An Open-label, Randomized Study to Evaluate the Long-term Clinical Safety and Efficacy of Subcutaneous Administration of Human Plasma-derived C1-esterase Inhibitor in the Prophylactic Treatment of Hereditary Angioedema
Phase: PHASE3
Conditions: Hereditary Angioedema Types I and II
Sponsor: CSL Behring

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2015 
Page 2 of 130 
(United States) 
Confidential 
List of Personnel and Organizations Responsible for Conduct of the Study 
 
A list of personnel and organizations responsible for the conduct of the study will be supplied 
to study sites as part of the Investigator’s Study File. This list will be updated by CSL (or 
delegate) and provided to the study sites as needed.  
 
 

PPD
PPD
PPD
PPD

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2015 
Page 4 of 130 
(United States) 
Confidential 
Signature of Investigator 
 
Study Title: An open-label, randomized study to evaluate the long-term clinical safety and 
efficacy of subcutaneous administration of human plasma-derived C1-esterase inhibitor in the 
prophylactic treatment of hereditary angioedema. 
Protocol Number: 
 CSL830_3002 
I have read the protocol titled “An open-label, randomized study to evaluate the long-term 
clinical safety and efficacy of subcutaneous administration of human plasma-derived 
C1-esterase inhibitor in the prophylactic treatment of hereditary angioedema.” 
By signing this protocol, I agree to conduct the clinical study, after approval by an 
Institutional Review Board or Independent Ethics Committee (as appropriate), in accordance 
with the protocol, the standards of Good Clinical Practice (as defined by the International 
Conference on Harmonisation), and applicable regulatory requirements.  
Changes to the protocol will only be implemented after written approval is received from 
CSL Behring GmbH (CSL) and the Institutional Review Board or Independent Ethics 
Committee (as appropriate), with the exception of medical emergencies.  
I will ensure that study staff fully understand and follow the protocol. 
 
 
 
 
Name of investigator 
Affiliation of investigator 
 
 
Date  
(DD MMM YYYY) 
 
 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2015 
Page 5 of 130 
(United States) 
Confidential 
Protocol Synopsis  
Title 
An open-label, randomized study to evaluate the long-term clinical 
safety and efficacy of subcutaneous administration of human 
plasma-derived C1-esterase inhibitor in the prophylactic treatment 
of hereditary angioedema 
Study Number 
CSL830_3002 
Sponsor 
CSL Behring GmbH (CSL) 
Development Phase 
3b 
Study Product 
CSL830 
Indication 
Hereditary Angioedema (Type I and II) 
Study Summary 
This is a multicenter, randomized, open-label, parallel-arm, phase 
3b study designed to investigate the clinical safety and efficacy of 
subcutaneously administered CSL830 in the prophylactic treatment 
of hereditary angioedema (HAE). The study will consist of 2 
treatment periods. Treatment Period 1 (24 weeks) will be a fixed-
dose period. Treatment Period 2 (28 weeks) will be a dose-
adjustment period to allow for individual optimization of 
prophylaxis. Subjects from the United States who complete 
Treatment Period 2 will be allowed to participate in an Extension 
Period to continue to receive treatment with open-label CSL830.  
Subjects belonging to the following categories will undergo 
assessment at a Screening Visit in order to confirm their eligibility: 
• “CSL830-Naïve” Subjects (subjects who did not participate in 
study CSL830_3001; subjects who participated in study 
CSL830_3001 but did not receive blinded investigational 
product). 
• “CSL830-Interrupted” Subjects (subjects who completed 
participation in study CSL830_3001, but who delayed entry 
into the current study [ie, > 1 week between the End of Study 
Visit of CSL830_3001 and the first visit of CSL830_3002 
Treatment Period 1]).  
Subjects belonging to the following category will not have a 
Screening Visit: 
• “CSL830-Continuation” Subjects (subjects who complete 
participation in study CSL830_3001 and who continue directly 
on to participate in the current study [ie, ≤ 1 week between the 
End of Study Visit of CSL830_3001 and the first visit of 
CSL830_3002 Treatment Period 1]).  
The eligibility of “CSL830-Continuation” Subjects will include 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2015 
Page 6 of 130 
(United States) 
Confidential 
evaluation based upon assessments performed in CSL830_3001 
(see additional details in the protocol body).  
Treatment Period 1 will begin with the Day 1 Visit and will end 
with the Week 25 Visit. Treatment Period 2 will begin either during 
the Week 25 Visit (if CSL830 is administered at the study visit) or 
immediately following the Week 25 Visit. Treatment Period 2 will 
end with the Week 53 Visit. 
Eligible subjects will be randomized to 1 of the following CSL830 
treatment groups at the first visit in Treatment Period 1: 
• 40 IU/kg CSL830 treatment group, OR  
• 60 IU/kg CSL830 treatment group.  
CSL830 will be administered as a single subcutaneous injection 
twice weekly either independently (ie, self-administered by the 
subject) or with assistance (ie, with the help of a caretaker such as 
a parent or guardian) at home during Treatment Period 1 and 
Treatment Period 2. Treatment will be administered in an open-
label manner.  
During the fixed-dose Treatment Period 1, subjects who experience 
very frequent HAE attacks (ie, ≥ 12 attacks, as defined per 
protocol, within a 4-week evaluation period) are eligible for 
CSL830 dose increases in increments of 20 IU/kg (up to a 
maximum dose of 80 IU/kg). All CSL830 dose increases are 
optional, and will be made only in subjects who are eligible, at the 
sole discretion of investigator. Dose increases during Treatment 
Period 1 are intended as rescue prophylaxis, to provide the 
opportunity for subjects who have very frequent HAE attacks to 
continue in the study during this otherwise fixed-dose treatment 
period.  
Beginning with the Week 25 Visit and throughout Treatment Period 
2, subjects who experience ≥ 3 HAE attacks (as determined per 
protocol) within an 8-week evaluation period are eligible for 
CSL830 dose increases in increments of 20 IU/kg (up to a 
maximum dose of 80 IU/kg). All CSL830 dose increases are 
optional, and will be made only in subjects who are eligible, at the 
sole discretion of investigator. Dose increases during Treatment 
Period 2 are intended to allow investigators to adjust/optimize the 
dose for subjects who may need a higher dose for prophylaxis.  
An evaluation period for any dose increase in either Treatment 
Period 1 or Treatment Period 2 is defined as beginning after a dose-
stable period (ie, 2 weeks after the initiation or dose increase of 
CSL830). 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2015 
Page 7 of 130 
(United States) 
Confidential 
Subjects will attend a Follow-up Visit occurring 14 days (± 3 days) 
after the final visit in Treatment Period 2 or any visit resulting in 
study discontinuation, unless informed consent/assent has been 
withdrawn or if the Extension Period starts prior to the scheduled 
Follow-up Visit. During the Follow-up Period, subjects will be 
followed for HAE attacks, the emergence of new adverse events 
(AEs), and the use of concomitant medication. 
Primary Objective(s) 
The primary objective is to assess the clinical safety of 
subcutaneously administered CSL830 in the long-term 
prophylactic treatment of HAE. 
Primary Endpoint(s) 
The primary endpoints are the person-time incidence rates of each 
of the following: 
• Adverse events leading to premature study discontinuation. 
• Thromboembolic events (TEEs). 
• Anaphylaxis. 
• HAE attacks resulting in in-patient hospitalization (where 
hospitalization is the consequence of the need for emergent 
medical care). 
• Solicited AEs (injection site reactions at the CSL830 injection 
site) graded as severe by the investigator. 
• Related serious adverse events (SAEs), other than events 
specified above. 
• Anti-C1-INH (anti-C1-esterase inhibitor) antibodies (inhibitory 
or non-inhibitory). 
The person-time incidence rates are the number of subjects 
experiencing each primary endpoint safety event during treatment 
with CSL830, divided by the sum of each subject’s time at risk. 
The primary endpoints will be assessed for Treatment Period 1, 
Treatment Period 2 and Treatment Periods 1 and 2 together. The 
primary endpoints will also be assessed for the Extension Period 
(only) and for the treatment periods overall for subjects who are 
included in the Extension Period. 
Secondary 
Objective(s) 
The secondary objectives are the following: 
1. To further characterize the clinical safety of subcutaneously 
administered CSL830 in the long-term prophylactic treatment 
of HAE. 
2. To characterize the clinical efficacy of subcutaneously 
administered CSL830 in the long-term prophylactic treatment 
of HAE. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2015 
Page 8 of 130 
(United States) 
Confidential 
Secondary 
Endpoint(s) 
1. The secondary safety endpoints are the following: 
a) The percentage of subjects experiencing the following 
events: SAEs, temporally-related AEs, increased risk scores 
for deep vein thrombosis (DVT) or pulmonary embolism 
(PE), TEEs, inhibitory anti-C1-INH antibodies, or clinically 
significant abnormalities in laboratory assessments (ie, lab 
abnormalities reported as AEs). 
b) The percentage of administrations of CSL830 resulting in 
solicited local AEs (discomfort [eg, pain, burning], 
swelling, bruising, or itching at the CSL830 injection site). 
c) The percentage of subjects who have at least 1 solicited 
local AE (discomfort [eg, pain, burning], swelling, bruising, 
or itching at the CSL830 injection site). 
d) The percentage of subjects who become seropositive for 
human immunodeficiency virus types 1 or 2 (HIV-1/-2), 
hepatitis B virus (HBV), or hepatitis C virus (HCV).  
The secondary safety endpoints will be assessed for Treatment 
Period 1, Treatment Period 2, and Treatment Periods 1 and 2 
(together). The secondary safety endpoints will also be assessed for 
the Extension Period (only) and for the treatment periods overall 
for subjects who are included in the Extension Period.  
2. Efficacy endpoints considered as secondary include the 
following:  
a) The percentage of subjects who experience a time-
normalized HAE attack frequency of < 1 HAE attack per 
4-week period. 
b) The percentage of subjects who are responders. “Response” 
is defined as a ≥ 50% relative reduction in the time-
normalized number of HAE attacks during treatment with 
CSL830, compared with the time-normalized number of 
attacks that is used to qualify the subject for participation in 
the study. 
The secondary efficacy endpoints will be assessed for Treatment 
Period 1, and Treatment Periods 1 and 2 (together). The secondary 
efficacy endpoints will also be assessed for the Extension Period 
(only) and for the treatment periods overall for subjects who are 
included in the Extension Period. 

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CCI

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2015 
Page 11 of 130 
(United States) 
Confidential 
• A Screening Period lasting up to 4 weeks (≤ 28 days), as 
needed. 
• Two treatment periods totaling 52 weeks (367 days ± 2 days). 
• A Follow-up Period lasting 2 weeks (14 days ± 3 days). 
Extension Period (Optional) 
The Extension Period (88 weeks) followed by the Extension Period 
follow-up (2 weeks) will begin at first subject first visit in the 
Extension Period and result in an anticipated total study duration of 
up to approximately 146 weeks for participating subjects. Subjects 
who have any Extension Period visits that occur within 6 weeks 
before the study end date will be handled as completers. These 
subjects will attend the final study visit (Extension Period Week 
88) in place of their next study visit or telephone contact and will 
receive follow-up telephone contact (Extension Period Week 90 ± 
3 days). Subjects who roll-over into the Extension Period prior to 
the Treatment Period 2 Follow-up Visit will be regarded as 
completers. All subjects who are not withdrawn from the study will 
be considered completers of the study.  
Study Population and 
Main Criteria for 
Eligibility 
Subjects must meet all of the following inclusion criteria in 
order to be enrolled (randomized) into the study: 
• Male or female. 
• Aged 6 years or older at the time of providing written informed 
consent/assent (as appropriate). 
• A diagnosis of HAE type I or II, as determined by the 
following: a clinical history consistent with HAE and C1-INH 
functional activity levels < 50%, concurrent with C4 antigen 
concentrations below normal limits. NOTE: Additional details 
on the application of this criterion to “CSL830-Continuation/-
Interrupted/-Naïve” Subjects are presented in the protocol 
body.  
• Have experienced HAE attacks (requiring acute treatment, 
medical attention or causing significant functional impairment), 
as described below: 
o For “CSL830 Naïve” Subjects:  
 “CSL830-Naïve” Subjects using intravenous C1-INH as 
routine (long-term) prophylaxis against HAE attacks must 
have experienced 4 HAE attacks over any consecutive 2-
month period before the initiation of intravenous C1-INH 
prophylaxis and before the CSL830_3002 Screening 
Visit, as documented in the subject medical records. 
 All other “CSL830-Naïve” Subjects (eg, treated using 
oral HAE prophylaxis against HAE attacks or on-demand 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2015 
Page 12 of 130 
(United States) 
Confidential 
treatment) must have experienced 4 HAE attacks over a 
consecutive 2-month period within the 3 months before 
the CSL830_3002 Screening Visit, as documented in the 
subject medical records.  
o For “CSL830-Continuation” Subjects AND “CSL830-
Interrupted” Subjects: Subjects must have experienced 
4 HAE attacks over a consecutive 2-month period within the 
3 months before the CSL830_3001 Screening Visit, as 
documented in the subject medical records (ie, the HAE 
attack frequency required for eligibility to participate in 
study CSL830_3001). 
• For subjects who have used oral medication for prophylaxis 
against HAE attacks (ie, androgens, tranexamic acid, 
progestins) during the 3 months before the first study visit: use 
of a stable regimen of oral prophylactic medication (ie, dose 
and administration frequency) during the 3 months before the 
first study visit and willingness to continue the stable regimen 
for at least 25 weeks. 
Subjects meeting any of the following exclusion criteria must 
not be enrolled (randomized) into the study: 
• Known incurable malignancies at the time of the first study 
visit. 
• Any clinical condition that is likely to interfere with evaluation 
of CSL830 or satisfactory conduct of the study. 
• A clinically significant history of poor response to C1-INH 
therapy for the management of HAE. 
• A suspected or confirmed diagnosis of acquired HAE or HAE 
with normal C1-INH (ie, HAE type III). 
• Assessed by the investigator as unable to have their HAE 
adequately managed pharmacologically with on-demand 
treatment, when that on-demand treatment is administered 
independently or with assistance. 
Study Product Dose, 
Dosing Regimen and 
Administration  
CSL830 is a C1-INH concentrate, which is a volume-reduced 
formulation of the marketed product, Berinert, currently licensed 
for the acute treatment of HAE attacks. CSL830 is a lyophilized 
powder (1500 IU C1-INH per single-use vial) reconstituted with 
3 mL water for injection.  
During Treatment Periods 1 and 2, subjects who do not increase 
their dose of CSL830 will administer CSL830 (40 IU/kg or 
60 IU/kg, per randomization) via a single SC injection, twice 
weekly. During Treatment Periods 1 and 2, the actual dose of 
CSL830 that is assigned will be rounded up to the nearest 500 IU, 

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2015 
Page 15 of 130 
(United States) 
Confidential 
respectively, until the time they undergo the final study visit. 
The analyses will be done both for Treatment Period 1 (only) and 
for Treatment Period 1 and 2 (together), unless otherwise noted. 
Furthermore, safety analyses will be summarized by subjects who 
are randomized to 40 IU/kg CSL830 and who have 1 dose 
increase; by subjects who are randomized to 40 IU/kg CSL830 and 
who have 2 dose increases; by subjects who are randomized to 
60 IU/kg CSL830 and who have 1 dose increase. These dosing 
groups will be given separately for Treatment Periods 1 and 2, 
depending if the dose increase takes place in Treatment Period 1 or 
2. 
The person-time incidence rate of each primary endpoint safety 
event will be assessed as primary safety analysis, as defined above 
and overall. 
Adverse events will be classified using the Medical Dictionary for 
Regulatory Activities (MedDRA). Serious AEs, temporally-related 
AEs, increased risk scores for DVT or PE, thromboembolic events, 
inhibitory anti-C1-INH antibodies, or clinically significant 
abnormalities in laboratory assessments occurring during treatment 
will be summarized for the safety analyses. 
Extension Period 
Data collected during the Extension Period will be summarized as 
follows:  
• For the Extension Period only (separate from data collected 
during Treatment Period 1 and Treatment Period 2 using 
descriptive statistics.) 
• For Treatment Period 1, Treatment Period 2 and the 
Extension Period (combined) 
Only data collected from subjects who are in enrolled the 
Extension Period will be included in these analyses. 
Interim Analyses 
Interim analyses will be conducted on an as-needed basis in order 
to support regulatory activities. The results of interim analyses are 
not intended to be used to stop or adapt the study. Additional 
details will be provided in the statistical analysis plan (SAP). 

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CSL Behring GmbH   
Study Number: CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2014 
Page 17 of 130 
(United States) 
Confidential 
 
Treatment Period 1 B, C 
Treatment Period 2 C 
Follow-up D 
Week 
1 
5 
9 
13 
17 
21 
25 
29 
33 
37 
41 
45 
49 
53 
See 
Footnote D. 
Day 
1 
29 
57 
85 
113 
141 
169 
197 
225 
253 
281 
309 
337 
367 
Window (days) 
 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
Collect eDiary 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X M 
Schedule next visit / contact 
X 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
[Abbreviations and footnotes are presented on the following page.] 

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CCI

CSL Behring GmbH   
Study Number: CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2014 
Page 19 of 130 
(United States) 
Confidential 
L: Beginning with the Week 25 Visit and throughout Treatment Period 2, subjects who experience ≥ 3 HAE attacks (as determined per protocol) within an 
8-week evaluation period are eligible for CSL830 dose increases in increments of 20 IU/kg (up to a maximum dose of 80 IU/kg). All CSL830 dose increases 
are optional, and will be made only in subjects who are eligible, at the sole discretion of investigator. An evaluation period for any dose increase is defined 
as beginning after a dose-stable period (ie, 2 weeks after the initiation or dose increase of CSL830). See Section 3.2 for additional details. 
M: The subject eDiary will not be collected from subjects at the last visit of Treatment Period 2 (Follow-up Visit) if they plan to participate in the Extension 
Period. 
 

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CSL Behring GmbH   
Study Number: CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2014 
Page 21 of 130 
(United States) 
Confidential 
E: The urine test for beta-human chorionic gonadotropin will be performed at the study site. All females are to be tested to assess eligibility prior 
to randomization and dosing. A urine pregnancy test will be conducted to assess eligibility ONLY if the CSL830_3001 End of Study Visit and 
the first visit of CSL830_3002 Treatment Period 1 (ie, Day 1) occur on different days. 
 

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CSL Behring GmbH   
Study Number: CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2014 
Page 24 of 130 
(United States) 
Confidential 
O: The subject eDiary will not be collected from subjects at the last visit of Treatment Period 2 (Follow-up Visit) if they plan to participate in the Extension Period.  

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CSL Behring GmbH   
Study Number: CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
10 JULY 2014 
Page 29 of 130 
(United States) 
Confidential 
Notes to the Schedule of Events for the Extension Period: 
A: This is the first visit of the Extension Period; the last visit of Treatment Period 2 and the first visit of the Extension Period should occur on the same day, 
when possible (however, subjects can elect to take a rest period of up to 30 days between the final visit of Treatment Period 2 and the first visit of the 
Extension Period).  
B:  This is the last on-site visit of Extension Period.  
C: This is the Extension Period Follow-up Contact. Subjects will attend a Follow-up Visit occurring 14 days (± 3 days) after the final visit in the Extension 
Period or any visit resulting in study discontinuation, unless informed consent/assent has been withdrawn. 
D: Visit 1 of the Extension Period can occur within 30 days after the last visit of Treatment Period 2.  
E:  To be repeated at Extension Period Visit 1only if the Final Visit of Treatment Period 2 and Extension Period Visit 1 are conducted on different days. 
F: The subject will be advised to resume usual medical care upon completion of the study. 
G:  Starting with the Extension Period Visit 1, the subject’s CSL830 by-weight dose will be rounded to the nearest (ie, up or down) 1000 IU for subject weighing 
≥ 40 kg; subjects weighing < 40 kg will continue to undergo rounding as during Treatment Periods 1 and 2 (ie, rounded up to the nearest 500 IU).  
H:  Beginning with the Extension Period Visit 1 and throughout the Extension Period, subjects who experience ≥ 3 HAE attacks (as determined per protocol) 
within an 8 week evaluation period are eligible for CSL830 dose increases in increments of 20 IU/kg (up to a maximum dose of 80 IU/kg). See Section 3.2 
for additional details. 
I: 
The subject diary will not be collected from subjects at the last visit of Treatment Period 2 (Follow-up Visit) if they plan to participate in the Extension 
Period. For subjects who elect to take a rest period between Treatment Period 2 and the Extension Period, the diary will not be used after the already planned 
Treatment Period 2 follow-up period (approximately 2 weeks); however, information for the period during which no diary is in use will be recorded (see 
Section 8.4.6.1.2 for additional details). The subject diary will only be used at the first visit of the Extension Period.  
J: The Quality of Life Questionnaire for Patients with Recurrent Swelling Episodes (AE Quality of Life) will be self-administered and assessed by the subjects 
at Weeks 6, 22, 46 and 70 of the Extension Period.  
K: The Hereditary Angioedema Quality of Life Questionnaire (HAE Quality of Life) will be self-administered and assessed by the subjects at Weeks 26, 50 and 
74 of the Extension Period. 

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 31 of 130 
(United States) 
Confidential 
3 
Study Design......................................................................................................... 47 
3.1 
Study Design and Rationale ............................................................................. 47 
3.1.1 
Screening Visit .............................................................................................. 48 
3.1.2 
Treatment Periods 1 and 2 ............................................................................ 48 
3.1.3 
Extension Period ........................................................................................... 49 
3.1.4 
Post-treatment Follow-up ............................................................................. 49 
3.1.5 
Enrollment Stopping Rules .......................................................................... 50 
3.1.6 
Enrollment Re-starting Rules ....................................................................... 50 
3.1.7 
Study Termination Rules .............................................................................. 50 
3.2 
Dose and Dosing Regimen ............................................................................... 50 
3.3 
Planned Study Duration ................................................................................... 52 
3.4 
Planned Number of Sites .................................................................................. 53 
3.5 
Planned Number of Subjects ............................................................................ 53 
3.6 
Study Monitoring Procedures........................................................................... 53 
3.6.1 
Steering Committee ...................................................................................... 53 
4 
Selection and Withdrawal of Subjects .................................................................. 54 
4.1 
Eligibility Criteria ............................................................................................ 54 
4.1.1 
Subject Classification ................................................................................... 54 
4.1.2 
Inclusion Criteria .......................................................................................... 55 
4.1.3 
Exclusion Criteria ......................................................................................... 57 
4.2 
Subject Withdrawal and Replacement .............................................................. 58 
4.2.1 
Subject Withdrawal ...................................................................................... 58 
4.2.2 
Procedures for Handling Withdrawals.......................................................... 58 
4.2.3 
Replacement Policy ...................................................................................... 59 
5 
Study Interventions ............................................................................................... 60 
5.1 
Description of Investigational Product ............................................................. 60 
5.1.1 
CSL830 ......................................................................................................... 60 
5.1.2 
Comparator Product ..................................................................................... 60 
5.2 
Packaging, Labeling, Supply and Storage ........................................................ 60 
5.2.1 
Packaging and Labeling ............................................................................... 60 
5.2.2 
Supply and Storage ....................................................................................... 61 
5.3 
Accountability and Destruction ........................................................................ 61 
5.4 
Other Intervention(s) ........................................................................................ 61 
6 
Allocation, Dosing and Administration ................................................................ 61 

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 38 of 130 
(United States) 
Confidential 
1 
Introduction 
1.1 
Background 
Hereditary angioedema (HAE) is a rare genetic disorder with 3 known types (I, II, and III) 
[Rosen et al 1965; Bork et al 2000]. Type I and II HAE are autosomal dominant inherited 
disorders, which are associated with a deficiency in C1-esterase inhibitor (C1-INH) 
[Donaldson and Evans 1963]. In type I HAE (common form genotype), an impaired synthesis 
of a normal and functionally active C1-INH molecule occurs [Rosen et al 1965]. This causes 
a reduction in the availability of functionally active C1-INH levels to between 6% and 25% 
of normal [Rosen et al 1965]. In type II HAE (variant form genotype), normal levels of a 
functionally impaired C1-INH molecule are synthesized, but the normal form of C1-INH is 
considerably reduced in the circulation. Type III HAE is even less frequent and is not 
associated with C1-INH deficiency [Bork et al 2000]. The prevalence of type I and II HAE is 
estimated to be in the order of 1:50,000 [Göring et al 1998, Kunschak et al 1998], with 
approximately 85% of subjects having type I HAE and approximately 15% of subjects 
having type II HAE [Longhurst and Bork 2006].  
HAE is a debilitating disease and subjects with frequent attacks are severely affected in their 
quality of life. Clinically, type I and II HAE are characterized by local 
subcutaneous (SC) / submucosal swellings of the skin (ie, edema of the extremities, facial 
edema, and edema of the genitals), abdominal pain attacks, and, rarely, life-threatening 
attacks of laryngeal edema [Bork 2008]. Attacks typically follow a course in which the 
edema increases for 24 to 36 hours and then slowly decreases during the following 48 to 
72 hours [Zuraw 2008].  
Treatment for type I and II HAE can be subdivided into the acute treatment of attacks and 
prophylaxis. The treatment of choice in the event of an HAE attack is the rapid replacement 
of the functionally missing plasma protein (ie, by intravenous [IV] administration of C1-INH 
concentrate or fresh frozen plasma) [Bork 2008, Gompels et al 2005, Longhurst 2005]. 
Recently, compounds including a kallikrein inhibitor and a bradykinin receptor antagonist 
have been added to the spectrum of anti-HAE medications [Cicardi et al 2010a, Cicardi et al 
2010b]. Attenuated androgens or antifibrinolytics are effective in some subjects as 
prophylactic therapy, but may have significant side effects [Banerji et al 2008, Göring et al 
1998]. Regular IV infusions of C1-INH can also be used for HAE prophylaxis [Zuraw et al 
2010]. However, repeated IV administration may not be practical for all patients, and IV 
access can become progressively more difficult with time.  

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 39 of 130 
(United States) 
Confidential 
A more convenient route of administration (eg, SC) may facilitate the use of C1-INH in HAE 
prophylaxis. The pharmacokinetics (PK) of subcutaneously administered C1-INH in patients 
with HAE have been investigated using a currently available formulation [Martinez-Saguer et 
al 2013]. The study examined 1000 units (U) of C1-INH, in a volume of 20 mL, administered 
intravenously or subcutaneously; subcutaneously administered C1-INH had a bioavailability 
of approximately 40%, and was generally well tolerated [Martinez-Saguer et al 2013].  
To further enhance the feasibility of SC administration of C1-INH, CSL830 has been 
developed as a human plasma-derived C1-INH concentrate that can be reconstituted in a low 
volume. CSL830 is being investigated for the prevention of HAE attacks. 
1.2 
Background Information on CSL830 
1.2.1 
Overview 
CSL830, which is a C1-INH concentrate, is a volume-reduced formulation of the marketed 
product, Berinert. Berinert is currently licensed for the acute treatment of HAE attacks in 
more than 30 countries. The manufacturing process of CSL830 is almost identical to that of 
Berinert. The major difference between these 2 products is the concentration of C1-INH after 
reconstitution; CSL830 contains 1500 IU of C1-INH to be reconstituted in 3 mL whereas 
Berinert contains 500 IU of C1-INH to be reconstituted in 10 mL. 
1.2.2 
Nonclinical Evaluation 
Berinert has been assessed in nonclinical evaluations. Berinert was well tolerated and no 
toxicity was observed in single-dose toxicity studies in rats and mice and a repeat dose 
toxicity study in rats. Information on nonclinical safety studies conducted with Berinert is 
available in the European Summary of Product Characteristics for Berinert and in the US 
Prescribing Information. 
Because CSL830 has a higher local protein concentration compared with Berinert, 
2 nonclinical local tolerance studies with CSL830 have been conducted in rabbits. In these 
2 nonclinical studies, administration of a single injection of CSL830 (3 mL; IV, SC, intra-
arterial, and intramuscular injection) revealed no findings of clinical significance and was 
locally well tolerated. 
1.2.3 
Previous Clinical Experience 
Currently, clinical data are available from two studies that were conducted with CSL830: 
study CSL830_1001 and study CSL830_2001. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 40 of 130 
(United States) 
Confidential 
Study CSL830_1001 was conducted in healthy subjects in order to compare the safety and 
PK of intravenously administered CSL830 and Berinert (the currently marketed C1-INH 
concentrate). CSL830 had acceptable safety and local tolerability profiles. There were no 
adverse events (AEs) causally related to CSL830 or Berinert, and there were no clinically 
significant abnormalities in laboratory parameters, viral safety assessments, vital signs, 
physical examinations, or electrocardiogram results. No anti-C1-INH antibodies were 
detected in any subject. There were no thromboembolic events (TEEs), and no surrogate 
markers suggestive of pulmonary embolism (PE) or deep vein thrombosis (DVT) were 
identified. CSL830 and Berinert also had comparable PK profiles following single-dose, IV 
administration. 
Study CSL830_2001 was conducted in subjects with HAE (type I or II) in order to 
characterize the PK, pharmacodynamics (PD), and safety of SC administration. Functional 
levels of C1-INH activity and levels of C1-INH antigen and C4 antigen were achieved with 
each CSL830 dosing regimen that was tested. Subcutaneous administration of CSL830 of up 
to 6,000 IU was tolerated with local site events. Safety events were not related to either 
absolute CSL830 dose or dose per body weight. There was no evidence of a dose-response 
relationship between the administered dose of CSL830 and the intensity of treatment-
emergent adverse events (TEAEs). Inhibitory auto- antibodies to C1-INH did not develop in 
any of the subjects in the study. Further, there were no TEEs. 
The efficacy and safety of SC CSL830 are currently being assessed in a double-blind, 
randomized, placebo-controlled, crossover phase 3 study (study identifier CSL830_3001) 
that is enrolling at least 80 subjects with HAE. During participation in CSL830_3001 
subjects are randomly assigned to either a 40 IU/kg CSL830 or 60 IU/kg CSL830 treatment 
sequence. Each sequence consists of 2 consecutive treatment periods. Each subject receives 
the assigned dose of CSL830 in 1 treatment period and placebo in the other treatment period. 
Subjects who participate in study CSL830_3001 will be eligible to participate in this long-
term safety study if they meet all eligibility criteria (see Section 4.1). 
1.3 
Study Overview 
This is a multicenter, randomized, open-label, parallel-arm, phase 3b study to investigate the 
clinical safety and efficacy of subcutaneously administered CSL830 in the prophylactic 
treatment of HAE. Section 3 presents a detailed overview of the study design and other 
supporting information. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 41 of 130 
(United States) 
Confidential 
1.4 
Potential Risks and Benefits  
Potential for Virus Transmission  
CSL830 contains human plasma-derived C1-INH and, therefore, has the potential for virus 
transmission to recipients. However, CSL830 has a high margin of virus safety. The risk of 
virus transmission is minimized by stringent donor selection and screening criteria, and by 
reducing enveloped and non-enveloped viruses using pasteurization, nanofiltration methods, 
and chromatography [De Serres et al 2003].  
During study CSL830_2001 (see Section 1.2.3), no new viral infections were detected in 
subjects who received CSL830. No changes in serology results for HIV (human 
immunodeficiency virus), hepatitis A virus, HBV (hepatitis B virus), HCV (hepatitis C virus) 
were observed from baseline to study exit. 
During this 12-month safety study, evidence of potential viral transmission will be collected 
as part of the safety evaluations.  
Immunogenicity or Anaphylactic-type Reactions  
Immunologic or anaphylactic-type reactions have been rarely reported with the use of 
C1-INH. Antibodies against C1-INH have been identified in patients with HAE, irrespective 
of whether they have received C1-INH. However, the presence of antibodies against C1-INH 
does not appear to inhibit the activity of C1-INH [data on file at CSL; Farkas et al 2007].  
The immunogenicity of CSL830 was examined as a part of study CSL830_2001 (see 
Section 1.2.3). C1-INH antibodies were detected for 7/18 subjects during that study; 
however, the presence of C1-INH antibodies was not associated with inhibition of C1-INH 
activity. There was no apparent relationship between the dose of CSL830 administered and 
the presence of C1-INH antibodies.  
The development of immune reactions to CSL830 will be monitored in this study, and will 
include testing for and characterization of (eg, idiotyping) anti-C1-INH antibodies.  
Thromboembolic Events  
Thromboembolic events have been occasionally reported following the use of C1-INH, 
especially in patients receiving off-label high doses of up to 500 U/kg IV in the setting of 
cardiac surgery and extracorporeal circulation. At the recommended IV doses, a causal 
relationship between TEEs and the use of C1-INH has not been established. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 42 of 130 
(United States) 
Confidential 
During study CSL830_2001 (see Section 1.2.3) no TEEs were reported. Further, no subject 
treated with CSL830 was considered to be at risk for DVT, when assessed using a clinical 
model scoring system.  
TEEs including DVT and PE will be monitored during this study (see Section 8.1.2).  
Local Tolerance 
Because of the SC route of administration and the high protein concentration of CSL830, 
transient local reactions may occur at CSL830 injection sites.  
During study CSL830_2001, a small proportion of subjects administered CSL830 
experienced local administration site reactions. The reactions were mostly mild to moderate 
in intensity, most resolved within 3 days.  
Local reactions will be documented as part of the safety evaluation during this study.  
Efficacy 
Intravenous C1-INH has been demonstrated to be effective in the prevention of HAE attacks 
[Zuraw et al 2010]. However, the efficacy of SC C1-INH for prophylaxis of HAE attacks has 
not been established, but is under evaluation as a part of the pivotal study CSL830_3001 (see 
Section 1.2.3). As such, throughout the current study, eligible subjects will be permitted to 
use medication for the treatment of breakthrough HAE attacks.  
Overview 
This clinical study may contribute to the development of a new therapy to effectively manage 
HAE. Given the low probability of potential risks and the study procedures that will closely 
monitor the safety of study subjects, the associated risk-benefit assessment of the study is 
acceptable for subjects enrolled in the study. 
2 
Study Objectives and Endpoints 
2.1 
Primary Objective and Endpoints 
2.1.1 
Primary Objective 
The primary objective is to assess the clinical safety of subcutaneously administered CSL830 
in the long-term prophylactic treatment of HAE. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 43 of 130 
(United States) 
Confidential 
2.1.2 
Primary Endpoints 
The primary endpoints are the person-time incidence rates of each of the following: 
• Adverse events leading to premature study discontinuation. 
• Thromboembolic events. 
• Anaphylaxis. 
• HAE attacks resulting in in-patient hospitalization (where hospitalization is the 
consequence of the need for emergent medical care). 
• Solicited AEs (injection site reactions at the CSL830 injection site) graded as severe 
by the investigator. 
• Related serious adverse events (SAEs), other than events specified above. 
• Anti-C1-INH antibodies (inhibitory or non-inhibitory). 
The person-time incidence rates are the number of subjects experiencing each primary 
endpoint safety event during treatment with CSL830, divided by the sum of each subject’s 
time at risk. 
The primary endpoints will be assessed for Treatment Period 1, Treatment Period 2 and 
Treatment Periods 1 and 2 (together). The primary endpoints will also be assessed for the 
Extension Period (only) and for the treatment periods overall for subjects who are included in 
the Extension Period. 
2.2 
Secondary Objectives and Endpoints 
2.2.1 
Secondary Objectives 
The secondary objectives are the following: 
1. To further characterize the clinical safety of subcutaneously administered CSL830 in 
the long-term prophylactic treatment of HAE. 
2. To characterize the clinical efficacy of subcutaneously administered CSL830 in the 
long-term prophylactic treatment of HAE. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 44 of 130 
(United States) 
Confidential 
2.2.2 
Secondary Endpoints 
1. The secondary safety endpoints are the following: 
a. The percentage of subjects experiencing the following events: SAEs, 
temporally-related AEs, increased risk scores for DVT or PE, TEEs, inhibitory 
anti-C1-INH antibodies, or clinically significant abnormalities in laboratory 
assessments (ie, lab abnormalities reported as AEs). 
b. The percentage of administrations of CSL830 resulting in solicited local AEs 
(discomfort [eg, pain, burning], swelling, bruising, or itching at the CSL830 
injection site). 
c. The percentage of subjects who have at least 1 solicited local AE (discomfort 
[eg, pain, burning], swelling, bruising, or itching at the CSL830 injection site). 
d. The percentage of subjects who become seropositive for HIV-1/-2, HBV, or 
HCV. 
The secondary safety endpoints will be assessed for Treatment Period 1, Treatment Period 2 
and Treatment Periods 1 and 2 (together). The secondary safety endpoints will also be 
assessed for the Extension Period (only) and for the treatment periods overall for subjects 
who are included in the Extension Period. 
2. Efficacy endpoints considered as secondary include the following:  
a. The percentage of subjects who experience a time-normalized HAE attack 
frequency of < 1 HAE attack per 4-week period. 
b. The percentage of subjects who are responders. “Response” is defined as a 
≥ 50% relative reduction in the time-normalized number of HAE attacks 
during treatment with CSL830, compared with the time-normalized number of 
attacks that is used to qualify the subject for participation in this study (see 
Section 4.1.2 [inclusion criterion 5]). 
The secondary efficacy endpoints will be assessed for Treatment Period 1, and Treatment 
Periods 1 and 2 (together). The secondary efficacy endpoints will also be assessed for the 
Extension Period (only) and for the treatment periods overall for subjects who are included in 
the Extension Period. 

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 47 of 130 
(United States) 
Confidential 
3 
Study Design 
3.1 
Study Design and Rationale 
This is a multicenter, randomized, open-label, parallel-arm, phase 3b study designed to 
investigate the clinical safety and efficacy of subcutaneously administered CSL830 in the 
prophylactic treatment of HAE. An overview of the study is depicted in Figure 1. 
Figure 1: 
Study Overview 
 
 
Footnotes to Figure 1: 
a  “CSL830-Interrupted” Subjects and “CSL830-Naïve” Subjects will participate in a Screening Visit in order to 
confirm their eligibility. “CSL830-Continuation” Subjects will not be required to participate in a Screening 
Visit. Instead, data from study CSL830_3001 will be used to confirm their eligibility (see Section 8.4.3.1). 
NOTE: The definitions for “CSL830-Continuation” Subjects, “CSL830-Interrupted” Subjects, and 
“CSL830-Naïve” Subjects are presented in Section 4.1.1. 
b  During the fixed-dose Treatment Period 1, subjects who experience very frequent HAE attacks (ie, ≥ 12 
attacks, as defined per protocol, within a 4-week evaluation period) are eligible for CSL830 dose increases in 
increments of 20 IU/kg (up to a maximum dose of 80 IU/kg). All CSL830 dose increases are optional, and 
will be made only in subjects who are eligible, at the sole discretion of investigator. An evaluation period for 
any dose increase is defined as beginning after a dose-stable period (ie, 2 weeks after the initiation or dose 
increase of CSL830). See Section 3.2 for additional details. 
c  Beginning with the Week 25 Visit and throughout Treatment Period 2, subjects who experience ≥ 3 HAE 
attacks (as determined per protocol) within an 8-week evaluation period are eligible for CSL830 dose 
increases in increments of 20 IU/kg (up to a maximum dose of 80 IU/kg). All CSL830 dose increases are 
optional, and will be made only in subjects who are eligible, at the sole discretion of investigator. An 
evaluation period for any dose increase is defined as beginning after a dose-stable period (ie, 2 weeks after the 
initiation or dose increase of CSL830). See Section 3.2 for additional details.  
d  For subjects (from the United States) enrolled in the Extension Period, their CSL830 dose will be escalated in 
increments of 20 IU/kg (up to a maximum dose of 80 IU/kg) according to the rules outlined for Treatment 
Period 2 (see Section 3.2), but their CSL830 by-weight dose will be rounded to the nearest (ie, up or down) 
1000 IU based on their assigned dose for subjects weighing ≥ 40 kg; subjects weighing < 40 kg will continue 
to undergo rounding as during Treatment Periods 1 and 2 (ie, rounded up to the nearest 500 IU).   
e Subjects will undergo a 2-week (± 3 days) follow-up contact after either completing or 
discontinuing/withdrawing from the Extension Period. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 48 of 130 
(United States) 
Confidential 
3.1.1 
Screening Visit 
A Screening Visit will be conducted within the 4 weeks before Treatment Period 1 in order to 
confirm the eligibility of the following subjects belonging to groups of subjects: 
• “CSL830-Naïve” Subjects: subjects who did not participate in study CSL830_3001; 
subjects who participated in study CSL830_3001 but did not receive blinded 
investigational product as a part of that study. 
• “CSL830-Interrupted” Subjects: subjects who completed participation in study 
CSL830_3001, but who delayed entry into the current study (ie, > 1 week between the 
End of Study Visit of CSL830_3001 and the first visit of CSL830_3002 Treatment 
Period 1). 
The first visit in Treatment Period 1 (ie, the Day 1 Visit) may occur on the same day as the 
Screening Visit. 
“CSL830-Continuation” Subjects will not have a Screening Visit. “CSL830-Continuation” 
Subjects are subjects who complete participation in CSL830_3001 and who continue directly 
on to participate in the current study [ie, ≤ 1 week between the End of Study Visit of 
CSL830_3001 and the first visit of CSL830_3002 Treatment Period 1].  
The eligibility of “CSL830-Continuation” Subjects will include evaluation based upon the 
assessments performed during study CSL830_3001 as described in Table 6 (see 
Section 8.4.3.1). For “CSL830-Continuation” Subjects, the End of Study Visit of 
CSL830_3001 and the first study visit of Treatment Period 1 of CSL830_3002 may occur on 
the same day. 
3.1.2 
Treatment Periods 1 and 2 
Treatment Period 1 will begin with the Day 1 Visit and will end with the Week 25 Visit. 
Treatment Period 2 will begin either during the Week 25 Visit (if CSL830 is administered at 
the study visit) or immediately following the Week 25 Visit. Treatment Period 2 will end with 
the Week 53 Visit. 
Eligible subjects will be randomized to 1 of the following CSL830 treatment groups at the 
first visit in Treatment Period 1: 
• 40 IU/kg CSL830 treatment group, OR  
• 60 IU/kg CSL830 treatment group.  

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 49 of 130 
(United States) 
Confidential 
CSL830 will be administered as a single subcutaneous injection twice weekly at home either 
independently (ie, self-administered by the subject) or with assistance (ie, with the help of a 
caretaker such as a parent or guardian) during Treatment Period 1 and Treatment Period 2.  
During the study, an investigator may increase a subject’s CSL830 dose if that subject is 
eligible for dose increase. A subject’s eligibility for a dose increase is related to the frequency 
of their HAE attacks and the rules are different during the “fixed dose” Treatment Period 1 
and the “dose optimization” Treatment Period 2. During Treatment Period 1, dose increases 
are intended as potential rescue prophylaxis for subjects who have very frequent attacks; 
these increases are intended to provide an opportunity for such subjects to remain in the 
study. During Treatment Period 2, dose increases are intended to allow the investigator to 
optimize the dose for subjects whom the investigator considers may benefit from a higher 
prophylaxis dose. Dose increase rules are presented in Section 3.2. 
The last visit of Treatment Period 2 will be the Week 53 Visit. 
3.1.3 
Extension Period 
The Extension Period will follow Treatment Period 2. The last visit (Week 53 Visit, Day 367) 
of Treatment Period 2 will serve as the first visit of the Extension Period (Extension Period 
Day 1), unless there is a rest period of up to 30 days. In this case, the first visit of the 
Extension Period will be a new (separate) visit. The Extension Period is intended to allow 
subjects from the United States who complete Treatment Period 2 according to the protocol 
to continue to receive treatment with open-label CSL830. During the Extension Period 
(unlike during Treatment Periods 1 and 2 during which the assigned by-weight dose was 
rounded up to the nearest 500 IU) for subjects weighing ≥ 40 kg, each subject’s dose will be 
rounded to the nearest 1000 IU (up or down) based on his/her assigned by-weight dose; 
subjects weighing < 40 kg will continue to undergo rounding as during Treatment Periods 1 
and 2 (ie, rounded up to the nearest 500 IU). During the Extension Period, each subject will 
continue to be eligible for dose escalation in increments of 20 IU/kg (up to a maximum dose 
of 80 IU/kg) according to the rules outlined for Treatment Period 2 (see Section 3.2). 
3.1.4 
Post-treatment Follow-up  
Subjects will attend a Follow-up Visit occurring 14 days (± 3 days) after the final visit in 
Treatment Period 2 or any visit resulting in study discontinuation, unless informed 
consent/assent has been withdrawn or if the Extension Period starts prior to the scheduled 
Follow-up Visit.  

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 51 of 130 
(United States) 
Confidential 
missed injection should be omitted, and the administration of CSL830 should occur at the 
next scheduled day and time. 
If a subject requires the use of C1-INH medication for the treatment of breakthrough HAE 
attacks within 24 hours before a scheduled injection of CSL830, the scheduled injection may 
be delayed by up to 24 hours. 
Additional information on the dosing regimen can be found in Section 6.2. 
CSL830 Dose Increase  
Some subjects may be eligible to increase the dose of CSL830 to which they were assigned at 
the beginning of Treatment Period 1.  
During the fixed-dose Treatment Period 1, subjects who experience very frequent HAE 
attacks (ie, ≥ 12 attacks, as defined per protocol, within a 4-week evaluation period) are 
eligible for CSL830 dose increases in increments of 20 IU/kg (up to a maximum dose of 80 
IU/kg). All CSL830 dose increases are optional, and will be made only in subjects who are 
eligible, at the sole discretion of investigator. Dose increases during Treatment Period 1 are 
intended as rescue prophylaxis, to provide the opportunity for subjects who have very 
frequent HAE attacks to continue in the study during this otherwise fixed-dose treatment 
period.  
Beginning with the Week 25 Visit and throughout Treatment Period 2, subjects who 
experience ≥ 3 HAE attacks (as determined per protocol) within an 8-week evaluation period 
are eligible for CSL830 dose increases in increments of 20 IU/kg (up to a maximum dose of 
80 IU/kg). All CSL830 dose increases are optional, and will be made only in subjects who are 
eligible, at the sole discretion of investigator. Dose increases during Treatment Period 2 are 
intended to allow investigators to adjust/optimize the dose for subjects who may need a 
higher prophylactic dose.  
During the Extension Period (unlike during Treatment Periods 1 and 2 during which the 
assigned by-weight dose was rounded up to the nearest 500 IU) for subjects weighing 
≥ 40 kg, each subject’s dose will be rounded to the nearest 1000 IU (up or down) based on 
his/her assigned by-weight dose; subjects weighing < 40 kg will continue to undergo 
rounding as during Treatment Periods 1 and 2 (ie, rounded up to the nearest 500 IU). During 
the Extension Period, each subject will continue to be eligible for dose escalation in 
increments of 20 IU/kg (up to a maximum dose of 80 IU/kg) according to the rules outlined 
for Treatment Period 2 (see above). 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 52 of 130 
(United States) 
Confidential 
An evaluation period for any dose increase in Treatment Period 1, Treatment Period 2, or the 
Extension Period is defined as beginning after a dose-stable period (ie, 2 weeks after the 
initiation or dose increase of CSL830). 
All CSL830 dose increases are optional, and will be made only in subjects who are eligible, 
at the sole discretion of investigator. CSL830 dose increases may be made in increments of 
20 IU/kg up to a maximum dose of 80 IU/kg. Subjects who are randomized to treatment with 
40 IU/kg CSL830 and who are eligible for a dose increase may undergo up to 2 independent 
20 IU/kg dose increases (at the sole discretion of the investigator), up to a maximum dose of 
80 IU/kg. Subjects who are randomized to treatment with 60 IU/kg CSL830 and who are 
eligible for a dose increase may undergo a single 20 IU/kg dose increase (at the sole 
discretion of the investigator), up to a maximum dose of 80 IU/kg.  
Assessment of Subject Weight 
The weight of the subject is assessed at study visits. The baseline body weight for “CSL830-
Naïve” and “CSL830-Interrupted” Subjects will be recorded at Screening. The baseline body 
weight for “CSL830-Continuation” Subjects will be recorded at the CSL830_3001 End of 
Study Visit.  
The actual dose of CSL830 will be adjusted, if necessary. The actual dose administered will 
be based on the weight at Day 1 of Treatment Period 1 and will only be adjusted if the patient 
has a body weight change of more than 10% compared to baseline. If a new body weight is 
used, this weight will become the new baseline weight and subsequent weight measures will 
be compared to this. If there is a change of more than 10% compared to this new baseline 
weight the dose will be adjusted again. This will be repeated throughout the study. 
3.3 
Planned Study Duration 
Treatment Period 1 and Treatment Period 2 
The duration of the study for an individual subject is expected to be up to 58 weeks. This 
estimation is based on: 
• A Screening Period lasting up to 4 weeks (≤ 28 days), as needed. 
• Two treatment periods totaling 52 weeks (367 days ± 2 days). 
• A Follow-up Period lasting 2 weeks (14 days ± 3 days). 
The overall study duration (ie, from the first subject’s first Screening Visit to the last subject’s 
Follow-up Visit) is planned to be 26 months, but will depend on recruitment. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 53 of 130 
(United States) 
Confidential 
Extension Period (Optional) 
The Extension Period (88 weeks) followed by the Extension Period follow-up (2 weeks) will 
begin at first subject first visit in the Extension Period and result in an anticipated total study 
duration of up to approximately 146 weeks for participating subjects. Subjects who have any 
Extension Period visits that occur within 6 weeks before the study end date will be handled as 
completers. These subjects will attend the final study visit (Extension Period Week 88) in 
place of their next study visit or telephone contact and will receive follow-up telephone 
contact (Extension Period Week 90 ± 3 days). Subjects who roll-over into the Extension 
Period prior to the Treatment Period 2 Follow-up Visit will be regarded as completers. All 
subjects who are not withdrawn from the study will be considered completers of the study. 
3.4 
Planned Number of Sites 
The study is planned to be conducted at approximately 50 study sites, with approximately 12 
United States sites conducting the Extension Period portion of the study.  
3.5 
Planned Number of Subjects 
The study plans to enroll subjects who complete participation in CSL830_3001. Additional 
subjects who have not participated in study CSL830_3001 will be enrolled so that the total 
number of subjects randomized is approximately 110.  
Assuming that up to 10% of subjects withdraw before the completion of the study, 100 
subjects are planned to complete the study. 
Subjects from the United States who have completed Treatment Period 1 and Treatment 
Period 2 according to the study protocol are eligible to enroll in the Extension Period. 
Approximately 50 of these subjects are anticipated to enroll in the Extension Period.  
3.6 
Study Monitoring Procedures 
3.6.1 
Steering Committee  
A Steering Committee has been established to provide scientific advice and safety monitoring 
for the study. 
Members of the Steering Committee will be listed in the Investigator Study File.  

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 54 of 130 
(United States) 
Confidential 
4 
Selection and Withdrawal of Subjects 
4.1 
Eligibility Criteria 
The study population will be selected on the basis of the inclusion and exclusion criteria 
described in Section 4.1.2 and Section 4.1.3, respectively. 
Subjects who have completed participation in CSL830_3001 will be offered treatment with 
CSL830 as a part of the study if they meet the eligibility criteria presented here. Additional 
subjects (ie, “CSL830-Naïve” Subjects [see Section 4.1.1]) will be eligible to participate in 
the current study in order to meet the planned sample size. 
Subject eligibility will be reviewed and documented by an appropriately medically qualified 
member of the investigator’s study team before a subject is enrolled in the study. 
4.1.1 
Subject Classification 
Before subject eligibility can be assessed against the inclusion and exclusion criteria, each 
subject will be classified into 1 of the following categories: 
Treatment Period 1 and Treatment Period 2 
• “CSL830-Naïve” Subjects: subjects who did not participate in study CSL830_3001; 
subjects who participate in study CSL830_3001 but did not receive blinded 
investigational product as a part of that study. 
NOTE: For “CSL830-Naïve” Subjects, the first study visit is the Screening Visit. 
• “CSL830-Interrupted” Subjects: subjects who completed participation in study 
CSL830_3001, but who delay entry into the current study (ie, > 1 week between the End 
of Study Visit of CSL830_3001 and the first visit of CSL830_3002 Treatment Period 1). 
NOTE: For “CSL830-Interrupted” Subjects, the first study visit is the Screening Visit. 
• “CSL830-Continuation” Subjects: subjects who complete participation in study 
CSL830_3001 and who continue directly on to participate in the current study 
(ie, ≤ 1 week between the End of Study Visit of CSL830_3001 and the first visit of 
CSL830_3002 Treatment Period 1).  
NOTE: For “CSL830-Continuation” Subjects, the first study visit is the first study visit in 
Treatment Period 1. For these subjects, the last study visit of CSL830_3001 and the first 
study visit of Treatment Period 1 from CSL830_3002 may occur on the same day. 

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CCI

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 56 of 130 
(United States) 
Confidential 
• For “CSL830-Naïve” Subjects:  
o “CSL830-Naïve” Subjects using intravenous C1-INH as routine (long-term) 
prophylaxis against HAE attacks must have experienced 4 HAE attacks over 
any consecutive 2-month period before the initiation of intravenous C1-INH 
prophylaxis and before the CSL830_3002 Screening Visit, as documented in 
the subject medical records. 
o All other “CSL830-Naïve” Subjects (eg, treated using oral HAE prophylaxis 
against HAE attacks or on-demand treatment) must have experienced 4 HAE 
attacks over a consecutive 2-month period within the 3 months before the 
CSL830_3002 Screening Visit, as documented in the subject medical records.  
• For “CSL830-Continuation” Subjects AND “CSL830-Interrupted” Subjects: 
Subjects must have experienced 4 HAE attacks over a consecutive 2-month period 
within the 3 months before the CSL830_3001 Screening Visit, as documented in 
the subject medical records (ie, the HAE attack frequency required for eligibility 
to participate in study CSL830_3001). 
6. For subjects who have used oral medication for prophylaxis against HAE attacks 
(ie, androgens, tranexamic acid, progestins) within 3 months of their first study visit: 
Use of a stable regimen of oral prophylactic medication (ie, dose and administration 
frequency) during the 3 months before their first study visit and willingness to 
continue the stable regimen for at least 25 weeks. 
NOTE: Subjects using oral medication for HAE prophylaxis are to maintain their 
stable, pre-study dose during Treatment Period 1, but may decrease their dose after 
entering Treatment Period 2. 
7. Investigator assesses that the subject is willing and able to adhere to all protocol 
requirements. 
8. Assessed by the investigator as able to appropriately store CSL830, and is capable of 
being trained to administer CSL830 (independently or with assistance) outside of the 
study center setting.  
9. Assessed by the investigator as able to have access to medication to treat 
breakthrough HAE attacks, and is capable of using medication to treat breakthrough 
attacks (independently or with assistance) outside of the study center setting. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 57 of 130 
(United States) 
Confidential 
4.1.3 
Exclusion Criteria 
Subjects meeting any of the following exclusion criteria must not be enrolled (randomized) 
into the study: 
1. Subjects who were enrolled in CSL830_3001 but who were withdrawn before 
completion of that study for any reason. 
2. Known incurable malignancies at the time of the first study visit. 
3. Any clinical condition that is likely to interfere with evaluation of CSL830 or 
satisfactory conduct of the study. 
4. A clinically significant history of poor response to C1-INH therapy for the 
management of HAE. 
5. A suspected or confirmed diagnosis of acquired HAE or HAE with normal C1-INH 
(ie, HAE type III). 
6. Assessed by the investigator as unable to have their HAE adequately managed 
pharmacologically with on-demand treatment, when that on-demand treatment is 
administered independently or with assistance. 
NOTE: This must be documented by the investigator in an individual acute action 
plan. 
7. Female subject of childbearing potential either not using or not willing to use a 
medically reliable method of contraception or not sexually abstinent during the study, 
or not surgically sterile.  
8. Female subjects who started taking or changed dose of any hormonal contraceptive 
regimen or hormone replacement therapy (ie, estrogen / progesterone containing 
products) during the 3 months before their first study visit, or who intend to initiate 
these therapies during the course of the study. 
9. Intention to become pregnant during the course of the study. 
10. Pregnancy or nursing mother. 
11. Participated in an interventional clinical study (other than CSL830_3001) during the 
30 days before the first administration of the investigational product or at any time 
during the study. 
12. Alcohol, drug or medication abuse within 1 year before the study. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 58 of 130 
(United States) 
Confidential 
13. Mental condition rendering the subject (or the subject’s legally acceptable 
representative[s]) unable to understand the nature, scope and possible consequences 
of the study. 
14. Known or suspected hypersensitivity to CSL830, or to any excipients of CSL830. 
15. Employee at the study site, or spouse / partner or relative of the investigator or 
sub-investigators. 
16. Any other issue that, in the opinion of the investigator, would render the subject 
unsuitable for participation in the study. 
4.2 
Subject Withdrawal and Replacement 
4.2.1 
Subject Withdrawal 
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or CSL for safety, behavioral or 
administrative reasons (eg, due to an AE, protocol violation, loss to follow-up, subject 
noncompliance, and study termination).  
In accordance with International Conference on Harmonisation (ICH) principles of Good 
Clinical Practice (GCP) the investigator always has the option to advise a subject to withdraw 
from the study if the subject's safety or well-being is compromised by his or her further 
participation in the study. Concern for the interests of the subject must always prevail over 
the interests of the study.  
If a subject is withdrawn from the study or further participation is declined, they will 
continue to have access to medical care and will be treated as per routine medical practice. 
4.2.2 
Procedures for Handling Withdrawals 
If a subject declines further participation or is withdrawn from the study, attempts will be 
made to complete and document the assessments scheduled for the last visit in Treatment 
Period 2 (ie, the Week 53 Visit) (see Section 8.4.4.7) or the last visit in the Extension Period 
(Extension Period Week 88)(see Section 8.4.6.20). These subjects will then attend a Follow-
up Visit occurring 14 days (± 3 days) after a visit resulting in study discontinuation, unless 
informed consent/assent has been withdrawn (see Section 8.4.5.1). If the subject is withdrawn 
from the study after receiving CSL830, every effort will be made to ensure that the relevant 
safety assessments are completed. The subject may also be asked by the investigator to 
complete other study assessments. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 59 of 130 
(United States) 
Confidential 
If the subject withdraws from the study, and also withdraws consent/assent (as appropriate) 
for disclosure of future information, CSL may retain and continue to use any data collected 
before such withdrawal of consent/assent (as appropriate). 
In the event that a subject withdraws from the study, the investigator should record the reason 
and date of withdrawal in the electronic case report form (eCRF) and in the subject's medical 
records. 
Subjects who discontinue or withdraw from Treatment Periods 1 or 2 will not be eligible to 
participate in the Extension Period. 
4.2.3 
Replacement Policy 
Subjects who discontinue participation in or are otherwise withdrawn from the study will not 
be replaced. Assuming that up to 10% of subjects withdraw before the completion of the 
study, 100 subjects are planned to complete the study. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 60 of 130 
(United States) 
Confidential 
5 
Study Interventions 
5.1 
Description of Investigational Product 
5.1.1 
CSL830 
Table 1:  
Description of CSL830 
Substance number 
CSL830 
Active substance 
C1-esterase inhibitor (C1-INH) 
Trade name 
Not Applicable 
Dosage form 
Lyophilized powder for reconstitution; 1500 IU C1-INH per 
single-use vial. 
Dose for Treatment 
Periods 1 and 2 
40 IU/kg and/or 60 IU/kg and/or 80 IU/kg (rounded up to the 
nearest 500 IU), as described in Section 3.2. 
Dose for Extension 
Period 
40 IU/kg and/or 60 IU/kg and/or 80 IU/kg (rounded up or 
down to the nearest 1000 IU for subjects weighing ≥ 40 kg; 
subjects weighing < 40 kg will continue to undergo rounding 
as during Treatment Periods 1 and 2 [ie, rounded up to the 
nearest 500 IU]), as described in Section 3.2. 
Mode of administration 
Subcutaneous injection 
Before use, each vial of CSL830 will be reconstituted with 3 mL water for injection. Each 
vial of CSL830 requires a reconstitution time of 10 minutes. 40 IU/kg CSL830 is equivalent 
to a volume of 0.08 mL/kg; 60 IU/kg CSL830 is equivalent to a volume of 0.12 mL/kg; 
80 IU/kg CSL830 is equivalent to a volume of 0.16 mL/kg. 
CSL830 will be manufactured by CSL in accordance with Good Manufacturing Practice 
guidelines and local regulatory requirements. 
5.1.2 
Comparator Product 
Not Applicable. 
5.2 
Packaging, Labeling, Supply and Storage 
5.2.1 
Packaging and Labeling 
CSL830 will be packaged and labeled according to current ICH Good Manufacturing 
Practice and GCP guidelines, and national legal requirements. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 61 of 130 
(United States) 
Confidential 
5.2.2 
Supply and Storage 
CSL830 will be supplied to the study sites by CSL.  
CSL830 must be stored under temperature-monitored conditions in a secure storage area as 
specified in the CSL830 Handling Instructions. 
5.3 
Accountability and Destruction 
All supplies of CSL830 must be accounted for throughout the study. At the end of the study, 
the original Drug Inventory Log, dated and signed by the investigator or delegate 
(eg, pharmacist), must be retained at the study site as verification of final accountability of 
CSL830. 
Records for the delivery of CSL830 to the study site, the inventory at the study site, the use 
by each subject, and the destruction or return of CSL830 to CSL must be maintained by the 
investigator (or delegate). The records will include dates, quantities, batch numbers and 
unique code numbers assigned to CSL830 and unique code numbers assigned to the subjects. 
Information on the destruction of CSL830 is provided in the CSL830 Handling Instructions. 
5.4 
Other Intervention(s) 
Not applicable. 
6 
Allocation, Dosing and Administration 
6.1 
Allocation to Treatment 
6.1.1 
Subject Assignment 
After providing written informed consent/assent (as appropriate), the subject will be issued 
with a study-level unique subject identification number. Each “CSL830-Continuation” and 
“CSL830-Naïve” Subject will re-use the subject numbers they used in study CSL830_3001. 
The subject identification number will be used to identify the subject for the duration of the 
study. Subject identification numbers will not be reassigned or reused.  
Subjects who are enrolled in the Extension Period will continue to receive the CSL830 dose 
that they were originally administered during Treatment Period 2.  This CSL830 dose may be 
escalated in increments of 20 IU/kg (up to a maximum dose of 80 IU/kg) according to the 
rules outlined for Treatment Period 2 (see Section 3.2).  

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 62 of 130 
(United States) 
Confidential 
6.1.2 
Randomization Procedures 
A stratified block randomization scheme will be used to ensure that subjects are randomized 
to a starting dose of CSL830 of either 40 IU/kg or 60 IU/kg in a balanced manner and to 
ensure that “CSL830-Continuation” Subjects, “CSL830-Interrupted” Subjects, and “CSL830-
Naïve” Subjects are distributed evenly between the 2 CSL830 treatment groups. 
Eligible subjects will be randomized to 1 of the 2 treatment groups (CSL830 40 IU/kg or 
CSL830 60 IU/kg) by means of interactive response technology (IRT). The IRT will assign 
the appropriate study treatment to each subject. CSL will supply the investigator with a user 
guide for the IRT.  
6.1.3 
Blinding Procedures 
Not applicable. 
6.2 
Dosing and Administration 
6.2.1 
Administration of the Investigational Product 
The investigator (or delegate) will only dispense the investigational product (ie, CSL830) to 
subjects included in this study following the procedures set out in this study protocol. 
CSL830 will be administered either independently (ie, self-administered by the subject) or 
with assistance (ie, with the help of a caretaker such as a parent or guardian) at home via a 
single SC injection in the abdomen. The injection site should be changed for each new 
administration of CSL830; ideally, the site of injection should alternate between the right and 
left sides of the abdomen and should be at least 5 cm (2 inches) away from the previous 
injection site.  
The abdomen is the preferred injection location in this study. However, if the investigator 
believes that another SC injection site (eg, outer thigh, upper arm) is more clinically 
appropriate for an individual subject, this location can also be used. 
Additional information on the CSL830 dose and dosing regimen can be found in Section 3.2. 
6.2.2 
Subject Training for Self-Administration of the 
Investigational Product 
The investigator must ensure that all subjects or their caregivers have been trained 
sufficiently to allow for home therapy to occur in Treatment Periods 1 and 2 and the 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 63 of 130 
(United States) 
Confidential 
Extension Period. Mandatory formal training will be performed on Day 1 of Treatment 
Period 1 for all subjects. “CSL830-Naïve” Subjects and “CSL830-Interrupted” Subjects will 
also have a second round of follow-up training on Day 4 of Treatment Period 1. During these 
training visits, subjects (or their caregivers, as appropriate) will administer CSL830 under the 
supervision of the investigator. Additional training (including at additional visits) may be 
conducted for any subject by the study site personnel, if required. Subjects weighing ≥ 40 kg 
who enroll in the Extension Period will receive training on the new dose rounding scheme 
(up or down to the nearest 1000 IU) on Visit 1 of the Extension Period; subjects weighing 
< 40 kg will continue to undergo rounding as during Treatment Periods 1 and 2 (ie, rounded 
up to the nearest 500 IU). 
NOTE: The Day 4 Visit may be waived for “CSL830-Interrupted” Subjects (only) if the 
investigator has confirmed that the subject can adequately treat themselves with CSL830 (ie, 
no further training is necessary). In this case, all activities scheduled for the Day 4 visit may 
be conducted at the Day 1 Visit. 
The training for self-administration of investigational product (ie, CSL830) will include the 
following: 
• Correct storage.  
• Correct reconstitution technique. 
• Correct administration technique. 
• Signs and symptoms of hypersensitivity reactions.  
• Procedures in case of suspected hypersensitivity reactions. 
• Correct completion of the eDiary (eg, recording of HAE symptoms, medication for the 
treatment of breakthrough HAE attacks, AE reporting). 
Complete instructions for the handling, reconstitution, and administration of CSL830 will be 
detailed in the CSL830 Handling Instructions. These instructions will be provided to each 
study center prior to enrollment of the first subject. Subjects will also be provided with 
written instructions for the preparation and administration of CSL830. 
6.3 
Treatment Compliance 
Subjects will record the dose and date of injection of CSL830 in the eDiary. In addition, 
subjects will bring their used / partially used vials of CSL830 to every study visit. Subjects 
will return all vials (ie, used, partially used, and unused) of CSL830 to the site at last visit in 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 64 of 130 
(United States) 
Confidential 
Treatment Period 2 and last visit in the Extension Period. Treatment compliance will be 
monitored by counting the used vials of CSL830, the results of which will be documented.  
7 
Contraindications, Permitted Therapies and Prohibited 
Therapies 
7.1 
Contraindications and Precautions to Further Dosing 
The following are considered contraindications for further administration of the 
investigational product (ie, CSL830) for an individual subject: 
• Anaphylaxis or severe and clinically significant allergic reaction causally related to 
CSL830. 
• Any other CSL830-related SAE or CSL830-related important medical event that is 
considered by the investigator and / or CSL to be serious and clinically significant, or that 
would suggest significant hazard to the subject following further administration of 
CSL830. 
• Administration of a prohibited concomitant therapy or a prohibited change in 
concomitant therapy (see Section 7.3). 
7.2 
Permitted Therapies 
The following therapies are PERMITTED during the Screening Period, Treatment Period 1, 
Treatment Period 2, the Follow-up Period, and the Extension Period: 
• Prescribed medication(s) required for the management of acute or chronic medical 
conditions, except those described in Section 7.3. 
• Over the counter medications and dietary supplements.  
• Medications (eg, IV C1-INH) for the pre-procedure prevention of acute HAE attacks, not 
to exceed 1 dose prior to each procedure. 
• Medications for the treatment of breakthrough HAE attacks, including the following: 
o Berinert (IV C1-INH). 
o Other plasma-derived or recombinant C1-INH, other than CSL830. 
o Firazyr (Icatibant). 
o Kalbitor (Ecallantide). 
o Fresh frozen plasma. 
The following therapy is PERMITTED during the Screening and Follow-up Periods (only): 
• Intravenous C1-INH for routine prophylaxis against HAE attacks.  

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 65 of 130 
(United States) 
Confidential 
The following therapies are PERMITTED if used at a stable dose for 3 months before the 
first study visit and used at the same dose during Treatment Period 1*: 
• Oral medications for HAE prophylaxis (eg, androgens, tranexamic acid, progestins) if 
used at a stable dose for 3 months before the first study visit*.  
NOTE: Subjects using oral medication for HAE prophylaxis may decrease their dose 
after entering Treatment Period 2 and the Extension Period. 
*  For “CSL830-Naïve” Subjects AND “CSL830-Interrupted” Subjects: the first study visit is the Screening Visit; 
For “CSL830-Continuation” Subjects: the first study visit is the first study visit in Treatment Period 1. 
7.3 
Prohibited Therapies 
Use of the following therapy is NOT permitted during Treatment Period 1, Treatment Period 
2, and the Extension Period for subjects who are using CSL830: 
• Intravenous C1-INH for routine prophylaxis against HAE attacks.  
NOTE: Use of IV C1-INH for the pre-procedure prevention of acute HAE attacks is 
permitted, not to exceed 1 dose prior to each procedure. 
Dose changes, including initiation or discontinuation, in the following therapy are NOT 
permitted during the 3 months before the first study visit* and throughout the study: 
• Hormonal contraceptive regimen or hormone replacement therapy 
(ie, estrogen / progesterone containing product). 
*  For “CSL830-Naïve” Subjects AND “CSL830-Interrupted” Subjects: the first study visit is the Screening Visit; 
For “CSL830-Continuation” Subjects: the first study visit is the first study visit in Treatment Period 1. 
7.4 
Dietary and Lifestyle Restrictions  
Not Applicable. 
7.5 
Overdose 
Overdose is defined as the accidental or intentional infusion or ingestion of any dose of a 
product that is considered excessive. In a previous study (CSL830_2001), doses up to 
6000 IU (up to 120 IU/kg) were administered twice weekly for 4 weeks without any safety 
issues. The effects of any potential overdose with CSL830 have not been otherwise studied.  
The development of thrombosis has been reported after administering IV C1-INH doses up to 
500 U/kg body weight when used off label in newborns and young children with congenital 
heart anomalies during or after cardiac surgery under extracorporeal circulation.  

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 66 of 130 
(United States) 
Confidential 
There is no specific antidote for excessive dosing of CSL830; in these circumstances, 
appropriate supportive management should be instituted. 
8 
Study Procedures and Visit Schedule 
8.1 
Clinical Procedures 
8.1.1 
Demographics and Safety Assessments 
The clinical procedures that will be conducted during this study related to the evaluation of 
population demographics and safety are provided in Table 2. Refer to the Laboratory Manual 
for details about the collection, storage, handling and transportation of biological specimens, 
and how the assessments should be performed. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 67 of 130 
(United States) 
Confidential 
Table 2:  
Clinical Procedures: Demographics and Safety Evaluation 
Assessment 
Description 
Demographics 
Year of birth, age, sex, race and ethnicity. 
Medical history 
Relevant medical history for the previous 6 months. 
Diagnosis of HAE and disease type. 
Prior therapy relating to HAE in the past 3 months. 
Contraception method (if relevant). 
Current therapies. 
Dipstick pregnancy test Urine test for beta-human chorionic gonadotropin (test conducted at the study site). 
Physical examination 
As per the site’s standard procedure. 
Vital signs 
Blood pressure (systolic and diastolic) and respiratory rate.  
Pulse rate (per minute) will be measured from the radial pulse counted manually or 
with an automatic blood pressure monitor over ≥15 seconds.  
Body temperature. 
Body weight and height (height measurement at Screening only or from 
CSL830_3001, as appropriate); body mass index will be determined from height 
and weight values. 
Urinalysis 
(Central laboratory) 
Bilirubin. 
Blood. 
Erythrocytes. 
Glucose. 
Ketones. 
Leukocyte esterase. 
Nitrite. 
pH. 
Protein. 
Specific gravity. 
Urobilinogen. 
 
Hematology  
(Central laboratory) 
Hemoglobin. 
Hematocrit. 
 
Blood cell counts: basophils, eosinophils, erythrocytes, leukocytes, lymphocytes, 
monocytes, neutrophils, platelets. 
Biochemistry  
(Central laboratory) 
ALT. 
Chloride. 
GGT. 
Creatinine. 
Lactate dehydrogenase. 
Glucose. 
Protein. 
Total bilirubin. 
Potassium. 
Albumin. 
AST. 
Urea. 
Calcium. 
Sodium. 
 
Coagulation 
(Central laboratory) 
INR. 
APTT. 
Fibrinogen. 
D-dimer. 
F1+2. 
 
Viral serology 
(Central laboratory) 
Blood samples to be tested for HIV-1/-2, HBV, and HCV. 
Immunogenicity 
(Central laboratory) 
Serum analyzed for the presence of binding antibodies specific to C1-INH. 
ALT = alanine aminotransferase; APTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; F1+2 = prothrombin fragment 1+2; GGT = Gamma glutamyl transferase; HAE = hereditary 
angioedema; HIV = human immunodeficiency virus; HBV = hepatitis B virus; HCV = hepatitis C virus; INR = 
international normalized ratio. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 68 of 130 
(United States) 
Confidential 
8.1.2 
Risk Assessments for Deep Vein Thrombosis and Pulmonary 
Embolism 
The clinical model scoring system that will be used for the risk assessment of DVT is 
described in Table 3. 
Table 3: 
Scoring System for the Risk Assessment of Deep Vein Thrombosis 
Clinical feature 1 
Score 
Active cancer (treatment ongoing or within previous 6 months or palliative). 
+1 
Paralysis, paresis, or recent plaster immobilization of the lower extremities. 
+1 
Recently bedridden for more than 3 days or major surgery, within 4 weeks. 
+1 
Localized tenderness along the distribution of the deep venous system. 
+1 
Entire leg swollen. 
+1 
Calf swelling by more than 3 cm when compared with the asymptomatic leg (measured 10 cm 
below tibial tuberosity). 
+1 
Pitting edema (greater in the symptomatic leg). 
+1 
Collateral superficial veins (non-varicose). 
+1 
Alternative diagnosis as likely or greater than that of deep vein thrombosis. 
-2 
1 In subjects with symptoms in both legs, the more symptomatic leg is used. From Wells et al 1997. 
If a subject has a risk score of ≥ 1, a lower extremity ultrasound examination will be arranged 
by the investigator to exclude DVT. If a DVT is confirmed on ultrasound examination, the 
event will be classified as an AE of special interest (AESI) (see Section 9.1.2) and will be 
reported as an SAE. 
The clinical model scoring system that will be used for the risk assessment of PE is described 
in Table 4. 
Table 4: 
Scoring System for the Risk Assessment of Pulmonary Embolism 
Clinical feature 1 
Score 
Previous pulmonary embolism or deep vein thrombosis. 
+1.5 
Heart rate >100 beats per minute. 
+1.5 
Immobilization or surgery in the previous 4 weeks. 
+1.5 
Clinical signs and symptoms of deep vein thrombosis (minimum of leg swelling and pain with 
palpation of the deep veins). 
+3 
Alternative diagnosis less likely than pulmonary embolism. 
+3 
Hemoptysis. 
+1 
Malignancy (on treatment, treated within the last 6 months, or palliative). 
+1 
1 From Wells et al 2000. 

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 70 of 130 
(United States) 
Confidential 
8.4 
Visit Schedule 
The timing and frequency of all clinical procedures are described in the following tables:  
• Schedule of Events for “CSL830-Continuation” Subjects. 
• Schedule of Laboratory Assessments for “CSL830-Continuation” Subjects. 
• Schedule of Events for “CSL830-Interrupted” Subjects and “CSL830-Naïve” Subjects. 
• Schedule of Laboratory Assessments for “CSL830-Interrupted” Subjects and “CSL830-
Naïve” Subjects. 
• 
Schedule of Events for the Extension Period. 
 
8.4.1 
Informed Consent / Assent 
All subjects must provide written informed consent/assent (as appropriate) before any study-
specific assessments or procedures are performed. Written informed consent/assent is not 
required for assessments or procedures performed according to standard of care (eg, for 
diagnosis or treatment); results from such assessments may be used in the determination of 
study eligibility. 
Subjects who participate in the Extension Period are to provide written informed 
consent/assent (as appropriate) before any study-specific assessments or procedures are 
performed during the Extension Period. 
8.4.2 
Screening 
The eligibility of “CSL830-Naïve” Subjects and “CSL830-Interrupted” Subjects will be 
assessed at a Screening Visit conducted within the 4 weeks before Treatment Period 1.  
The Screening Visit and the Day 1 Visit of Treatment Period 1 can occur on the same day. If a 
subject fails Screening at a combined Screening Visit / Day 1 Visit, then the subject will be 
treated as a screen failure. 
“CSL830-Naïve” Subjects include the following: 
• Subjects who did not participate in CSL830_3001. 
• Subjects who participated in CSL830_3001 but did not receive blinded investigational 
product as a part of that study. 
NOTE: For “CSL830-Naïve” Subjects, the first study visit is the Screening Visit. 
“CSL830-Interrupted” Subjects include the following: 

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CCI

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 75 of 130 
(United States) 
Confidential 
• Review the individual acute action plan with subject. 
• Train subject: 
o Instruct on use of the eDiary. 
o Instruct on the CSL830 injection technique. 
o Instruct on the CSL830 dosing regimen. 
o Supervise (observe) subject’s first administration of CSL830. 
o Provide written instructions on the handling, reconstitution, and self-administration of 
CSL830; the suggested interval between each administration of CSL830 is 3 or 4 
days.  
• Schedule the next telephone contact and the next study visit. 
8.4.3.2 
Week 1, Day 4 
“CSL830-Naïve” Subjects and “CSL830-Interrupted” Subjects will attend a study visit on 
Day 4 (+ 1 day).  
The Day 4 Visit may be waived for “CSL830-Interrupted” Subjects (only) if the investigator 
has confirmed that the subject can adequately treat himself/herself with CSL830 (ie, no 
further training is necessary). In this case, all activities scheduled for the Day 4 Visit may be 
conducted at the Day 1 Visit. 
“CSL830-Continuation” Subjects are not required to attend a study visit on Day 4. 
The following procedures will be performed by the investigator or delegate: 
• Review subject eDiary; record information on HAE attacks in eCRF. 
• Confirm access to on-demand medication for the treatment of breakthrough HAE attacks. 
• Record AEs. 
• Record concomitant therapies. 
• Train subject: 
o Instruct on use of the eDiary. 
o Instruct on the CSL830 injection technique. 
o Instruct on the CSL830 dosing regimen. 
o Supervise subject’s second administration of CSL830. 
• Dispense CSL830/study supplies to subject. 
• Perform CSL830 accountability.  
• Schedule the next telephone contact and the next study visit. 

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CCI
CCI

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 77 of 130 
(United States) 
Confidential 
• Perform CSL830 accountability. 
• Confirm access to on-demand medication for the treatment of breakthrough HAE attacks. 
• Record AEs. 
• Record concomitant therapies. 
• If considered necessary, reinstruct subject on injection technique, dosing regimen, and use 
of eDiary. 
• Dispense CSL830/study supplies to subject.  
• Schedule the next telephone contact and the next study visit. 
8.4.3.5 
Week 13 
Subjects will be contacted by telephone on Day 85 (± 2 days) to record AEs and concomitant 
therapies. 
8.4.3.6 
Week 17 
Subjects will attend a study visit on Day 113 (± 2 days). 
The following procedures will be performed by the investigator or delegate: 
• Vital signs, including weight. 
• Assess risk of DVT and PE. 
• Review subject eDiary; record information on HAE attacks in eCRF. 
• Assess subject for CSL830 dose continuation or CSL830 dose increase. 
o During the fixed-dose Treatment Period 1, subjects who experience very frequent 
HAE attacks (ie, ≥ 12 attacks, as defined per protocol, within a 4-week evaluation 
period) are eligible for CSL830 dose increases in increments of 20 IU/kg (up to a 
maximum dose of 80 IU/kg). All CSL830 dose increases are optional, and will be 
made only in subjects who are eligible, at the sole discretion of investigator. An 
evaluation period for any dose increase is defined as beginning after a dose-stable 
period (ie, 2 weeks after the initiation or dose increase of CSL830). A dose increase in 
Treatment Period 1 is intended as rescue prophylaxis, to provide the opportunity for 
subjects who have very frequent HAE attacks to continue in the study during the 
otherwise fixed-dose Treatment Period 1. 
• Perform CSL830 accountability. 
• Confirm access to on-demand medication for the treatment of breakthrough HAE attacks. 
• Record AEs. 
• Record concomitant therapies. 

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CCI

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 82 of 130 
(United States) 
Confidential 
8.4.4.5 
Week 45 
Subjects will attend a study visit on Day 309 (± 2 days). 
The following procedures will be performed by the investigator or delegate: 
• Vital signs including weight. 
• Assess risk of DVT and PE. 
• Review subject eDiary; record information on HAE attacks in eCRF. 
• Assess subject for CSL830 dose continuation or CSL830 dose increase. 
o During Treatment Period 2, subjects who experience ≥ 3 HAE attacks (as determined 
per protocol) within an 8-week evaluation period are eligible for CSL830 dose 
increases in increments of 20 IU/kg (up to a maximum dose of 80 IU/kg). All CSL830 
dose increases are optional, and will be made only in subjects who are eligible, at the 
sole discretion of investigator. An evaluation period for any dose increase is defined 
as beginning after a dose-stable period (ie, 2 weeks after the initiation or dose increase 
of CSL830). See Section 3.2 for additional details. A dose increase in Treatment 
Period 2 is intended to allow investigators to adjust/optimize the dose for subjects 
who may need a higher prophylactic dose. 
• Perform CSL830 accountability. 
• Confirm access to on-demand medication for the treatment of breakthrough HAE attacks. 
• Record AEs. 
• Record concomitant therapies. 
• If considered necessary, reinstruct subject on injection technique, dosing regimen, and use 
of eDiary. 
• Dispense CSL830/study supplies to subject.  
• Schedule the next telephone contact and the next study visit. 
8.4.4.6 
Week 49 
Subjects will be contacted by telephone on Day 337 (± 2 days) to record AEs and 
concomitant therapies. 
8.4.4.7 
Week 53 
Subjects will attend a study visit on Day 367 (± 2 days). See also Section 8.4.6.1 for the 
Week 53 Visit of the Extension Period, which may also be the first visit of the Extension 
Period. 

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 84 of 130 
(United States) 
Confidential 
8.4.5 
Subject Follow-up 
8.4.5.1 
Follow-up Visit 
Subjects will attend a Follow-up Visit occurring 14 days (± 3 days) after the final visit in 
Treatment Period 2 or any visit resulting in study discontinuation, unless informed 
consent/assent has been withdrawn or if the Extension Period starts prior to the scheduled 
Follow-up Visit. See Section 8.4.6 for information on how subjects may continue onto the 
Extension Period from Treatment Period 2. 
The following procedures will be performed by the investigator or delegate: 
• Review subject eDiary; record information on HAE attacks in eCRF. 
• Collect eDiary from subject (only if subject is not going to participate in the Extension 
Period). 
• Record AEs. 
• Record concomitant therapies. 
8.4.6 
Extension Period 
8.4.6.1 
 Extension Period Week 1  
The assessments performed for the Extension Period Visit 1 depend on whether a subject 
starts the Extension Period on the same day as the final visit for Treatment Period 2.  Please 
see the specific instructions as noted below. 
8.4.6.1.1 Extension Period Starts on the Same Day as Treatment Period 2 
Completion (Week 53 of Treatment Period 2) 
The following procedures will be performed by the investigator or delegate for subjects who 
start the Extension Period on the same day that they complete Treatment Period 2 in addition 
to the procedures performed on the final visit of Treatment Period 2. The Extension Period 
Visit 1 procedures will not be repeated if they were already performed for the final visit of 
Treatment Period 2 (see Section 8.4.4.7). 
• Ensure that the subject completed an informed consent form (ICF) if he/she did not 
already consent to participate in the Extension Period. 
• Schedule the next study visit. 
• Instruct the subject on dosing volume. Note: Determine volume to be administered 
based on new algorithm for subjects weighing ≥ 40 kg (subjects weighing < 40 kg 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 85 of 130 
(United States) 
Confidential 
will continue to undergo rounding as during Treatment Periods 1 and 2 [ie, rounded 
up to the nearest 500 IU]):  1. Determine weight-based dose. Round (up or down to 
the nearest 1000 IU), 2. Determine the volume to be administered, and 3. Instruct the 
subject on the volume to be administered twice weekly.  
• Dispense CSL830 and other supplies to subjects. 
 
Table 7 shows the assessments from Treatment Period 2 (Week 53 Visit) that will be used for 
Visit 1 of the Extension Period when the Extension Period starts on the Same Day and 
Treatment Period 2. 
Table 7:  
Assessments from Treatment Period 2 (Week 53 Visit) to Be Used 
for Visit 1 of the Extension Period When the Extension Period 
Starts on the Same Day as Treatment Period 2 
Assessments from Treatment Period 2 (Week 53 Visit) 
Study Center Visit 
Physical Examination 
Indwelling Catheter (yes/no) 
Vital Signs, including Body Weight 
Assess Risk of DVT and PE 
Urine Pregnancy Test A 
Confirm Access to On-demand HAE Medication 
CSL830 Accountability 
Concomitant Medication 
Adverse Events 
Abbreviations: DVT = deep vein thrombosis; HAE = hereditary angioedema; PE = pulmonary embolism. 
A The results of the urine pregnancy test can only be used to satisfy the applicable eligibility criterion if the 
Treatment Period 2 End of Study Visit and the first visit of the Extension Period (ie, Day 367) occur on 
exactly the same day. Otherwise, a new pregnancy test must be performed at the first study visit in the 
Extension Period in order to confirm eligibility. 
 
8.4.6.1.2 Extension Period Does Not Start on the Same Day as Treatment 
Period 2 Completion 
It is strongly preferred that subjects initiate the Extension Period on the same day they 
complete Treatment Period 2; however, a period of up to 30 days is allowed between the final 
visit of Treatment Period 2 and the first visit of the Extension Period.   
The procedures outlined above in Section 8.4.6.1.1 will be conducted with the following 
exceptions for subjects who do not start the Extension Period on the same day that they 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 86 of 130 
(United States) 
Confidential 
complete Treatment Period 2.  For subjects who have an interrupted course/elect to take a rest 
period (of up to 30 days) of CSL830 treatment between Treatment Period 2: 
1. The Treatment Period 2 End-of-Study Follow-up Visit will remain an on-site visit and 
will occur 14 days (± 3 days) after the last visit (Week 53) in Treatment Period 2 if the 
subject’s Extension Period starts after the scheduled Follow-up Visit. (No Treatment 
Period 2 Follow-up Visit is required if the subject’s Extension Period starts prior to 
the scheduled Follow-up Visit), and  
2. The diary will not be used after the already planned Treatment Period 2 follow-up 
period (approximately 2 weeks); however, the following information will be 
reviewed, documented in the medical record, and recorded at the Extension Period 
Visit 1 for the period during which no diary is in use: 
• Any additional information on relevant medical history,  
• Any HAE attacks,  
• Any medication taken, and  
• Any adverse events 
Table 8 shows the assessments from Treatment Period 2 (Week 53 Visit) that will be repeated 
for Visit 1 of the Extension Period when the Extension Period does not start on the Same Day 
and Treatment Period 2. 

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 96 of 130 
(United States) 
Confidential 
NOTE: A pre-planned surgery must have been pre-planned prior to the subject’s 
participation in the study (ie, at the time of signing informed consent/assent [as 
appropriate]). This information must be presented in the subject’s source 
documentation.  
o Hospitalizations that occur for procedures not due to an AE (eg, cosmetic surgery). 
o Hospitalizations for a diagnostic procedure where the hospital stay is less than 
24 hours in duration or for normal management procedures. 
• Overdose of the investigational product or any concomitant therapy that does not result in 
any adverse signs or symptoms.  
• HAE attacks; unless the attack meets the criteria of an SAE (see Section 9.1.3) or unless 
the attack significantly worsens following on-demand treatment (eg, with IV Berinert). 
For laboratory safety parameters, any instances of absolute values being outside the reference 
range or changes at any visit after study start that are considered by the investigator as 
clinically significant must recorded in the eCRF as AEs. In addition, at the investigator’s 
discretion, any changes or trends over time in laboratory parameters can be recorded in the 
eCRF as AEs if such changes or trends are considered to be clinically relevant, even if the 
absolute values are within the reference range. 
Laboratory findings do not need to be reported as AEs in the following cases: 
• Laboratory parameters already beyond the reference range at Screening, unless a further 
increase/decrease can be considered an exacerbation of a pre-existing condition.  
• Abnormal laboratory parameters caused by mechanical or physical influences on the 
blood sample (eg, in vitro hemolysis) and flagged as such by the laboratory in the 
laboratory report. 
• Abnormal parameters that are obviously biologically implausible (eg, values that are 
incompatible with life or outside the measuring range). 
• An abnormal laboratory value that cannot be confirmed after repeat analysis, preferably 
in the same laboratory (ie, the previous result could be marked as not valid and should not 
necessarily be reported as an AE).  
9.1.2 
Adverse Event of Special Interest 
There are several AEs that will be monitored closely as AESIs to enable an adequate risk-
benefit evaluation of CSL830 versus standard therapy. Additional data may be requested for 
these events. The AESIs will be: 
• Thrombotic or thromboembolic events. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 97 of 130 
(United States) 
Confidential 
• Anaphylaxis (defined as severe and clinically relevant systemic allergic reaction with 
sudden onset and rapid progression. Clinical criteria for the diagnosis of anaphylaxis are 
presented in Table 9). 
Table 9: 
Clinical Criteria for the Diagnosis of Anaphylaxis 
Anaphylaxis is highly likely when any 1 of the following 3 criteria is fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-
uvula) AND at least 1 of the following: 
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow [PEF], hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia 
[collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for 
that patient (minutes to several hours): 
a. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-
tongue-uvula) 
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia) 
c. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence) 
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in 
systolic BP* 
b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that 
person’s baseline 
PEF = peak expiratory flow; BP = blood pressure. 
*  Low systolic blood pressure for children is defined as less than 70 mm Hg from 1 month to 1 year, 
less than (70 mm Hg + [2 × age]) from 1 to 10 years, and less than 90 mm Hg from 11 to 17 years. 
Reference: Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et 
al. Second symposium on the definition and management of anaphylaxis: summary report—
Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis 
Network symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391-7. 
9.1.3 
Serious Adverse Event 
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any 
dose: 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 98 of 130 
(United States) 
Confidential 
• Results in death: The event must be the cause of death for the SAE to meet this serious 
criterion. 
• Is life-threatening: The term “life-threatening” refers to an event in which the subject was 
at risk of death at the time of the event; it does not refer to an event that hypothetically 
might have caused death if it had been more severe. 
• Requires in-patient hospitalization or prolongation of existing hospitalization: CSL 
considers “hospitalization or prolongation of existing hospitalization” for at least 
24 hours as the defining criterion for an SAE. Hospital admissions for planned surgery or 
for normal disease management procedures (eg, chemotherapy) are not considered as 
defining criteria for SAEs.  
• Results in persistent or significant disability or incapacity. 
• Is a congenital anomaly or birth defect. 
• Is medically significant: A medically significant event is defined as an event that does not 
necessarily meet any of the SAE criteria, but which is judged by a physician to potentially 
jeopardize the subject or require medical or surgical intervention to prevent 1 of the 
above outcomes listed as an SAE criterion. 
Adverse events that do not fall into the above categories are defined as non-serious AEs. 
9.2 
Severity of Adverse Events 
9.2.1 
Unsolicited Adverse Events 
The severity of each AE (ie, non-serious and serious AEs) is to be assessed using the 
following criteria: 
Table 10: 
Severity of Unsolicited Adverse Events 
Severity 
Definition 1 
Mild 
A type of AE that is usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily living. 
Moderate 
A type of AE that is usually alleviated with additional specific therapeutic intervention. The 
event interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the subject. 
Severe 
A type of AE that interrupts usual activities of daily living, or significantly affects clinical 
status, or may require intensive therapeutic intervention. 
1 CDISC SDTM Severity Intensity Scale for Adverse Event Terminology 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 99 of 130 
(United States) 
Confidential 
9.2.2 
Solicited Local Adverse Events (Injection Site Reactions) 
Solicited local AEs are injection site reactions at the CSL830 injection site that are 
specifically asked for and recorded.  
Subjects will record the occurrence of local AEs (injection site reactions) in their eDiary by 
answering the following question: “Have you experienced any local reactions at the injection 
site (eg, discomfort, swelling, bruising, or itching)? (yes/no)”. Subjects will be instructed to 
take notes (outside of the diary) to describe any local AEs they experience and to report that 
information to their investigator. Each investigator will use the information from the diary 
and the subject to identify and grade the intensity of each symptom. Each symptom will be 
entered as an independent AE.  
Solicited local AEs are defined and graded as follows: 
Table 11: 
Intensity of Solicited Local Adverse Events 
Solicited Local 
Adverse Event 
Intensity Grading 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Discomfort at the 
injection site after 
the injection 
procedure (eg, pain, 
burning) 
Present but does not 
interfere with activity 
Repeated use of non-
narcotic pain reliever for 
over 24 hours or interferes 
with activity 
Any use of narcotic pain 
reliever or prevents daily 
activity 
Swelling at the 
injection site worse 
than at the end of 
the injection 
procedure 
Up to 2.5 cm larger than 
at the end of the injection 
procedure and does not 
interfere with activity 
2.6 to 5.0 cm larger than at 
the end of the injection 
procedure or interferes with 
activity 
Over 5.0 cm larger than 
at the end of the 
injection procedure or 
prevents daily activity 
Bruising at the 
injection site 
Up to 2.5 cm 
2.6 to 5.0 cm 
Greater than 5.0 cm 
Itching at the 
injection site 
Present but does not 
interfere with activity 
Interferes with activity 
Prevents daily activity 
9.3 
Causality of Adverse Events 
The causal relationship of an AE to CSL830 must always be assessed by the investigator. All 
AEs will be classified as either related or not related to CSL830. If a causality assessment is 
not provided for an AE (including an SAE), that AE will be considered related to CSL830.  

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 100 of 130 
(United States) 
Confidential 
The degree of certainty with which an AE is attributed to CSL830 or an alternative cause (eg, 
natural history of the underlying disease, concomitant therapy) will be determined by how 
well the event can be understood in terms of: 
• Known pharmacology of CSL830. 
• Clinically and / or pathophysiologically plausible context. 
• Reaction of a similar nature previously observed with similar products, or reported in the 
literature for similar products as being product related (eg, headache, facial flushing, 
pallor). 
• Plausibility supported by the temporal relationship (eg, the event being related by time to 
administration or termination of treatment with CSL830, drug withdrawal or reproduced 
on re-challenge). 
9.4 
Observation Periods for Adverse Events 
Treatment Period 1 and Treatment Period 2 
The observation period for AE (and SAE) reporting in an individual subject will start at the 
time of giving written informed consent/assent (as appropriate) for participation in this study 
and finish with the final study visit.  
Extension Period 
The observation period for AE (and SAE) reporting in an individual subject will start at the 
time of giving written informed consent/assent (as appropriate) for participation in the 
Extension Period and finish with the follow-up visit contact.  
If the investigator becomes aware of an SAE that has started after the observation period has 
finished, and the event could in some way be associated with the investigational product, then 
this must also be reported to CSL Global Clinical Safety and Pharmacovigilance (see 
Section 9.6). 
9.5 
Adverse Event Reporting 
9.5.1 
Adverse Events 
At each clinical evaluation, the investigator (or delegate) will determine whether any AEs 
have occurred. AEs will be recorded in the AE page of the eCRF. If known, the medical 
diagnosis of an AE should be recorded in preference to the listing of individual signs and 
symptoms. The investigator must follow up on the course of an AE until resolution or 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 101 of 130 
(United States) 
Confidential 
stabilization. If an AE is ongoing after the final study visit, the AE will continue to be 
followed up until resolution, stabilization, or for 30 days after the final administration of 
CSL830, whichever is sooner. 
If, during the study period, a subject presents with a pre-existing condition that was not noted 
at the time of study entry, the condition should be retrospectively recorded in the Medical 
History section of the eCRF. 
9.5.2 
Adverse Events of Special Interest 
Adverse events of special interest should be considered medically significant and are 
therefore SAEs. The expedited reporting procedures for SAEs are described in detail in 
Section 9.6.1. 
9.6 
Serious Adverse Event Reporting 
This study will comply with all applicable regulatory requirements and adhere to the full 
requirements of ICH Topic E2A (Clinical Safety Data Management: Definitions and 
Standards for Expedited Reporting). 
For SAEs occurring during the study, the investigator or delegate will enter all relevant 
information in the AE page of the eCRF. An electronic document containing the AE page and 
other applicable pages of the eCRF must be sent (via facsimile or email) to the sponsor 
together with a Notification of Serious Adverse Event at Investigator Site cover page, 
which has been signed and dated by the Investigator. If an electronic document is not able to 
be generated (eg, internet access problem), a handwritten paper SAE report must be 
completed, which must be signed and dated by the investigator. In this case, the investigator 
should follow-up with a completed, signed, and dated electronic document. 
All SAEs that occur during the course of the study, whether or not causally related to 
CSL830, must be reported immediately (within 24 hours of the investigator becoming 
aware of the event) to CSL.  
Adverse events occurring in the period between the time the subject gave written informed 
consent/assent (as appropriate) and the first exposure to CSL830 that meet 1 or more of the 
seriousness criteria for AEs must be reported to CSL in the same manner as other SAEs and 
will be included in the clinical study database.  

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 102 of 130 
(United States) 
Confidential 
Any SAE that occurs after the final study visit that is considered to be causally related to 
CSL830 must be reported immediately (ie, within 24 hours of the investigator becoming 
aware of the event) to CSL. 
Contact details and guidance for reporting SAEs will be provided to study site before the 
study starts. 
9.6.1 
 Requirements for Immediate Reporting of Serious Adverse 
Events 
The minimum reporting requirements for immediate reporting of SAEs include: 
• Identifiable subject. 
• Suspected medicinal product and / or procedure. 
• Event term. 
• Identifiable reporting source. 
In addition, the investigator must: 
• Report all SAEs to the relevant institutional review board (IRB) / independent ethics 
committee (IEC) within the timeframe specified by the IRB / IEC. 
• Submit follow-up reports to CSL Clinical Safety and Pharmacovigilance until the SAE 
has resolved, or, in the case of permanent impairment, until stabilized. 
• Ensure that the causality assessment for all SAEs is entered in the eCRF. 
If the minimum requirements for reporting are fulfilled, the investigator should not wait to 
receive additional information to fully document the event before notifying CSL.  
When submitting SAE reports and any other related reports (eg, discharge summaries) to 
CSL, subjects should be identified only by their subject number and study number. The 
investigator should not include the subject’s name, date of birth, or address. 
In cases of death, the investigator should supply CSL and the IEC / IRB (as applicable) with 
any additional information as it becomes available (eg, autopsy reports and detailed medical 
reports). 
The procedure to be followed if an ongoing AE becomes an SAE after the end of the 
observation period for AEs is described in Section 9.4. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 103 of 130 
(United States) 
Confidential 
9.7 
Other Significant Event Reporting 
9.7.1 
Overdose 
Details (ie, volume, location of infusions, infusion rate) of overdose of CSL830 or any 
concomitant therapy must be recorded in the eCRF. Any overdose of CSL830 that results in 
any adverse signs or symptoms, and considered by the investigator to be medically 
significant, must be reported as an SAE (see Section 9.1.3). 
9.7.2 
Pregnancy and Lactation  
Females who are pregnant, intending to be pregnant or nursing are not eligible to enroll or 
continue to participate in this study. C1-esterase inhibitor approved for intravenous treatment 
or prophylaxis of HAE is a Pregnancy Category C medication. 
A female subject who becomes pregnant while participating in the study must notify the 
investigator immediately. The subject must discontinue treatment with CSL830. If the female 
subject is in the active Treatment Period of the study, her participation will be discontinued 
and the procedure for discontinuation of a subject will be followed, as described in 
Section 4.2. 
CSL must be notified within 5 days of the investigator becoming aware of the pregnancy.  
Whenever possible, a pregnancy in a subject exposed to the investigational product should be 
followed to term so as to assess any potential occurrence of congenital anomalies or birth 
defects. Any follow-up information, including premature termination and the status of the 
mother and child after delivery, should be reported by the investigator to CSL using a 
Pregnancy Reporting / Outcome Form. 
If the partner of a male subject participating in this study becomes pregnant, the male subject 
should inform the investigator as soon as possible. The investigator will attempt to obtain 
written permission directly from the pregnant female that her gynecologist can be contacted 
by the investigator and/or the sponsor. In this case, the investigator may contact the 
gynecologist of the pregnant female to review potential risks of C1-INH and the pregnancy 
will be followed to its outcome.  
9.8 
IRB / IEC Reporting Requirements 
The time frame within which an IRB / IEC must be notified of deaths and CSL830-related 
unexpected SAEs is stipulated by each IRB / IEC. It is the investigator’s responsibility to 

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 112 of 130 
(United States) 
Confidential 
• The number of subjects who are randomized to treatment with 40 IU/kg CSL830. 
• The number of subjects who are randomized to treatment with 60 IU/kg CSL830. 
• The number of subjects who undergo 1 CSL830 dose increase in Treatment Period 1. 
• The number of subjects who undergo 1 CSL830 dose increase in Treatment Period 2. 
• The number of subjects who undergo 2 CSL830 dose increases in Treatment Period 1. 
• The number of subjects who undergo 2 CSL830 dose increases in Treatment Period 2.  
• The number of subjects who administer the same CSL830 dose over Treatment Period 1. 
• The number of subjects who administer the same CSL830 dose over Treatment Period 2. 
• The number of subjects who administer the same CSL830 dose over Treatment Periods 1 
and 2. 
• The number of subjects who complete Treatment Period 2.  
• The number of subjects who discontinue participation in the study (including the reason 
for discontinuation).  
Disposition data (including the reason for discontinuing use of CSL830 or withdrawing from 
the study) will be listed by site and subject. All Screen Failures will be listed. 
The number of subjects in each analysis population will be summarized (by subjects who are 
randomized to 40 IU/kg CSL830; by subjects who are randomized to 60 IU/kg CSL830; and 
overall). The number of subjects in each analysis population will also be summarized (by 
subjects who are randomized to 40 IU/kg CSL830 and who have 1 dose increase; by subjects 
who are randomized to 40 IU/kg CSL830 and who have 2 dose increases; by subjects who 
are randomized to 60 IU/kg CSL830 and who have 1 dose increase; and overall) for both 
Treatment Period 1 (only) and for Treatment Periods 1 and 2 (together). A by-subject listing 
will be produced including the assignment of subjects to analysis populations. 
Extension Period 
The above described summaries for subject disposition will be performed for subjects who 
continued into the Extension Period by treatment and overall, except for the number of 
subjects who provide consent/assent (as appropriate) and the number of subjects who 
complete Treatment Period 2. In addition, the following will be presented by treatment and 
overall: 
• The number of subjects who undergo no CSL830 dose increase in the extension 
Period 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 113 of 130 
(United States) 
Confidential 
• The number of subjects who undergo 1 CSL830 dose increase in the extension period 
• The number of subjects who undergo 2 CSL830 dose increases in the extension 
period  
• The number of subjects who undergo no CSL830 dose increase in Treatment Period 1, 
Treatment Period 2, and the Extension Period 
11.3.1.2 
Subject Characteristics 
Subject characteristics will be presented in summary tables for the ITT and Safety 
Populations.  
Treatment Period 1 and Treatment Period 2 
Subject characteristics will be presented in summary tables for all subjects in the ITT and 
Safety Populations. Demographic and baseline characteristics and medical history will be 
summarized (by subjects who are randomized to 40 IU/kg CSL830; by subjects who are 
randomized to 60 IU/kg CSL830; and overall). Demographic and baseline characteristics and 
medical history will also be summarized (by subjects who are randomized to 40 IU/kg 
CSL830 and who have 1 dose increase; by subjects who are randomized to 40 IU/kg CSL830 
and who have 2 dose increases; by subjects who are randomized to 60 IU/kg CSL830 and 
who have 1 dose increase; and overall) for both Treatment Period 1 (only) and for Treatment 
Periods 1 and 2 (together). This will include age (years), sex, race, ethnicity, height, weight, 
and body mass index (BMI; calculated as kg/m²). Medical history will be presented by 
system organ class (SOC) and preferred term (PT), and will be classified using the latest 
version of the Medical Dictionary for Regulatory Activities (MedDRA). Continuous data will 
be summarized by descriptive statistics and categorical data will be summarized by frequency 
counts and percentages. A by-subject listing of demographic characteristics, baseline 
characteristics, and medical history will also be presented. 
Extension Period 
The above described summaries for demographic and baseline characteristics and medical 
history will be also performed for subjects who participated in the Extension Period. The only 
difference is that data will also be summarized by treatment group and dose increase in the 
Extension Period. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 114 of 130 
(United States) 
Confidential 
11.3.2 
Efficacy Analyses 
11.3.2.1 
Primary Efficacy Analysis 
There is no primary efficacy analysis. The primary analysis for study CSL830_3002 is 
safety-based and can be found in Section 11.3.3.1. 
11.3.2.2 
Secondary Efficacy Analyses 
The ITT and PP Populations will be used as analysis populations for efficacy analyses. 
Treatment Period 1 and Treatment Period 2 
All subjects in the ITT and all subjects in the PP Population will be used as analysis 
populations for efficacy analyses. The number and percentage of subjects who are responders 
at the last visit in Treatment Period 1 and at the last visit in Treatment period 2, when 
“response” is defined as a ≥ 50% relative reduction in the time-normalized number of HAE 
attacks during treatment with CSL830, compared with the time-normalized number of attacks 
used to qualify for participation in the current study will be assessed. The number and 
percentage of subjects will be summarized (by subjects who are randomized to 40 IU/kg 
CSL830; and by subjects who are randomized to 60 IU/kg CSL830). Subjects who undergo a 
dose increase will be flagged in the listing. 
The number and percentage of subjects who experience a time-normalized HAE attack 
frequency of < 1 HAE attack per 4-week period will be summarized at the last visit in 
Treatment Period 1 and at the last visit in Treatment Period 2 (by subjects who are 
randomized to 40 IU/kg CSL830 and by subjects who are randomized to 60 IU/kg CSL830). 
Subjects who undergo a dose increase will be flagged in the listing. 
A within-subject analysis will give the number and percentage of subjects who are responders 
or non-responders before a dose increase, after a first dose increase, and after a second dose 
increase (only applicable for subjects who are randomizes to the 40 IU/kg CSL830 treatment 
group) summarized by subjects who are randomized to the 40 IU/kg CSL830 and by subjects 
who are randomized to the 60 IU/kg CSL830 treatment group. Furthermore, a within-subject 
analysis will give the number and percentage of subjects who experience or who do not 
experience a time-normalized HAE attack frequency of < 1 HAE attack per 4-week period 
before a dose increase, after a first dose increase, and after a second dose increase (only 
applicable for subjects who are randomizes to the 40IU/kg treatment group) summarized by 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 115 of 130 
(United States) 
Confidential 
subjects who are randomized to the 40 IU/kg and by subjects who are randomized to the 60 
IU/kg treatment group. 
The secondary efficacy analyses will be done both for Treatment Period 1 (only) and for 
Treatment Periods 1 and 2 (together). 
A descriptive subgroup analysis will be done for subjects who use oral agents for the 
treatment of HAE and for subjects who do not. A descriptive subgroup analysis will be done 
for subjects who previously used intravenously administered C1-INH for routine (long-term) 
prophylaxis. Additional subgroup analyses will be conducted for subjects who participated in 
study CSL830_3001 and for subjects who did not AND for subjects who are aged < 18 years 
and ≥ 18 years. Subjects who use oral agents for the treatment of HAE will be flagged in the 
listings. 
Extension Period 
For the subjects who are in the Extension Period, the above described analyses of the number 
and percentage of subjects who are responders and the number and percentage of subjects 
who experience a time-normalized number of HAE attacks of < 1 HAE attack per 4-week 
period will be summarized for the Extension Period by treatment (40 IU/kg CSL830; 60 
IU/kg CSL830) and for all treatment periods. 
11.3.3 
Safety Analyses 
The Safety Population will be used for analyses of safety. 
Treatment Period 1 and Treatment Period 2 
All subjects in the Safety Population will be included in the safety analyses. The primary 
safety analysis will be performed by treatment group (ie, subjects who are randomized to 40 
IU/kg CSL830 and by subjects who are randomized to 60 IU/kg CSL830). Data collected 
from those subjects will be included in the 40 IU/kg and 60 IU/kg CSL830 treatment groups, 
respectively, until the time they undergo the final study visit or they undergo a CSL830 dose 
increase, whichever comes first. 
A secondary safety analysis will be performed by treatment group [ie, subjects who are 
randomized to 40 IU/kg CSL830 and by subjects who are randomized to 60 IU/kg CSL380, 
regardless of any dose increase(s)]. Data collected from those subjects will be included in the 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 116 of 130 
(United States) 
Confidential 
40IU/kg and 60IU/kg CSL830 treatment groups, respectively, until the time they undergo the 
final study visit. 
The analyses will be done both for Treatment Period 1 (only) and for Treatment Period 1 and 
2 (together), unless otherwise noted. 
Furthermore, safety analyses will be summarized by subjects who are randomized to 
40 IU/kg CSL830 and who have 1 dose increase; by subjects who are randomized to 
40 IU/kg CSL830 and who have 2 dose increases; by subjects who are randomized to 
60 IU/kg CSL830 and who have 1 dose increase.  
After the dose increase, data collected from subjects who undergo a 20 IU/kg dose increase 
from 40 IU/kg to 60 IU/kg or from 60 IU/kg to 80 IU/kg in Treatment Period 1will be 
summarized separately for the 60 IU/kg and 80 IU/kg CSL830 doses. Furthermore, data 
collected from subjects who undergo a 20 IU/kg dose increase from 40 IU/kg to 60 IU/kg or 
from 60 IU/kg to 80 IU/kg in Treatment Period 2 will also be summarized separately for the 
60 IU/kg and 80 IU/kg CSL830 doses. 
After a second dose increase, data collected from subjects who undergo a 20 IU/kg x 2 dose 
increase from 60 IU/kg to 80 IU/kg in Treatment Period 1will be summarized separately for 
the 80 IU/kg CSL830 dose. Furthermore, data collected from subjects undergo a 20 IU/kg x 2 
dose increase from 60 IU/kg to 80 IU/kg in Treatment Period 2 will also be summarized 
separately for the 80 IU/kg CSL830 dose. 
Subjects who undergo a CSL830 dose increase will be flagged in the listing 
A descriptive subgroup analysis will be done for subjects who use oral agents for the 
treatment of HAE and for subjects who do not. A descriptive subgroup analysis will be done 
for subjects who previously used intravenously administered C1-INH for routine (long-term) 
prophylaxis. Additional subgroup analyses will be conducted for subjects who participated in 
study CSL830_3001 and for subjects who did not AND for subjects who are aged < 18 years 
and ≥ 18 years. Subjects who use oral agents for the treatment of HAE will be flagged in the 
listings. 
Extension Period 
Data collected from subjects in the Extension Period will be summarized as follows:  

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 117 of 130 
(United States) 
Confidential 
• For the Extension Period only (separate from data collected during Treatment 
Period 1 and Treatment Period 2) 
• For Treatment Period 1, Treatment Period 2 and the Extension Period 
(combined) 
Only data collected from subjects who are enrolled in the Extension Period will be included 
in these analyses. 
11.3.3.1 
Primary Safety Analysis 
The person-time incidence rate of each primary endpoint safety event will be assessed as 
defined above in Section 11.3.3 and overall. The person-time incidence rates are the number 
of subjects experiencing each primary endpoint safety event during the respective treatment 
duration with CSL830, divided by the sum of each subject’s time at risk in the respective 
treatment. The person-time incidence rate of each primary endpoint safety event will be 
assessed for Treatment Period 1 and for the Treatment Periods 1 and 2 overall. For the 
subjects who are in the Extension Period, the person-time incidence rate of each primary 
endpoint safety event will also be assessed for the Extension Period and for the treatment 
periods overall. 
Adverse events will be classified using the Medical Dictionary for Regulatory Activities 
(MedDRA). 
11.3.3.2 
Secondary Safety Analyses 
Adverse event data will be presented in individual listings and summary tables.  
The number and percentage of subjects experiencing SAEs, temporally-related AEs, 
increased risk scores for DVT or PE, thromboembolic events, inhibitory anti-C1-INH 
antibodies, or clinically significant abnormalities in laboratory assessments during treatment 
will be summarized as defined above in Section 11.3.3 and overall. The number and 
percentage of subjects who become seropositive for HIV-1, HIV-2, HBV, or HCV will be 
summarized as defined above in Section 11.3.3 and overall. The number and percentage of 
subjects experiencing solicited local AEs, the number of solicited local AEs, and the number 
of solicited local AEs per administration will be summarized as defined above in 
Section 11.3.3 and overall. The number and percentage of administrations of CSL830 
resulting in solicited local AEs will be summarized as defined above in Section 11.3.3 and 
overall. An overall summary of AEs will be given.  

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CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 122 of 130 
(United States) 
Confidential 
12 
Quality Assurance 
The study may be subject to an audit by CSL, an authorized representative(s) of CSL and / or 
inspections by an authorized regulatory authority (eg, US Food and Drug Administration 
[FDA]). Regulatory authorities may request access to all study documentation, including 
source documents for inspection and copying, in keeping with local regulations. CSL will 
immediately notify the investigator of an upcoming audit / inspection. 
In the event of an audit, all pertinent study-related documentation must be made available to 
the auditor(s). If an audit or inspection occurs, the investigator at each study site will permit 
the auditor / inspector direct access to all relevant documents and allocate their time as well 
as the time of relevant staff to discuss the findings and any relevant issues. 
13 
Regulatory and Ethics Considerations 
13.1 
Regulatory Considerations 
CSL or its agents will submit the appropriate documents to the local regulatory agencies and 
will await approval before study start. 
This study will be conducted under an a Clinical Trial Application, a Clinical Trial 
Notification or an FDA Investigational New Drug application, as appropriate, and 
documented in accordance with the applicable regulatory guidelines and requirements. 
The procedures set out in this study protocol are designed to ensure that CSL and the 
investigator abide by the principles of the current ICH GCP guideline on the conduct, 
evaluation and documentation of this study, as described in ICH Topic E6 (Guideline for 
GCP). The study will also be carried out according to all applicable international and national 
regulatory requirements. 
13.2 
Institutional Review Board / Independent Ethics Committee 
The investigator must submit the protocol and informed consent forms (ICFs) for review by 
an authorized and properly constituted (according to local guidelines) IRB / IEC. Written 
approval must be received from the IRB / IEC before commencement of the study. 
13.3 
Subject Information and Informed Consent 
Informed consent/assent must be implemented in this clinical study before protocol-specified 
procedures are carried out. Information should be given in both oral and written form 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 123 of 130 
(United States) 
Confidential 
whenever possible and deemed appropriate by the IRB / IEC. Subjects, their relatives (or if 
necessary, legally acceptable representatives) must be given ample opportunity to inquire 
about details of the study. 
Should there be any amendments to the protocol that would directly affect the subject’s 
participation in the study (eg, a change in any procedure), the ICF must be amended to 
incorporate this modification. Subjects must be informed of the change and they must sign 
the amended ICF/assent form indicating that they re-consent to participate in the study. 
13.4 
Subject Identification and Confidentiality 
All subject names and contact details will be kept confidential. Subjects will be identified 
throughout documentation and evaluation by the number allotted to them during the study. 
Each subject will be told that all study findings will be handled in the strictest confidence. 
The investigator at the study site will be responsible for retaining sufficient information about 
each subject (eg, name, address, phone number and identity in the study) so that regulatory 
agencies or CSL may access this information should the need arise. These records should be 
retained in a confidential manner as long as legally mandated according to local 
requirements. 
Subject medical records pertaining to the study may be inspected / audited at any time by 
CSL employees or their duly authorized representatives, a regulatory authority or the 
IRB / IEC. All records accessed will be strictly confidential. Consent to participate in the 
study includes consent to these inspections / audits. 
13.5 
 Indemnity and Compensation 
It is CSL policy that persons who participate in CSL’s clinical studies should be no worse off 
for their having been involved in the study. These persons include the subjects / volunteers, 
the investigator, the hospital and the IRB / IEC.  
CSL has taken out insurance to cover its obligations under both the Indemnity and the 
Compensation guidelines for injury to subjects involved in the study. 
Other details regarding compensation and the obligations of the investigator / CSL are 
provided in the Clinical Trial Agreement for the study (see Section 14.1). 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 124 of 130 
(United States) 
Confidential 
14 
Administrative Considerations 
14.1 
Clinical Trial Agreement 
This study will be conducted under a Clinical Trial Agreement between CSL (“Sponsor”) and 
the institution(s) representing the investigational study site(s) (“Authority”). Financial 
support to the investigational site(s) will be detailed in the Clinical Trial Agreement. The 
Clinical Trial Agreement must be signed before the commencement of the study and will 
clearly delineate the responsibilities and obligations of investigator and CSL, and will form 
the contractual basis under which the clinical study will be conducted.  
14.2 
Clinical Study Registration and Results Disclosure  
CSL will provide the relevant study protocol information in public database(s) before or at 
commencement of the study. CSL may also provide study information for inclusion in 
national registries according to local regulatory requirements. 
Results of this study will be disclosed according to the relevant regulatory requirements. All 
publications in peer-reviewed medical journals resulting from this study will be listed in the 
original study protocol registration record. 
14.3 
Implementation of the Protocol / Protocol Amendment(s) 
With the exception of medical emergencies, no changes or deviations in the conduct of the 
signed protocol will be permitted without documented approval of the CSL Medical Monitor 
and the IRB / IEC. In the event of a medical emergency, the investigator at the study site will 
institute any medical procedures deemed appropriate. However, all such procedures must be 
promptly reported to the CSL Medical Monitor and the IRB / IEC. 
Modifications to the protocol that may affect subject safety or the way the study is to be 
conducted will be documented in a protocol amendment, which must be approved by the 
IRB / IEC. 
Administrative changes to the protocol, defined as minor corrections and / or clarifications 
that have no effect on the way the study is to be conducted, will not require IRB / IEC 
approval, but will be submitted to the IRB / IEC for their information. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
Country-Specific Amendment No. 1 
 10 JULY 2015 
Page 125 of 130 
(United States) 
Confidential 
14.4 
Protocol Deviations 
All instances where the requirements of the study protocol were not complied with will be 
tracked. Corresponding subjects may be withdrawn from the study at the discretion of the 
investigator and / or CSL. Study protocol deviations arise when subjects who have been 
entered in the study deviate from the IRB / IEC-approved study protocol.  
If a major protocol deviation (ie, a deviation that could have a significant effect on the 
subject’s safety, rights, or welfare and / or on the integrity of the study data) occurs, the 
investigator must notify CSL and the appropriate IRB / IEC as soon as possible or as per 
local requirements.  
14.5 
Documentation and Record Keeping  
14.5.1 
Data Collection 
The investigator (or delegate) will maintain individual records for each subject. These 
records should include dates when a subject visited the study site, records of vital signs, 
medical history, or physical examinations, administration of CSL830 or concomitant therapy, 
any AEs experienced, and other notes as appropriate. These records constitute source data.  
An eCRF will be provided by CSL (or delegate) for each subject enrolled into the study. The 
investigator is responsible for ensuring accurate and proper completion of the eCRF in a 
timely manner so that it always reflects the latest observations on the subjects enrolled in the 
study. All entries on the eCRF must be backed up by source data unless there is prior 
agreement that the eCRF is the source data.  
All source data will be kept according to all applicable regulatory requirements. Source data 
must be completed legibly for each subject enrolled into the study and signed by the 
investigator (or delegate). 
The subject eDiary will be completed by the subject. At each clinic visit, the subject will 
present the completed diary to the investigator for review of entries and transfer of relevant 
information to the eCRF. 
14.5.2 
Data Quality Assurance 
Data generated throughout the study will be monitored and the eCRFs checked against the 
subject records for completeness and accuracy. CSL’s study monitor will perform this 
function. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
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Following completion of eCRF pages and entry of the data into a database, the data will be 
checked electronically for consistency and plausibility. Queries will be generated for 
questionable data and clarification sought from the investigator. These data queries must be 
resolved in a timely manner by the investigator (or delegate). 
14.5.3 
Record Retention 
An investigator study file prepared by CSL (or delegate), containing all applicable documents 
for use at the study site, will be made available to the investigator before the start of the 
study. All study documentation and materials maintained in the investigator study file must 
be kept in conformance with applicable national laws and regulations.  
All study documentation and materials maintained in the investigator study file at the study 
site must be available for inspection by the CSL’s study monitor (or delegate) to determine 
that all required documentation is present and correct.  
The study may be audited or inspected by qualified delegates from CSL or a competent 
regulatory authority. 
Following completion of the study, the investigator is responsible for archiving the 
investigator’s study file, the subject’s records and the source data according to applicable 
regulatory requirements.  
14.6 
Study and Site Closure 
CSL reserves the right to prematurely discontinue or suspend the study either at a particular 
site or at all study sites at any time and for any reason. If such action is taken, the CSL Study 
Monitor (or delegate) will discuss this with the investigator at each study site at that time and 
notify the investigators in writing. If the study is suspended or terminated for safety reasons, 
all investigators and the relevant regulatory agencies will be immediately notified of the 
action and the reason for it. The investigator at each study site will advise the IRB / IEC 
overseeing the study at their site. 
14.7 
Clinical Study Report 
A clinical study report will be written after the completion of the study. CSL or its agent will 
write the report in consultation with the investigator or, if applicable, a nominated 
coordinating investigator (or delegate). It is required by CSL that the coordinating 
investigator will sign the clinical study report.  

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
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 10 JULY 2015 
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(United States) 
Confidential 
Progress reports may be provided to the relevant regulatory bodies in accordance with their 
requirements. 
14.8 
Use of Data and Publications 
The rights and obligations of investigators and CSL concerning any formal presentation or 
publication of data collected as a direct or indirect result of this study will be addressed 
specifically in the Clinical Trial Agreement for the study. 

CSL Behring GmbH   
Study Number: 
CSL830_3002 
Study Product: 
CSL830 
 
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 10 JULY 2015 
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15 
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Study Product: 
CSL830 
 
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CSL Behring GmbH   
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Study Product: 
CSL830 
 
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 10 JULY 2015 
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Confidential 
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