Trial Outcomes & Findings for Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency (NCT NCT00261833)

NCT ID: NCT00261833

Last Updated: 2015-01-19

Results Overview

As measured by centralized, standardized computer tomographic (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 rate of decline in each treatment group.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 180 participants
• Primary outcome timeframe: Over a 2-year period
• Results posted on: 2015-01-19

Participant Flow

This multicenter, multinational study enrolled participants at 28 study centers in Europe, North America, and Australia.

Screening took place 1 to 4 weeks prior to the first dose of randomized investigational product (ie, either Zemaira® or placebo). A total of 208 participants were screened; 28 of these did not fulfill all eligibility criteria and were therefore screening failures.

Participant milestones

Measure	Zemaira® Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo Lyophilized preparation: 60 mg/kg body weight/week intravenous
Overall Study STARTED	93	87
Overall Study COMPLETED	84	69
Overall Study NOT COMPLETED	9	18

Reasons for withdrawal

Measure	Zemaira® Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo Lyophilized preparation: 60 mg/kg body weight/week intravenous
Overall Study Death	1	3
Overall Study Adverse Event	1	4
Overall Study Withdrawal by Subject	5	7
Overall Study Protocol Violation	0	1
Overall Study Suspicion of pulmonary cancer	0	1
Overall Study Lung transplantation	1	1
Overall Study Missing reason	1	0
Overall Study Not interested in being participant	0	1

Baseline Characteristics

Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency

Baseline characteristics by cohort

Measure	Zemaira® n=93 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=87 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous	Total n=180 Participants Total of all reporting groups
Age, Continuous	53.81 years STANDARD_DEVIATION 6.193 • n=5 Participants	52.40 years STANDARD_DEVIATION 7.812 • n=7 Participants	53.13 years STANDARD_DEVIATION 7.374 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	37 Participants n=7 Participants	82 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	50 Participants n=7 Participants	98 Participants n=5 Participants
Baseline percent predicted forced expiratory volume in 1 second (FEV1)	47.4 percentage STANDARD_DEVIATION 12.1 • n=5 Participants	47.2 percentage STANDARD_DEVIATION 11.1 • n=7 Participants	47.3 percentage STANDARD_DEVIATION 11.6 • n=5 Participants
Baseline diffusion capacity of carbon monoxide (DLCO)	13.6 mL/min/mmHg STANDARD_DEVIATION 5.3 • n=5 Participants	15.0 mL/min/mmHg STANDARD_DEVIATION 5.6 • n=7 Participants	14.3 mL/min/mmHg STANDARD_DEVIATION 5.5 • n=5 Participants
Number of participants with ZZ genotype (A1-PI deficiency), or SZ, Z / Null or Other genotype ZZ	83 participants n=5 Participants	83 participants n=7 Participants	166 participants n=5 Participants
Number of participants with ZZ genotype (A1-PI deficiency), or SZ, Z / Null or Other genotype SZ	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Number of participants with ZZ genotype (A1-PI deficiency), or SZ, Z / Null or Other genotype Z / Null	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Number of participants with ZZ genotype (A1-PI deficiency), or SZ, Z / Null or Other genotype Other	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants

PRIMARY outcome

Timeframe: Over a 2-year period

Population: All randomized participants with at least 1 valid CT scan.

As measured by centralized, standardized computer tomographic (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 rate of decline in each treatment group.

Outcome measures

Measure	Zemaira® n=92 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=85 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Annual Rate of Change in Lung Density FRC	-1.55 g/L per year Standard Error 0.24	-2.02 g/L per year Standard Error 0.26
Annual Rate of Change in Lung Density TLC + FRC combined	-1.50 g/L per year Standard Error 0.22	-2.12 g/L per year Standard Error 0.24
Annual Rate of Change in Lung Density TLC	-1.45 g/L per year Standard Error 0.23	-2.19 g/L per year Standard Error 0.25

SECONDARY outcome

Timeframe: Over a 2-year period

Population: All participants with A1-PI deficiency who were included in the study and randomized.

Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion. The annual rate was based on the total number of exacerbations and the total number of participant study days for all participants in the specified analysis population and adjusted to 365.25 days.

Outcome measures

Measure	Zemaira® n=93 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=87 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Annual Rate of Pulmonary Exacerbations	1.70 exacerbations per participant year Interval 1.51 to 1.89	1.42 exacerbations per participant year Interval 1.23 to 1.61

SECONDARY outcome

Timeframe: From baseline to 2 years

Population: All participants with A1-PI deficiency who were included in the study, randomized, and had a baseline and at least one endpoint assessment available.

Percent change from baseline to Month 24.

Outcome measures

Measure	Zemaira® n=89 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=84 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Percent Change in FEV1	-4.29 percent change Standard Error 1.26	-2.06 percent change Standard Error 1.30

SECONDARY outcome

Timeframe: Over a 2-year period

Population: All participants with A1-PI deficiency who were included in the study and randomized.

Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion.

Outcome measures

Measure	Zemaira® n=93 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=87 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Time to First Pulmonary Exacerbation	0.60 Years Interval 0.33 to 1.11	0.73 Years Interval 0.46 to 1.17

SECONDARY outcome

Timeframe: From baseline to 2 years

Population: All participants with A1-PI deficiency who were included in the study, randomized, and had a baseline and at least 1 endpoint assessment available.

Change from baseline to Month 24 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.

Outcome measures

Measure	Zemaira® n=80 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=67 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Change in Lung Density TLC + FRC combined	-2.33 g/L Standard Error 0.45	-3.37 g/L Standard Error 0.50
Change in Lung Density TLC (N=66 for placebo)	-2.22 g/L Standard Error 0.47	-3.54 g/L Standard Error 0.52
Change in Lung Density FRC	-2.44 g/L Standard Error 0.50	-3.33 g/L Standard Error 0.56

SECONDARY outcome

Timeframe: From baseline to 2 years

Population: All participants with A1-PI deficiency who were included in the study, randomized, and had a baseline and at least one endpoint assessment available.

Exercise capacity was measured as distance walked, using the incremental shuttle walk test. Change from baseline to end of treatment (2 years) in exercise capacity was analysed using an analysis of covariance (ANCOVA).

Outcome measures

Measure	Zemaira® n=89 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=82 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Change in Exercise Capacity	1.77 metre Standard Error 13.0	14.86 metre Standard Error 13.5

SECONDARY outcome

Timeframe: From baseline to 2 years

Population: All participants with A1-PI deficiency who were included in the study, randomized, and had a baseline and at least one endpoint assessment available.

Patient-reported symptoms were measured using the symptoms score component of the St George's Respiratory Questionnaire (SGRQ). SGRQ scores range from 0 to 100, with higher scores indicating more limitations and negative values for change indicating improvement. Change from baseline to end of treatment (2 years) in SGRQ was analysed using an ANCOVA.

Outcome measures

Measure	Zemaira® n=85 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=73 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Change in Patient-reported Symptoms	-1.19 units on a scale Standard Error 1.79	-0.09 units on a scale Standard Error 1.93

SECONDARY outcome

Timeframe: Over a 2-year period

Population: All participants receiving at least 1 infusion of either Zemaira® or placebo.

Number of participants with at least one AE, and the number of participants with mild, moderate or severe AEs. AE intensity was defined as mild (does not interfere with routine activities), moderate (interferes with routine activities), or severe (impossible to perform routine activities).

Outcome measures

Measure	Zemaira® n=93 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=87 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Frequency and Intensity of Adverse Events (AEs) At least 1 AE	92 participants	86 participants
Frequency and Intensity of Adverse Events (AEs) Mild AEs	13 participants	16 participants
Frequency and Intensity of Adverse Events (AEs) Moderate AEs	54 participants	43 participants
Frequency and Intensity of Adverse Events (AEs) Severe AEs	25 participants	27 participants

SECONDARY outcome

Timeframe: From baseline to 2 years

Population: All participants with A1-PI deficiency who were included in the study, randomized, and had a baseline and at least one endpoint assessment available.

Percent change from baseline to Month 24.

Outcome measures

Measure	Zemaira® n=89 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=84 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Percent Change in Percent Predicted FEV1	-4.16 percent change Standard Error 1.27	-1.90 percent change Standard Error 1.31

SECONDARY outcome

Timeframe: From baseline to 2 years

Population: All participants with A1-PI deficiency who were included in the study, randomized, and had a baseline and at least one endpoint assessment available.

Percent change from baseline to Month 24.

Outcome measures

Measure	Zemaira® n=89 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=84 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Percent Change in FEV1 Divided by Forced Vital Capacity	-2.68 percent change Standard Error 1.36	1.56 percent change Standard Error 1.40

SECONDARY outcome

Timeframe: From baseline to 2 years

Population: All participants with A1-PI deficiency who were included in the study, randomized, and had a baseline and at least one endpoint assessment available.

Percent change from baseline to Month 24.

Outcome measures

Measure	Zemaira® n=89 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=84 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Percent Change in DLCO	-3.16 percent change Standard Error 1.96	-1.85 percent change Standard Error 2.03

SECONDARY outcome

Timeframe: Over a 2-year period

Population: All participants with A1-PI deficiency who were included in the study and randomized.

Defined as the percentage of total treatment duration across participants for 1) exacerbations overall, 2) antibiotic treatment for exacerbations, and 3) hospitalization for exacerbations. Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion.

Outcome measures

Measure	Zemaira® n=93 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=87 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Duration of Pulmonary Exacerbations Relative to Treatment Duration Exacerbations (n = 68, 59)	77.2 percentage of total treatment duration Standard Deviation 98.8	58.9 percentage of total treatment duration Standard Deviation 109.1
Duration of Pulmonary Exacerbations Relative to Treatment Duration Antibiotic treatment (n = 59, 52)	6.32 percentage of total treatment duration Standard Deviation 6.75	5.55 percentage of total treatment duration Standard Deviation 6.80
Duration of Pulmonary Exacerbations Relative to Treatment Duration Hospitalization (n = 19, 16)	6.22 percentage of total treatment duration Standard Deviation 8.79	2.16 percentage of total treatment duration Standard Deviation 1.67

SECONDARY outcome

Timeframe: Over a 2-year period

Population: All participants with A1-PI deficiency who were included in the study and randomized.

Defined as the number of participants requiring 1) antibiotic treatment for exacerbations, and 2) hospitalization for exacerbations. Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion.

Antibiotic treatment usage was reported by quarterly interval.

Outcome measures

Measure	Zemaira® n=93 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=87 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Severity of Pulmonary Exacerbations 3 hospitalizations	1 participants	3 participants
Severity of Pulmonary Exacerbations >3 hospitalizations	1 participants	0 participants
Severity of Pulmonary Exacerbations Antibiotics: Day 1 to <Month 3	22 participants	19 participants
Severity of Pulmonary Exacerbations Antibiotics: Month 3 to <Month 6	29 participants	20 participants
Severity of Pulmonary Exacerbations Antibiotics: Month 6 to <Month 9	24 participants	15 participants
Severity of Pulmonary Exacerbations Antibiotics: Month 9 to <Month 12	21 participants	17 participants
Severity of Pulmonary Exacerbations Antibiotics: Month 12 to <Month 15	30 participants	21 participants
Severity of Pulmonary Exacerbations Antibiotics: Month 15 to <Month 18	21 participants	15 participants
Severity of Pulmonary Exacerbations Antibiotics: Month 18 to <Month 21	26 participants	15 participants
Severity of Pulmonary Exacerbations Antibiotics: Month 21 to <Month 24	20 participants	15 participants
Severity of Pulmonary Exacerbations Total hospitalizations	13 participants	9 participants
Severity of Pulmonary Exacerbations 0 hospitalizations	80 participants	78 participants
Severity of Pulmonary Exacerbations 1 hospitalization	10 participants	5 participants
Severity of Pulmonary Exacerbations 2 hospitalizations	1 participants	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Outcome measures

Measure	Zemaira® n=90 Participants Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=83 Participants Lyophilized preparation: 60 mg/kg body weight/week intravenous
Baseline Lung Density at Total Lung Capacity (TLC) and Forced Residual Capacity (FRC) TLC	45.5 g/L Standard Deviation 15.8	48.9 g/L Standard Deviation 15.5
Baseline Lung Density at Total Lung Capacity (TLC) and Forced Residual Capacity (FRC) FRC	47.6 g/L Standard Deviation 15.7	50.7 g/L Standard Deviation 15.0

Adverse Events

Zemaira®

Serious events: 28 serious events

Other events: 90 other events

Deaths: 0 deaths

Placebo

Serious events: 28 serious events

Other events: 84 other events

Deaths: 0 deaths

Serious adverse events

Measure	Zemaira® n=93 participants at risk Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=87 participants at risk Lyophilized preparation: 60 mg/kg body weight/week intravenous
Infections and infestations Pneumonia	3.2% 3/93 • Number of events 3 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	4.6% 4/87 • Number of events 6 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Lower respiratory tract infection	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	4.6% 4/87 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Diverticulitis	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	2.3% 2/87 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Bronchitis	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Appendicitis	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Cellulitis	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Gastroenteritis viral	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Graft infection	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Pyelonephritis	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Sepsis	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Urinary tract infection	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	9.7% 9/93 • Number of events 18 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	2.3% 2/87 • Number of events 3 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 1/93 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	2.3% 2/87 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.2% 2/93 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	2.2% 2/93 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid tumour benign	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Abdominal pain	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Gastroesophageal reflux disease	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Ileus	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Nausea	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Adhesion	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Chest pain	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Condition aggravated	1.1% 1/93 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Influenza like illness	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Pyrexia	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Musculoskeletal and connective tissue disorders Back pain	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Nervous system disorders Dizziness	1.1% 1/93 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Nervous system disorders Neuropathy peripheral	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Nervous system disorders Syncope	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Surgical and medical procedures Aortic aneurysm repair	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Surgical and medical procedures Tonsillectomy	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Surgical and medical procedures Transurethral prostatectomy	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Cardiac disorders Angina pectoris	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Cardiac disorders Palpitations	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Injury, poisoning and procedural complications Joint injury	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Injury, poisoning and procedural complications Post procedural haemorrhage	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Psychiatric disorders Confusional state	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Psychiatric disorders Suicide attempt	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Renal and urinary disorders Hydronephrosis	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Renal and urinary disorders Nephrolithiasis	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Vascular disorders Deep vein thrombosis	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Vascular disorders Hypotension	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Eye disorders Eye inflammation	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Hepatobiliary disorders Cholelithiasis	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Immune system disorders Anaphylactic reaction	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Metabolism and nutrition disorders Hyponatraemia	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Small intestinal obstruction	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	0.00% 0/87 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.

Other adverse events

Measure	Zemaira® n=93 participants at risk Alpha1-proteinase inhibitor: 60 mg/kg body weight/week intravenous	Placebo n=87 participants at risk Lyophilized preparation: 60 mg/kg body weight/week intravenous
Gastrointestinal disorders Toothache	5.4% 5/93 • Number of events 7 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	10.3% 9/87 • Number of events 10 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Diarrhoea	8.6% 8/93 • Number of events 9 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	8.0% 7/87 • Number of events 9 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Nasopharyngitis	32.3% 30/93 • Number of events 54 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	29.9% 26/87 • Number of events 61 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Lower respiratory tract infection	19.4% 18/93 • Number of events 88 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	19.5% 17/87 • Number of events 68 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Upper respiratory tract infection	16.1% 15/93 • Number of events 28 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	16.1% 14/87 • Number of events 26 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Influenza	15.1% 14/93 • Number of events 14 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	11.5% 10/87 • Number of events 12 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Sinusitis	12.9% 12/93 • Number of events 17 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	12.6% 11/87 • Number of events 19 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Bronchitis	12.9% 12/93 • Number of events 25 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	11.5% 10/87 • Number of events 15 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Pneumonia	8.6% 8/93 • Number of events 12 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	11.5% 10/87 • Number of events 19 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Urinary tract infection	8.6% 8/93 • Number of events 12 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	6.9% 6/87 • Number of events 9 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Gastroenteritis	4.3% 4/93 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	6.9% 6/87 • Number of events 6 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Rhinitis	7.5% 7/93 • Number of events 8 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	3.4% 3/87 • Number of events 3 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Pharyngitis	4.3% 4/93 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	5.7% 5/87 • Number of events 8 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Respiratory tract infection	1.1% 1/93 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	9.2% 8/87 • Number of events 12 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Infections and infestations Tooth abscess	1.1% 1/93 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	5.7% 5/87 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	29.0% 27/93 • Number of events 93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	21.8% 19/87 • Number of events 53 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	23.7% 22/93 • Number of events 36 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	11.5% 10/87 • Number of events 13 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Respiratory, thoracic and mediastinal disorders Cough	22.6% 21/93 • Number of events 33 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	9.2% 8/87 • Number of events 9 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.2% 16/93 • Number of events 28 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	9.2% 8/87 • Number of events 9 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Condition aggravated	21.5% 20/93 • Number of events 62 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	16.1% 14/87 • Number of events 41 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Fatigue	8.6% 8/93 • Number of events 14 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	11.5% 10/87 • Number of events 12 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Pyrexia	12.9% 12/93 • Number of events 14 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	6.9% 6/87 • Number of events 8 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Oedema peripheral	6.5% 6/93 • Number of events 6 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	11.5% 10/87 • Number of events 14 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Influenza like illness	4.3% 4/93 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	5.7% 5/87 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
General disorders Chest pain	5.4% 5/93 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 1 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Nervous system disorders Headache	40.9% 38/93 • Number of events 101 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	39.1% 34/87 • Number of events 108 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Nervous system disorders Dizziness	6.5% 6/93 • Number of events 13 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	9.2% 8/87 • Number of events 8 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Nausea	15.1% 14/93 • Number of events 22 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	9.2% 8/87 • Number of events 11 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Abdominal pain upper	9.7% 9/93 • Number of events 11 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	6.9% 6/87 • Number of events 11 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.4% 5/93 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	5.7% 5/87 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Vomiting	5.4% 5/93 • Number of events 10 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	5.7% 5/87 • Number of events 6 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Abdominal discomfort	2.2% 2/93 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	6.9% 6/87 • Number of events 8 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Gastrointestinal disorders Gastritis	6.5% 6/93 • Number of events 9 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	1.1% 1/87 • Number of events 2 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Musculoskeletal and connective tissue disorders Back pain	11.8% 11/93 • Number of events 11 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	10.3% 9/87 • Number of events 11 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Musculoskeletal and connective tissue disorders Arthralgia	6.5% 6/93 • Number of events 9 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	6.9% 6/87 • Number of events 9 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Musculoskeletal and connective tissue disorders Muscle spasms	7.5% 7/93 • Number of events 10 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	4.6% 4/87 • Number of events 7 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.4% 5/93 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	4.6% 4/87 • Number of events 8 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Musculoskeletal and connective tissue disorders Pain in extremity	5.4% 5/93 • Number of events 6 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	4.6% 4/87 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Injury, poisoning and procedural complications Contusion	0.00% 0/93 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	5.7% 5/87 • Number of events 5 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Vascular disorders Hypertension	6.5% 6/93 • Number of events 6 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	11.5% 10/87 • Number of events 10 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.
Psychiatric disorders Anxiety	5.4% 5/93 • Number of events 12 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.	4.6% 4/87 • Number of events 4 • For the duration of the study (25 months; 1 month screening period, 24 months treatment period). The randomized, double-blind investigational product (Zemaira® or placebo) was administered as 60 mg once per week for 24 months. In exceptional cases, a dose of 120 mg could be given to cover a 2-week period. The safety population comprised all participants receiving at least 1 infusion of either Zemaira® or placebo.

Additional Information

Clinical Trial Disclosure Manager

CSL Behring

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Email: clinicaltrials@cslbehring.com

Results disclosure agreements

• Principal investigator is a sponsor employee CSL agreements and restrictions on publishing may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and generally requires that reports based on single-site data not precede the primary publication of the entire clinical trial.
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Restriction type: OTHER