. CT scans were acquired at 2 inspiration states: TLC (Total Lung Capacity; ie, full inspiration) and FRC (Functional Residual Capacity; ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average rate of decline in the early start and delayed start subgroups from a linear random regression model with country, inspiration state (only for 'TLC and FRC state'), time (time elapsed since Day 1 [CE1226_4001]), treatment and treatment by time interaction as fixed effects and subject and subject by time interaction as random coefficients.

Outcome measures

Measure	Zemaira® (Delayed Start) n=64 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=75 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Rate of Change of Adjusted Lung Density TLC + FRC combined	-1.352 g/L per year Standard Error 0.2961	-1.632 g/L per year Standard Error 0.2824
Rate of Change of Adjusted Lung Density TLC	-1.256 g/L per year Standard Error 0.2891	-1.627 g/L per year Standard Error 0.2743
Rate of Change of Adjusted Lung Density FRC	-1.482 g/L per year Standard Error 0.3346	-1.658 g/L per year Standard Error 0.3186

SECONDARY outcome

Timeframe: From baseline to 2 years

Population: ITT population. Subjects may not have been included in all efficacy analyses because of missing efficacy assessments.

Absolute change from baseline to 2 years as measured by centralized, standardized CT lung densitometry. CT scans were acquired at 2 inspiration states: TLC (ie, full inspiration) and FRC (ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average absolute change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect. The baseline is the last assessment from the preceding study CE1226_4001.

Outcome measures

Measure	Zemaira® (Delayed Start) n=60 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=64 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Absolute Change in Adjusted Lung Density TLC + FRC combined, n = 64, 60	-2.502 g/L Standard Error 0.6142	-3.031 g/L Standard Error 0.5888
Absolute Change in Adjusted Lung Density TLC, n = 64, 59	-2.485 g/L Standard Error 0.6142	-2.971 g/L Standard Error 0.5826
Absolute Change in Adjusted Lung Density FRC, n = 64, 60	-2.953 g/L Standard Error 0.6993	-2.934 g/L Standard Error 0.6671

SECONDARY outcome

Timeframe: From baseline to 2 years

Population: ITT population. Subjects may not have been included in all efficacy analyses because of missing efficacy assessments.

Percent change from baseline to 2 years as measured by centralized, standardized CT lung densitometry. CT scans were acquired at 2 inspiration states: TLC (ie, full inspiration) and FRC (ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average percent change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect. The baseline is the last assessment from the preceding study CE1226_4001.

Outcome measures

Measure	Zemaira® (Delayed Start) n=60 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=64 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Percent Change in Adjusted Lung Density TLC and FRC combined, n = 64, 60	-7.035 Percent change from baseline Standard Deviation 1.4671	-6.741 Percent change from baseline Standard Deviation 1.4031
Percent Change in Adjusted Lung Density TLC, n = 64, 59	-6.674 Percent change from baseline Standard Deviation 1.5061	-6.825 Percent change from baseline Standard Deviation 1.4286
Percent Change in Adjusted Lung Density FRC, n = 64, 60	-8.281 Percent change from baseline Standard Deviation 1.5752	-6.494 Percent change from baseline Standard Deviation 1.5027

SECONDARY outcome

Timeframe: From baseline to 2 years

Population: ITT population. Subjects may not have been included in all efficacy analyses because of missing efficacy assessments.

Patient-reported symptoms were measured using the St George's Respiratory Questionnaire (SGRQ). SGRQ total, symptoms, activity and impact scores range from 0 to 100, with higher scores indicating more limitations, and change from baseline below zero (0) is favorable, indicating improvement.

Outcome measures

Measure	Zemaira® (Delayed Start) n=58 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=67 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Change in Subject-reported Symptoms Total score, n = 62, 56	1.499 units on a scale (change from baseline) Standard Deviation 12.0507	1.185 units on a scale (change from baseline) Standard Deviation 13.624
Change in Subject-reported Symptoms Symptoms score, n = 67, 58	0.728 units on a scale (change from baseline) Standard Deviation 19.2189	6.601 units on a scale (change from baseline) Standard Deviation 22.29
Change in Subject-reported Symptoms Activity score, n = 67, 57	2.831 units on a scale (change from baseline) Standard Deviation 14.0013	0.55 units on a scale (change from baseline) Standard Deviation 14.1429
Change in Subject-reported Symptoms Impact score, n = 65, 57	1.626 units on a scale (change from baseline) Standard Deviation 13.5699	-0.22 units on a scale (change from baseline) Standard Deviation 15.8999

SECONDARY outcome

Timeframe: From baseline up to 2 years

Population: ITT population. Subjects may not have been included in all efficacy analyses because of missing efficacy assessments.

Outcome measures

Measure	Zemaira® (Delayed Start) n=56 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=69 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Percent Change in Lung Function as Measured by Forced Expiratory Volume in 1 Second (FEV1)	-8.666 Percent change from baseline Standard Deviation 10.9057	-8.610 Percent change from baseline Standard Deviation 12.9541

SECONDARY outcome

Timeframe: From baseline up to 2 years

Population: ITT population. Subjects may not have been included in all efficacy analyses because of missing efficacy assessments.

Outcome measures

Measure	Zemaira® (Delayed Start) n=56 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=69 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Percent Change in Lung Function as Measured by Ratio of FEV1/FVC (Forced Vital Capacity)	-5.441 Percent change from baseline Standard Deviation 10.8993	0.560 Percent change from baseline Standard Deviation 12.9685

SECONDARY outcome

Timeframe: From baseline up to 2 years

Population: ITT population. Subjects may not have been included in all efficacy analyses because of missing efficacy assessments.

Outcome measures

Measure	Zemaira® (Delayed Start) n=54 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=68 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Percent Change in Lung Function as Measured by Percent Predicted FEV1	-6.958 Percent change from baseline Standard Deviation 11.0846	-7.165 Percent change from baseline Standard Deviation 13.2053

SECONDARY outcome

Timeframe: Up to 2 years

Population: ITT population.

Outcome measures

Measure	Zemaira® (Delayed Start) n=64 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=76 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Number of Subjects With Pulmonary Exacerbations No exacerbation	16 participants	13 participants
Number of Subjects With Pulmonary Exacerbations Overall (at least 1 exacerbation)	48 participants	63 participants
Number of Subjects With Pulmonary Exacerbations Moderate exacerbation	46 participants	60 participants
Number of Subjects With Pulmonary Exacerbations Severe exacerbation	11 participants	17 participants
Number of Subjects With Pulmonary Exacerbations Neither moderate or severe exacerbation	17 participants	21 participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: ITT population.

Annual exposure-adjusted incidence rate of pulmonary exacerbations.

Outcome measures

Measure	Zemaira® (Delayed Start) n=64 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=76 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Annual Rate in Subject Years of Pulmonary Exacerbations	1.39 Exacerbations/subject year Interval 1.18 to 1.59	1.71 Exacerbations/subject year Interval 1.49 to 1.92

SECONDARY outcome

Timeframe: Up to 2 years

Population: ITT population.

Outcome measures

Measure	Zemaira® (Delayed Start) n=64 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=76 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Time to First Pulmonary Exacerbation	0.602 years Interval 0.287 to 0.843	0.405 years Interval 0.315 to 0.687

SECONDARY outcome

Timeframe: From baseline up to 2.5 years

Population: Safety population comprises all subjects who were included in the study and who received at least 1 dose of Zemaira during study CE1226\_3001.

Percentage of subjects with treatment-emergent adverse events (TEAEs): overall, by severity, by relatedness, by seriousness, and which occurred within 24 hours of Zemaira administration.

Outcome measures

Measure	Zemaira® (Delayed Start) n=64 Participants Subjects who received placebo in study CE1226\_4001 and only began to receive Zemaira® treatment upon entry into study CE1226\_3001 represent the Delayed Start group. This group had a maximal exposure of 2 years at the end of study CE1226\_3001.	Zemaira® (Early Start) n=76 Participants Those subjects who had already been allocated to receive Zemaira® treatment during study CE1226\_4001 represent the Early Start group. This group had received up to 4 years of continuous therapy at the end of study CE1226\_3001.
Percentage of Subjects With Treatment Emergent Adverse Events Moderate TEAE	51.6 percentage of subjects	50.0 percentage of subjects
Percentage of Subjects With Treatment Emergent Adverse Events Severe TEAE	29.7 percentage of subjects	30.3 percentage of subjects
Percentage of Subjects With Treatment Emergent Adverse Events Any TEAE	96.9 percentage of subjects	100 percentage of subjects
Percentage of Subjects With Treatment Emergent Adverse Events Mild TEAE	15.6 percentage of subjects	19.7 percentage of subjects
Percentage of Subjects With Treatment Emergent Adverse Events Any treatment related TEAE	10.9 percentage of subjects	14.5 percentage of subjects
Percentage of Subjects With Treatment Emergent Adverse Events Any serious TEAE	35.9 percentage of subjects	36.8 percentage of subjects
Percentage of Subjects With Treatment Emergent Adverse Events Any TEAE within 24 hours	79.7 percentage of subjects	86.8 percentage of subjects

Adverse Events

Zemaira®

Serious events: 51 serious events

Other events: 137 other events

Deaths: 0 deaths

Serious adverse events

Measure	Zemaira® n=140 participants at risk The safety population comprised all subjects enrolled in study CE1226\_3001 and who received at least 1 administration of Zemaira® during study CE1226\_3001.
Vascular disorders Deep vein thrombosis	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Injury, poisoning and procedural complications Humerus fracture	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Injury, poisoning and procedural complications Infusion related reaction	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Surgical and medical procedures Hysterectomy	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Surgical and medical procedures Lung transplant	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Surgical and medical procedures Strangulated hernia repair	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Cardiac disorders Palpitations	1.4% 2/140 • Number of events 4 • Up to 2.5 years Treatment-emergent adverse events are presented
Cardiac disorders Angina unstable	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Cardiac disorders Cardiac failure	0.71% 1/140 • Number of events 2 • Up to 2.5 years Treatment-emergent adverse events are presented
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	12.1% 17/140 • Number of events 43 • Up to 2.5 years Treatment-emergent adverse events are presented
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.4% 2/140 • Number of events 2 • Up to 2.5 years Treatment-emergent adverse events are presented
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Respiratory, thoracic and mediastinal disorders Nocturnal dyspnoea	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Nervous system disorders Transient ischaemic attack	1.4% 2/140 • Number of events 2 • Up to 2.5 years Treatment-emergent adverse events are presented
Nervous system disorders Cerebral thrombosis	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Nervous system disorders Dizziness	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Nervous system disorders Hypotonia	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Nervous system disorders Lumbar radiculopathy	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Nervous system disorders Syncope	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
General disorders Condition aggravated	2.1% 3/140 • Number of events 4 • Up to 2.5 years Treatment-emergent adverse events are presented
General disorders Chest pain	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Abdominal pain	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Abdominal wall haematoma	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Diarrhoea	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Enterocolitis	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Ileus	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Inguinal hernia	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Melaena	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Nausea	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Pancreatitis	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Vomiting	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.4% 2/140 • Number of events 2 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Pneumonia	4.3% 6/140 • Number of events 6 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Lower respiratory tract infection	2.9% 4/140 • Number of events 8 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Infective exacerbation of chronic obstructive airways disease	1.4% 2/140 • Number of events 2 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Anal abscess	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Diverticulitis	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Herpes zoster	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Influenza	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Lung abscess	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Meningitis	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Pneumonia bacterial	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Upper respiratory tract infection	0.71% 1/140 • Number of events 1 • Up to 2.5 years Treatment-emergent adverse events are presented

Other adverse events

Measure	Zemaira® n=140 participants at risk The safety population comprised all subjects enrolled in study CE1226\_3001 and who received at least 1 administration of Zemaira® during study CE1226\_3001.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	35.7% 50/140 • Number of events 137 • Up to 2.5 years Treatment-emergent adverse events are presented
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	13.6% 19/140 • Number of events 21 • Up to 2.5 years Treatment-emergent adverse events are presented
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.1% 17/140 • Number of events 40 • Up to 2.5 years Treatment-emergent adverse events are presented
Respiratory, thoracic and mediastinal disorders Cough	10.7% 15/140 • Number of events 27 • Up to 2.5 years Treatment-emergent adverse events are presented
Nervous system disorders Headache	20.0% 28/140 • Number of events 58 • Up to 2.5 years Treatment-emergent adverse events are presented
General disorders Condition aggravated	19.3% 27/140 • Number of events 71 • Up to 2.5 years Treatment-emergent adverse events are presented
General disorders Oedema peripheral	8.6% 12/140 • Number of events 13 • Up to 2.5 years Treatment-emergent adverse events are presented
General disorders Pyrexia	7.1% 10/140 • Number of events 15 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Diarrhoea	7.9% 11/140 • Number of events 11 • Up to 2.5 years Treatment-emergent adverse events are presented
Gastrointestinal disorders Nausea	7.1% 10/140 • Number of events 11 • Up to 2.5 years Treatment-emergent adverse events are presented
Musculoskeletal and connective tissue disorders Back pain	10.7% 15/140 • Number of events 19 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Nasopharyngitis	28.6% 40/140 • Number of events 72 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Lower respiratory tract infection	14.3% 20/140 • Number of events 106 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Upper respiratory tract infection	11.4% 16/140 • Number of events 37 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Influenza	10.7% 15/140 • Number of events 17 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Oral candidiasis	9.3% 13/140 • Number of events 37 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Bronchitis	8.6% 12/140 • Number of events 22 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Pneumonia	7.1% 10/140 • Number of events 17 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Sinusitis	5.7% 8/140 • Number of events 15 • Up to 2.5 years Treatment-emergent adverse events are presented
Infections and infestations Urinary tract infection	5.7% 8/140 • Number of events 14 • Up to 2.5 years Treatment-emergent adverse events are presented

Additional Information

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