Conditions: Primary Immune Deficiency Disorder
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 64
Healthy volunteers: no

Brief summary:
CLINICAL PHASE 3 STUDY TO MONITOR THE SAFETY, TOLERABILITY, AND EFFICACY OF SUBCUTANEOUS HUMAN IMMUNOGLOBULIN (CUTAQUIG®) ADMINISTERED AT MODIFIED DOSING REGIMENS IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASES

Detailed description:

Arms:
arm 1: Increased volume at each infusion site - patients will receive CUTAQUIG weekly and increase infusion volumes every 4 weeks arm 2: Increased infusion rate - patients will receive CUTAQUIG weekly and increase infusion rates every 4 weeks arm 3: Every other week dosing - patients will receive CUTAQUIG every other week at the equivalent of twice their body-weight dependent \[mg/kg\] weekly dose

Interventions: intervention 1: CUTAQUIG
Intervention descriptions: intervention 1: Human normal immunoglobulin

Protocol document:
Prot_000.pdf: 
Property of Octapharma. Do not copy or distribute without written permission.
This document contains confidential and proprietary information of Octapharma AG. 
Do not copy or distribute without written permission. 
090-CSP-SCGAM-06-V02/DOC ID3022
CLINICAL STUDY PROTOCOL 
SCGAM-06 
CLINICAL PHASE 3 STUDY TO MONITOR THE SAFETY,
TOLERABILITY, AND EFFICACY OF SUBCUTANEOUS
HUMAN IMMUNOGLOBULIN (CUTAQUIG®) ADMINISTERED
AT MODIFIED DOSING REGIMENS IN PATIENTS WITH
PRIMARY IMMUNODEFICIENCY DISEASES
Investigational Product: 
CUTAQUIG® 
Indication: 
Primary immunodeficiency diseases
Study Design: 
Prospective, open-label, non-controlled, three-
arm, multicenter, phase 3 study
Sponsor: 
Octapharma USA, 121 River St.
Hoboken, NJ 07030
Study Number: 
SCGAM-06 
BB-IND Number: 
15617 
Development Phase:
Phase 3 
Planned Clinical Start:
3rd Quarter 2019 
Planned Clinical End:
1st Quarter 2021 
Date of Protocol:
28-Aug-2019
Version: 
02 
This document contains confidential and proprietary information of Octapharma. 
Copying or distribution of this document is only permitted with the written permission of Octapharma. 
Any commercial use of the information is subject to the permission of Octapharma and a license fee. 


Property of Octapharma. Do not copy or distribute without written permission.
Study Protocol No. SCGAM-06 Version 02 
CONFIDENTIAL 
28-Aug-2019
Page 2 of 87 
STUDY OUTLINE 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
Title of Study: 
Clinical phase 3 study to monitor the safety, tolerability, and efficacy of subcutaneous
human immunoglobulin (CUTAQUIG®) administered at modified dosing regimens in
patients with primary immunodeficiency diseases
Indication: 
Primary immunodeficiency diseases 
Number of Study Center(s):
Approximately 15 study sites in the United States of America
Objectives:
Co-Primary Objectives:
The co-primary objectives of this study are to assess CUTAQUIG administered using
the following infusion parameters:
•
Compare total IgG trough levels from weekly infusions to every other week
infusions
•
Safety and tolerability when administered at increased infusion volumes at
each infusion site
•
Safety and tolerability when administered at increased infusion flow rates at
each infusion site
•
Safety and tolerability when administered on an every other week dosing
regimen
Secondary Objectives: 
The secondary objectives of this study are to: 
•
Assess the effect of CUTAQUIG on quality-of-life (QoL) measures
•
Obtain further data on the safety and efficacy of CUTAQUIG


Property of Octapharma. Do not copy or distribute without written permission.
Study Protocol No. SCGAM-06 Version 02 
CONFIDENTIAL 
28-Aug-2019
Page 3 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
Tertiary Objective:
A tertiary objective of this study is to evaluate patient satisfaction of various study 
parameters 
(such 
as 
switching 
to
CUTAQUIG
from 
another 
SCIG
product, satisfaction with infusion pump, changes in infusion regimen parameters,
general infection/general observations) using a study-specific questionnaire.
Study Design: 
The study is a prospective, open-label, non-controlled, 3-arm, multicenter, phase 3 
study.
Patients with a history of primary immunodeficiency (PI) disease that are currently 
on a stable dose of subcutaneously administered immunoglobulin (SCIG) treatment
may be enrolled.
Stabilization Period 
After completing the Screening Period and being assigned to 1 of 3 cohorts (as
described below), patients will enter a 4-week Stabilization Period. During this
period, patients will receive their first 4 CUTAQUIG infusions (Stabilization Period
Weeks 0, 1, 2, and 3) at the same body-weight dependent dose (mg/kg) and infusion
flow rate (mL/hr/site) as their previous SCIG product; however, this flow rate should
not exceed maximum infusion rates listed in protocol.
Note: patients entering the study for participation in Cohort 3 must already be
established on a weekly infusion schedule for a minimum of 12 weeks prior to the
Screening Visit.
Patients entering the study already established on every other week dosing must
enter either Cohort 1 or Cohort 2 and will be required to dose weekly beginning at
the Stabilization Week 0.
Note: patients entering the study currently active and established on CUTAQUIG in 
Study SCGAM-03 will have already been stabilized on CUTAQUIG and would go 
directly into the Treatment Period following the Screening Visit. The Screening Visit 
of Study SCGAM-06 will occur on the same day as the final dosing visit for Study 
SCGAM-03. Procedures performed for Study SCGAM-03 that are also required for 
the Study SCGAM-06 Screening Visit do not need to be repeated at the same visit. 
Patients that completed the SCGAM-03 study and went on a commercial SCIG 


Property of Octapharma. Do not copy or distribute without written permission.
Study Protocol No. SCGAM-06 Version 02 
CONFIDENTIAL 
28-Aug-2019
Page 4 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
product prior to screening for SCGAM-06 are required to enter the Stabilization
Period.
Treatment Period 
After completing the 4-week Stabilization Period, patients will enter the Treatment
Period and begin their infusion parameters according to cohort assignment as
described below:
Cohort 1 (increased volume at each infusion site – patients will receive CUTAQUIG
weekly and increase infusion volumes every 4 weeks): Patients will return to the
clinic for the Treatment Period Baseline Visit at which they will receive the same
body-weight dependent (mg/kg) dose but the volume will be increased by up to the
maximum allowed volume increase per infusion site of 25 mL/site for patients ≥40 kg
or 10 mL/site for patients <40 kg. This volume increase per infusion site can be
achieved by reducing the total number of injection sites while maintaining similar or 
lower flow rates as received with their prior treatment. When introducing increased
volumes to an infusion site, Investigators must attempt to maintain flow rates similar
to or lower than prior infusions. This may require adjusting pump rate, tubing size, 
needle gauge, etc. Patients will receive this new volume per site for 4 weekly 
infusions (Treatment Period Baseline and Weeks 1, 2, and 3), and return to the clinic
at Week 4 for their next infusion at an increased volume at each infusion site. This
cycle will continue, with infusion volumes increasing by up to a maximum allowed
volume increase per infusion site of 25 mL/site for patients ≥40 kg or 10 mL/site for
patients <40 kg every 4th infusion until reaching a patient’s maximum dose (in mL),
maximum tolerated volume (maximum volume based on Investigator’s decision of
patient’s tolerance), or 100 mL at 1 injection site – whichever is reached first.
Note: Sites are encouraged to enroll patients into Cohort 1 who are already on a
dosing regimen using at least 3 infusion sites to ensure that volume increases remain
below the protocol-specified limits. Patients dosing with 1 infusion site cannot enter 
Cohort 1.
Investigators should be aware that special considerations are required for volume 
increases in patients with 2 infusion sites receiving a total dose (volume) of more 
than 50 mL. To ensure that volume increases do not exceed 25 mL/site, the 
infusions must be split between the 2 syringes, such that each infusion site will 
receive a different total volume. For example, if a patient is receiving a total dose of 
60 mL divided equally between 2 infusion sites (eg, 30 mL/site), the first syringe 
could be increased to an infusion volume of 50 mL (an increase of 20 mL) and the 


Property of Octapharma. Do not copy or distribute without written permission.
Study Protocol No. SCGAM-06 Version 02 
CONFIDENTIAL 
28-Aug-2019
Page 5 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
second syringe would have an infusion volume of 10 mL. If this is tolerated, the next
infusion volume increase could be 60 mL at 1 infusion site (an increase of 10 mL)
and remain below the maximum allowed volume increase of 25 mL/site.
Cohort 2 (increased infusion rate - patients will receive CUTAQUIG weekly and
increase infusion rates every 4 weeks): Patients will return to the clinic for the
Treatment Period Baseline Visit, at which they will receive the same body-weight
dependent (mg/kg) dose of CUTAQUIG but the infusion rate per site will be
increased up to a maximum allowed flow rate increase per infusion site of
25 mL/hr/site for patients ≥40 kg or 10 mL/hr/site for patients <40 kg. Patients will
receive this new flow rate for 4 weekly infusions (Treatment Period Baseline and
Weeks 1, 2, and 3), and return to the clinic at Week 4 for their next infusion at an
increased infusion rate. This cycle will continue, with maximum allowed flow rate
increases per infusion site of up to 25 mL/hr/site for patients ≥40 kg or up
10 mL/hr/site for patients <40 kg every 4th infusion until reaching either: 1) a 
maximum flow rate (100 mL/hr/site) or the maximum flow rate achievable by the
pump, or 2) the maximum tolerated flow rate (maximum flow rate based on
Investigator’s decision of patient’s tolerance) – whichever is reached first.
Note: Clinical sites are encouraged to enroll patients that are either currently infusing
with 24-gauge needle sets or willing to switch to 24-gauge needle sets. Patients 
using 27-gauge needles will not be able to achieve adequate infusion rates for this 
cohort as the needle gauge will not allow for this.
Cohort 3 (every other week dosing - patients will receive CUTAQUIG every other
week at the equivalent of twice their body-weight dependent [mg/kg] weekly dose):
Patients will return to the clinic for the Treatment Period Baseline Visit to receive
their first double mg/kg weekly dose and begin an every other week dosing schedule.
Infusion volume increases when switching from weekly dosing to every other week 
dosing must not exceed a maximum allowed volume increase per infusion site of 
25 mL/site for patients ≥40 kg or an increase of 10 mL/site for patients <40 kg at the 
Treatment Period Baseline Visit. If a patient’s doubling of their weekly dose requires 
dosing with a volume of more than the maximum allowed increase in volume per 
injection site (25 mL/site or 10 mL/site, dependent on patient body weight), then they 
will be required to increase the number of infusion sites to remain below the 
maximum body-weight dependent volume increase. If this occurs, after 2 infusions 
the patient may remove one of the newly introduced injection sites as long as the 
volume per injection site increase limit is not exceeded. Infusion flow rates will be 


Property of Octapharma. Do not copy or distribute without written permission.
Study Protocol No. SCGAM-06 Version 02 
CONFIDENTIAL 
28-Aug-2019
Page 6 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
determined by the patient and Investigator, but initially should not exceed the
patient’s prior infusion rate, nor the maximum infusion rates listed in the protocol.
Patients entering Cohort 3 must already be established on weekly dosing for a
minimum of 12 weeks prior to Screening.
Note: Patients entering the study already established on an every other week
infusion schedule must participate in either Cohort 1 or Cohort 2 if they agree to
begin dosing every week beginning at Stabilization Period Week 0.
Study sites will be encouraged to enroll patients into all open cohorts.
The Sponsor will notify study sites when a cohort has filled and is no longer open to
recruitment.
Patients who enter and participate in one cohort may not enter another cohort at a
later time.
Patients entering the study currently active and established on CUTAQUIG in Study 
SCGAM-03 will have the Treatment Period Baseline Visit performed on the same
day as Termination Visit on Study SCGAM-03. Patients must first complete their
termination procedures for SCGAM-03, prior to their first infusion for Study 
SCGAM-06. Procedures that are performed on the same day as part of Study 
SCGAM-03 termination that are also required as part of Study SCGAM-06 Baseline, 
do not need to be repeated. Patients who completed the SCGAM-03 study and went
on a commercial SCIG product prior to screening for SCGAM-06 are required to
complete the Stabilization Period.
Number of Patients:
Approximately 65 patients are planned for this study.
•
At least 15 patients in Cohort 1
•
At least 15 patients in Cohort 2
•
At least 35 patients in Cohort 3
Patient Selection Criteria: 
Inclusion Criteria: 
1. Age ≥2 years and ≤75 years.
2. Confirmed diagnosis of primary immunodeficiency (PI) disease as defined by
the European Society for Immunodeficiencies and Pan American Group for


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Study Protocol No. SCGAM-06 Version 02 
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Page 7 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
Immunodeficiency and requiring immunoglobulin replacement therapy due to
hypogammaglobulinaemia or agammaglobulinaemia. Note: The exact type of
PI disease will be recorded.
3. Established on a consistent or stable mg/kg dose of any SCIG treatment for
a minimum of 3 months prior to Screening. Note: patients entering Cohort 3 
must be on weekly SCIG infusions for a minimum of 12 weeks.
4. Availability of the Immunoglobulin G (IgG) trough levels of 2 previous SCIG
infusions within 1 year of Screening, with 1 trough level obtained within
3 months prior to enrollment, and maintenance of trough serum IgG levels
≥5.0 g/L in 2 previous infusions. Patients with no prior IgG trough level within
3 months prior to enrollment may use the Screening IgG trough level as their
2nd reading.
5. Voluntarily given, fully informed signed informed consent. For patients under
the legal age of consent, voluntarily given, fully-informed, signed informed
consent will be provided by patient’s parent or legal guardian, and assent will
be provided by patient (per age-appropriate Institutional Review Board [IRB]
requirements).
6. Females of childbearing potential, who are not nursing and have no plans for 
pregnancy during the course of the study, must have been using at least
1 acceptable form of birth control for a minimum of 30 days prior to the
Screening visit and must agree to use at least 1 acceptable method of
contraception for 30 days after the last dose of CUTAQUIG. Acceptable
methods include: intrauterine device (IUD), hormonal contraception, male or 
female condom, spermicide gel, diaphragm, sponge, cervical cap, or
abstinence. 
7. For female patients of child-bearing potential, a negative result in a urine
pregnancy test conducted at the Screening visit.
8. Willingness to comply with all aspects of the protocol, including blood
sampling, for the duration of the study.
Exclusion Criteria: 
1. Evidence of active infection within 4 weeks of Screening or during the
Screening Period.
2. Current or clinically-significant history of any cardiovascular, respiratory,
hepatic, renal, gastrointestinal, endocrine, neurological, immunological
(excluding PI), hematologic, and/or psychiatric disorder(s), or a history of any


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Study Protocol No. SCGAM-06 Version 02 
CONFIDENTIAL 
28-Aug-2019 
 
Page 8 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019 
 
other illness that, in the opinion of the Investigator, might confound the results 
of the study, or pose additional risk to the patient by participation in the study. 
3. Known history of adverse reactions to immunoglobulin A (IgA) in other 
products. 
4. Body mass index (BMI) >40 kg/m2 for patients entering Cohort 2 or Cohort 3. 
There are no BMI restrictions for Cohort 1. 
5. Ongoing history of hypersensitivity or persistent reactions to blood or plasma 
derived products, or any component of the investigational product (such as 
Polysorbate 80). 
6. Requirement of any routine premedication for IgG administration. 
7. History of malignancies of lymphoid cells and immunodeficiency with 
lymphoma. 
8. Severe liver function impairment (aspartate aminotransferase [AST] or 
alanine aminotransferase [ALT] >3 times above upper limit of normal). 
9. Known protein-losing enteropathies or clinically significant proteinuria. 
10. Presence of renal function impairment  or predisposition for acute renal failure 
(eg, any degree of pre-existing renal insufficiency or routine treatment with 
known nephritic drugs). 
11. Treatment with oral or parenteral steroids for ≥30 days, or when given 
intermittently or as bolus at daily doses ≥0.15 mg/kg when taken within 
30 days of Screening. Note: Short or intermittent courses of steroids (ie, a 
steroid burst) of >0.15 mg/kg/day is allowed for treatment of a short-term 
condition such as an asthma exacerbation.  
12. Treatment with immunosuppressive or immunomodulatory drugs (except 
Omalizumab). 
13. Use of HYQVIA (Immune Globulin Infusion 10% [Human] with Recombinant 
Human Hyaluronidase) within 3 months prior to first CUTAQUIG infusion. 
14. Live viral vaccination (such as measles, rubella, mumps, and varicella) within 
2 months prior to first CUTAQUIG infusion. 
15. Exposure to blood or any blood product or derivative, other than sub-
cutaneous IgG used for regular PI disease treatment, within 3 months before 
the first CUTAQUIG infusion. 
16. Treatment with any investigational medicinal product within 3 months prior to 
first CUTAQUIG infusion. Note: Patients participating in Study SCGAM-03 will 
be allowed to enter this study without the 3-month waiting period for an 
Investigational Product. Patients receiving another investigational SCIG 


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Study Protocol No. SCGAM-06 Version 02 
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Page 9 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
product within 3 months prior to the first CUTAQUIG infusion may be
considered for enrollment after Sponsor approval.
17.Presence of any condition that is likely to interfere with the evaluation of
CUTAQUIG or satisfactory conduct of the trial.
18.Known or suspected to abuse alcohol, drugs, psychotropic agents, or other
chemicals within the past 12 months prior to first CUTAQUIG infusion.
19.Known active or chronic hepatitis B, hepatitis C, or HIV infection. Past
hepatitis B or hepatitis C infection that has been cured is allowed.
Test Product, Dose, and Mode of Administration:
CUTAQUIG, human normal immunoglobulin for subcutaneous (SC) administration.
CUTAQUIG will be administered by SC infusion every week (±2 days, Cohort 1 and
Cohort 2), every other week (±2 days, Cohort 3) at the doubled weekly dose. The
dosing frequency will be determined by cohort assignment.
Patients will receive the same mg/kg body weight dose as their previous SCIG
product prior to study entry.
If, during the study, a patient's body weight changes by >5% from the first infusion of
IMP, the dose will be adjusted to keep a constant mg/kg body weight basis.
Additional adjustments will be made by the Investigator at study visits if the patient’s
body weight changes >5% from the previous adjusted weight.
Each patient’s CUTAQUIG dose may be individualized, if considered necessary by 
the Investigator, by titrating upward or downward.
Batch (lot) numbers will be reported in the final report of the study.
Duration of Treatment: 
Individual patient participation will be approximately 30 to 32 weeks: 
•
Screening Period: 1 to 2 weeks*
•
Stabilization Period: 4 weeks**
•
CUTAQUIG Treatment Period: 24 weeks (6 months)
•
Termination Visit: 1 week after last CUTAQUIG infusion for Cohort 1 and
Cohort 2; 2-weeks after last CUTAQUIG infusion for Cohort 3


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Study Protocol No. SCGAM-06 Version 02 
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28-Aug-2019
Page 10 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
* Patients entering the study established on weekly SCIG infusions will have a 
1-week (±2 days) Screening Period. Patients entering the study established on every
other week dosing will have a 2-week (±2 days) Screening Period.
** Patients entering the study currently active and established on CUTAQUIG in
Study SCGAM-03 will skip Stabilization Period.
Reference Therapy, Dose, Mode of Administration:
Not applicable.
Study Outcome Parameters (Primary and Secondary Endpoints):
Primary Endpoint Parameters:
The co-primary objectives are to compare total IgG trough levels from weekly 
infusions to every other week infusions, to assess safety and tolerability of
CUTAQUIG being administered according to 3 different infusion parameters, and to
assess efficacy parameters when switching from weekly infusions to every other
week infusions. These will be assessed using the following safety variables:
•
Change in individual total IgG trough levels from weekly infusions to every 
other week infusions
•
Occurrence of treatment-emergent AEs (TEAEs) throughout the entire
Stabilization and Treatment Periods starting with the first infusion of
investigational medicinal product (IMP)
•
Occurrence of TEAEs temporally associated with CUTAQUIG delivered
during the Treatment Period
•
Occurrence of TEAEs temporally associated with CUTAQUIG delivered
during the Stabilization Period
•
TEAEs by speed of infusion
•
Local infusion-site reactions
•
Laboratory parameters (hematology, clinical chemistry, and basic urinalysis)
Secondary Endpoint Parameters: 
Secondary objectives will evaluate quality of life, along with additional evaluations of 
CUTAQUIG safety and efficacy being administered according to 3 different infusion 
parameters. These will be assessed using the following variables: 


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Study Protocol No. SCGAM-06 Version 02 
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28-Aug-2019
Page 11 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
•
Quality of Life questionnaires
•
Measurement of individual profiles of IgG trough levels over time (all cohorts)
•
Monitoring for all infectious disease occurrence, resolution, and antibiotic use
•
Occurrence of serious bacterial infections (SBIs)
•
Vital signs (blood pressure, pulse, body temperature, respiratory rate)
Tertiary Endpoint Parameters: 
The tertiary objective will evaluate patient satisfaction of the study parameters (such
as switching to CUTAQUIG from another SCIG product, satisfaction with infusion
pump,
changes in
infusion
regimen
parameters,
general
infection/general
observations). This will be assessed using the following parameter:
•
Subject Questionnaire
Study Procedures: 
Investigators will enroll patients into the study only after written informed consent has
been obtained (and written assent where appropriate). During the Screening Period,
sites must obtain written approval from Octapharma prior to patients entering the
Stabilization Period (or Treatment Period, for subjects who are currently active and
established on CUTAQUIG in Study SCGAM-03).
The Flow Chart of Assessments includes full details regarding all of the procedures
that will be performed at each study visit. Below is a brief summary of the procedures
that will be performed during the study.
Screening Period:
The Screening Visit should occur on approximately the same day the patient is
scheduled to infuse with their personal SCIG product (or their final infusion of
CUTAQUIG in Study SCGAM-03, if appropriate) in order to get an accurate IgG
trough level. After written informed consent/assent has been obtained, patients will
be evaluated for study eligibility according to the inclusion/exclusion criteria. These
evaluations will include demographics, medical history, physical examinations
(including body weight and vital signs), current medication use, blood and urine
sample collection (for evaluation of clinical safety laboratory parameters, and IgG
trough levels as specified in the Flow Chart of Assessments. Following the
completion of all Screening procedures, the patient will dose with their personal SCIG


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Study Protocol No. SCGAM-06 Version 02 
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28-Aug-2019
Page 12 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
product (or CUTAQUIG from Study SCGAM-03, if applicable) at their typical dose
and infusion rate.
During the Screening Period (and after the infusion with their personal SCIG product
or CUTAQUIG from Study SCGAM-03, if applicable), patients must not receive any 
other IgG product; therefore, it is anticipated that patients will receive their first dose
of CUTAQUIG between 5 days and 16 days after the Screening Visit.
Patients may be enrolled into any open cohort, based on Investigator and patient
preference: however, patients entering the study already established on every other 
week dosing must enter either Cohort 1 or Cohort 2. After receiving written approval
from the Sponsor, which will include confirmation that the chosen cohort is still open
for enrollment, patients who have met all of the inclusion criteria and none of the
exclusion criteria will return to the clinic for their first CUTAQUIG infusion in the
Stabilization Period.
Patients entering the study currently active and established on CUTAQUIG in Study 
SCGAM-03 will have their Screening Visit procedures performed on the same day
as their last infusion visit on Study SCGAM-03. Patients must first complete their final
infusion for Study SCGAM-03 prior to being consented for Study SCGAM-06.
Procedures performed on the same day for Study SCGAM-03 that are also required
as part of Study SCGAM-06 do not need to be repeated. These patients will proceed
directly into the Treatment Period following completion of Screening. All other 
patients, including patients who completed their participation in Study SCGAM-03 
and went on a commercial SCIG product prior to the Screening Visit, will need to
complete the Stabilization Period.
Stabilization Period
Study-required assessments will be performed as specified in the Flow Chart of 
Assessments including safety evaluations before and after each infusion. These 
assessments will include updating medical history and current medication use, 
measuring body weight and vital signs, collecting blood and urine samples (for 
evaluation of clinical safety laboratory parameters and for hepatitis C), and collecting 
serum retention samples. Patients will receive their infusion of CUTAQUIG and will 
be monitored for infusion site reactions and AEs. Any concomitant medication use 
after the start of the infusion will be recorded. 
Prior to leaving the study site, patients will be dispensed CUTAQUIG for in-home 
infusions between site visits, along with detailed infusion instructions. Patients will 


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Study Protocol No. SCGAM-06 Version 02 
CONFIDENTIAL 
28-Aug-2019
Page 13 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
also be provided with a study diary in which they will record details of their home
treatment infusions, AEs, and relevant concomitant medication use. Patients
entering the study will have experience with SCIG infusions; however, if necessary,
they will be provided with additional training on using an infusion pump.
Treatment Visits: 
Study-required assessments will be performed as specified in the Flow Chart of
Assessments per cohort assignment, including safety evaluations before and after
each infusion. At all on-site visits the following assessments will be performed:
measurements of body weight and vital signs, collection of blood samples for IgG
trough levels, infusion of CUTAQUIG, monitoring for infusion site reactions and AEs,
review and dispensing of patient diary, and updating concomitant medication use.
For all cohorts at Baseline, Week 12, and Week 24, the following evaluations will
also be performed: physical examination and blood and urine sample collection for 
evaluation of clinical safety laboratory parameters (including urine pregnancy tests). 
All patients (or parents/guardians, as age-appropriate) will complete a QoL
questionnaire prior to IMP infusion at the Baseline Visit. Patients who entered the
Treatment Period after participation in Study SCGAM-03 (and therefore skipping the
Stabilization Period) will have serum retention and hepatitis C samples collected at
the Baseline Visit.
Prior to leaving the study site, patients will be dispensed CUTAQUIG for in-home
infusions between site visits, along with detailed infusion instructions. Patients will
also be provided with a study diary in which they will record details of their home
treatment infusions, adverse events, and relevant concomitant medication use.
Termination Visit:
Patients in Cohort 1 and Cohort 2 will have their Termination Visit 1 week (± 2 days) 
after last infusion, and patients in Cohort 3 will have their Termination Visit 2 weeks 
(± 2 days) after the last infusion. All Termination Visit procedures must be performed 
prior to the patient receiving any other IgG product.  
For either regular or early termination, a Termination Visit will include study 
assessments as indicated in the Flow Chart of Assessments. These assessments 
will include physical examinations (including body weight and vital signs), collection 
of blood and urine samples (for clinical safety laboratory parameters, and IgG trough 
levels), collection of serum retention and hepatitis C samples, collection of AEs and 


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Study Protocol No. SCGAM-06 Version 02 
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Page 14 of 87 
Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
concomitant medication use, evaluation for infusion site reactions, and completion of
both a QoL questionnaire and the Subject Questionnaire.
Independent Data Monitoring Committee: 
An independent Data Monitoring Committee will periodically review relevant data
with emphasis on AEs, including SAEs, and thromboembolic events. 
Statistical Analysis: 
This is an open-label, non-controlled, 3-arm study to primarily monitor safety and
tolerability for 3 different dosing regimens and to assess efficacy parameters when
switching from weekly to every other week infusions of CUTAQUIG. The co-primary 
endpoints and most of the secondary endpoints will be assessed by means of
descriptive statistics. One of the primary endpoints, namely the efficacy of
CUTAQUIG to maintain total IgG trough levels when administered every other week,
will be statistically tested, and the number of patients to be enrolled in Cohort 3 was
determined accordingly.
The following populations will be considered for the statistical analysis:
•
Safety Analysis Set: all patients who received at least part of one infusion of
CUTAQUIG.
•
Full Analysis Set (FAS): all patients in the Safety Analysis Set who satisfy all
major eligibility criteria and for whom any post-baseline data is available (per
intention-to-treat principle). This set of eligible patients will be used for
measurement of treatment effects.
•
Per-Protocol (PP) Set: all patients in the FAS, excluding those with substantial
protocol deviations which may have an impact on the analysis of the
co-primary endpoints. This is the set of patients who participated in the study
as intended and for whom the co-primary endpoints can be evaluated as
planned.
Only substantial protocol deviations with the potential to significantly affect the study 
results or to invalidate the interpretation of the data obtained will lead to exclusion of 
patients from the PP set. The membership of each patient in the respective analysis 
populations will be determined before statistical analysis in a data review meeting by 
a panel consisting of a medical expert from the Sponsor, the clinical study manager, 
the data manager, and the study statistician. 


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Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019
In the event that a patient is not treated according to the dosing regimen described
for their assigned cohort, the original cohort assignment will still be used for Safety 
and ITT analyses (SAF and FAS populations). These patients will be removed from
the PP population due to protocol violations.
Statistical Analysis Plan: 
A formal statistical analysis plan describing all details of the analyses to be performed
will be prepared by the study statistician and approved by the Sponsor prior to start
of the statistical analysis.
The safety analysis will comprise descriptive statistics, tabulations and listings of all
TEAEs, safety laboratory results, vital signs and physical examination findings. All
reported AEs will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA).
For each TEAE, the time relative to the start of the infusion will be calculated and the
TEAE will be classified as temporally associated if the onset is during the infusion or
within 72 hours after the end of the infusion.
All reported AEs will be listed and tabulated in full detail, in particular the following
key figures will be presented for each cohort and for the study as a whole:
•
Total number of TEAEs reported in the Stabilization and Treatment Periods
•
Number of TEAEs temporally associated with CUTAQUIG delivered during
the Treatment Period
•
Number of TEAEs temporally associated with CUTAQUIG delivered during
the Stabilization Period
•
Infusion rate at the onset of temporally associated TEAEs (frequencies and
percentages)
•
Narratives will be prepared describing each death, other serious adverse
events (SAEs), and other significant AEs that are judged to be of special
interest because of clinical importance.
The QoL data will be presented descriptively by visit, along with the change from 
Baseline Visit. 
The Subject Questionnaire data will be presented descriptively. 


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Name of Sponsor/Company: 
Octapharma USA, 121 River St. Hoboken, NJ  07030 
Name of Investigational Product: 
CUTAQUIG 
Protocol Identification Code: 
SCGAM-06 
Name of Active Ingredient: 
Human Normal Immunoglobulin 
Date of Final Protocol: 
28-Aug-2019 
 
All IgG measurements will be listed and summarized descriptively by time point. 
Individual courses of IgG trough levels will be presented graphically as Trellis plots. 
For Cohort 3 the change in trough total IgG levels from baseline weekly infusions to 
Week 24 (or Early Termination, if appropriate) of every other week infusions will be 
evaluated by means of a paired t-test. 
 
 


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TABLE OF CONTENTS 
STUDY OUTLINE ....................................................................................................................... 2 
PROTOCOL SIGNATURES .................................................................................................... 21 
TABLE OF CONTENTS ........................................................................................................... 23 
TABLE OF TABLES ................................................................................................................ 26 
LIST OF ABBREVIATIONS ..................................................................................................... 27 
GLOSSARY OF TERMS .......................................................................................................... 28 
1 
INTRODUCTION..............................................................................................................30
1.1 
BACKGROUND .........................................................................................................30
1.2 
RATIONALE FOR CONDUCTING THE STUDY...............................................................33
1.3 
BENEFIT-RISK STATEMENT......................................................................................34
2 
STUDY OBJECTIVES......................................................................................................36
2.1 
CO-PRIMARY OBJECTIVES.......................................................................................36
2.2 
SECONDARY OBJECTIVES........................................................................................36
2.3 
TERTIARY OBJECTIVE ..............................................................................................36
3 
INVESTIGATIONAL PLAN..............................................................................................37
3.1 
PRIMARY AND SECONDARY ENDPOINTS...................................................................37
3.1.1 Primary Endpoints......................................................................................37
3.1.2 Secondary Endpoints.................................................................................37
3.1.3 Tertiary Endpoint........................................................................................37
3.2
OVERALL STUDY DESIGN AND PLAN ........................................................................38
3.3
DISCUSSION OF STUDY DESIGN AND CHOICE OF CONTROL GROUP(S).....................39
3.3.1 Study Design..............................................................................................39
3.3.2 Dosing ........................................................................................................39
3.3.3 Control Group(s) ........................................................................................42
3.3.4 Study Parameters ......................................................................................43
4 
STUDY POPULATION.....................................................................................................44
4.1 
POPULATION BASE ..................................................................................................44
4.1.1
Inclusion Criteria ........................................................................................ 44 
4.1.2 Exclusion Criteria ....................................................................................... 44 
4.2 
PRIOR AND CONCOMITANT THERAPY ....................................................................... 46 
4.2.1 Permitted Concomitant Therapy ................................................................ 46 
4.2.2 Forbidden Concomitant Therapy ............................................................... 46 
4.3 
WITHDRAWAL AND REPLACEMENT OF PATIENTS ...................................................... 47 
4.3.1 Premature Patient Withdrawal ................................................................... 47 
4.3.2 Patient Replacement Policy ....................................................................... 47 
4.4 
ASSIGNMENT OF PATIENTS TO TREATMENT GROUPS ............................................... 48 
4.5 
RELEVANT PROTOCOL DEVIATIONS ......................................................................... 48 
4.6 
SUBSEQUENT THERAPY ........................................................................................... 48 
5 
INVESTIGATIONAL MEDICINAL PRODUCT(S) ........................................................... 49 
5.1 
CHARACTERIZATION OF INVESTIGATIONAL PRODUCT(S) ........................................... 49 
5.2 
PACKAGING AND LABELLING .................................................................................... 49 
5.3 
CONDITIONS FOR STORAGE AND USE ...................................................................... 49 


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5.4 
DOSE AND DOSING SCHEDULE ................................................................................ 50 
5.5 
PREPARATION AND METHOD OF ADMINISTRATION .................................................... 50 
5.5.1 Infusion Sites ............................................................................................. 51 
5.5.2 Infusion Volume ......................................................................................... 51 
5.5.3 Infusion Flow Rates ................................................................................... 51 
5.6 
BLINDING, EMERGENCY ENVELOPES, AND BREAKING THE STUDY BLIND .................. 52 
5.7 
TREATMENT COMPLIANCE ....................................................................................... 52 
5.7.1 Drug Dispensing and Accountability.......................................................... 52 
5.7.2 Assessment of Treatment Compliance ..................................................... 53 
6 
STUDY CONDUCT .......................................................................................................... 54 
6.1 
OBSERVATIONS BY VISIT ......................................................................................... 54 
6.1.1 Screening Visit ........................................................................................... 54 
6.1.2 CUTAQUIG Stabilization Period (Stabilization Period Week 0 through 
Stabilization Period Week 4) ..................................................................... 55 
6.1.3 CUTAQUIG Treatment Visits (Baseline [Week 0] through Week 24) ....... 55 
6.1.4 Termination Visit ........................................................................................ 57 
6.1.5 Time Windows Used in this Study, including Tolerances ......................... 57 
6.2 
DURATION OF STUDY ............................................................................................... 58 
6.2.1 Planned Duration for an Individual Patient ................................................ 58 
6.2.2 Planned Duration for the Study as a Whole .............................................. 58 
6.2.3 Premature Termination of the Study ......................................................... 58 
7 
ASSESSMENTS AND METHODS .................................................................................. 60 
7.1 
DEMOGRAPHIC AND BASELINE INFORMATION ........................................................... 60 
7.1.1 Demographic and Baseline Characteristics .............................................. 60 
7.1.2 Medical History .......................................................................................... 60 
7.1.3 Prior and Concomitant Medication Use ..................................................... 60 
7.1.4 Documentation of Previous SCIG Treatment and IgG Trough Levels ..... 60 
7.2 
EFFICACY ASSESSMENTS ........................................................................................ 60 
7.3 
SAFETY ASSESSMENTS ........................................................................................... 63 
7.3.1 Adverse Events .......................................................................................... 63 
7.3.2 Local Site Reactions .................................................................................. 66 
7.3.3 Serious Adverse Events ............................................................................ 67 
7.3.4 Laboratory Tests ........................................................................................ 68 
7.3.5 Serum Retention Samples ......................................................................... 69 
7.3.6 Vital Signs .................................................................................................. 69 
7.3.7 Physical Examination including Height and Weight .................................. 69 
7.3.8 Other Relevant Safety Information ............................................................ 70 
7.4 
OTHER ASSESSMENTS ............................................................................................ 71 
7.4.1 Drug Concentration Measurements (IgG Trough Levels) ......................... 71 
7.4.2 Quality of Life Assessment ........................................................................ 71 
7.4.3 Subject Questionnaire ............................................................................... 71 
7.5 
APPROPRIATENESS OF MEASUREMENTS .................................................................. 71 
8 
DATA HANDLING AND RECORD KEEPING ................................................................ 72 
8.1 
DOCUMENTATION OF DATA ...................................................................................... 72 
8.1.1 Source Data and Records ......................................................................... 72 
8.1.2 Electronic Case Report Forms .................................................................. 72 
8.1.3 Changes to Electronic Case Report Form Data ........................................ 73 


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8.2 
INFORMATION TO INVESTIGATORS ............................................................................ 73 
8.3 
RESPONSIBILITIES ................................................................................................... 74 
8.4 
PROVISION OF ADDITIONAL INFORMATION ................................................................ 74 
8.5 
INDEPENDENT DATA MONITORING COMMITTEE ........................................................ 74 
9 
STATISTICAL METHODS AND SAMPLE SIZE ............................................................. 76 
9.1 
DETERMINATION OF SAMPLE SIZE............................................................................ 76 
9.2 
STATISTICAL ANALYSIS ............................................................................................ 76 
9.2.1 Populations for Analysis ............................................................................ 77 
9.2.2 Efficacy Analysis Plan ................................................................................ 77 
9.2.3 Safety Analysis Plan .................................................................................. 78 
9.2.4 Handling of Missing Data ........................................................................... 79 
9.3 
RANDOMIZATION, STRATIFICATION, AND CODE RELEASE ......................................... 79 
9.4 
INTERIM ANALYSIS ................................................................................................... 79 
10 
ETHICAL/REGULATORY, LEGAL AND ADMINISTRATIVE ASPECTS ...................... 80 
10.1 ETHICAL/REGULATORY FRAMEWORK ....................................................................... 80 
10.2 APPROVAL OF STUDY DOCUMENTS.......................................................................... 80 
10.3 PATIENT INFORMATION AND INFORMED CONSENT .................................................... 80 
10.4 PROTOCOL AMENDMENTS ....................................................................................... 81 
10.5 CONFIDENTIALITY OF PATIENT DATA ........................................................................ 81 
11 
QUALITY CONTROL AND QUALITY ASSURANCE ..................................................... 82 
11.1 PERIODIC MONITORING ........................................................................................... 82 
11.2 AUDIT AND INSPECTION ........................................................................................... 82 
12 
REPORTING AND PUBLICATION ................................................................................. 83 
12.1 CLINICAL STUDY REPORT ........................................................................................ 83 
12.2 PUBLICATION POLICY............................................................................................... 83 
13 
LIABILITIES AND INSURANCE ..................................................................................... 84 
14 
REFERENCES ................................................................................................................. 85 
15 
APPENDICES .................................................................................................................. 87 


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TABLE OF TABLES 
Table 1: Screening and Stabilization Periods – Flow Chart of Assessments ......... 17 
Table 2 
Cohort 1 (Increased Volume) – Flow Chart of Assessments .................... 18 
Table 3: Cohort 2 (Increased Infusion Rate) – Flow Chart of Assessments ........... 19 
Table 4: Cohort 3 (Every Other Week Dosing) – Flow Chart of Assessments ....... 20 
Table 5: Biochemical Characteristics of CUTAQUIG ............................................... 49 
Table 6: Infusion Volume and Flow Rate by Patient Weight ................................... 52 
Table 7: Study Visit Times and Windows Used in this Study .................................. 57 
Table 8: Diagnostic Criteria for Serious Bacterial Infection Types .......................... 61 
Table 9: Laboratory Tests and Time Points ............................................................. 68 


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LIST OF ABBREVIATIONS 
Abbreviation 
Description 
ADR 
Adverse drug reaction 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration–time curve 
BL 
Baseline 
BMI 
Body mass index  
Cmax 
Maximum concentration of drug 
Cmin 
Minimum concentration of drug 
CRO 
Contract research organization 
CSF 
Cerebrospinal fluid 
eCRF 
Electronic Case Report Form 
EDC 
Electronic data capture 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
IDMC 
Independent Data Monitoring Committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IMP 
Investigational medicinal product 
IRB 
Institutional Review Board 
IV 
Intravenous 
IVIG 
Intravenously administered immunoglobulin 
LDH 
Lactate dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
NAT 
Nucleic acid testing 
PI 
Primary immunodeficiency 
PK 
Pharmacokinetic(s) 
PP 
Per protocol 
QoL 
Quality of life 
SAE 
Serious adverse event 
SBI 
Serious bacterial infection 
SC 
Subcutaneous 
SCIG 
Subcutaneously administered immunoglobulin 
SF-10 
Short Form Health Survey, 10 item 
SF-36 
Short Form Health Survey, 36 item 
TEAE 
Treatment-emergent adverse event 
TEE 
Thromboembolic event 
Tmax 
Time to maximum plasma concentration 
WBC 
White blood cell 


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GLOSSARY OF TERMS 
Term 
Definition 
Treatment Period Baseline 
The first visit during the Treatment Period  
CUTAQUIG-naïve patients 
Patients who did not participate in Study SCGAM-03 
Cohort 1 (increased volume) 
This cohort will evaluate the safety and tolerability of CUTAQUIG delivered at 
increased volume per site than delivered with previous SCIG treatments. 
During the Stabilization Period, patients will receive CUTAQUIG at the same 
body-weight dependent (mg/kg) dose and infusion flow rate as their previous 
SCIG product; however, this flow rate should not to exceed maximum infusion 
rates listed in protocol. During the Treatment Period, patients will return to the 
clinic at Baseline to receive their first dose of CUTAQUIG with an infusion 
volume increase of up to the maximum allowed volume increase per infusion 
site of 25 mL/site for patients ≥40 kg or 10 mL/site for patients <40 kg. Every 
4 weeks the infusion volume will be increased again by up to 25 mL/site or 
10 mL/site for patients <40 kg until reaching a maximum dose (in mL), or 
maximum tolerated volume (maximum volume based on Investigator’s 
decision of patient’s tolerance), or 100 mL at 1 injection site  – whichever is 
reached first. 
Cohort 2 (increased flow rate) 
This cohort will evaluate the safety and tolerability of CUTAQUIG delivered at 
increased flow rates than those delivered with previous SCIG treatments. 
During the Stabilization Period, patients will receive CUTAQUIG at the same 
body-weight dependent (mg/kg) dose and infusion flow rate as their previous 
SCIG product; however, this flow rate should not exceed maximum infusion 
rates listed in protocol. During the Treatment Period, patients will return to the 
clinic at Baseline to receive their first dose of CUTAQUIG with an infusion rate 
increase up to a maximum allowed flow rate increase per infusion site of 
25 mL/hr/site for patients ≥40 kg or 10 mL/hr/site for patients <40 kg. Every 
4 weeks the infusion flow rates will be increased again by up to 25 mL/hr/site 
for patients ≥40 kg or 10 mL/hr/site for patients <40 kg until either 1) a 
maximum flow rate (100 mL/hr/site) or the maximum flow rate achievable by 
the pump, or 2) the maximum tolerated flow rate (based on Investigator’s 
decision of patient’s tolerance) – whichever is reached first. 
Cohort 3 (every other week 
dosing) 
This cohort will evaluate the safety and tolerability of CUTAQUIG delivered at 
the same or equivalent of twice the weekly mg/kg dose administered every 
other week with previous SCIG treatment. During the Stabilization Period, 
patients will receive CUTAQUIG at the same body-weight dependent (mg/kg) 
dose and infusion flow rate as their previous SCIG product; however, this flow 
rate must not to exceed maximum infusion rates listed in protocol. During the 
Treatment Period, patients will return to the clinic at Baseline to receive their 
first double mg/kg weekly dose and begin an every other week dosing 
schedule. When switching from weekly to every other week dosing, infusion 
volume increases per site must not exceed a maximum allowed volume 
increase per infusion site of 25 mL/site for patients ≥40 kg or 10 mL/site for 
patients <40 kg at the Treatment Period Baseline Visit. If a patient’s doubling 
of their weekly dose requires dosing with a volume of more than the maximum 
allowed volume increase per injection site (25 mL/site or 10 mL/site, 
dependent on patient body weight), they will be required to increase the 
number of infusion sites to remain below the maximum body-weight dependent 
volume increase. If this occurs, after 2 infusions the patient may remove 1 of 
the newly introduced injection sites as long as the volume per injection site 
increase limit is not exceeded. 
CUTAQUIG 
Immune 
Globulin 
Subcutaneous 
(Human). 
BLA 
approval 
received 
December 12, 2018 by US FDA. 
Enrolled 
Patients will be considered enrolled into the study after written informed 
consent (and assent, if age-appropriate) has been obtained.  
Infusion site 
An anatomical location of IMP infusion. 


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Term 
Definition 
Stabilization Period 
Patients will receive CUTAQUIG infusions at the same body-weight dependent 
(mg/kg) dose and infusion flow rate (ml/hr/site) as their previous SCIG product; 
however, this flow rate should not exceed maximum infusion rates listed in 
protocol. Patients entering the study currently active and established on 
CUTAQUIG in Study SCGAM-03 will have already been stabilized on 
CUTAQUIG and will proceed directly into the Treatment Period following 
completion of Screening. All other patients, including patients who completed 
their participation in Study SCGAM-03 and went on a commercial SCIG 
product prior to the Screening Visit, will need to complete the Stabilization 
Period 
Treatment Period 
Patient will receive CUTAQUIG infusions according their assigned cohort 
parameters. 


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1 
INTRODUCTION 
1.1 Background 
The primary therapeutic use of γ-immunoglobulins (Immunoglobulin G or IgG) is to 
provide antibodies to prevent viral and bacterial diseases (replacement therapy) in 
patients with primary immunodeficiency (PI) syndromes who have significant defects 
of antibody formation (humoral immunity). 
The PI syndromes are a heterogeneous group of disorders with an intrinsic defect of 
the tissues, cells, or proteins of the immune system resulting in immune deficiency. 
Many of these disorders are characterized by hypogammaglobulinaemia with or 
without defective antibody production. Children and adults with PI disease have an 
increased risk of recurrent bacterial and viral infections that typically attack the 
respiratory tract (sinusitis, bronchitis, pneumonia) but can also affect the 
gastrointestinal tract (gastroenteritis). They can be severe and can lead to substantial 
morbidity. Responses to antibacterial therapy are often poor. At present, most PI 
diseases are not curable, but immunoglobulins have shown to decrease the total 
number of severe infections and the duration of hospitalization. 
In the earlier years (around 1950), the IgG preparations were administered 
intramuscularly. This route of administration causes substantial discomfort and 
restricts the amount of IgG that can be given to the patients. During the last 20 years, 
several IgG preparations have been developed for intravenous (IV) and subcutaneous 
(SC) administration, and their use has further contributed to the successful treatment 
of patients with PI disorders. 
Administration via the SC route offers some advantages over IV infusion from a 
patient’s and a physician’s perspective and therefore become an alternative treatment 
option to the IV treatment. After the introduction of small, portable syringe drivers, this 
route of administration has gained even more popularity in Europe and the US as a 
practical, effective and safe treatment, because home therapy can also be 
recommended with this kind of administration. 
There are two major differences in the pharmacokinetic (PK) characteristics of 
intravenously administered immunoglobulins (IVIG) and subcutaneously administered 
immunoglobulins (SCIG): delayed absorption and reduced bioavailability. 
Following IV administration, the plasma concentration peaks immediately upon 
termination of the infusion, frequently reaching concentrations more than twice as high 
as the trough level. After SC administration, the absorption of IgG into the 
subcutaneous tissue is slower; the IgG must be delivered into the blood stream by the 
lymphatic system. Thus, with SCIG, the intravascular IgG concentration increases 
gradually, peaking at 48 to 72 hours. Most other features of SCIG treatment are 
consequences of these fundamental differences.[1] 
Studies of the PK of SCIG have shown a lower bioavailability than IVIG. This 
decreased bioavailability may involve degradation in the tissues and/or local binding 
in the intercellular matrix. Because of this expectation, several studies were designed 
to directly determine the bioavailability of SCIG as compared to IVIG.[2] 


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On converting from IVIG to SCIG replacement therapy for PI disease, the equivalent 
monthly dose of IgG is usually determined in one of two ways: 
• 1:1 dosing: The single IVIG dose administered every 3 (or 4) weeks is split into 
3 (or 4) equal weekly SCIG infusions. 
• Dosing based on the area under the curve (AUC). The SCIG dose is calculated 
from PK data to provide a monthly exposure to IgG equivalent to that with IVIG. 
The former is common in Europe, while the latter is a requirement of the US Food and 
Drug Administration (FDA) for SCIG labelling studies.[3] A recent study demonstrated 
the dose conversion factor for CUTAQUIG was 1.37.[4] Also, the CUTAQUIG Package 
Insert recommends a dose conversion factor of 1.4.[5] 
No differences have been reported in the half-life of SCIG and IVIG. With modern IgG 
preparations, half-lives have generally been reported to be about 30 to 35 days. Thus, 
there is no clinically significant difference in the half-life of IgG between the two 
administration routes.[1] 
However, SCIGs are usually given weekly, compared with IVIG regimens in which a 
large dose is given every 3rd or 4th week. The use of smaller doses at more frequent 
intervals results in stable, higher trough IgG serum concentrations which remain 
constant between consecutive SCIG infusions.[6] 
In 3 prior studies comparing IVIG and SCIG in PI patients, the mean peak serum IgG 
level immediately after IV infusions was 2303 mg/dL.[7-9] In contrast, the mean peak 
with SCIG was 1410 mg/dL and the time for the peak IgG concentration (Tmax) was 
62.6 h (2.6 days).[10] 
With weekly SCIG administrations, only about 4.5 days elapse between the Tmax of 
one dose and the administration of the next dose. Given the half-life of 30 days, this 
means that the IgG plasma concentration has dropped by only about 10% to 20% 
before the serum level starts to rise again. In contrast, with IVIG dosing intervals of 
3 to 4 weeks (about one half-life), the drop in plasma concentration will be about 40% 
to 50% by the time the next dose is due. These differences in the dosing intervals used 
in most SCIG versus IVIG regimens result in more stable serum IgG levels with 
SCIG.[1,10] 
Pooled data from 7 studies in which equivalent monthly SC IgG doses were given 
weekly versus IVIG every 21 to 28 days showed that trough serum IgG levels were 
10% to 20% higher with weekly SC doses than with the same total monthly IVIG dose. 
After 6 to 12 weekly infusions, near-steady-state IgG levels were achieved with 
differences between minimum and peak concentrations of only 5% to 10% of the 
overall mean.[1,10] 
Population PK modelling has been used to predict IgG exposure following a range of 
SCIG dosing regimens including frequent weekly dosing (1 to 7 times per week) and 
every other week dosing. This broad range of SCIG dosing regimens was simulated 
to predict steady-state serum IgG exposures. This PK modelling study consisting of 
2,500 patients was simulated to compare steady-state IgG concentration time profiles 
between weekly SCIG administrations with other frequencies, including daily through 
every other week dosing. The results produced overlapping steady-state 
concentration-time profile and similar AUC, Cmax, and Cmin values. This simulation 


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concluded that the same total weekly SCIG dose can be administered at different 
intervals, frequent or every other week, with minimal impact on serum IgG levels.[11] 
No clinical data are available that would allow comparison of the long-term efficacy of 
SCIG versus IVIG administration on the development of bronchiectasis or other 
changes on lung scans, nor on deterioration of pulmonary function in patients who 
have PI. Similarly, no data are available comparing the efficacy of SCIG versus IVIG 
on the persistence or progression of chronic sinus disease in PI patients with that 
problem, or on other complications of PI.[12] 
Orange et al (2012) reviewed the clinical efficacy of SCIG and identified 13 clinical 
studies in a total of 482 patients representing more than 27,500 infusions. The rate of 
serious bacterial infections (SBIs) was the most common primary efficacy endpoint in 
these studies. Secondary endpoints included overall infections (ie, infections not 
meeting SBI criteria), missed days at work or school, days in hospital and days on 
antibiotics. Definitions of overall infections and SBI were not standardized across 
studies. In 6 studies, SBIs were defined by FDA criteria and included bacterial 
pneumonia, meningitis, sepsis, osteomyelitis or visceral abscess. In 2 studies, an SBI 
was defined as an infection requiring hospitalization.[3] 
The rate of SBI was reported in 11 studies and varied from 0 to 0.09 events per patient 
per year. Infections were reported in 11 studies and varied from 2 to 5.18 events per 
patient per year. These rates are overall at least as low as those reported for IVIG 
studies. 
To provide adequate protection from infection, a serum IgG concentration of >5 g/L 
following IgG therapy has been recommended. Several retrospective studies and one 
prospective study, however, have shown that higher serum IgG concentrations 
resulting from higher doses of IVIG are associated with a decreased incidence of 
infections.[3] 
A previous meta-analysis in 16 individual studies of IVIG focused on the diagnosis of 
pneumonia, the most comparable endpoint, and demonstrated a statistically significant 
inverse correlation between higher IgG dose and a lower incidence of pneumonia, with 
a 27% decrease in incidence of pneumonia for every 100 mg/kg increase in dose.[13] 
Despite its well-established safety profile, IVIG often leads to undesired symptoms 
ranging from mild systemic adverse reactions (including flushing, fever, muscle aches, 
tiredness, headache, and dizziness) to severe reactions (including chest pain, 
tachycardia, changes in blood pressure, aseptic meningitis, thrombosis, and renal 
failure).[4] 
The slower rate of rise towards the peak serum IgG level and the truncation of its height 
are believed to be responsible for the much lower incidence of systemic adverse 
events (AEs) with SCIG. This is consistent with observations that many AEs of IVIG 
infusions are rate-related and have been repeatedly confirmed.[12] 
On the other hand, local reactions at SC injection sites are common. These reactions 
are rarely severe and are accepted by most patients. In the meta-analysis by Orange 
et al the reporting rate varied from 0.028 to 0.697 per infusion demonstrating that the 
majority of patients tolerate SCIG well.[3] 


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CUTAQUIG, the investigational medicinal product (IMP) in this study, is an 
immunoglobulin preparation from human normal plasma and is manufactured by 
Octapharma. It contains 16.5% (165 mg/mL) protein. The product is formulated for SC 
infusion by pump or syringe. 
A recent study of 61 patients who were previously treated with IVIG received a total of 
64 weekly SCIG infusions of CUTAQUIG (equating to 3,497 total infusions of 
CUTAQUIG); no serious bacterial infections developed among any patients during the 
study. The rate of other infections per person-year during the primary observation 
period was 3.43 (upper 95% CI: 4.57).[4] 
CUTAQUIG was approved by the US FDA in December 2018 for the treatment of 
primary humoral immunodeficiency in adults. Further information on the IMP can be 
found in the Investigator’s Brochure and the US FDA-approved Package Insert.[5] 
1.2 Rationale for Conducting the Study 
The administration of immunoglobulins via the SC route offers several advantages 
over IV infusion from a patient’s and a physician’s perspective. Replacement therapy 
by rapid SC infusion with a pump was introduced during the late 1980s. Several reports 
have shown that the SC method is feasible, safe, efficient, cost-effective, and highly 
appreciated by the patients.[4,14-22] 
Self-administration at home with small portable pumps or syringes can easily be 
learned by patients, which is another advantage of SC administered immunoglobulins 
(SCIG). It may remarkably improve the patient’s quality of life and compliance as it 
reduces the frequency of hospitalizations and the need for in-home health care 
visitations. Administration of IgG via the SC route provides more stable and well-
balanced IgG plasma levels until the end of the treatment interval, in contrast with the 
peak IgG plasma concentrations attained with IVIG solutions which weaken at the end 
of dose. When effective IVIG therapy cannot be continued because of the lack of 
peripheral and central vein access, SCIG might also be an alternative treatment option. 
Patients may desire dosing flexibility to accommodate their personal schedules or 
reduce the number of injection sites; therefore, this study is investigating modified 
dosing regimens. These modifications include dosing at higher infusion rates to 
shorten the duration of infusions, dosing every other week (rather than every week) to 
reduce the overall number of infusions, and increased volume at injection site(s) to 
reduce the number of injection sites. These modifications may reduce dosing 
commitments by shortening infusion times or increasing time intervals between 
infusions or decreasing injection sites, which may correlate to increased drug 
compliance. 
Experience has shown that replacement therapy with immunoglobulins is lifesaving. If 
replacement is started early, and if appropriate amounts are given with sufficient 
frequency, the cycle of recurrent infections and progressive lung damage can be 
arrested. Near to normal serum IgG levels can be easily maintained. 
Post-dose peak levels of SCIG are usually reached 3 to 6 days after infusion. It has 
been shown that after infusion, exogenous IgG is distributed relatively rapidly between 
plasma and extravascular fluid until approximately half is partitioned in the 
extravascular space. Therefore, a rapid initial drop in serum IgG is to be expected. 


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Several factors such as the endogenous production, the actual catabolism rate, the 
underlying disease or inter-patient variability help to explain the wide range observed 
for terminal half-lives. PK data are required for each new product to ensure that it will 
not behave differently from existing preparations, in terms of appropriate dose and 
timing of the infusions. 
The Sponsor is currently conducting clinical studies that are investigating the PK 
characteristics (SCGAM-01), along with the efficacy and safety, of CUTAQUIG, 
(SCGAM-01 and SCGAM-03) in order to provide guidance on the dosing when 
switching patients from IV to SC treatment in patients suffering from PI disease. 
This current study (SCGAM-06) is designed to evaluate modified dosing regimens that, 
by reducing dosing time commitments or injection sites or allowing greater flexibility 
with dosing, may result in increased patient compliance and treatment satisfaction. 
To that aim, the principal purposes of this study are to:  
• Compare total IgG trough levels from weekly infusions to every other week 
infusions 
• Assess safety and tolerability of CUTAQUIG when administered at increased 
infusion volumes 
• Assess safety and tolerability of CUTAQUIG when administered at increased 
infusion rates 
• Assess safety and tolerability of CUTAQUIG when administered every other 
week 
• Assess the effect of CUTAQUIG on quality-of-life (QoL) measures 
• Acquire additional safety and efficacy data on CUTAQUIG 
• Assess patient satisfaction with the study parameters using the Subject 
Questionnaire 
The study will be conducted in compliance with the protocol, International Conference 
on Harmonisation-Good Clinical Practice (ICH-GCP), US FDA Code of Federal 
Regulations, and other local regulatory requirements. 
1.3 Benefit-Risk Statement 
Patients with PI need life-long treatment with immunoglobulins. Replacement therapy 
is expected to achieve protective trough levels of 5 g/L to 6 g/L. 
Standard measures are taken to prevent infections resulting from the use of medicinal 
products prepared from human blood or plasma. Despite this, when medicinal products 
prepared from human blood or plasma are administered the possibility of transmitting 
infective agents cannot totally be excluded. The virus inactivation methods for 
CUTAQUIG are described in the Investigator's Brochure. 
The safety profile of SCIG is well characterized, and the same type of adverse 
reactions may be expected from CUTAQUIG. No new or unknown safety problems are 
expected to emerge for CUTAQUIG which are not already described in the 
Investigator's Brochure. 
It can be reasonably assumed that CUTAQUIG exhibits the same effectiveness as 
other SCIG approved products. 


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Results from Study SCGAM-01 were analyzed in Q1 2017 and none of the results or 
data acquired in that study affect the above benefit–risk assessment. 


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2 
STUDY OBJECTIVES 
2.1 Co-Primary Objectives 
The co-primary objectives of this study are to assess CUTAQUIG administered using 
the following infusion parameters: 
• Compare total IgG trough levels from weekly infusions to every other week 
infusions 
• Safety and tolerability when administered at increased infusion volumes at each 
infusion site 
• Safety and tolerability when administered at increased infusion flow rates at 
each infusion site 
• Safety and tolerability when administered on an every other week dosing 
regimen 
2.2 Secondary Objectives 
The secondary objectives of this study are to: 
• Assess the effect of CUTAQUIG on quality-of-life (QoL) measures 
• Obtain further data on the safety and efficacy of CUTAQUIG 
2.3 Tertiary Objective 
A tertiary objective of this study is to evaluate patient satisfaction of study parameters 
(such as switching to CUTAQUIG from another SCIG product, satisfaction with 
infusion pump, changes in infusion regimen parameters, general infection/general 
observations) using a study-specific questionnaire (Subject Questionnaire) 


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3 
INVESTIGATIONAL PLAN 
3.1 Primary and Secondary Endpoints 
3.1.1 Primary Endpoints 
There is no single primary endpoint in this study. The co-primary objectives are to 
compare total IgG trough levels from weekly infusions to every other week infusions 
and to assess safety and tolerability of increased infusion volumes and increased 
infusion rates at each infusion site and every other week dosing. These will be 
assessed using the following variables: 
• Change in individual total IgG trough levels from weekly infusions to every other 
week infusions (Cohort 3) 
• Occurrence of treatment-emergent AEs (TEAEs) throughout the entire 
Stabilization and Treatment Periods starting with the first infusion of IMP 
• Occurrence of TEAEs temporally associated with CUTAQUIG delivered during 
the Treatment Period 
• Occurrence of TEAEs temporally associated with CUTAQUIG delivered during 
the Stabilization Period 
• TEAEs by speed of infusion 
• Local infusion-site reactions 
• Laboratory parameters (hematology, clinical chemistry, urinalysis) 
3.1.2 Secondary Endpoints 
Secondary assessment criteria will evaluate quality of life, along with additional 
evaluations of CUTAQUIG safety and efficacy being administered according to 
3 different infusion parameters. These will be assessed using the following variables: 
• QoL assessments using the Short Form Health Survey, 36 item (SF-36) or 
10 item (SF-10) 
• Occurrence of serious bacterial infections (SBIs) 
• Annual rate of all infections of any kind or seriousness 
• Time to resolution of infections 
• Use of antibiotics (number of days and annual rate) 
• Individual profiles of IgG trough levels over time (all cohorts) 
• Vital signs (blood pressure, pulse, body temperature, respiratory rate)  
3.1.3 Tertiary Endpoint 
Tertiary assessment criteria will evaluate the patient’s satisfaction with the study 
parameters (such as switching to CUTAQUIG from another SCIG product, satisfaction 
with infusion pump, changes in infusion regimen parameters, general infection/general 
observations), which will be assessed using a study-specific questionnaire (Subject 
Questionnaire). 


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3.2 Overall Study Design and Plan 
The study is a prospective, open-label, non-controlled, 3-arm, multicenter, phase 3 
safety study with observation of patients receiving weekly doses of CUTAQUIG at 
increasing infusion volumes or flow rates, receiving every other week doses of 
CUTAQUIG at double the weekly dose, over a period of up to approximately 6 months. 
Patients with a history of PI disease that are currently on a stable dose of SCIG 
treatment will be enrolled into 1 of 3 cohorts as defined below: 
Cohort 1 (increased infusion volume): This cohort will include patients who consent to 
receiving CUTAQUIG at increasing infusion volumes at each site until reaching a 
maximum dose (in mL), maximum tolerated volume (maximum infusion volume per 
site based on Investigator’s decision of patient’s tolerance), or 100 mL at 1 injection 
site is reached – whichever is reached first. 
Cohort 2 (increased infusion rate): This cohort will include patients who consent to 
receiving CUTAQUIG at increasing flow rates until either 1) a maximum flow rate 
(100 mL/hr/site) or the maximum flow rate achievable by the pump, or 2) the maximum 
tolerated flow rate (maximum flow rate based on Investigator’s decision of patient’s 
tolerance) – whichever is reached first.  
Cohort 3 (every other week dosing): This cohort will include patients who consent to 
receiving CUTAQUIG every other week at the same or equivalent of twice their weekly 
body-weight dependent (mg/kg) dose. Infusion flow rates will be determined by the 
patient and Investigator, but initially should not exceed the patient’s prior infusion rate. 
Patients in this cohort must be currently on a weekly infusion regimen for a minimum 
of 12 weeks prior to entering the study. 
All Cohorts: All study sites will be encouraged to enroll patients into all open cohorts. 
It is at the Investigator’s discretion, with input from the patient, to determine the optimal 
cohort based on medical history, patient preference, etc. However, patients entering 
the study already established on every other week dosing will only be permitted to 
enter Cohort 1 or Cohort 2, and must agree to begin dosing every week beginning at 
Stabilization Period Week 0. The Sponsor will notify study sites when a cohort has 
been filled and is no longer open to recruitment. Study-related procedures will begin 
only after written informed consent (and assent, if age-appropriate) has been obtained 
from the patient. 
After completing the Screening Period during which they will be assigned to 1 of the 
3 study cohorts, patients will enter a 4-week Stabilization Period. During the 
Stabilization Period, patients will receive CUTAQUIG infusions at the same body-
weight dependent dose and infusion rate as their previous SCIG product prior to 
entering the Treatment Period; however, this flow rate should not to exceed maximum 
infusion rates listed in protocol (Section 5.5.3). Patients will receive 4 CUTAQUIG 
infusions during the Stabilization Period. Patients entering the study currently active 
and established on CUTAQUIG in Study SCGAM-03 will have already been stabilized 
on CUTAQUIG and will go directly into the Treatment Period following the Screening 
Visit. Patients that completed the SCGAM-03 study and went on a commercial SCIG 
product prior to entering SCGAM-06 are required to enter the Stabilization Period. 
During the Treatment Period, patients will receive CUTAQUIG infusions according to 
their assigned-cohort infusion parameters. 


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Throughout the study, the following interventions and procedures will be performed at 
predefined time points (Section 6.1.2 and the Flow Charts of Assessments Table 1 
[Screening and Stabilization Periods], Table 2 [Cohort 1], and Table 3 [Cohort 2], 
Table 4 [Cohort 3]): blood draws for laboratory assessments, body weight 
measurement, patient diary review, physical examination including vital signs, local 
infusion-site reaction assessments, urine sampling, urine pregnancy tests, QoL 
assessments, and the Subject Questionnaire. AEs and any changes in concomitant 
medications will be recorded throughout the study period. 
Patients who enter and participate in one cohort may not enter another cohort at a later 
time. 
An Independent Data Monitoring Committee (IDMC) will periodically review relevant 
data throughout the study with emphasis on adverse events including serious adverse 
events and thromboembolic events. 
The study will be conducted at study sites in the USA. 
3.3 Discussion of Study Design and Choice of Control Group(s) 
3.3.1 Study Design 
The study design is in line with similar study protocols conducted with other SCIG 
brands.[21,23,24] 
3.3.2 Dosing 
Stabilization Period: CUTAQUIG will be administered subcutaneously every week 
(±2 days).  
Treatment Period: CUTAQUIG will be administered subcutaneously every week 
(±2 days) (or every other week [±2 days], if applicable) for Cohort 1 (increased infusion 
volume) and Cohort 2 (increased infusion rate). For Cohort 3, CUTAQUIG will be 
administered every other week (±2 days) at double the weekly dose.  
Cohort 1 (increased volume at each infusion site – patients will receive CUTAQUIG 
weekly and increase infusion volumes every 4 weeks): Patients will return to the clinic 
for the Treatment Period Baseline Visit, at which they will receive the same body-
weight dependent (mg/kg) dose but the volume will be increased by up to the maximum 
allowed volume increase per infusion site of 25 mL/site for patients ≥40 kg or 
10 mL/site for patients <40 kg. This volume increase per infusion site can be achieved 
by reducing the total number of injection sites while keeping the same or lower flow 
rates as received with their prior treatment. When introducing increased volumes to an 
infusion site, Investigators must attempt to maintain flow rates similar to or lower than 
prior infusions. This may require adjusting pump rate, tubing size, needle gauge, etc. 
Patients will receive this new volume per site for 4 weekly infusions (Treatment Period 
Baseline and Weeks 1, 2, and 3), and return to the clinic at Week 4 for their next 
infusion at an increased volume at each infusion site. This cycle will continue, with 
infusion volumes increasing by up to a maximum allowed volume increase per infusion 
site of 25 mL/site for patients ≥40 kg or 10 mL/site for patients <40 kg every 4th infusion 
until reaching a patient’s maximum dose (in mL), maximum tolerated volume 
(maximum volume based on Investigator’s decision of patient’s tolerance), or 100 mL 


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at 1 injection site – whichever is reached first. For patients with maximum volume that 
exceeds 100 mL at 1 injection site, 2 injection sites should be used. 
The following change in volume increments should be followed: 
• Baseline: Reduce the number of injection sites by 1 (eg, patients using a 
4 needle set will reduce to a 3 needle set). Tubing set, needle gauge, and pump 
rates (if applicable) may be adjusted to minimize flow rate variations. 
Investigators must ensure minimal flow rate changes at each injection site when 
increasing volume. Continue with the same infusion parameters at Weeks 1, 2, 
and 3. 
• Week 4: If the volume increase administered at Baseline through Week 3 is 
tolerated, reduce the number of injections sites again by 1 (eg, patients using a 
3 needle set will reduce to a 2 needle set). Tubing set, needle gauge, and pump 
rates (if applicable) may be adjusted to minimize flow rate variations. 
Investigators must ensure minimal flow rate changes at each injection site when 
increasing volume. Continue with the same infusion parameters at Weeks 5, 6, 
and 7. 
• Week 8: If the volume increase administered at Week 4 through Week 7 is 
tolerated, reduce the number of injection sites again by 1 (eg, patients using a 
2 needle set will reduce to a 1 needle set). Tubing set, needle gauge, and pump 
rates (if applicable) may be adjusted to minimize flow rate variations. 
Investigators must ensure minimal flow rate changes at each injection site when 
increasing volume. Continue with the same infusion parameters at Weeks 9, 10, 
and 11. 
• Weeks 12, 16, and 20: If the volume increase administered at Week 8 through 
Week 11 is tolerated, continue the step-down process until reaching the 
patient’s maximum dose (in mL), maximum tolerated volume (maximum volume 
based on Investigator’s decision of patient’s tolerance), or 100 mL at 1 injection 
site (whichever is reached first) as described above. The same step-down 
procedure should be repeated as described at Week 16 and Week 20, if needed 
and based on the Investigator’s decision of patient’s tolerance.  
Investigators should be aware that special considerations are required for volume 
increases in patients with 2 infusion sites receiving a total dose (volume) of more than 
50 mL divided between 2 infusion sites. To ensure that volume increases do not 
exceed 25 mL/site, the infusions must be split between the 2 syringes, such that each 
infusion site will receive a different total volume. For example, if a patient is receiving 
a total dose of 60 mL divided equally between 2 infusion sites (eg, 30 mL/site), the first 
syringe could be increased to an infusion volume of 50 mL (an increase of 20 mL) and 
the second syringe would have an infusion volume of 10 mL. If this is tolerated, the 
next infusion volume increase could be 60 mL at 1 infusion site (an increase of 10 mL) 
and remain below the maximum allowed volume increase of 25 mL/site. 
If adverse drug reactions (ADRs) occur during an infusion, the patient may go back to 
the previous regimen that was tolerated if deemed necessary by the Investigator 
and/or patient; this would include reintroducing an injection site. This infusion regimen 
will continue until the next study visit at which the patient would again attempt to 
remove an injection site. If ADRs occur again, the patient may again go back to the 
previous stable regimen if deemed necessary until the next study visit. Following 


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unsuccessful attempts to increase volume, the Investigator and patient can cease or 
hold additional attempts and remain in the study; however, every effort to increase 
injection site volumes should be attempted. 
Optional: When modifying the number of injection sites after previous unsuccessful 
attempts, the Investigator can make adjustments to lower the flow rate. This may 
include decreasing pump flow rate, revising the tubing, or changing needle gauge. 
Note: Sites are encouraged to enroll patients into Cohort 1 who are already on a 
dosing regimen using at least 3 infusion sites to ensure that volume increases remain 
below limits listed in Table 6. Patients dosing with 1 infusion site cannot enter Cohort 1. 
Cohort 2 (increased infusion rate - patients will receive CUTAQUIG weekly and 
increase infusion rates every 4 weeks): Patients will return to the clinic for the 
Treatment Period Baseline Visit, at which they will receive the same body-weight 
dependent (mg/kg) dose of CUTAQUIG but the infusion rate per site will be increased 
by up to a maximum allowed flow rate increase per infusion site of 25 mL/hr/site for 
patients ≥40 kg or 10 mL/hr/site for patients <40 kg. Patients will receive this new flow 
rate for 4 weekly infusions (Treatment Period Baseline and Weeks 1, 2, and 3), and 
return to the clinic at Week 4 for their next infusion at an increased infusion rate. This 
cycle will continue, with maximum allowed flow rate increases per infusion site of up 
to 25 mL/hr/site for patients ≥40 kg or 10 mL/hr/site for patients <40 kg every 4th 
infusion until reaching either 1) a maximum flow rate (100 mL/hr/site) or the maximum 
flow rate achievable by the pump, or 2) the maximum tolerated flow rate (maximum 
flow rate based on Investigator’s decision of patient’s tolerance) – whichever is 
reached first.  
The following rate increases should be followed: 
• Baseline: Increase infusion rates up to 25 mL/hr/site. This can be accomplished 
by increasing the tubing set, needle gauge, and adjusting pump rates (if 
applicable). Continue with the same infusion parameters at Weeks 1, 2, and 3. 
• Week 4: If the infusion rate increase administered at Baseline through Week 3 
is tolerated, increase infusion rates again by up to 25 mL/hr/site for patients 
≥40 kg or 10 mL/hr/site for patients <40 kg. This can be accomplished by 
increasing the tubing set, increasing needle gauge, or adjusting pump rates (if 
applicable). Continue with the same infusion parameters at Weeks 5, 6, and 7. 
• Week 8: If the infusion rate increase administered at Week 4 through Week 7 
was tolerated, increase infusion rates again by up to 25 mL/hr/site for patients 
≥40 kg or 10 mL/hr/site for patients <40 kg. This can be accomplished by 
revising the tubing, increasing needle gauge, or adjusting pump rates (where 
applicable). Continue with the same infusion parameters at Weeks 9, 10, 
and 11. 
• Weeks 12, 16 and 20: If necessary and if the infusion rate increase 
administered at Week 8 through Week 11 was tolerated, the patient should 
continue the rate increase process as described above. 
Note: Clinical sites are encouraged to enroll patients that are either currently infusing 
with 24-gauge needle sets or willing to switch to 24-gauge needle sets. Patients using 
27-gauge needles will not be able to achieve adequate infusion rates for this cohort as 
the needle gauge will not allow for this. 


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If ADRs occur during an infusion, the patient may go back to the previous regimen that 
was tolerated if deemed necessary by the Investigator and/or patient; this would 
include decreasing the infusion flow by decrease tubing size, increasing needle gauge, 
or adjusting pump rates. This tolerated infusion regimen will continue until the next 
study visit, at which the patient would attempt to again increase the infusion rate. 
If ADRs occur again, the patient may again go back to the previous stable regimen if 
deemed necessary until the next study visit. If multiple attempts to increase rate are 
unsuccessful, Investigators should continue attempting to increase rates, but by lower 
amounts than those previously attempted. Investigators should refer to the provided 
flow rate tubing calculators to identify optimal rate parameters. Following unsuccessful 
attempts to increase infusion rate, the Investigator and patient can cease or hold 
additional attempts and the patient may remain in the study; however, every effort to 
increase infusion rates should be attempted. 
Cohort 3 (every other week dosing - patients will receive CUTAQUIG every other week 
at the equivalent of twice their weekly body-weight dependent [mg/kg] dose): Patients 
will return to the clinic for the Treatment Period Baseline Visit to receive their first 
double mg/kg weekly dose and begin an every other week dosing schedule. Infusion 
volume increases when switching from weekly dosing to every other week dosing must 
not exceed a maximum allowed volume increase per infusion site of 25 mL/site for 
patients ≥40 kg or 10 mL/site for patients <40 kg at the Treatment Period Baseline 
Visit. If a patient’s doubling of their weekly dose requires dosing with a volume of more 
than the maximum allowed increase in volume per injection site (25 mL/site or 
10 mL/site, dependent on patient body weight), then they will be required to increase 
the number of infusion sites to remain below the maximum body-weight dependent 
volume increase. If this occurs, after 2 infusions the patient may remove one of the 
newly introduced injection sites as long as the volume per injection site increase limit 
is not exceeded. Infusion flow rates will be determined by the patient and Investigator, 
but initially should not exceed the patient’s prior infusion rate, nor the maximum 
infusion rates listed in the protocol. If a patient initially does not tolerate the dosing 
regimen, the Investigator should decrease the infusion rate to a tolerable rate (revising 
the tubing, number of injection sites, needle gauge, etc.).  
Note: Patients entering must already be established on weekly dosing for a minimum 
of 12 weeks prior to Screening. 
All Cohorts: If, during the study, a patient's body weight changes by >5% from the 
first infusion of IMP, the dose will be adjusted to keep a constant mg/kg body weight 
basis. Additional adjustments will be made if the patient’s body weight changes >5% 
from the previous adjusted weight. In addition, individual patient doses may be titrated 
up or down, per Investigator discretion. 
Dosing will take place on site at study visits, and otherwise at the patient's home by 
self-administration or with assistance (relative, caregiver, etc.). The Termination Visit 
must occur prior to the patient receiving any other IgG product. 
3.3.3 Control Group(s) 
Not applicable: all patients will receive active treatment with CUTAQUIG. 


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3.3.4 Study Parameters 
The outcome measures in this study are consistent with previous studies of other IVIG 
or SCIG products and are also in compliance with the US FDA Guidance for Industry 
on Safety, Efficacy, and Pharmacokinetic Studies to Support Marketing of Immune 
Globulin Intravenous (Human) as Replacement Therapy for Primary Humoral 
Immunodeficiency.[25] 
QoL questionnaires (SF-10 Health Survey from parent or guardian of patients 
<14 years of age and SF-36 Health Survey in patients ≥14 years of age) used in this 
study are standardized, validated instruments that have been widely used in clinical 
studies, including studies in the PI disease population. 


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4 
STUDY POPULATION 
4.1 Population Base 
Approximately 65 male or female patients, between 2 years and 75 years of age, 
suffering from PI will be eligible for inclusion.  
4.1.1 Inclusion Criteria 
Patients who meet all of the following criteria are eligible for the study: 
1. Age ≥2 years and ≤75 years. 
2. Confirmed diagnosis of primary immunodeficiency (PI) disease as defined by 
ESID and PAGID and requiring immunoglobulin replacement therapy due to 
hypogammaglobulinaemia or agammaglobulinaemia. Note: The exact type of 
PI disease will be recorded. 
3. Established on a consistent or stable mg/kg dose of any SCIG treatment for a 
minimum of 3 months prior to Screening. Note: patients entering Cohort 3 must 
be on weekly SCIG infusions for a minimum of 12 weeks. 
4. Availability of the Immunoglobulin G (IgG) trough levels of 2 previous SCIG 
infusions within 1 year of Screening, with 1 trough level obtained within 
3 months prior to enrollment, and maintenance of trough serum IgG levels 
≥5.0 g/L in 2 previous infusions. Patients with no prior IgG trough level within 
3 months prior to enrollment may use the Screening IgG trough level as their 
2nd reading. 
5. Voluntarily given, fully informed, signed informed consent. For patients under 
the legal age of consent, voluntarily given, fully-informed, signed informed 
consent will be provided by patient’s parent or legal guardian, and assent will 
be provided by patient (per age-appropriate Institutional Review Board [IRB] 
requirements) 
6. Females of childbearing potential, who are not nursing and have no plans for 
pregnancy during the course of the study, must have been using at least 
1 acceptable form of birth control for a minimum of 30 days prior to the 
Screening visit and must agree to use at least 1 acceptable method of 
contraception for 30 days after the last dose of CUTAQUIG. Acceptable 
methods include: intrauterine device (IUD), hormonal contraception, male or 
female condom, spermicide gel, diaphragm, sponge, or cervical cap, or 
abstinence. 
7. For female patients of child-bearing potential, a negative result in a urine 
pregnancy test conducted at the Screening visit. 
8. Willingness to comply with all aspects of the protocol, including blood sampling, 
for the duration of the study. 
4.1.2 Exclusion Criteria 
Patients who meet any of the following criteria are not eligible for the study: 
1. Evidence of an active infection within 4 weeks of Screening or during the 
Screening Period. 


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2. Current or clinically-significant history of any cardiovascular, respiratory, 
hepatic, renal, gastrointestinal, endocrine, neurological, immunological 
(excluding PI), hematologic, and/or psychiatric disorder(s), or a history of any 
other illness that, in the opinion of the Investigator, might confound the results 
of the study, or pose additional risk to the patient by participation in the study.  
3. Known history of adverse reactions to immunoglobulin A (IgA) in other products. 
4. Body mass index (BMI) >40 kg/m2 for patients entering Cohort 2 or Cohort 3. 
There are no BMI restrictions for Cohort 1. 
5. Ongoing history of hypersensitivity or persistent reactions to blood or plasma 
derived products, or any component of the investigational product (such as 
Polysorbate 80). 
6. Requirement of any routine premedication for IgG administration. 
7. History of malignancies of lymphoid cells and immunodeficiency with 
lymphoma. 
8. Severe liver function impairment (aspartate aminotransferase [AST] or alanine 
aminotransferase [ALT] >3 times above upper limit of normal). 
9. Known protein-losing enteropathies or clinically significant proteinuria. 
10. Presence of renal function impairment or predisposition for acute renal failure 
(eg, any degree of pre-existing renal insufficiency or routine treatment with 
known nephritic drugs). 
11. Treatment with oral or parenteral steroids for ≥30 days, or when given 
intermittently or as bolus at daily doses ≥0.15 mg/kg when taken within 30 days 
of Screening. Note: Short or intermittent courses of steroids (ie, a steroid burst) 
of >0.15 mg/kg/day is allowed for treatment of a short-term condition such as 
an asthma exacerbation.  
12. Treatment with immunosuppressive or immunomodulatory drugs (except 
Omalizumab). 
13. Use of HYQVIA (Immune Globulin Infusion 10% [Human] with Recombinant 
Human Hyaluronidase) within 3 months prior to first CUTAQUIG infusion. 
14. Live viral vaccination (such as measles, rubella, mumps, and varicella) within 
2 months prior to first CUTAQUIG infusion. 
15. Exposure to blood or any blood product or derivative, other than sub-cutaneous 
IgG used for regular PI disease treatment, within 3 months before the first 
CUTAQUIG infusion. 
16. Treatment with any investigational medicinal product within 3 months prior to 
first CUTAQUIG infusion. Note: Patients participating in Study SCGAM-03 will 
be allowed to enter this study without the 3-month waiting period for an 
Investigational Product. Patients receiving another investigational SCIG product 
within 3 months prior to the first CUTAQUIG infusion may be considered for 
enrollment after Sponsor approval. 
17. Presence of any condition that is likely to interfere with the evaluation of 
CUTAQUIG or satisfactory conduct of the trial. 
18. Known or suspected to abuse alcohol, drugs, psychotropic agents, or other 
chemicals within the past 12 months prior to first CUTAQUIG infusion. 


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19. Known active or chronic hepatitis B, hepatitis C or HIV infection. Past 
hepatitis B or hepatitis C infection that has been cured is allowed. 
4.2 Prior and Concomitant Therapy 
Details on any relevant medications taken within 8 weeks prior to enrollment must be 
recorded in the electronic Case Report Form (eCRF). The following medications that 
are considered relevant for the previous 8 weeks include:  
• Antibiotics 
• Corticosteroids,  
• Premedication (if used) 
• Immunosuppressive or immunomodulatory drugs 
• blood or any blood product or derivative 
• IVIG, SCIG, or other IgG preparations 
All new and ongoing concomitant medications taken during the Screening Period and 
throughout the study will be captured in the eCRF.  
4.2.1 Permitted Concomitant Therapy 
Local anesthetics (EMLA® or lidocaine cream, plaster, or other similar products) to 
reduce pain associated with needle insertion are allowed. The use of such 
medication(s) must be recorded. 
Routine premedication to alleviate potential tolerability problems is not allowed during 
the study. However, patients who experience 2 consecutive TEAEs during the study 
(that are likely to be prevented by premedication) are permitted to receive antipyretics, 
antihistamines, or antiemetic drugs. Non-steroidal anti-inflammatory drugs should be 
avoided. 
4.2.2 Forbidden Concomitant Therapy 
Treatment with any IMP (other than IgG products [including CUTAQUIG] administered 
during Study SCGAM-03) within 3 months before first infusion of CUTAQUIG, or 
during the study, is forbidden. Patients receiving another investigational SCIG product 
within 3 months prior to the first CUTAQUIG infusion may be considered for enrollment 
after Sponsor approval. 
Administration of any blood- or plasma-derived product is forbidden during the study 
and should only be given for emergency reasons. Patients will be withdrawn from the 
study if IgG preparations other than CUTAQUIG are administered during the study. 
Premedication for study CUTAQUIG infusions shall not be given, with the exception of 
permitted therapy as stated above (for patients with 2 consecutive TEAEs). 
Corticosteroids shall not be given as a premedication to alleviate potential tolerability 
problems. 
Treatment with oral or parenteral steroids for ≥30 days (long term daily >0.15 mg of 
prednisone equivalent/kg/day). Exception: Requirement for short or intermittent 
courses (ie, a steroid burst) of >0.15 mg/kg/day is allowed for treatment of a short-term 
condition such as an asthma exacerbation. 


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Immunosuppressive and immunomodulatory drugs are forbidden, with the exception 
of Omalizumab. 
CUTAQUIG must not be mixed with other medicinal products. 
4.3 Withdrawal and Replacement of Patients 
4.3.1 Premature Patient Withdrawal 
Patients have the right to withdraw from the study at any time for any reason, without 
the need to justify their decision. The Investigator also has the right to withdraw 
patients in case of AEs, poor compliance, or other reasons. Because an excessive rate 
of withdrawals can render the study noninterpretable, any unnecessary withdrawal of 
patients should be avoided. 
For any withdrawals after study entry, the Investigator will obtain all the required details 
and document the reason(s) for discontinuation. If the reason for withdrawal of a 
patient is an AE, the main specific event or laboratory test will be recorded, and the 
Investigator will make thorough efforts to clearly document the outcome. 
Reasons for premature patient withdrawal may include the following: 
• Patient decision: Should a patient decide to withdraw from the study, the 
Investigator will make a reasonable effort to complete and report all information 
available at time of withdrawal. The Investigator will document the reason(s) for 
the patient's discontinuation. 
• Withdrawal for safety reason: If the reason a patient is removed from the study 
is an AE or an abnormal laboratory test result, this specific event or test will also 
be recorded; the Investigator will make a reasonable effort to clearly document 
the outcome. 
• Administration of other immunoglobulin preparation: If for any reason a patient's 
therapy is changed to another IVIG or SCIG preparation within this study, the 
patient will be withdrawn from the study. 
• Pregnancy: Pregnant patients may not be included in this study. A pregnancy 
test is mandatory for all females of child bearing potential at the Screening Visit, 
at the Treatment Period Weeks 12, 24 and at the Termination Visit. All female 
patients of childbearing potential are responsible for using effective 
contraception during their study participation. If a pregnancy occurs, treatment 
with CUTAQUIG must be stopped immediately and Octapharma’s Central Drug 
Safety Unit must be informed. 
If a patient is withdrawn, the Investigator will schedule an (Early) Termination Visit. At 
this visit, all investigations including laboratory tests should be performed to allow the 
patient to be included in both safety and efficacy evaluations. This Termination Visit is 
identical to the follow-up visit of the last CUTAQUIG administration. 
4.3.2 Patient Replacement Policy 
Patients withdrawn from the study for any reason will not be replaced.  


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4.4 Assignment of Patients to Treatment Groups 
This is an open-label non-randomized study. Patients will be enrolled into Cohort 1, 2, 
or 3 according to Investigator and patient preference. However, patients entering the 
study already established on an every other week infusion schedule of another SCIG 
product may only participate in Cohort 1 or Cohort 2. 
All study sites will be permitted to enroll patients in open cohorts. The Sponsor will 
notify study sites when a cohort has filled and is no longer open to recruitment. 
Patients will not be allowed to switch cohorts during the study.  
Patients who enter and participate in one cohort may not enter another cohort at a later 
time.  
4.5 Relevant Protocol Deviations 
In case of any major protocol deviation, the Investigator and Octapharma will decide 
on the further participation of the patient in this study after having discussed all relevant 
aspects. 
A list of all included patients with all deviations from the intended study procedures and 
other criteria that may affect the validity of patient data for statistical analysis will be 
prepared after the clinical phase of the study is completed. The list will be discussed 
by a panel consisting of the clinical study manager, a medical expert of the Sponsor, 
the data manager and the study statistician. This panel will decide upon the inclusion 
of each patient in the analysis populations prior to database lock. 
4.6 Subsequent Therapy 
After a patient completes the study, or if a patient decides to withdraw from the study 
or is withdrawn by the Investigator, he/she may be switched back to the treatment that 
he/she received before participation in the study or to another commercially available 
IVIG or SCIG product, per treating physician discretion. 


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5 
INVESTIGATIONAL MEDICINAL PRODUCT(S) 
5.1 Characterization of Investigational Product(s) 
Name of Medicinal Product: 
CUTAQUIG 
Active ingredient of CUTAQUIG: Human normal immunoglobulin 
Table 5: 
Biochemical Characteristics of CUTAQUIG 
Name of Ingredient 
Amount 
Total protein (of which ≥96% is human IgG) 
150 – 180 mg per mL 
Maltose 
70 – 90 mg per mL 
Octoxynol 
≤5 µg per mL 
TNBP 
≤1 µg per mL 
IgA 
≤0.6 mg per mL 
Polysorbate 80 
10 – 60 µg per mL 
pH 
5.0 – 5.8 
Osmolality 
310 – 380 mosmol/kg 
Polymers + Aggregates 
≤5% of the total chromatogram area 
Monomers + Dimers 
≥90% of the total chromatogram area 
Fragments 
≤5% of the total chromatogram area 
Sodium 
≤30 mmol/L 
Each batch (lot) of CUTAQUIG is prepared from at least 3,500 donations of human 
fresh frozen plasma. Effective viral reduction is obtained via a combination of 
3 validated manufacturing steps: cold-ethanol fractionation, solvent/detergent 
treatment with TNBP and Octoxynol, and pH 4 treatment. The manufacture of 
CUTAQUIG is based on the Octagam manufacturing process including an additional 
adsorption step onto commercially available and widely used chromatography column 
for the removal of coagulation factor XI. The process is identical up to the step of 
diafiltration. After this step the product solution is concentrated to a target 
concentration of 200 g/L. Polysorbate 80 and maltose are added during final 
formulation to final concentrations of 10 µg/mL to 60 µg/mL and 70 mg/mL to 
90 mg/mL, respectively. 
5.2 Packaging and Labelling 
CUTAQUIG is delivered in 12 mL or 48 mL single-use glass vials. Each CUTAQUIG 
vial will be labeled in accordance with national regulations. Sample labels will be 
provided and filed with the Investigational Product File at each investigator site and in 
the Sponsor TMF. 
5.3 Conditions for Storage and Use 
CUTAQUIG must be stored and transported light-protected at 36°F to 46°F (2°C to 
8°C). 
CUTAQUIG must not be frozen. 
CUTAQUIG vials must not be shaken. 


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CUTAQUIG must not be used after its expiration date. 
CUTAQUIG must not be mixed with other medicinal products. 
Authorized personnel at the individual study centers will ensure that the IMP is stored 
in appropriate conditions in a secure refrigerator with restricted access and in 
compliance with national regulations. 
5.4 Dose and Dosing Schedule 
CUTAQUIG will be administered by subcutaneous infusion either every week 
(±2 days) or every other week (±2 days) at double the weekly dose. The dosing 
frequency will be determined by the cohort assignment (Section 3.3.2). 
A minimum interval of 4 days must be observed between 2 single subcutaneous 
infusions. 
Patients will receive the same mg/kg body weight dose as their previous SCIG product 
prior to study entry that will be calculated at Screening. The dose (mg/kg) will be 
calculated by taking a patient’s total dose in milligrams (mg) of their prior SCIG and 
dividing by the patient’s weight (kg) at the Screening Visit. This will provide the 
milligrams of CUTAQUIG required. Study site personnel will use dose calculation 
worksheets provided by the Sponsor to determine each patient’s required quantity 
(mg) of CUTAQUIG. 
If, during the study, body weight changes by >5% from the first infusion of IMP, the 
dose will be adjusted to keep a constant mg/kg body weight basis. Additional 
adjustments will be made by the Investigator at study visits if the patient’s body weight 
changes >5% from the previous adjusted weight. In addition, individual patient doses 
may be titrated up or down, per Investigator discretion. 
CUTAQUIG infusions will be administered at the clinic and will be self-administered at 
home in between scheduled site visits. 
Each study visit may deviate from the planned date; however, the deviations must not 
cumulate. Study visit weeks and time windows are presented in Table 7. 
An individual patient’s CUTAQUIG dose may be adjusted, if considered necessary by 
the Investigator, by titrating upward or downward; this dose adjustment should be 
based on the difference between the patient’s measured serum total IgG trough levels 
while on CUTAQUIG and each patient's target serum total IgG trough level.  
5.5 Preparation and Method of Administration 
CUTAQUIG vials must be allowed to warm to room or body temperature before 
infusion. 
After CUTAQUIG vials have been brought to room or body temperature, they should 
be inspected visually for particulate matter and discoloration prior to administration. 
The solution should be clear or slightly opalescent. DO NOT USE IF TURBID and/or 
DISCOLORATION IS OBSERVED. Solutions that are cloudy or vials that have a 
deposit must not be used and must be returned to the clinical site by the patient. 


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CUTAQUIG will be delivered by subcutaneous infusion using syringe drivers in order 
to deliver the protocol-specified infusion rate. 
The correct amount of IgG will be transferred from the 12 mL or 48 mL vials into 
syringes that are suitable for use with the selected syringe driver. 
Used, partially used vials from home infusions must be returned to the study site; all 
used and partially used vials must be discarded according to local policies and 
procedures.  
Any vials returned to the site by the patient, due to deficiency in vial use or complaint 
regarding the drug or vials, must be retained by the study site and must not be 
destroyed. The study site must notify Octapharma and retain the vials on-site until 
arrangements are made for them to be returned to Octapharma.  
Aseptic techniques must be used throughout the infusion procedure. 
As appropriate based on cohort assignment, syringe drivers, syringes, and standard 
infusion materials will be provided by the site for in-home infusions. The patient, his/her 
relative, and/ or caregiver will be instructed in the use of the following: 
• syringe driver 
• infusion techniques 
• patient diary completion 
• measures to be taken in case of severe AEs 
At the Stabilization Period Week 0 Visit and the Treatment Period Baseline Visit, 
patients will perform the infusions at the study site and will be assessed for proper 
infusion technique. Patients will be re-trained on proper technique, if necessary.  
5.5.1 Infusion Sites 
No more than 6 infusion sites should be used simultaneously. 
Infusion sites should be at least 2 inches (approximately 5 cm) apart. 
The anatomical location of infusion sites may be changed with weekly or every other 
week administration as necessary. 
5.5.2 Infusion Volume 
The maximum infusion volume is 100 mL per infusion site. 
5.5.3 Infusion Flow Rates 
• The maximum recommended flow rate is 100 mL/hr/infusion site. 
• The maximum infusion rate for all sites combined is 240 mL/hr. 
• Infusion volumes and flow rates may only be increased if the previous 
2 administrations were tolerated by the patient, and deemed appropriate by the 
Investigator.  
• Infusion volume and flow rate should be increased gradually as tolerated to 
prevent infusion site reactions. See the parameters listed in Table 6. 


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Table 6: 
Infusion Volume and Flow Rate by Patient Weight 
 
Recommended Increase for 
Patients 
<40 kg 
Recommended Increase for 
Patients 
≥40 kg 
Infusion Volume 
mL/site per infusion cycle 
Approximately ≤10 mL/site 
Approximately ≤25 mL/site 
Infusion Flow Rate 
mL/hour/site per infusion cycle 
≤10 mL/hour/site 
≤25 mL/hour/site 
Note: To account for non-precision flow rates of pumps, actual flow rate increases will be dependent on tubing size, number of 
infusion sites, and needle gauge. Minor deviations in flow rates (<2 mL/site) would not be considered protocol deviations. 
Instructions for performing volume increases in Cohort 1 patients who are using 
2 infusions sites with a total volume of ≥50 mL are provided in Section 3.3.2. 
If AEs occur during an infusion, the flow rate and volume may be reduced if deemed 
necessary by the Investigator and/or patient to the previous flow rate and volume at 
which no AE occurred. If appropriate, the infusion may be interrupted until symptoms 
subside. The infusion may then be resumed at a flow rate or volume tolerated by the 
patient. 
5.6 Blinding, Emergency Envelopes, and Breaking the Study Blind 
Not applicable for this open-label study. 
5.7 Treatment Compliance 
5.7.1 Drug Dispensing and Accountability 
Any IMP provided to the site will be accounted for. This includes IMP received at the 
site and IMP dispensed to patients. A Drug Inventory and Dispensing Log will be kept 
current by the Investigator, detailing the dates and quantities of IMP received and 
dispensed to each patient and the remaining quantity.  
Sponsor or designee will deliver CUTAQUIG to the participating Investigator sites. 
Each Investigator will keep current drug inventory and dispensing log, detailing the 
dates, batch (lot) numbers, and quantities of IMP received and dispensed to each 
patient and the remaining quantity. A packet containing IMP Release, Confirmation of 
receipt, transport temperature log, and signed packing slip should be made available 
for the study monitor to review. 
The inventory and drug dispensing log will be available to the monitor to verify drug 
accountability during the study. The study monitor will review all empty and partially 
used vials of IMP and will cross-check versus the patient source documentation 
(records), eCRF, and drug dispensing log. 
After this check, and after the Sponsor has granted written approval of destruction, 
empty or partially used vials should be destroyed at the study site following local 
policies. The destruction must be documented. 
For home treatments, a sufficient number of CUTAQUIG vials will be dispensed to 
each patient. The Investigator or his/her designee will document the date, vial 
quantities, and batch (lot) number(s) of IMP dispensed to a given patient (using the 
corresponding patient number). Patients will be instructed to return used or expired 


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vials to the study site at their on-site visits, and to return all used and unused vials at 
the (Early) Termination Visit. 
Patient-returned IMP (used or unused) must not be re-dispensed and must be 
destroyed after completion of drug accountability.  
5.7.2 Assessment of Treatment Compliance 
Patients will receive infusions at the clinic and at home (administered by the patient, 
his/her relative, or caregiver). Infusion details will be documented together with the 
batch number(s) in the eCRF. 
Throughout the study, patients will be asked to document on a diary the date, batch 
(lot) numbers, number of vials, speed of infusion, infusion site(s), occurrence of 
infections, TEAEs and local tissue reactions at infusion sites, missed days from work 
or school, inpatient hospital stays, and any changes in concomitant therapy between 
visits. The diary will be reviewed during the patient’s infusion visit at the study site. 


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6 
STUDY CONDUCT 
6.1 Observations by Visit 
Observations by visit are provided in the following tables: 
Table 1 
Screening and Stabilization Periods – Flow Chart of Assessments 
Table 2 
Cohort 1 (Increased Flow Volume) – Flow Chart of Assessments 
Table 3 
Cohort 2 (Increased Infusion Rate) – Flow Chart of Assessments 
Table 4 
Cohort 3 (Every Other Week Dosing) – Flow Chart of Assessments 
Descriptions of the assessments and methods performed at study visits are provided 
in Section 7. 
Descriptions of visit windows are provided in Table 7. 
6.1.1 Screening Visit  
Study-related procedures will begin only after written informed consent (and assent, if 
appropriate) has been obtained from the patient and/or their legal guardians. 
Note: Patients who participated in Study SCGAM-03 must receive their final infusion 
of CUTAQUIG for Study SCGAM-03 prior to being consented for Study SCGAM-06. 
At the Screening Visit the following activities will be performed: 
• Written (signed and dated) informed consent (and assent, if age appropriate) 
• Check of inclusion and exclusion criteria 
• Record demographic data 
• Document medical history 
• Record previous drug and non-drug therapies 
• General physical examination, including body weight and vital signs 
• Draw blood samples for total IgG trough level 
• Draw blood samples for safety laboratory parameters 
• Collect urine sample including sample for urine pregnancy test (females of 
childbearing potential, only) 
• Infusion by the patient of their personal, commercially available SCIG product 
at the same body-weight dependent dose (mg/kg) and infusion flow rate 
(ml/hr/site) as their previous infusions; however, this flow rate should not to 
exceed maximum infusion rates listed in protocol (Section 5.5.3). Patients who 
participated in Study SCGAM-03 will have already received a CUTAQUIG 
infusion on the same day prior to providing written informed consent (and 
assent, if appropriate) for Study SCGAM-06. 
• Receive written approval from the Sponsor, which will include confirmation that 
the chosen cohort is open for enrollment, prior to entering the patient into the 
Stabilization Period.  
It is anticipated that the patients will receive their first dose of CUTAQUIG 5 days to 
16 days after the Screening Visit, depending when their last infusion occurred. 


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6.1.2 CUTAQUIG Stabilization Period (Stabilization Period Week 0 through 
Stabilization Period Week 4) 
After completing the Screening Period and receiving written Sponsor Acknowledgment 
of the cohort assignment during the Treatment Period, patients will enter a 4-week 
Stabilization Period during which they will receive CUTAQUIG infusions at the same 
body-weight dependent (mg/kg) dose and infusion flow rate (ml/hr/site) as their 
previous SCIG product; however, this flow rate should not to exceed maximum infusion 
rates listed in protocol (Section 5.5.3). 
Patients entering the study currently active and established on CUTAQUIG in Study 
SCGAM-03 will have already been stabilized on CUTAQUIG and will skip the 
Stabilization Period to go directly into the Treatment Period. Patients that completed 
the SCGAM-03 study and went on a commercial SCIG product prior to entering 
SCGAM-06 are required to enter the Stabilization Period.  
Patients entering the study already established on every other week dosing for either 
Cohort 1 or Cohort 2 will be required to dose weekly beginning at the Stabilization 
Week 0. 
At Stabilization Period Week 0, the CUTAQUIG administration will be performed on-
site. Otherwise, CUTAQUIG will be administered at home (Section 3.3.2).  
The following activities will be performed before the on-site CUTAQUIG administration:  
• Record body weight  
• Collect vital signs 
• Draw blood samples for total IgG trough level 
• Draw blood samples for safety laboratory parameters 
• Draw blood for serum retention samples 
• Update medical history 
The following activities will be performed during or after CUTAQUIG administration 
• CUTAQUIG infusion by the patient at the same body-weight dependent (mg/kg) 
dose and infusion flow rate (ml/hr/site) as their previous SCIG product; however, 
this flow rate should not to exceed maximum infusion rates listed in protocol 
(Section 5.5.3). 
• Assess patient infusion technique and, if necessary, re-train on proper 
administration  
• Assess for local infusion-site reactions  
The following activities will be performed after CUTAQUIG administration: 
• Assess for local infusion-site reactions  
• AE assessment and record any changes in concomitant medications use during 
the study visit  
• Dispense patient diary 
6.1.3 CUTAQUIG Treatment Visits (Baseline [Week 0] through Week 24) 
After completing the 4-week Stabilization Period (or Screening Visit for patients who 
are currently enrolled in Study SCGAM-03), patients will enter the Treatment Period 


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and begin their infusion parameters according to their corresponding cohort 
assignment (Section 3.3.2).  
On study visit days, CUTAQUIG administration will be performed on site; otherwise, 
CUTAQUIG will be administered at home. 
During the Treatment Period, the following on-site visits are required as specified 
below: 
Cohort 1 
Baseline, Weeks 4, 8, 12, and 24 
Cohort 2 
Baseline, Weeks 4, 8, 12, and 24  
Cohort 3 
Baseline, Weeks 4, 12, and 24  
For Cohort 1 and Cohort 2, if a patient has reached their maximum achievable volume 
or flow rate per infusion site at Week 12, they do not need to complete remaining 
interim (4-week interval) on-site study visits at Week 16 and Week 20. 
The following activities will be performed before on-site CUTAQUIG administrations: 
• General physical examination (See Table 2 [Cohort 1], Table 3 [Cohort 2], and 
Table 4 [Cohort 3] for assessment schedules) 
• Record body weight (all visits) 
• Draw blood samples for total IgG trough level (See Table 9 for collection 
schedule) 
• Draw blood samples for safety laboratory parameters (See Table 9 for collection 
schedule) 
• Draw blood for serum retention samples, for patients who were previously 
enrolled in SCGAM-03 and did not participate in the Stabilization Period 
(Baseline Visit, only) 
• Collect urine sample including sample for urine pregnancy test (females of 
childbearing potential, only) (See Table 9 for collection schedule) 
• Collect vital signs (all visits) 
• Complete QoL questionnaire (Baseline Visit, only) 
The following activities will be performed during or after CUTAQUIG administration: 
• Collect patient diary. The Investigator will review diary entries and query the 
patient about any AEs that may have occurred and any changes in concomitant 
therapies (medication and non-drug therapy). Any updates to concomitant 
medication use and adverse events will be recorded. Relevant diary data will be 
transferred to the eCRF. Discrepancies between patient diary entries and eCRF 
entries must be explained by the Investigator. 
• Infusion of CUTAQUIG by the patient, according to cohort assignment (every 
visit – see Section 3.3.2 for dosing information) 
• Assess patient infusion technique and, if necessary, re-train on proper 
administration 
The following activities will be performed after CUTAQUIG administration: 
• Assess for local infusion-site reactions (every visit, prior to discharging patient) 
• AE assessment and record any changes in concomitant medications use during 
the study visit (every visit, prior to discharging the patient) 


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• Dispense patient diary  
6.1.4 Termination Visit  
The Termination Visit must occur prior the patient receiving another IgG product. This 
visit will take place 1 week after the last infusion for Cohort 1 and Cohort 2, or 2 weeks 
after the last infusion for Cohort 3; however, these visits may occur sooner if a patient 
withdraws early from the study or if the study is ended earlier by one of the events 
described in Section 6.2.3. 
The Termination Visit will include the following assessments: 
• General physical examination 
• Collect vital signs 
• Draw blood samples for safety laboratory parameters  
• Draw blood for serum retention samples  
• Draw blood samples for total IgG trough level 
• Collect urine sample including sample for urine pregnancy test (females of 
childbearing potential, only) 
• Complete QoL questionnaire 
• Complete Subject Questionnaire 
• Collect and review patient diary as at the earlier visits (Section 6.1.2) and record 
any AEs and/or changes in concomitant medication use 
• Assess for local infusion-site reactions 
After the Termination Visit, the clinical study is considered completed for the patient. 
No further study-related assessments will be performed, unless safety concerns 
(eg, ongoing AEs, newly-reported SAEs [Section 7.3.8.1]) require follow-up. 
6.1.5 Time Windows Used in this Study, including Tolerances 
In this study, the following time windows and tolerances apply: 
Table 7: 
Study Visit Times and Windows Used in this Study 
Time point 
Time stated 
Tolerance 
Stabilization Period Week 0: Cohort 1 
and Cohort 2 
1 week after Screening Visit 
± 2 days  
Stabilization Period Week 0: Cohort 3  
2 weeks after Screening Visit 
± 2 days  
Treatment Period Baseline Visit  
 
4 weeks after Stabilization 
Period Week 0  
± 3 days 
Treatment Period required on-site 
visits: Cohort 1 and Cohort 2 
Weeks 4, 8, 12, and 24 
± 1 week 
Treatment Period required on-site 
visits: Cohort 3 
Weeks 4, 12, and 24 
± 1 week 
Treatment Period optional on-site 
visits: all cohorts 
Weeks 16, and 20 
± 1 week 
Interval between Last Treatment Visit 
and (Early) Termination Visit: Cohort 1 
and Cohort 2 
1 week 
± 2 days (and prior to another 
IgG product) 


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Time point 
Time stated 
Tolerance 
Interval between Last Treatment Visit 
and (Early) Termination Visit: Cohort 3 
2 weeks 
± 2 days (and prior to another 
IgG product) 
Blood and urine sampling 
Before IMP administrations 
conducted at the study site 
none 
CUTAQUIG infusions at patient’s home 
Every week (every 7 days), or 
Every other week (every 14 
days) at double the weekly dose 
±2 days 
±2 days 
Study visit days and windows/tolerances are not additive, but always refer back to the 
first visit time point for each study period.  
6.2 Duration of Study 
6.2.1 Planned Duration for an Individual Patient 
The duration for each patient in the study will be approximately 30 to 32 weeks: 
approximately 1 to 2 weeks in the Screening Period, 4 weeks in the Stabilization 
Period, 24 weeks in the Treatment Period, and 1 to 2 weeks to Termination Visit. 
Patients entering the study established on weekly SCIG infusions will have a 1 week 
Screening Period. Patients entering the study established on every other week dosing 
will have a 2 week Screening Period. 
Patients entering the study currently active and established on SCGAM-03 CUTIQUIG 
will skip the 4 week Stabilization Period. 
6.2.2 Planned Duration for the Study as a Whole 
The study will be considered completed when all patients have completed the 
Termination Visit. 
The estimated study start (enrollment of first patient) is the 3rd quarter 2019. 
Recruitment duration is expected to be approximately 18 months; therefore, the 
estimated study completion (last patient last visit) is anticipated in the 1st quarter 2021. 
6.2.3 Premature Termination of the Study 
Both the responsible Investigators and the Sponsor reserve the right to terminate the 
study at any time. Should this be necessary, study close-out procedures will be 
arranged on an individual site basis after review and consultation by both parties. In 
terminating the study, the Sponsor and the Investigator will ensure that adequate 
consideration is given to the protection of the patients' interests. 
Furthermore, the Investigator should promptly inform the IRB and provide a detailed 
written explanation. Pertinent regulatory authorities and IRBs will be informed in 
accordance with applicable regulatory requirements. 
6.2.3.1 Early Termination of the Entire Clinical Study 
At any time, the study as a whole will be terminated prematurely if: 
• New toxicological or pharmacological findings or safety reports invalidate the 
earlier positive benefit-risk assessment. 


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• If more than 2 independent thromboembolic events (TEEs) (ie, ischemic stroke, 
transient ischemic attack, cerebral infarction, cerebrovascular accident, 
cerebral thrombosis, embolic infarctions, [acute] myocardial infarction, deep 
vein thrombosis, pulmonary embolism, venous thrombosis excluding 
thrombophlebitis) are observed fulfilling the following criteria: 
– Assessed as probably or possibly related to CUTAQUIG treatment by 
Investigator and/or Sponsor 
– Confirmed by the IDMC  
• Any other reason rendering the continuation of the study impossible for the 
Sponsor 
6.2.3.2 Early Termination at an Individual Study Site 
At any time, the study can be terminated at an individual study site if the site: 
• Cannot comply with the requirements of the protocol 
• Cannot comply with applicable standards 
• Does not meet the required recruitment rate 
Should the study be prematurely terminated, all study materials, including IMP, must 
be returned to the Sponsor. 


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7 
ASSESSMENTS AND METHODS 
7.1 Demographic and Baseline Information 
Demographic and baseline information will be recorded during the Screening Visit. 
7.1.1 Demographic and Baseline Characteristics 
Demographic and baseline characteristics are sex, age, race and ethnic origin, height, 
weight, calculated BMI, and ABO Rhesus blood type. 
7.1.2 Medical History  
Medical history (conditions and surgical treatment) will be obtained by patient 
interview. Records of past diseases and treatments (eg, hospital discharge letters) will 
be obtained for the study files, if available. Any untoward medical events that occur 
from the time/date of informed consent signature until the first Study SCGAM-06 
specified CUTAQUIG dose will be recorded as medical history. 
7.1.3 Prior and Concomitant Medication Use 
Prior and concomitant medications and therapies will be obtained by patient interview. 
See Section 4.2 for details on prior and concomitant medication collections.  
7.1.4 Documentation of Previous SCIG Treatment and IgG Trough Levels 
Documentation of consistent or stable doses of SCIG treatment will be collected from 
patients’ medical records. 
Documentation of IgG trough levels will be collected from pre-study laboratory results 
obtained prior to enrollment; 2 prior IgG trough levels are required within 1 year of 
Screening, with 1 trough level obtained within 3 months prior to enrollment. If no prior 
IgG trough level is available within 3 months prior to Screening, the Screening IgG 
trough level may be used as the 2nd reading. 
7.2 Efficacy Assessments 
To study the effectiveness of CUTAQUIG to maintain total IgG trough levels when 
administered every other week, in the prevention of infections, and changes in patient 
QoL assessments, the following measurements will be recorded and efficacy 
parameters assessed, throughout the study: 
• Change in IgG trough levels when switched from every week to every other 
week administration (Cohort 3) (See Section 7.4.1) 
• Number of episodes of SBI, per person-year on treatment, along with type and 
severity of infection, and time to resolution 
• Number of episodes of any other infections (including acute sinusitis, 
exacerbation of chronic sinusitis, acute otitis media, acute bronchitis, infectious 
diarrhea etc.), along with type and severity of infection, and time to resolution 
• Number of days of use and annual rate of antibiotics (oral, parenteral, oral plus 
parenteral, prophylactic and therapeutic), along with type and dosage of 
antibiotic 


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• QoL assessments (See Section 7.4.2) 
For data collection of bacterial infections, in addition to on-site AE assessments, each 
patient will be provided with an individual diary to be completed by the patient during 
the home therapy time. The patient's diary will be checked for accuracy of the data by 
the Investigator and collected at each study visit. The data will be then transferred into 
the eCRF. A new diary will be handed out to the patient for the following period until 
the next infusion visit at the site. 
For the purpose of this study the following events will be considered as SBIs, to be 
included in the primary efficacy analysis: 
• Bacterial pneumonia 
• Bacteremia/sepsis 
• Osteomyelitis/septic arthritis 
• Visceral abscess 
• Bacterial meningitis 
The presence of any of these infections should be verified by the specific differentiated 
diagnostic examinations [25] given in Table 8. 
Table 8: 
Diagnostic Criteria for Serious Bacterial Infection Types 
Infection: Bacteremia/sepsisa 
• Symptoms: chills, rigors. 
• Physical findings: fever, hypothermia, tachycardia, tachypnea, hypocarbia, 
hypotension (systolic blood pressure <90 mm Hg or a reduction of >40 mm Hg 
from baseline in the absence of other causes of hypotension), altered mental 
status, petechiae, purpura, oligouria, cutaneous vasodilation/vasoconstriction. 
• Laboratory tests: positive blood cultureb, leukocytosis (white blood cell 
(WBC) count 
• >12,000/mm3), differential WBC count demonstrating >10% immature (band) 
neutrophils, leukopenia, thrombocytopenia, coagulopathy, lactic acidosis. 
Infection: Bacterial Meningitis 
• Symptoms: headache, stiff neck, mental status changes, irritability, decreased 
feeding (infants), photophobia, nausea/vomiting, rigors, seizures. 
• Physical findings: Kernig’s sign, Brudzinski’s sign, meningococcal rash, fever 
of >38°C oral or >39°C rectal. 
• Laboratory tests: positive cerebrospinal fluid (CSF) Gram stain and/or 
culture and/or positive CSF bacterial antigen assay, positive blood 
culturec, CSF leukocytosis with neutrophil predominance, decrease in CSF 
glucose. 
Infection: Osteomyelitis/Septic Arthritis 
• Symptoms: pain, decreased range of motion, tenderness, edema, redness, 
warmth over the involved site (local inflammatory symptoms/signs may be 
lacking in adults). 


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• Physical findings: evidence of soft tissue infection adjacent to the involved 
bone/joint, drainage from sinus tract from involved bone, fever of >38°C oral 
or >39°C rectal. 
• Laboratory tests: positive blood culture, positive probe to bone, positive bone 
aspirate culture, positive bone biopsy culture, positive bone histopathology, 
positive joint fluid Gram stain and culture. 
• Imaging studies: positive X-ray, nuclear medicine bone scan, magnetic 
resonance imaging scan, or computed tomography scan showing bony 
destruction with radiolucent areas; for chronic osteomyelitis: sequestra, 
involucra. 
Infection: Bacterial Pneumoniad 
• Symptoms: productive cough/change in character of sputum, dyspnea or 
tachypnea, chills, chest pain, rigors, headache, fatigue, sweats, anorexia, 
myalgia. 
• Physical findings: rales; pulmonary consolidation as reflected by: dullness on 
percussion, bronchial breath sounds, egophony; fever >38°C oral or >39°C 
rectal, or <36°C, hypothermia (temperature <36°C oral or <37°C rectal). 
• Laboratory tests: leukocytosis, differential WBC count of >10% band 
neutrophils, leukopenia, hypoxemia (PaO2 <60 mm Hg on room air), positive 
blood culture, Gram stain and culture of deep expectorated sputum e, positive 
culture with or without positive Gram stain of transtracheal aspirate, pleural 
fluid culture, lung biopsy, bronchoscopy with bronchoalveolar lavage or 
protected brush sampling. 
• Imaging studies: Pulmonary infiltrate with consolidation on chest X-ray 
(new in comparison with baseline chest X-ray) 
Infection: Visceral Abscess 
• Symptoms: abdominal pain, anorexia, weight loss, cough/pleuritic chest pain 
(hepatic abscess), rigors (seldom present). 
• Physical findings: intermittent fevers (temperature >38°C oral or >39°C rectal), 
abdominal tenderness, palpable mass, hepatomegaly, jaundice. 
• Laboratory tests: positive Gram stain and/or culture from the infected site, 
with isolation of an appropriate pathogen, positive blood culture, 
leukocytosis with accompanying left shift, differential WBC count of >10% 
immature (band) neutrophils, elevated serum amylase concentration 
(pancreatic abscess), elevated alkaline phosphatase concentration (hepatic 
abscess) pyuria in renal abscess. 
• Imaging studies: typical findings on ultrasound, computed tomography 
scan, magnetic resonance imaging scan, or radionuclide scan 
Notes to Table 8: 
Items in bold are considered essential diagnostic features. 
a. Two of the following should be present to make the diagnosis of sepsis in adults: temperature >38°C 
oral/>39°C rectal or <36°C oral or <37°C rectal; heart rate >90 beats/min; respiratory rate 
>20 breaths/min, or PaCO2 <32 mm Hg; WBC count >12,000/mm3, <4,000/mm3, or >10% immature 
(band) forms. For pediatric patients, the definition of sepsis using age-specific criteria as 


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recommended by the International Consensus Conference on Pediatric Sepsis should be 
employed.[26] 
b. Indwelling catheter- or vascular access device-related blood-borne infections are not included 
because evidence is lacking that these are preventable with IVIG replacement therapy. For patients 
without indwelling catheters or vascular access devices, a single blood culture positive for a 
pathogenic organism will meet the diagnostic criteria for bacteremia. Patients meeting criteria for 
positive blood culture but without 2 or more of the sepsis criteria listed above will be classified as 
having bacteremia. 
c. A blood culture positive for growth of Streptococcus pneumoniae, Neisseria meningitides, or 
Haemophilus influenzae, in combination with CSF leukocytosis and/or decrease in CSF glucose, 
can serve to confirm the diagnosis of acute bacterial meningitis. 
d. For the diagnosis of pneumonia in adults, commonly at least 2 of the listed symptoms and/or signs 
should be present in conjunction with at least one laboratory and one imaging studies diagnostic 
element. However, for the purposes of counting serious bacterial infection episodes in a clinical trial 
of IVIG, the finding of a new pulmonary infiltrate with consolidation on chest X-ray is considered 
sufficient. To establish the diagnosis of bacterial pneumonia for pediatric patients, most of the same 
diagnostic criteria listed may be used, with the following exceptions: Because pediatric patients may 
not produce a sputum specimen for culture, blood cultures or serology may be substituted to identify 
the etiologic bacterial pathogen. In infants age 3 to 24 months, who tend to have a higher baseline 
temperature, fever is defined as a rectal temperature >38.3°C (101°F). In children >2 years, fever 
is more commonly defined as a rectal temperature >38°C (100.4°F). In pediatric patients, elevations 
of WBC counts >15,000/mm3 are frequent but could be variable in patients with bacterial 
pneumonia, or leukopenia with WBC count <5000/mm3 may be observed, usually associated with 
severe infection. 
e. It is recommended to obtain a deep expectorated sputum gram stain to demonstrate the presence 
of microorganisms on examination of 10-20 oil immersion microscopic fields and <10 squamous 
epithelial cells and >25 polymorphonuclear leukocytes at 10X low power magnification to determine 
suitability of sputum culture. 
7.3 Safety Assessments 
The following safety assessments shall be collected: 
• Adverse events (AEs) and serious adverse events (SAEs) temporally 
associated with the administration of IMP (for definitions and reporting 
requirements, see Section 7.3.1 for AEs and Section 7.3.3 for SAEs) 
• Pregnancies (Section 7.3.8.2) 
7.3.1 Adverse Events 
7.3.1.1 Definitions 
Adverse event (AE): An AE is any untoward medical occurrence in a study patient 
receiving an IMP and which does not necessarily have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use 
of an IMP, whether or not related to the IMP. 
An AE is defined as treatment-emergent (TEAE) if the event began or worsened after 
the start of first infusion of trial medication. For patients in this study, “treatment-
emergent” will refer to events with onset date/time after the start of the first CUTAQUIG 
infusion at the Stabilization Period Week 0 Visit. 


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Adverse drug reaction (ADR): An ADR is any noxious and unintended response to an 
IMP related to any dose. The phrase “response to an IMP” means that a causal 
relationship between the IMP and an AE carries at least a reasonable possibility (ie, the 
relationship cannot be ruled out). 
Other Significant AEs: Any non-serious AE or marked laboratory abnormality that 
results in: 
• withdrawal of IMP treatment 
• and/or dose reduction 
• and/or initiation of significant additional concomitant therapy (ie, medications 
given intravenously) 
Withdrawal due to AE/ADR: AE/ADR leading to discontinuation of treatment with IMP. 
Any such events will be followed up by the Investigator until the event is resolved or 
until the medical condition of the patient is stable. All follow-up information collected 
will be made available to the Sponsor. 
7.3.1.2 Collection 
The condition of the patient will be monitored throughout the study. At each visit, 
whether scheduled or unscheduled, AEs will be elicited using a standard non-leading 
question such as “How have you been since the last visit/during the previous study 
period?” In addition, patient diaries (if applicable) will be checked by the Investigator 
for any documented event. 
Any AE which occurs during the study from the time/date of first dose of CUTAQUIG 
through the Termination Visit will be noted in detail on the appropriate pages of the 
eCRF. Any untoward medical events that occur from the time/date of informed consent 
signature until the first CUTAQUIG dose will be recorded as medical history. If the 
patient reports several signs or symptoms representing one syndrome or diagnosis, 
the diagnosis should be recorded in the eCRF. The Investigator will grade the severity 
of all AEs (mild, moderate or severe), the seriousness (non-serious or serious), and 
causality, as defined below (Section 7.3.1.3, Section 7.3.3, and Section 7.3.1.4, 
respectively). The Sponsor is also responsible to assess the expectedness of each 
ADR (expected or unexpected), as defined below (Section 7.3.1.5). 
In the event of clinically significant abnormal laboratory findings, the tests will be 
confirmed and followed-up until they have returned to normal and/or an adequate 
explanation is available. 
Diseases, signs and symptoms and/or laboratory abnormalities already existing before 
the first administration of IMP are not considered as AEs when observed at a later 
stage unless they represent an exacerbation in intensity or frequency (worsening). 
The Investigator should always provide detailed information concerning any 
abnormalities and the nature of, and reasons for, any necessary action(s), as well as 
any other observations or comments which are useful for the interpretation and 
understanding of patients’ AEs. 


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7.3.1.3 Severity 
The intensity/severity of AEs will be graded as follows: 
• Mild: an AE, usually transient, which causes discomfort but does not interfere 
with the patient’s routine activities 
• Moderate: an AE which is sufficiently discomforting to interfere with the 
patient’s routine activities 
• Severe: an AE which is incapacitating and prevents the pursuit of the patient’s 
routine activities 
The severity grading of an AE is up to the medical judgement of the Investigator and 
will be decided on a case-by-case basis. 
7.3.1.4 Causality 
The relationship of AEs to the administered IMP will be assessed by the Investigator: 
• Probable: reports including good reasons and sufficient documentation to 
assume a causal relationship, in the sense of plausible, conceivable, likely, but 
not necessarily highly probable. A reaction that follows a reasonable temporal 
sequence from administration of the IMP; or that follows a known or expected 
response pattern to the suspected medicine; or that is confirmed by stopping or 
reducing the dosage of the medicine and that could not reasonably be explained 
by known characteristics of the patient’s clinical state. 
• Possible: reports containing sufficient information to accept the possibility of a 
causal relationship, in the sense of not impossible and not unlikely, although the 
connection is uncertain or doubtful, for example because of missing data or 
insufficient evidence. A reaction that follows a reasonable temporal sequence 
from administration of the IMP; that follows a known or expected response 
pattern to the suspected medicine; but that could readily have been produced 
by a number of other factors 
• Unlikely: reports not following a reasonable temporal sequence from IMP 
administration. An event which may have been produced by the patient’s clinical 
state or by environmental factors or other therapies administered. 
• Not related (unrelated): events for which sufficient information exists to 
conclude that the etiology is unrelated to the IMP. 
• Unclassified: reports which for one reason or another are not yet assessable, 
eg, because of outstanding information (can only be a temporary assessment). 
Sites are encouraged not to use this category unless necessary, as it will be 
assumed there is a causal relationship and may lead to premature fulfillment of 
Suspected Unexpected Serious Adverse Reaction (SUSAR) criteria. 
7.3.1.5 Classification of ADRs by Expectedness 
ADRs will be classified by the Sponsor as either expected or unexpected: 
• Expected: an ADR that is listed in the current edition of the Investigator’s 
Brochure or other reference safety information. 


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• Unexpected: an ADR that is not listed in the current edition of the Investigator’s 
Brochure or other reference safety information, or that differs because of greater 
severity or greater specificity. 
7.3.1.6 Outcome of AEs 
Outcome of all reported AEs will be documented as follows: 
• Recovered, resolved 
• Recovering, resolving 
• Not recovered, not resolved 
• Recovered, resolved with sequelae 
• Fatal 
• Unknown 
NOTE: A patient’s death per se is not an event, but an outcome. The event which 
resulted in the patient’s death must be fully documented and reported, even in case 
the death occurs within 4 weeks after IMP treatment end and regardless of whether or 
not it is considered treatment-related. 
7.3.1.7 Action(s) taken 
AEs requiring action or therapy must be treated with recognized standards of medical 
care to protect the health and well-being of the patient. Appropriate resuscitation 
equipment and medicines must be available to ensure the best possible treatment in 
an emergency situation. 
The action taken by the Investigator must be documented: 
a) General actions taken in the event of an AE 
– None 
– Medication (other than IMP) or other (eg, physical) therapy started 
– Test performed 
– Other (to be specified) 
b) IMP-related actions taken in the event of an AE 
– None 
– Product withdrawn 
– Dose reduced 
– Dose increased 
The Investigator will follow up on each AE until it has resolved or until the medical 
condition of the patient is stable, and all relevant follow-up information will be reported 
to the Sponsor. 
7.3.2 Local Site Reactions 
Local infusion-site reactions will be assessed by both patients and investigators. 


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Patients will grade the overall perception of local reactions in their diaries after each 
infusion using a 4-point rating scale: 0=none, 1=mild, 2=moderate, 3=severe. 
Investigators will evaluate local reactions after infusion at every study visit, using a 
4-point rating scale: 0=none, 1=mild, 2=moderate, 3=severe. 
The following observations must not be reported as local infusion site reactions as all 
of these can be expected in all patients: 
• Local mass (usually reported as "swelling") caused by the injected CUTAQUIG 
volume 
• Small blood drops at the infusion site caused by the needle sticks 
• Short and immediate pain at the infusion site caused by the puncture itself 
Any other local infusion site reactions such as redness, pain (other than the pain 
caused by the puncture itself), pruritus, rash or other skin reactions, bleedings (other 
than small blood drops caused by the needle stick), local thrombosis, induration or 
swellings (caused by other grounds than the injected volume) must be reported on the 
adverse events page in the eCRF. 
7.3.3 Serious Adverse Events 
A serious AE (SAE) is any untoward medical occurrence that at any dose: 
• results in death 
• is life-threatening (see below) 
• requires hospitalization or prolongation of existing hospitalization 
• results in persistent or significant disability/incapacity 
• is a congenital anomaly/birth defect 
• is another important medical event 
NOTE: The term ‘life-threatening’ refers to an event in which the patient was, in the 
view of the reporting Investigator, at immediate risk of death at the time of the event; it 
does not refer to an event which may hypothetically have caused death had it been 
more severe. 
Medical judgment should be exercised in deciding whether an AE/ADR is serious in 
other situations: Important AEs/ADRs that are not immediately life-threatening or do 
not result in death or hospitalization but may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the definitions above, should 
also be considered serious. 
In addition, although not classified under the seriousness criteria, all suspected 
transmissions of an infectious agent should be reported as SAE. A suspected virus 
transmission means that virus antigen has been detected in the patient. A passive 
transmission of antibodies alone does not constitute a suspected virus transmission. 


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7.3.3.1 SAE Reporting 
All SAEs, whether or not they are suspected to be related to study treatment, are to be 
reported immediately to the Octapharma Project Manager by email and 
to 
. 
In addition, within 24 hours after recognition of the event, an Octapharma Serious 
Adverse Event Report must be completed and submitted to: 
Octapharma’s Corporate Drug Safety Unit 
OCTAPHARMA Pharmazeutika Produktionsges.m.b.H. 
Oberlaaer Strasse 235, 1100 Vienna, Austria 
 
 
 
SAE reporting procedures are outlined in the Site Safety Reporting Manual that will be 
provided to each site and will be communicated at the site initiation visit. 
Waivers from the SAE Reporting Requirement 
Waivers from the SAE reporting requirement include surgeries that are elective or were 
planned before study entry or prolongations of existing hospitalizations for economic 
or social, but not medical, reasons. Such surgeries or prolongations of hospitalizations 
should not be considered SAEs. In addition, any AE that meets the criteria of an SAE 
but begins prior to the start of the first infusion will be waived from the SAE reporting 
requirements.  
7.3.4 Laboratory Tests 
The following laboratory tests will be performed during the course of the study to 
investigate the efficacy, safety, and tolerability of CUTAQUIG (Table 9). At each visit, 
laboratory tests will be performed before CUTAQUIG infusions at the study site.  
The following laboratory parameters will be investigated during the study at the time 
points specified in the FLOW CHARTS OF ASSESSMENTS. 
Table 9: 
Laboratory Tests and Time Points 
Test 
Timing 
Laboratory 
Total serum IgG trough levels 
Screening Visit; Stabilization Period Week 0; 
all subsequent Treatment Period Visits, and 
Termination Visit 
Central 
Hematology (complete blood 
count, WBC differential, 
hematocrit, hemoglobin) 
Screening Visit; Stabilization Period Week 0; 
Treatment Period Baseline, Week 12, and 
Week 24; and Termination Visit  
Local 
Clinical chemistry (sodium, 
potassium, glucose, ALT, AST, 
LDH, total bilirubin, blood urea 
nitrogen or blood urea, 
creatinine) 
Screening Visit; Stabilization Period Week 0; 
Treatment Period Baseline, Week 12, and 
Week 24; and Termination Visit 
Local 


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Test 
Timing 
Laboratory 
Urinalysis (pH, glucose, ketones, 
leukocytes, hemoglobin) 
Screening Visit; Stabilization Period Week 0; 
Treatment Period Baseline, Week 12, and 
Week 24; and Termination Visit 
Local 
Urine pregnancy test (females of 
childbearing potential) 
Screening Visit; Stabilization Period Week 0; 
Treatment Period Baseline, Week 12 and 
Week 24; and Termination Visit 
Local 
Virology (HCV-Nucleic Acid 
Testing [NAT]) 
Stabilization Period Week 0: CUTAQUIG—
naïve patients and SCGAM-03 patients if 
commercial SCIG product used following 
completion of SCGAM-03. 
Treatment Period Baseline: patients currently 
active and established on CUTAQUIG in 
SCGAM-03 at the Screening Visit 
Termination Visit: all patients 
Central 
Serum retention samples 
Stabilization Period Week 0: CUTAQUIG—
naïve patients and SCGAM-03 patients if 
commercial SCIG product used following 
completion of SCGAM-03. 
Treatment Period Baseline: patients currently 
active and established on CUTAQUIG in 
SCGAM-03 at the Screening Visit 
Termination Visit: all patients 
Central 
The methods of determination and normal ranges for each parameter will be provided 
in the clinical study report.  
7.3.5 Serum Retention Samples 
Serum retention samples will be collected at Stabilization Period Week 0 for 
CUTAQUIG-naïve patients or SCGAM-03 patients that have gone on a commercial 
SCIG product, at Treatment Period Baseline for patients who are enrolled in 
SCGAM-03 and directly entering SCGAM-06, and at the Termination Visit for all 
patients (Table 9). These samples will be shipped to a central laboratory for retention 
and possible future testing of Hepatitis A, B, C, and HIV I/II. Instructions for sample 
handling will be provided in the Study Laboratory Manual.  
7.3.6 Vital Signs  
Vital signs will be measured at the time points specified in the FLOW CHARTS OF 
ASSESSMENTS and include blood pressure, body temperature, pulse, and respiratory 
rate. 
7.3.7 Physical Examination including Height and Weight 
Physical examinations will be performed according to each study site’s routine 
procedures by study personnel who are qualified to perform such evaluations. These 
examinations will be as comprehensive as necessary to detect relevant somatic or 
neurological diseases. If any findings are abnormal, the Investigator will document the 
start date and whether or not the abnormal finding is still present at the start of 
treatment. 


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Both height and weight will be measured at Screening. In addition, weight will be 
measured at all visits prior to dosing in order to allow for dose calculations. 
7.3.8 Other Relevant Safety Information 
7.3.8.1 Post-study related safety reports 
Any SAE which occurs up to 4 weeks after the Termination Visit should be reported by 
the Investigator to the Sponsor in case the Investigator becomes aware of it. Proactive 
monitoring for post-study SAEs is not required. 
If a post-study SAE is identified, the Investigator should complete an SAE form and 
also record the relationship of the SAE to the IMP in the SAE report. 
Any death occurring within 4 weeks after Termination Visit should also be reported, 
regardless of whether or not it is considered treatment-related. 
7.3.8.2 Pregnancies  
Every effort will be made to avoid a pregnancy during the use of an IMP. Pregnancies 
occurring during the study (fetal exposure to the IMP) need to be reported.  
In case of a pregnancy during the study, the Investigator should complete the 
Pregnancy Notification Form and email or fax it to the Sponsor’s representative 
(Section 7.3.3.1). 
7.3.8.3 Drug overdose, interaction, or medication error 
The following safety relevant information should be reported as AE or as an SAE if the 
reaction fulfils one of the criteria for seriousness (Section 7.3.3). 
a) Drug overdose 
An overdose is a deliberate or inadvertent administration of a treatment at a dose 
higher than specified in the protocol and higher than the known therapeutic dose that 
is of clinical relevance. The reaction must be clearly identified as an overdose. 
b) Drug interaction 
A drug interaction is a situation in which a substance or medicinal product affects the 
activity of an IMP, ie, increases or decreases its effects, or produces an effect that 
none of the products would exhibit on its own. The reaction must be clearly identified 
as a drug interaction. 
c) Medication error 
A medication error involves the inadvertent administration or unintended use of a 
medicinal product which may be caused by the naming, presentation of 
pharmaceutical form/packaging, or instructions for use/labelling. The reaction must be 
clearly identified as a medication error. 


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7.4 Other Assessments 
7.4.1 Drug Concentration Measurements (IgG Trough Levels) 
Samples for total IgG trough levels measurements will be taken at the Screening Visit, 
before any infusion given at the study site (Section 7.1.4), and at the (Early) 
Termination Visit (Table 9). 
7.4.2 Quality of Life Assessment 
QoL assessments will be made using the SF-10 from a parent or guardian of patients 
<14 years of age and the SF-36 Health Survey in patients ≥14 years of age. The QoL 
assessments will take place at the Treatment Period Baseline Visit and at the (Early) 
Termination Visit.  
7.4.3 Subject Questionnaire 
The Subject Questionnaire will be completed asking for their opinions related to their 
participation on the trial. This will be completed by all patients (or with the assistance 
of a parent/guardian for children, when applicable) at the (Early) Termination Visit. 
7.5 Appropriateness of Measurements 
Safety will be monitored by standard assessments including monitoring AEs, local 
infusion site reactions, vital signs, laboratory safety tests, and physical examinations. 
Therapeutic efficacy, defined as the prevention of SBI, is a very important clinical 
aspect of any IgG replacement therapy and best characterizes benefit to the patient. 
Determination of the pre-next-dose trough level of IgG is a standard method for 
determination of the correct dose for the individual patient. 
The QoL questionnaires are standardized, validated instruments that have been widely 
used in clinical studies, including studies with PI patients.  


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8 
DATA HANDLING AND RECORD KEEPING 
To ensure that data in the eCRFs are accurate and complete and in accordance with 
source records, source data verification will be performed in accordance with 
Octapharma standards. The extent of source data verification will be defined in detail 
in the monitoring manual. 
8.1 Documentation of Data 
8.1.1 Source Data and Records 
Source data are defined as all information related to clinical findings, observations, or 
other activities in the study; written down in original records or certified copies of 
original records; or electronic medical records; allowing reconstruction and evaluation 
of the clinical study. 
The Investigator will maintain adequate source records (eg, case histories or patient 
files) for each patient enrolled. Source records should be preserved for the maximum 
period of time required by local regulations. 
For each patient enrolled, the Investigator will indicate in the source record(s) that the 
patient participates in this study. 
All data entered in the eCRF must be supported by source data in the patient records, 
with exceptions listed in Section 8.1.2. 
The Investigator will permit study-related monitoring, audit(s), IEC/IRB review(s), and 
regulatory inspection(s), by providing direct access to the source data/records. 
The Investigator may authorize site staff (eg, sub-Investigators, research nurses) to 
enter study data into the eCRF. This must be documented in the Delegation of 
Authority Log and signed by the Investigator. 
The following data must be verifiable from the source records: patient number, sex, 
weight, date of birth, written informed consent (and assent, if appropriate), medical 
history, main inclusion and exclusion criteria, local laboratory test results, PID-relevant 
concomitant therapies (medication and non-drug therapy), any AE occurring in the 
course of the study, details of infusions (batch number, number of vials used, date, 
dose, rate, and infusion site(s)), date and reason for early termination (if applicable). 
As part of the source records, laboratory data will be reviewed by the Investigator, 
assessed as to their clinical significance, signed, and dated. 
8.1.2 Electronic Case Report Forms 
For each patient enrolled, an eCRF will be completed within the EDC system and 
approved by the Investigator or an authorized sub-Investigator.  
Study site staff (eg, research nurse) will be responsible for entering patient data into 
the validated EDC system. All site personnel will be trained on the EDC system and 
study specific eCRF before receiving access to the live database for data entry. 
The site will be provided with approved eCRF Completion Guidelines which will assist 
in data entry and data issues/questions. The site will be notified once the database is 


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active to begin data entry. Additional site training may be provided as refreshers 
throughout the study, if needed. All persons allowed to enter or change eCRF data 
must be listed in the Delegation of Authority Log. 
If any errors in the eCRFs are found during the data review process, discrepancies will 
be generated programmatically within the EDC system and manual queries will be 
generated by either a monitor or Data Management. The programmed edit checks fire 
automatically once an eCRF page is saved within the system. The outputs of the 
programmed checks are referred to as discrepancies. Discrepancies are generated by 
the input of illogical eCRF data with the purpose to clarify the context or insertion of 
illogical or missing data with the site or designee. 
All discrepancies (programmed and manual) will be submitted to the site personnel or 
monitor for the site within the EDC system. Once the site responds to a discrepancy, 
Data Management or the monitor will review the new or changed data to ensure an 
appropriate response and close the discrepancy within the system. 
8.1.3 Changes to Electronic Case Report Form Data 
Monitors will perform source data verification (SDV) as defined for the study. 
Errors occurring in the EDC system can only be corrected by the Investigator(s) or 
authorized site personnel. An audit trail documents all changes to the data over the 
entire study period. If data are changed as a result of a query, a comment must be 
entered stating the reason for the change before closing the query. In addition, any 
change to a previously saved eCRF page that has not had a query generated will need 
to have a reason specified for the data change. 
Once queries have been resolved by the site staff, the resolutions are assessed by 
Data Management. If the query response provided confirms the data as correct, the 
discrepancy will be closed. If the response does not adequately address the question 
raised, a new query will be issued for further clarification. 
Manual checks will be performed, and programs will be run throughout the study until 
the data are clean (all discrepancies resolved) and the database is ready for lock. 
Source data verification will be confirmed as complete by the monitor and all eCRFs 
will be approved by the Investigator before database lock. 
8.2 Information to Investigators 
An Investigator’s Brochure will be provided to the Investigator before the start of the 
study. This brochure contains all information in the Sponsor’s possession necessary 
for the Investigator to be fully and accurately informed about the safety of the IMP 
under evaluation and the respective benefit-risk ratio. 
The Investigator’s Brochure will be updated by the Sponsor at regular intervals and the 
event that relevant new information concerning the IMP becomes available. 
All participating investigators will be informed about relevant study procedures, about 
the methods for rating relevant study outcomes, and how to enter data into the eCRF 
in order to reduce discrepancies. At the study initiation visit, the eCRF will be explained 
to all study site staff entitled to document data in the eCRF. 


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Investigators will be kept informed of important information related to the safe use of 
the IMP as the study proceeds. 
8.3 Responsibilities 
The Principal Investigator is accountable for the conduct of the clinical study at each 
study site. Responsibilities may be delegated to appropriately qualified persons. 
A Delegation of Authority Log will be completed and signed by the Principal 
Investigator. In accordance with this authority log, study site staff (eg, sub-
Investigators, study coordinators, nurses) will be authorized to perform specific tasks 
relating to study conduct. 
At each study site, the Investigator is responsible for maintaining all records to enable 
the conduct of the study to be fully documented. Essential documents as required by 
Good Clinical Practice (GCP) guidelines and regulations (eg, copies of the protocol, 
study approval letters, all original informed consent forms and assent forms (as age 
appropriate), site copies of all eCRFs, drug dispensing and accountability logs, 
correspondence pertaining to the study) should be filed accurately and retained by the 
Investigator for the maximum period of time required by local regulations. 
The Investigator is responsible for maintaining a confidential patient identification code 
list which provides the unique link between named source records and eCRF data for 
the Sponsor. The Investigator must arrange for the retention of this confidential list for 
the maximum period of time required by local regulations. 
No study document should be destroyed without prior written agreement between the 
Investigator and the Sponsor. Should the Investigator elect to assign the study 
documents to another party or move them to another location, the Sponsor must be 
notified in writing. 
8.4 Provision of Additional Information 
On request, the Investigator will supply the Sponsor with additional data relating to the 
study or copies of relevant source records; the Investigator must ensure that patient 
confidentiality is maintained on any source documents provided to the Sponsor. This 
is particularly important when source data are illegible or when errors in data 
transcription are encountered. 
In the event of particular issues or governmental queries, it may also be necessary to 
have access to the complete study records, provided that the patient’s confidentiality 
is protected in accordance with applicable regulations. 
8.5 Independent Data Monitoring Committee 
The Sponsor will establish an IDMC.  
The IDMC will be composed of recognized experts in the field of immunology who are 
not actively recruiting patients. 
During the study, the IDMC will periodically review relevant data and will give advice 
on the continuation, modification, or termination of the study (Section 6.2.3). A study-


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specific Charter will define in detail the composition, responsibilities, and procedures 
of the IDMC. 


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9 
STATISTICAL METHODS AND SAMPLE SIZE 
Statistical analysis will be delegated under an agreement of transfer of responsibilities 
to an external CRO. All Octapharma procedures and policies must be met by this CRO. 
Discrepancies or exceptions will be approved by the Sponsor's Manager of Biometrics. 
A formal statistical analysis plan describing all details of the analyses to be performed 
will be prepared by the study statistician and approved by the Sponsor prior to the start 
of the statistical analysis. 
9.1 Determination of Sample Size 
Approximately 65 patients who meet eligibility criteria will be enrolled in the study: 
• At least 15 patients in Cohort 1 
• At least 15 patients in Cohort 2 
• At least 35 patients in Cohort 3 
The co-primary endpoints will be analyzed descriptively, and no formal sample size 
calculation was done for the overall number of patients enrolled. 
For Cohort 3 we plan for a confirmative analysis to evaluate whether the total IgG 
trough levels are maintained by an every other week dosing regimen; the following pair 
of hypotheses will be tested: 
Ha: Teow > Tw  – 1   vs.   H0: Teow  ≤ Tw - 1 
where Teow is the mean total IgG trough on steady-state dosing every other week, Tw 
is the same for weekly dosing, and a maximum decrease of 1 g/L for the mean total 
IgG trough level is considered acceptable. 
Tw will be determined after completion of the Stabilization Period, Teow at the final study 
visit. 
This one-sided hypothesis will be tested by a paired t-test at the alpha=2.5% level of 
significance. Assuming 3.0 for the standard deviation common to both members of a 
pair, and 0.8 as the correlation between members of a pair, this results in a required 
minimum of 31 evaluable patients to achieve a power of 80%. 
9.2 Statistical Analysis 
All data collected will be listed and presented descriptively in full detail, by cohort as 
well as in total, to facilitate comparison between the different dosing regimens. 
As detailed in Section 9.1, the change in total IgG trough levels when switching from 
weekly to bi-weekly infusions will be tested in Cohort 3 by means of a one-sided, paired 
t-test at the α=0.025 level of significance. 
Descriptive summaries will be presented for each of the primary and secondary 
variables according to their individual data types. The results of this study will be 
presented at the descriptive level only; any additional p-value or confidence interval 
presented is to be understood in the exploratory sense. 


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9.2.1 Populations for Analysis 
The following populations will be considered for the statistical analysis: 
• Safety Analysis Set: all patients who received at least part of one infusion of 
CUTAQUIG. 
• Full Analysis Set (FAS): all patients in the Safety Analysis Set who satisfy all 
major eligibility criteria and for whom any post-baseline data is available (per 
intention-to-treat principle). This set of eligible patients will be used for 
measurement of treatment effects. 
• Per-Protocol (PP) Set: all patients in the FAS, excluding those with substantial 
protocol deviations which may have an impact on the analysis of the co-primary 
endpoint. This is the set of patients who participated in the study as intended 
and for whom the co-primary endpoint can be evaluated as planned. 
Only substantial protocol deviations with the potential to significantly affect the study 
results or to invalidate the interpretation of the data obtained will lead to exclusion of 
patients from the PP set; protocol deviations to be considered will include (but will not 
be limited to): 
• Violations of the study entry criteria 
• Administration of any other blood or plasma-derived product or of any other 
immunoglobulin preparations during Study SCGAM-06 
• Any prohibited concomitant medication (including long term daily corticosteroid 
use of >0.15 mg of prednisone or equivalent/kg/day [with the exception of short 
or intermittent courses as described in Section 4.2.2], immunosuppressive and 
immunomodulatory drugs) 
• Failure to attend two scheduled consecutive visits OR three or more scheduled 
visits during the study for reasons other than clinical reasons 
Efficacy endpoints will be analyzed using the FAS. Safety endpoints will be analyzed 
using the Safety Analysis Set. Selected analyses will be repeated for the PP population 
as detailed in the SAP and its appendices. 
In the event that a patient is not treated according to the dosing regimen described for 
his assigned cohort, the original cohort assignment will still be used for safety and the 
ITT analyses (SAF and FAS populations). These patients will be removed from the PP 
population due to protocol violations. 
The membership of each patient in the respective analysis populations will be 
determined before the statistical analysis in a data review meeting by a panel 
consisting of a medical expert from the Sponsor, the clinical study manager, the data 
manager and the study statistician. 
9.2.2 Efficacy Analysis Plan 
The rate of SBI per person-year (bacterial pneumonia, bacteremia/sepsis, 
osteomyelitis/septic arthritis, visceral abscess, bacterial meningitis) during the 
CUTAQUIG treatment period will be presented as point estimates of the rate along 
with a 99% CI. Calculation of this confidence interval will account for intra-patient 
correlation in incidents following a compound Poisson process model. Furthermore, all 
observed SBIs will be listed individually and in full detail. 


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The duration of infection will be summarized by standard descriptive statistics by type 
of infection and by severity. The individual characteristics of each infection, including 
the time to resolution will be listed. 
The use of antibiotics will be reported as a detailed list of all such medications, and the 
number of patients treated with antibiotics, the number of treatment episodes and the 
number of treatment days will be tabulated. 
The US FDA Guidance for Industry on Safety, Efficacy, and Pharmacokinetic Studies 
to Support Marketing of Immune Globulin Intravenous (Human) as Replacement 
Therapy for Primary Humoral Immunodeficiency suggests that, based on historical 
data, a statistical demonstration of a serious bacterial infection rate per person-year 
less than 1.0 is adequate to provide substantial evidence of efficacy.[25] Therefore, 
this background information will be used for a descriptive evaluation of the serious 
bacterial infection rate in this study as described above. Exploratory statistical testing 
may be performed if considered appropriate. 
The QoL data will be presented descriptively by visit, along with the change from 
Baseline, defined as the Treatment Period Baseline Visit. 
For Cohort 3, the change in total IgG trough levels when switching from weekly to every 
other week infusions will be tested confirmatory by means of a one-sided, paired t-test 
at the α=0.025 level of significance. The following pair of hypotheses will be tested: 
Ha: Teow > Tw – 1   vs.   H0: Teow ≤ Tw - 1 
where Teow is the mean total IgG trough on steady-state dosing every other week, Tw 
is the same for weekly dosing, and a maximum decrease of 1 g/L for the mean total 
IgG trough level is considered acceptable. 
Tw will be determined after completion of the Stabilization Period, Teow at the final study 
visit. 
9.2.3 Safety Analysis Plan 
The safety analysis will comprise descriptive statistics, tabulations, and listings of all 
TEAEs, safety laboratory results, vital signs, and physical examination findings. 
9.2.3.1 Adverse Events 
All reported AEs will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA). 
An AE is defined as treatment-emergent if first onset or worsening is after start of the 
first infusion of CUTAQUIG. Only TEAEs are accounted for in the analysis. 
Any untoward medical events that occur between informed consent and the start of 
the first infusion of CUTAQUIG will be considered pre-treatment AEs. These events 
will not be entered into the safety database as they are not TEAE. 
For each TEAE, the time relative to the start of the infusion will be calculated and the 
TEAE will be classified as temporally associated if the onset time is during the infusion 
or within 72 hours after the end of the infusion. 


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All reported AEs will be listed and tabulated in full detail, in particular the following data 
will be presented: 
• Total number of TEAEs reported 
• Number of TEAEs 
• Infusion rate at the onset of TEAEs 
• Narratives will be prepared describing each death, other SAEs, and other 
significant AEs that are judged to be of special interest because of clinical 
importance 
9.2.4 Handling of Missing Data 
In general, missing data will not be imputed: calculations pertaining to person-year 
computations will be based on observed values only. Only in case of missing body 
weight will the last available weight measurement be used for calculating the dose per 
kg body weight (last observation carried forward [LOCF]). 
9.3 Randomization, Stratification, and Code Release 
There is no randomization or stratification in this study. Assignments to the 3 study 
cohorts will be based on patient eligibility and Investigator and patient preference. 
9.4 Interim Analysis 
No interim analysis is planned.  


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10 ETHICAL/REGULATORY, LEGAL AND ADMINISTRATIVE ASPECTS 
10.1 Ethical/Regulatory Framework 
This study will be conducted in accordance with the ethical principles that have their 
origins in the Declaration of Helsinki. Before submission of the study protocol to the 
IRB and Competent Authority, the study will be registered in ClinicalTrials.gov. The 
study protocol and any subsequent substantial amendment(s), as well as a sample of 
the information sheet, informed consent form, assent form, any other materials 
provided to the patients, and further requested information will be submitted to the IRB 
and the Competent Authority. The study will be conducted in compliance with the 
protocol, GCP and the applicable regulatory requirements. 
The study will be conducted under a US Investigational New Drug (IND) application, 
and therefore must meet the applicable US FDA requirements including Statement of 
Investigator Form 1572 and financial disclosure statement. 
The regulatory application or submission for regulatory approval will be made by the 
Sponsor as required by national law. Study approval must be available before any 
patient is exposed to a study-related procedure. 
The Competent Authorities and the IRBs will be notified of the end of the clinical study 
in accordance with local regulations. 
10.2 Approval of Study Documents 
The study protocol, a sample of the patient information and informed consent form, 
assent form, and further requested information will be submitted to the appropriate IRB 
and the competent Authority. The study approval letter must be available before any 
IMP may be shipped to the study sites and any patient is exposed to a study-related 
procedure. 
The Sponsor, the Investigator and any third party (eg, CRO) involved in obtaining 
approval, must inform each other in writing that all ethical and legal requirements have 
been met before the first patient is enrolled in the study. 
10.3 Patient Information and Informed Consent 
The Investigator will obtain freely given written consent from each patient after an 
appropriate explanation of the aims, methods, anticipated benefits, potential hazards 
and any other aspect of the study which is relevant to the patient’s decision to 
participate. The informed consent form must be signed, with name, date, and time 
noted by the patient, before the patient is exposed to any study-related procedure, 
including screening tests for eligibility. 
For patients not qualified to give legal consent, written consent must be obtained from 
the legal parent/guardian. If children are old enough to understand the risks and 
benefits of the study, they should also be informed and provide their written consent 
using an assent form. 
The Investigator will explain to each single patient that the patients are completely free 
to refuse to enter the study or to withdraw from it at any time, without any 


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consequences for their further care and without the need to justify their withdrawal. 
The Investigator will date and sign the informed consent form of each patient enrolled. 
Each patient (and legal guardian, as age appropriate) will give written consent that 
his/her source records may be reviewed by study monitors, quality assurance auditors, 
and/or health authority inspectors, in accordance with applicable regulations. These 
persons are bound by confidentiality obligations. 
10.4 Protocol Amendments 
Any prospective change to the protocol will be agreed between the Investigator 
(Coordinating Investigator in multicenter studies) and the Sponsor before its 
implementation. Any such amendments will be submitted to the IRB and/or Competent 
Authority responsible as required by applicable regulations. IRB approval will at a 
minimum be requested for any change to this protocol which could affect the safety of 
the patients, the objective/design of the study, any increase in dosage or duration of 
exposure to the IMP, an increase in the number of patients treated, the addition of a 
new test or procedure, or the dropping of a test intended to monitor safety. 
10.5 Confidentiality of Patient Data 
The Investigator will ensure that patient confidentiality is preserved. In eCRFs or any 
other documents submitted to the Sponsor, patients will not be identified by name or 
initials but by a unique patient identifier. Documents not intended for submission to the 
Sponsor, including but not limited to the confidential patient identification code list, 
original consent and assent forms, and source records, will be maintained by the 
Investigator in strict confidence. 


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11 QUALITY CONTROL AND QUALITY ASSURANCE 
11.1 Periodic Monitoring 
The monitor will contact and visit the Investigator periodically to review all study-related 
source data/records, verify the adherence to the protocol and the completeness, 
correctness, and accuracy of all eCRF entries compared to source data. The 
Investigator will co-operate with the monitor to ensure that any discrepancies identified 
are resolved. 
For this study, the first monitoring visit shall take place shortly after the inclusion of the 
first patient. Thereafter, monitoring frequency will be based on enrollment status and 
study progress, as outlined in the Study Monitoring Plan.  
The monitor must be given direct access to source documents (original documents, 
data, and records). Direct access includes permission to examine, analyze, verify and 
reproduce any records and reports that are important to the evaluation of the clinical 
study. Source data will be available for all data in the eCRFs, including all laboratory 
results. 
11.2 Audit and Inspection 
The Investigator will make all study-related source data and records available to a 
qualified quality assurance auditor mandated by the Sponsor, or to IRB/Regulatory 
Authority inspectors, after reasonable notice. The main purposes of an audit or 
inspection are to confirm that the rights and welfare of the patients have been 
adequately protected, and that all data relevant for the assessment of safety and 
effectiveness of the IMP have been reported to the Sponsor. 


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12 REPORTING AND PUBLICATION 
12.1 Clinical Study Report 
The Sponsor will prepare a clinical study report (in accordance with relevant guidelines 
and Octapharma Standard Operating Procedures) timely after the completion of the 
study. The Coordinating Investigator will approve the final study report after review. 
12.2 Publication Policy 
The results of this study may be published or presented at scientific meetings. If the 
Investigator wants to publish or present study results, the Investigator agrees to inform 
the Sponsor and to submit all manuscripts or abstracts to the Sponsor before 
submission to an editorial board or scientific review committee. This will allow the 
Sponsor to protect proprietary information and to provide comments based on 
information that may not yet be available to the Investigator. 
In accordance with standard editorial and ethical practice, the Sponsor will support 
publication of multicenter studies only in their entirety and not as individual center data. 
Authorship will be determined by mutual agreement. 


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13 LIABILITIES AND INSURANCE 
To cover any damage or injury occurring to a patient in association with the 
investigational medicinal product or the participation in the study, the Sponsor will 
contract insurance in accordance with local regulations. 
All participating investigators are responsible for dispensing the IMP in adherence to 
this protocol, and for its secure storage and safe handling throughout the study. 


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14 REFERENCES 
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Berger M, Jolles S, Orange JS, et al: Bioavailability of IgG Administered by the 
Subcutaneous Route. J Clin Immunol. 2013. doi:10.1007/s10875-013-9876-3- 
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Orange JS, Belohradsky BH, Berger M, et al: Evaluation of correlation between 
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Kobayashi RH, Gupta S, Melamed I, et al: Clinical Efficacy, Safety and 
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Wasserman RL, Melamed I, Kobrynski L, et al: Efficacy, Safety, and 
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Berger M, Rojavin M, Kiessling P, et al: Pharmacokinetics of subcutaneous 
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Sidhu, J., Rojavin, M., Pfister, M., Edelman, J.: Enhancing Patient Flexibility of 
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Berger M: Subcutaneous Administration of IgG. Immunol Allergy Clin North Am. 
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Orange JS, Grossman WJ, Navickis RJ, et al: Impact of trough IgG on 
pneumonia incidence in primary immunodeficiency: A meta-analysis of clinical 
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Hammarstrom 
L, 
Smith 
CI: 
Home 
treatment 
of 
hypogammaglobulinaemia with subcutaneous gammaglobulin by rapid infusion. 
Lancet. 1991;338:162-166. 
15. 
Borte M, Bernatowska E, Ochs HD, et al: Efficacy and safety of home-based 
subcutaneous immunoglobulin replacement therapy in pediatric patients with 
primary immunodeficiencies. Clin Exp Immunol. 2011; 


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Study Protocol No. SCGAM-06 Version 02 
CONFIDENTIAL 
28-Aug-2019 
 
Page 86 of 87 
16. 
Borte M, Quinti I, Soresina A, et al: Efficacy and Safety of Subcutaneous 
Vivaglobin® Replacement Therapy in Previously Untreated Patients with 
Primary Immunodeficiency: A Prospective, Multicenter Study. J Clin Immunol. 
2011. doi:10.1007/s10875- 011-9588-5- 
17. 
Gardulf A, Bjorvell H, Gustafson R, et al: Safety of rapid subcutaneous 
gammaglobulin infusions in patients with primary antibody deficiency. 
Immunodeficiency. 1993;4:81-84. 
18. 
Gardulf A, Bjorvell H, Andersen V, et al: Lifelong treatment with gammaglobulin 
for primary antibody deficiencies: the patients' experiences of subcutaneous 
self-infusions and home therapy. J Adv Nurs. 1995;21:917-927. 
19. 
Gardulf A, Moller G, Jonsson E: A comparison of the patient-borne costs of 
therapy with gamma globulin given at the hospital or at home. Int J Technol 
Assess Health Care. 1995;11:345-353. 
20. 
Gardulf A, Hammarstrom L: Subcutaneous Administration of Immunoglobulins: 
What Are the Advantages? Clin Immunother. 1996;6:108-116. 
21. 
Hagan JB, Fasano MB, Spector S, et al: Efficacy and Safety of a New 20% 
Immunoglobulin Preparation for Subcutaneous Administration, IgPro20, in 
Patients 
with 
Primary 
Immunodeficiency. 
J 
Clin 
Immunol. 
2010. 
doi:10.1007/s10875-010-9423-4- 
22. 
Jolles S, Bernatowska E, de GJ, et al: Efficacy and safety of Hizentra® in 
patients with primary immunodeficiency after a dose-equivalent switch from 
intravenous or subcutaneous replacement therapy. Clin Immunol. 2011. 
doi:10.1016/j.clim.2011.06.002- 
23. 
Wasserman RL, Melamed I, Nelson RP, et al: Pharmacokinetics of 
Subcutaneous IgPro20 in Patients with Primary Immunodeficiency. Clin 
Pharmacokinet. 2011;50:405-414. 
24. 
Ochs HD, Gupta S, Kiessling P, et al: Safety and efficacy of self-administered 
subcutaneous immunoglobulin in patients with primary immunodeficiency 
diseases. J Clin Immunol. 2006;26:265-273. 
25. 
Guidance for Industry - Safety, Efficacy, and Pharmacokinetic Studies to 
Support Marketing of Immune Globulin Intravenous (Human) as Replacement 
Therapy for Primary Humoral Immunodeficiency. 2008. 
26. 
Goldstein B, Giroir B, Randolph A: International pediatric sepsis consensus 
conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr 
Crit Care Med. 2005;6:2-8. 


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15 APPENDICES 
Not applicable. 
 

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Statistical Analysis Plan 
Study ID 
SCGAM-06 
Study title 
Clinical phase 3 study to monitor the safety, tolerability, 
and efficacy of subcutaneous human immunoglobulin 
(CUTAQUIG) administered at modified dosing regimens 
in patients with primary immunodeficiency diseases 
Study phase 
III 
Document author 
, Octapharma
Document version 
3.0 
Supersedes 
2.0 
Effective date 
February 13, 2022 
Doc ID 
3461 
Protocol version this 
SAP is based upon 
Version 02, dated August 28, 2019
Approved by 
Name
Function, affiliation
Date and signature 
, Octapharma 
This document contains confidential and proprietary information of Octapharma. 
Copying or distribution of this document is only permitted with the written permission of Octapharma. 
Any commercial use of the information is subject to the permission of Octapharma and a license fee. 


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Document History 
Version 
Date 
Author 
Description 
Final v1.0 19-Mar-2019
New Document 
V2.0 
20-May-2021
Revision to definition of Teow to include early 
termination subjects 
v3.0 
11-Feb-2022
Additional detail added to SAP to clarify intended 
table and listing output. 
Abbreviations 
AE 
Adverse Event 
IMP 
Investigational Medicinal Product
ALAT 
Alanine Aminotransferase 
ITT 
Intention-To-Treat
ASAT 
Aspartate Aminotransferase 
IVIG 
Intravenous Immunoglobulin
BMI 
Body Mass Index 
LDH 
Lactate Dehydrogenase
CBC 
Complete Blood Count 
MedDRA 
Medical Dictionary for Regulatory Activities
CHQ-PF50 
Child Health Questionnaire - Parent Form 
NAT
Nucleic Acid Test 
CI 
Confidence Interval 
PI 
Primary Immunodeficiency 
CSR 
Clinical Study Report 
PP 
Per Protocol 
(e)CRF 
(Electronic) Case Report Form
PT 
Preferred Term 
ELISA 
Enzyme-Linked Immunosorbent Assay
QoL 
Quality of Life 
FAS 
Full Analysis Set
TEAE 
Treatment Emergent Adverse Event 
FDA 
Food and Drug Administration
TEE 
Thromboembolic Event 
GCP 
Good Clinical Practice
WBC 
White Blood Cell 
HBV 
Hepatitis B Virus 
SAF 
Safety Set 
HCV
Hepatitis C Virus 
SAP 
Statistical Analysis Plan 
HIV 
Human Immunodeficiency Virus 
SBI 
Serious Bacterial Infections 
ICH 
International Conference on Harmonisation 
SOC 
System Organ Class 
IgG 
Immunoglobulin G 


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Contents 
1. 
Preface ............................................................................................................................................. 4 
2. 
Purpose ............................................................................................................................................ 5 
3. 
Study Objectives and Endpoints ...................................................................................................... 6 
3.1. 
Study Objectives ...................................................................................................................... 6 
3.1.1. 
Primary Objectives .......................................................................................................... 6 
3.1.2. 
Secondary Objective ........................................................................................................ 6 
3.2. 
Study Endpoints (Target Variables) ......................................................................................... 6 
3.2.1. 
Primary Target Variables ................................................................................................. 6 
3.2.2. 
Secondary Target Variables ............................................................................................. 6 
3.3. 
Overall Study Design and Plan ................................................................................................. 7 
3.4. 
Selection of Study Population ................................................................................................. 8 
4. 
Sequence of Planned Analyses ........................................................................................................ 9 
4.1. 
Final Analyses and Reporting .................................................................................................. 9 
5. 
Sample Size Determination ........................................................................................................... 10 
5.1. 
Patient Replacement Policy ................................................................................................... 10 
5.2. 
Premature Termination of the Study .................................................................................... 10 
6. 
Analysis Populations ...................................................................................................................... 12 
7. 
General Issues for Statistical Analysis ........................................................................................... 13 
7.1. 
Analysis Software .................................................................................................................. 13 
7.2. 
Withdrawals .......................................................................................................................... 13 
7.3. 
Handling of Missing Data ....................................................................................................... 13 
7.4. 
Derived and Computed Variables.......................................................................................... 13 
8. 
Study Subjects and Demographics ................................................................................................ 16 
8.1. 
Disposition of Subjects and Withdrawals .............................................................................. 16 
8.2. 
Protocol Violations ................................................................................................................ 16 
8.3. 
Demographics and Other Baseline Characteristics ............................................................... 16 
8.4. 
Measurement of Treatment Compliance .............................................................................. 17 
9. 
Efficacy Analysis............................................................................................................................. 18 
10. Safety and Tolerability Analyses .................................................................................................... 19 
10.1. Adverse Events ...................................................................................................................... 19 
10.2. Infusions with One or More Temporally Associated AEs ...................................................... 20 
10.3. Clinical Laboratory Evaluations ............................................................................................. 20 
10.4. Vital Signs .............................................................................................................................. 21 
10.5. Further Safety Evaluations .................................................................................................... 21 
10.5.1. 
Physical Examination ..................................................................................................... 21 
11. Reporting Conventions .................................................................................................................. 23 
11.1. General Reporting Conventions ............................................................................................ 23 
11.2. Population Summary Conventions ........................................................................................ 23 
12. References ..................................................................................................................................... 25 
13. Tables, Listings and Figures ........................................................................................................... 26 
 


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1. Preface 
This Statistical Analysis Plan (SAP) describes the planned analysis and reporting for Octapharma 
Protocol SCGAM-06: Clinical phase 3 study to monitor the safety, tolerability, and efficacy of 
subcutaneous human immunoglobulin (CUTAQUIG) administered at modified dosing regimens in 
patients with primary immunodeficiency diseases 
This phase III study is conducted in the USA with the primary focus to monitor the safety, tolerability 
and efficacy properties of CUTAQUIG in patients when administered at a modified dosing regimens in 
patients with primary immunodeficiency diseases.  
The structure and content of this SAP provides sufficient detail to meet the requirements identified 
by the FDA and International Conference on Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical Trials1.  
The following documents were reviewed in preparation of this SAP: 
• 
Clinical Study Protocol SCGAM-06, Version 02, dated August 28, 2019 
The reader of this SAP is encouraged to also read the clinical protocol for details on the planned 
conduct of this study. Operational aspects related to collection and timing of planned clinical 
assessments are not repeated in this SAP unless relevant to the planned analyses. 
 
1 International Conference on Harmonization. (1998). Guidance on Statistical Principles. ICH Topic E9 (Statistical 
Principles for Clinical Trials) (p. 37). London: International Conference on Harmonization. 


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2. Purpose 
This SAP outlines all statistical analyses to be performed on data collected in the SCGAM-06 study, 
and the resulting output that will be compiled to support the completion of the Clinical Study Report 
(CSR). 
The planned analyses identified in this SAP will be included in regulatory submissions and/or future 
manuscripts. Exploratory analyses not necessarily identified in this SAP may be performed to support 
the clinical development program. Any post-hoc or unplanned analyses performed that are not 
identified in this SAP will be clearly identified in the respective CSR. 
The statistical output provided to the medical writer of the CSR will closely follow the ICH guideline 
for industry on topic E3 (Structure and Content of Clinical Study Reports2) to facilitate the subsequent 
compilation of the CSR. 
This statistical output will consist of tables, figures and listings, including 
• 
Tables, figures and listings used or referenced in, or appended to the CSR as detailed in the 
remainder of this SAP (section 14 of the CSR) 
o Demographic data summary figures and tables 
o Efficacy data summary figures and tables 
o Safety data summary figures and tables 
 
• 
Listings provided as appendices to the CSR 
o Patient data listings (section 16.2 of the CSR) 
o Individual patient data listings (section 16.4 of the CSR) will be covered by inclusion 
of SAS datasets into the electronic submission to the authorities 
A detailed list of all tables, figures and listings will be supplied in a separate document later when all 
feedback from authorities will be available. 
 
2 International Conference on Harmonization. (1996). Structure and Content of Clinical Study Reports. Structure 
and Content of Clinical Study Reports (Guideline for Industry) (S. 37). London: International Conference on 
Harmonization. 


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3. Study Objectives and Endpoints 
3.1. 
Study Objectives  
3.1.1. 
Primary Objectives 
The co-primary objectives of this study are to assess CUTAQUIG administered using the following 
infusion parameters: 
• 
Compare total IgG trough levels from weekly infusions to every other week infusions 
• 
Safety and tolerability when administered at increased infusion volumes at each infusion site 
• 
Safety and tolerability when administered at increased infusion flow rates at each infusion site 
• 
Safety and tolerability when administered on an every other week dosing regimen 
3.1.2. 
Secondary Objective 
The secondary objectives of this study are to: 
• 
Assess the effect of CUTAQUIG on quality-of-life (QoL) measures  
• 
Obtain further data on the safety and efficacy of CUTAQUIG 
3.2. 
Study Endpoints (Target Variables) 
3.2.1. 
Primary Target Variables 
The co-primary objectives are to compare total IgG trough levels from weekly infusions to every 
other week infusions and to assess safety and tolerability of increased infusion volumes and 
increased infusion rates at each infusion site and every other week dosing. These will be assessed 
using the following variables: 
• 
Change in individual total IgG trough levels from weekly infusions to every other week 
infusions (Cohort 3) 
• 
Occurrence of treatment-emergent AEs (TEAEs) throughout the entire Stabilization and 
Treatment Periods starting with the first infusion of IMP 
• 
Occurrence of TEAEs temporally associated with CUTAQUIG delivered during the Treatment 
Period 
• 
Occurrence of TEAEs temporally associated with CUTAQUIG delivered during the Stabilization 
Period 
• 
TEAEs by speed of infusion 
• 
Local infusion-site reactions 
• 
Laboratory parameters (hematology, clinical chemistry, urinalysis) 
3.2.2. 
Secondary Target Variables 
Secondary assessment criteria will evaluate quality of life, along with additional evaluations of 
CUTAQUIG safety and efficacy being administered according to 3 different infusion parameters. 
These will be assessed using the following variables: 
• 
QoL assessments using the Short Form Health SurveySF-36 or SF-10 
• 
Occurrence of serious bacterial infections (SBIs)  
• 
Annual rate of all infections of any kind or seriousness 
• 
Time to resolution of infections 
• 
Use of antibiotics (number of days and annual rate) 
• 
Individual profiles of IgG trough levels over time (all cohorts) 


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• 
Vital signs (blood pressure, pulse, body temperature, respiratory rate) 
3.3. 
Overall Study Design and Plan 
Study SCGAM-06 is designed as a prospective, open-label, non-controlled, 3-arm, multicenter, phase 3 
study with observation of patients receiving weekly doses of CUTAQUIG at increasing infusion volumes 
or flow rates, receiving every other week doses of CUTAQUIG at double the weekly dose, over a period 
of up to approximately 6 months. 
The study will be conducted at approximately 15 study sites in the United States of America. 
Patients who participated in the SCGAM-03 trial may be provided the opportunity to participate along 
with new patients.  
After completing the Screening Period and being assigned to 1 of 3 cohorts (as described below), 
patients will enter a 4-week Stabilization Period that will allow one to adjust and familiarize to 
CUTAQUIG.  Patients completing the SCGAM-03 study at the same time of screening for the SCGAM-
06 study will not be required to go into the Stabilization Period.  Following the Stabilization Period, 
patients will enter a 24 week Treatment Period and begin their infusion parameters according to their 
Cohort assignments:  
Cohort 1 (increased volume at each infusion site – patients will receive CUTAQUIG weekly and increase 
infusion volumes every 4 weeks): Patients will return to the clinic for the Treatment Period Baseline 
Visit, at which they will receive the same body-weight dependent (mg/kg) dose but the volume per 
site will be increased by up to 25 mL/site for patients ≥40 kg or 10 mL/site for patients <40 kg. Patients 
will receive this new volume per site for 4 weekly infusions (Treatment Period Baseline and Weeks 1, 
2, and 3), and return to the clinic at Week 4 for their next infusion at an increased volume at each 
infusion site. This cycle will continue, with infusion volumes increasing up to 25 mL/site for patients 
≥40 kg or 10 mL/site for patients <40 kg every 4th infusion until reaching a patient’s maximum dose 
(in mL), maximum tolerated volume (maximum volume based on Investigator’s decision of patient’s 
tolerance), or 100 mL at 1 injection site – whichever is lower.   
Cohort 2 (increased infusion rate - patients will receive CUTAQUIG weekly and increase infusion rates 
every 4 weeks): Patients will return to the clinic for the Treatment Period Baseline Visit, at which they 
will receive the same body-weight dependent (mg/kg) dose of CUTAQUIG but the infusion rate per site 
will be increased by up to 25 mL/hr/site for patients ≥40 kg or 10 mL/hr/site for patients <40 kg. 
Patients will receive this new flow rate for 4 weekly infusions (Treatment Period Baseline and Weeks 
1, 2, and 3), and return to the clinic at Week 4 for their next infusion at an increased infusion rate. This 
cycle will continue, with flow rates increased up to 25 mL/hr/site for patients ≥40 kg or 10 mL/hr/site 
for patients <40 every 4th infusion until reaching either a maximum flow rate (100 mL/hr/site) or 
maximum tolerated flow rate (maximum flow rate based on Investigator’s decision of patient’s 
tolerance) is reached.  
Cohort 3 (every other week dosing - patients will receive CUTAQUIG every other week at the equivalent 
of twice their weekly body-weight dependent [mg/kg] dose): Patients will return to the clinic for the 
Treatment Period Baseline visit to receive their first double mg/kg weekly dose and begin an every 
other week dosing schedule. Infusion volumes increases per site must not exceed 25 mL at the 
Treatment Period Baseline visit. If a patient’s doubling of their weekly dose requires dosing with a 
volume of more than 25 mL per injection site, then they will be required to increase the number of 
infusion sites to remain below the maximum of 25 mL/site volume increase. If this occurs, after 2 
infusions the patient may remove one of the newly introduced injection sites as long as the 25 mL/site 
increase limit is not exceeded.  
Approximately 65 patients between the ages of >2 years and <75 years are planned for enrollment 
for the study into one of the following three cohorts:  
• 
 At least 15 patients in Cohort 1 


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• 
At least 15 patients in Cohort 2 
• 
At least 35 patients in Cohort 3 
 
3.4. 
Selection of Study Population 
The study population consists of patients of both sexes who have a confirmed diagnosis of PI and 
require immunoglobulin replacement therapy due to hypogammaglobulinaemia or 
agammaglobulinaemia. All patients are established on a consistent or stable mg/kg dose of any SCIG 
treatment for a minimum of 3 months prior to Screening (Note: patients entering Cohort 3 must be 
on weekly SCIG infusions for a minimum of 12 weeks). IgG trough levels of 2 previous SCIG infusions 
are required within one year of Screening, with 1 trough level obtained within 3 months prior to 
enrollment. A trough serum IgG level ≥5.0 g/L in 2 previous infusions is required. Patients with no 
prior IgG trough level within 3 months prior to enrollment may use the Screening IgG trough level as 
their 2nd reading. 


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4. Sequence of Planned Analyses 
4.1. 
Final Analyses and Reporting 
As stated in section 3.3, each patient is treated with CUTAQUIG over a total period of approximately 
28 weeks; one to two weeks after the last infusion a follow-up visit is performed, and the patient will 
be switched to a commercially available immunoglobulin product at the discretion of the 
investigator. Once the last patient has completed the study, data validation will be completed and 
the database will be locked according to the applicable standard operating procedures. This process 
includes a data review, the identification and classification of any protocol violations as detailed in 
section 6, and thus the patient disposition with respect to the analysis populations.  
As patients exit the trial, all data will be reviewed and source data verified. Once a patient’s data is 
considered clean within the eCRF, the patient may be soft locked in order to facilitate database lock 
in the near future. 
All final, planned, analyses identified in the protocol and in this SAP will be performed only after the 
last patient has completed the study, the subject disposition has been agreed and documented, and 
the final SAP has been approved. 
Key statistics and study results will be made available to the study team following database lock and 
prior to completion of the final CSR by means of tables, figures and listings. 
Any, post-hoc, exploratory analyses completed to support planned study analyses, which were not 
identified in the final SAP, will be documented and reported in appendices to the CSR. Any results 
from these unplanned analyses will also be clearly identified in the text of the CSR. 


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5. Sample Size Determination 
Approximately 65 patients who meet eligibility criteria will be enrolled in the study: 
• 
At least 15 patients in Cohort 1 
• 
At least 15 patients in Cohort 2 
• 
At least 35 patients in Cohort 3 
The co-primary endpoints will be analyzed descriptively, and no formal sample size calculation was 
done for the overall number of patients enrolled. 
For Cohort 3 we plan for a confirmative analysis to evaluate whether the total IgG trough levels are 
maintained by an every other week dosing regimen; the following pair of hypotheses will be tested: 
Ha: Teow > Tw – 1   vs.   H0: Teow ≤ Tw - 1 
where Teow is the mean total IgG trough on steady-state dosing every other week, Tw is the same for 
weekly dosing, and a maximum decrease of 1 g/L for the mean total IgG trough level is considered 
acceptable. 
Tw will be determined after completion of the Stabilization Period, Teow at a given subject’s final study 
visit where a valid IgG trough level is collected and reported within a suitable visit window.  If a subject 
terminates from the study prior to the end of study visit (2 weeks following Week 24 infusion), or if a 
completed subject’s end of study IgG trough is not valid or not collected, then the last study visit where 
a valid IgG trough level was collected will be considered Teow . 
This one-sided hypothesis will be tested by a paired t-test at the alpha=2.5% level of significance. 
Assuming 3.0 for the standard deviation common to both members of a pair, and 0.8 as the correlation 
between members of a pair, this results in a required minimum of 31 evaluable patients to achieve a 
power of 80%. 
5.1. 
Patient Replacement Policy 
Patients withdrawn from the study for any reason will not be replaced.   
5.2. 
Premature Termination of the Study 
Both, the responsible Investigators and the Sponsor, reserve the right to terminate the study as a 
whole or center-wise at any time. Should this be necessary, the procedures will be arranged on an 
individual study basis after review and consultation by both parties. In terminating the study, the 
Sponsor and the Investigator will ensure that adequate consideration is given to the protection of the 
patients' interests. Premature termination will be notified in accordance with applicable regulatory 
requirements. Please refer to the protocol for further details on premature termination. 
 
At any time, the study as a whole will be terminated prematurely if: 
• 
New toxicological or pharmacological findings or safety reports invalidate the earlier positive 
benefit-risk assessment. 
• 
If more than independent 2 TEEs (ie, ischemic stroke, transient ischemic attack, cerebral 
infarction, cerebrovascular accident, cerebral thrombosis, embolic infarctions, [acute] 
myocardial infarction, deep vein thrombosis, pulmonary embolism, venous thrombosis 
excluding thrombophlebitis) are observed fulfilling the following criteria: 
o Assessed as probably or possibly related to CUTAQUIG treatment by Investigator 
and/or Sponsor 
o Confirmed by the IDMC  


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• 
Any other reason rendering the continuation of the study impossible for the Sponsor 
 
At any time, the study can be terminated at an individual study site if: 
• 
The site cannot comply with the requirements of the protocol 
• 
The site cannot comply with applicable standards 
• 
The site does not meet the required recruitment rate 
Should the study be prematurely terminated, all study materials, including IMP, must be returned to 
the Sponsor. 
 
 


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6. Analysis Populations 
The following populations will be considered for the statistical analysis: 
The safety analysis set (SAF) consists of all patients who received at least part of one infusion of 
CUTAQUIG. 
The full analysis set (FAS) is defined as all patients in the Safety Analysis Set who satisfy all major 
eligibility criteria and for whom any post-baseline data is available (per intention-to-treat principle). 
This set of eligible patients will be used for measurement of treatment effects. It is expected that the 
FAS will coincide with the safety set. 
The per-protocol (PP) set consists of all patients in the FAS, excluding those with substantial protocol 
deviations which may have an impact on the analysis of the co primary endpoints. This is the set of 
patients who participated in the study as intended and for whom the co primary endpoints can be 
evaluated as planned. 
Only protocol deviations with the potential to significantly affect the study results or to invalidate the 
interpretation of the data obtained will lead to exclusion of patients from the PP set. 
Efficacy endpoints will be analyzed using the FAS. Safety endpoints will be analyzed using the Safety 
Analysis Set. Selected analyses will be repeated for the PP population as detailed in the SAP and its 
appendices. 
In the event that a patient is not treated according to the dosing regimen described for his assigned 
cohort, the original cohort assignment will still be used for safety and the ITT analyses (SAF and FAS 
populations). These patients will be removed from the PP population due to protocol violations. 
 
The membership of each patient in the respective analysis populations will be determined before 
statistical analysis in a data review meeting by a panel consisting of a medical expert from the Sponsor, 
the clinical study manager, the data manager and the study statistician. Protocol deviations to be 
considered will include (but not limited to): 
• 
Violations of the study entry criteria. 
• 
Administration of any other blood or plasma-derived product or of any other 
immunoglobulin preparations during the SCGAM-06 study. 
• 
Any prohibited concomitant medication.   
• 
Failure to attend two scheduled consecutive visits OR three or more scheduled visits during 
the study for reasons other than clinical reasons. 
Any analysis might be repeated on basis of the PP analysis set if indicated by the data or in case the PP 
population differs from the FAS by 3 patients or more, to allow for an assessment of the robustness of 
the results with respect to protocol violations. 
All protocol violations documented during the conduct of the study or identified at the data review 
process prior to DB lock will be reviewed and classified as substantial or non-substantial and with 
respect to its effect on the planned analysis. Only substantial protocol violations with the potential to 
significantly affect the study results or to invalidate the interpretation of the data obtained will lead 
to exclusion of patients from the PP set.   


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7. General Issues for Statistical Analysis 
Descriptive summaries will be presented for each of the primary and secondary variables. In general, 
summaries will be completed for all patients overall and by study cohort if applicable.  
Continuous, quantitative variable summaries will in general include the number of patients with non-
missing values (N), mean, standard deviation, median, minimum and maximum, 1st and 3rd quartile. 
Categorical, qualitative variable summaries will include the frequency and percentage of patients 
who are in the particular category. In general the denominator for the percentage calculation will be 
based upon the total number of patients in the analysis population unless otherwise specified. 
7.1. 
Analysis Software 
Statistical analyses will be performed using SAS Software version 9.3 or higher. Also, PRO CoRE 2.1 
Smart Measurement® System software will be used to derive the component scores for the SF-36 
and SF-10 questionnaires. 
7.2. 
Withdrawals 
Patients who withdraw from the study prematurely will be considered in all data presentations for 
which they contribute data; in particular for the analysis of annual rates they will be considered with 
their actual observation periods. 
7.3. 
Handling of Missing Data 
In general, missing data will not be imputed: calculations pertaining to person-year computations will 
be based on observed values only. 
For missing weight measurements the last available body weight will be used for all calculations 
related to dosing; in individual patient data listings missing data will however not be replaced by 
imputed values. 
No analyses of the patterns of missing data will be done. 
For adverse events the following will be applied: 
An Adverse Event (AE) is defined as treatment-emergent, if first onset or worsening is after start of 
the first infusion of CUTAQUIG. 
If the start date and time of an AE are partially or completely missing, the AE will be assumed to be 
treatment-emergent if it cannot be definitely shown that the AE did not occur or worsen during the 
treatment emergent period (worst case approach). Missing dates and times will not be replaced. 
For medications the following will be applied: A medication will be considered prior if it starts before 
and ends before the day of first dose of study drug. A medication will be considered concomitant if it 
is taken on or after the day of first dose of study drug. A medication will be assumed to be 
concomitant if it cannot be definitely shown that the medication was not administered on or after 
the first dose of study drug. Missing dates will not be replaced. 
7.4. 
Derived and Computed Variables 
The following derived and computed variables have been initially identified as important for the 
analysis of the primary and secondary target variables. It is expected that additional variables will be 
required. The SAP will not be amended for additional variables that are not related to the primary 
target or key secondary target variables. Any additional derived or computed variables will be 


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identified and documented in the SAS programs that create the analysis files. If the SAP is not 
amended, further derivations related to primary and secondary target variables will be described in 
the CSR. 
• 
Age will be derived according to the usual definition that a person is n years old until she or 
he has completed her or his (n+1)th year of life, using the date of informed consent as the 
reference date. This is also the definition that will be applied for evaluation of the age related 
inclusion criteria  
[Unit: years] 
• 
Body Mass Index: BMI = (Body weight) / Height2 
[Unit: kg/m2] 
• 
The CUTAQUIG stabilization period is defined for patients that did not participate in the 
SCGAM-03 trial as the period between the day of first treatment with study drug to the end 
of the observation period.  This will usually be the treatment period baseline visit. 
• 
The CUTAQUIG treatment period is defined as the period between the day of first treatment 
with study drug in a modified dosing regimen to the end of the observation period. For 
patients that previously completed the SCGAM-03 trial, this is also the period of first 
treatment with the SCGAM-06 study drug.  The end of the observation period will usually be 
the termination visit. 
• 
The rate of serious bacterial infections per year during regularly repeated treatment with 
CUTAQUIG will be calculated as r = (Total number of serious bacterial infections occurring in 
the stabilization and treatment periods) / (Sum of stabilization and treatment periods)[Unit: 
1/years] 
• 
The rate of other infections will be derived using the same method 
Calculation of the confidence intervals of these rates will account for intra-patient correlation in 
incidents following a compound Poisson process model.[1]  
With Ci infections for the ith patient, and C total infections, the adjusted 2-sided 98% CI is 
calculated by:  
[𝑒
ln(𝑟)−2.33∙√∑𝐶𝑖
2
𝐶2 ; 𝑒
ln(𝑟)+2.33∙√∑𝐶𝑖
2
𝐶2 ] 
If there are 0 infections, an alternative method will be used to approximate the upper bound 
on the 98% confidence interval using a chi-square distribution and the following SAS code: 
 
data poisson; 
  events=0; 
  sumyrs=xxx; 
  ul=cinv(0.99,2*(events+1))/2; 
  rate=events/sumyrs; 
  ulinc=ul/sumyrs; 
run; 
where  
sumyrs = duration of treatment in years 
events = total number of events 


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rate = total number of events per person-year 
ulinc = two-sided 98% CI - upper limit 
 
• 
The rate of infusions with one or more temporally associated AEs will be calculated for each 
patient as r = (Number of infusions with one or more temporally associated AEs) / (Number 
of infusions started). An AE is defined as a temporally associated if, and only if, the onset (or 
worsening) is either during an infusion of study medication or within 72 hours of the end of 
the infusion. 
[Unit: N/A] 
 


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8. Study Subjects and Demographics 
8.1. 
Disposition of Subjects and Withdrawals 
All patients enrolled in the study will be accounted for. Descriptive summaries of population data will 
be provided overall and by study cohort; these will include 
• 
The frequency and percent of patients in each analysis population, age strata (pediatric and 
adult) and enrollment group  
• 
The disposition of patients (including number of patients enrolled, number of patients 
treated, number of completers) 
• 
study withdrawals by reason of withdrawal 
8.2. 
Protocol Violations 
Protocol violations will be checked on complete data for all patients prior to defining the analysis 
populations. 
The final decision regarding inclusion/exclusion of patients from the analysis sets will be taken based 
on protocol adherence reports during data review meetings before database lock, data release and 
final analysis applying the definitions in section 6. 
Major protocol violations as well as all violations leading to exclusion from the PP population will be 
summarized by type of violation. Individual patients with these protocol violations will be listed. 
8.3. 
Demographics and Other Baseline Characteristics 
Descriptive summaries of the demographic and other baseline characteristics will be completed for 
the populations specified below, overall and by study cohort as applicable; these include: 
• 
Demographics (Age, Gender, Race/Ethnicity, Height, Weight, BMI (calculated), ABO blood 
type, primary immunodeficiency disease type) 
(SAF, FAS, PP) 
• 
Medical History (SAF) 
Medical history will be coded with the Medical Dictionary for Regulatory Activities (MedDRA, 
according to the version specified in the Data Management Plan). Incidences of findings in 
medical history will be summarized by MedDRA system organ class (SOC) and preferred term 
(PT)  
• 
Prior and Concomitant Medications (SAF) 
Prior medications will be presented by non-SCIG product and SCIG product. Concomitant 
medications will be presented by pre-medication and non-pre-medication. A medication will 
be considered a pre-medication if it is given prior to an infusion to prevent one or more 
previously experienced infusion-related symptoms. 
Medications will be coded using the WHO Drug Dictionary (according to the version specified 
in the Data Management Plan). Incidences of prior and concomitant medications will be 
summarized by ATC level 2 and ATC level 4 
• 
Baseline Physical Examination, including vital signs (SAF) at Screening, Stabilization Period 
Baseline (Week 0), and Treatment Period Baseline 


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8.4. 
Measurement of Treatment Compliance 
The following parameters will be listed and summarized per patient and/or per infusion: 
• 
Body weight 
• 
Actual dose (total and per kg body weight, based on the latest available weight 
measurement) 
• 
Total dose of CUTAQUIG administered 
• 
Total number of infusions administered 
• 
Total volume of solution administered 
• 
Infusion times 
• 
Overall amount of product administered (only included in data listings) 
• 
Maximal volume administered (in total and per kg body weight) 
• 
Injection sites 
• 
Injection flow rates 
Deviations from the planned treatment schedule will be examined by summarizing the number of 
patients with infusions, and the number of infusions, that deviate from the scheduled intervals by 
more than 2 days, and by listing all cases with more than two days deviation individually. The number 
of patients with infusions, and the number of infusions with an incorrect dose administered will also 
be summarized. 
Study drug exposure will be summarized by planned volume (mL), volume infused (mL), CUTAQUIG 
dose administered (mg), and CUTAQUIG dose administered by baseline body weight (mg/kg). 


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9. Efficacy Analysis 
The rate of SBI per person-year (bacterial pneumonia, bacteremia/sepsis, osteomyelitis/septic 
arthritis, visceral abscess, bacterial meningitis) during treatment with CUTAQUIG will be summarized 
descriptively and a two-sided 98% CI will be presented. Calculation of this CI will account for intra-
patient correlation in incidents following a compound Poisson process model. This analysis will also 
include summaries of the number of patients with any SBI, the number of SBIs, and the duration of 
treatment (annualized). Furthermore, all observed SBIs will be listed individually and in full detail. 
Infections will be analyzed in the same manner as SBIs, except the analysis will be presented by 
Stabilization Group and Treatment Group separately. Further, the duration of infection will be 
summarized  by severity. The individual characteristics of each infection, including the time to 
resolution will be listed. 
The use of antibiotics will be summarized descriptively and reported as a detailed list of all such 
medications, and the number of patients treated with antibiotics, the number of treatment episodes 
and the number of treatment days will be tabulated. Similarly, systemic antibiotic usage will be 
presented where antibiotics with the following routes will be excluded: SC, SUBL, OCUL, OTIC, RECT, 
TOP, BUC, NASAL, TDERM, TOP OD, TOP OS, or TOP OU.   
The QoL SF-10 and SF-36 data will be presented descriptively by summarizing derived component 
scores from PRO CoRE 2.1 Smart Measurement® System software. Observed andchange from baseline 
(defined as the Treatment Period Baseline Visit) data will be summarized by visit for the following 
derived component scores: 
SF-10- Physical Summary Score and Psychosocial Summary Score; 
SF-36- Physical Functioning 0-100 and Norm-based Score, Role Physical 0-100 and Norm-based Score, 
Bodily Pain 0-100 and Norm-based Score, General Health 0-100 and Norm-based Score, Vitality 0-100 
and Norm-based Score, Social Functioning 0-100 and Norm-based Score, Role Emotional 0-100 and 
Norm-based Score, Mental Heath 0-100 and Norm-based Score, Physical Component Score, and 
Mental Component Score. 
The derived scores and the responses from the SF-10 and SF-36 survey questions will be presented in 
the listings. 
Total serum IgG trough levels will be summarized for observed and change from baseline during the 
Treatment Period for Cohort 1, 2, and 3. 
For Cohort 3, the change in total IgG trough levels when switching from weekly to every other week 
infusions will be tested confirmatory by means of a one-sided, paired t-test at the α=0.025 level of 
significance. The following pair of hypotheses will be tested: 
Ha: Teow > Tw – 1   vs.   H0: Teow ≤ Tw - 1 
where Teow is the mean total IgG trough on steady-state dosing every other week, Tw is the same for 
weekly dosing, and a maximum decrease of 1 g/L for the mean total IgG trough level is considered 
acceptable. 
Tw will be determined after completion of the Stabilization Period, Teow at a given subject’s final study 
visit where an IgG trough level is collected and reported within a suitable visit window.  If a subject 
terminates from the study prior to the end of study visit (2 weeks following Week 24 infusion), then 
the last study visit where a valid IgG trough level was collected will be considered Teow . 
 


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10. 
Safety and Tolerability Analyses 
The safety analysis will comprise descriptive statistics, tabulations and listings of all TEAEs, safety 
laboratory results, vital signs and physical examination findings. 
10.1. 
Adverse Events 
All reported AEs will be coded according to MedDRA. 
An AE is defined as treatment-emergent, if first onset or worsening is after start of the first infusion of 
CUTAQUIG. Only treatment-emergent AEs (TEAEs) are accounted for in the analysis. 
For each TEAE, the time relative to the start of the infusion will be calculated and the TEAE will be 
classified as temporally associated if the onset is during the infusion or within 72 hours after the end 
of the infusion. 
All reported events will be listed and tabulated in full detail; in particular the following key statistics 
will be presented in a summary table: 
• 
Total number of TEAEs reported. 
Number of patients with 
• 
Any TEAE 
• 
Any drug related TEAE 
• 
 Any TEAE 
• 
 Any Drug Related TEAE 
• 
 Any Temporally Associated TEAE during Stabilization Period 
• 
 Any Temporally Associated TEAE during Treatment Period 
• 
 Any Local Site Reaction 
• 
 Any Severe TEAE 
• 
 Any Serious AE 
• 
 Product Withdrawn due to TEAE 
• 
 Study Discontinuation due to TEAE 
• 
 AE Outcome of Death 
Also, the follow TEAE tabulations of patient incidence will be presented: 
• 
Temporally associated treatment-emergent adverse events during stabilization period by 
system organ class and preferred term 
• 
Temporally associated treatment-emergent adverse events during treatment period by 
system organ class and preferred term 
• 
Local site reaction treatment-emergent adverse events by system organ class and preferred 
term 
• 
Treatment-emergent adverse events excluding local site reactions by system organ class and 
preferred term 
• 
Serious treatment-emergent adverse events by system organ class and preferred term 
• 
Serious treatment-emergent adverse events leading to study discontinuation by system 
organ class and preferred term 
• 
Non-serious treatment-emergent adverse events by system organ class and preferred term 
• 
Treatment-emergent adverse events leading to product withdrawal by system organ class 
and preferred term 


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• 
Treatment-emergent adverse events leading to early study discontinuation by system organ 
class and preferred term 
• 
Treatment-emergent adverse events by highest relationship to treatment by system organ 
class and preferred term 
• 
Treatment-emergent adverse events by maximum severity by system organ class and 
preferred term 
• 
Infusion total flow rate and temporally associated treatment-emergent adverse events 
• 
Infusion total flow rate associated with temporally related treatment-emergent adverse 
events- non-local site reactions 
• 
Infusion total flow rate associated with temporally related treatment-emergent adverse 
events- local site reactions only 
• 
Infusion total flow rate/number of lines associated with temporally related treatment-
emergent adverse events- local site reactions only 
• 
Percentage of infusions with one or more temporally associated TEAE 
The following table listings of interest will be presented: 
• 
Table listing of serious treatment-emergent adverse events 
• 
Table listing of related treatment-emergent adverse events 
• 
Table listing of related serious treatment-emergent adverse events 
• 
Table listing of treatment-emergent adverse events leading to death 
• 
Table listing of treatment emergent adverse events leading to study drug discontinuation 
• 
Table listing of treatment-emergent adverse events leading to study discontinuation 
• 
Table listing of local site reactions 
• 
Table listing of treatment-emergent incidences of fever safety 
Further, all AE data collected, including the infusion rate at onset of TEAE will be presented in by-
patient listings. 
Narratives will be prepared describing each death, other SAEs, and other significant AEs that are 
judged to be of special interest because of clinical importance 
10.2. 
Infusions with One or More Temporally Associated AEs 
The number of infusions with at least one temporally associated adverse event (including AEs judged 
not to be related to CUTAQUIG by the investigator) over the total number of infusions will be 
calculated for each patient, and the ratio will be presented, including the associated upper one-sided 
95% confidence limit. The calculation of this confidence interval will take into account the observed 
intra-patient correlation - this is necessary because each patient may experience more than one 
infusion with an associated AE; it can therefore not be assumed that the observed events are 
statistically independent. 
10.3. 
Clinical Laboratory Evaluations 
The following laboratory tests will be performed during the course of the study to investigate the 
safety and tolerability of CUTAQUIG; for the timing of these lab panels and tests please refer to 
section 7.3.4 (Laboratory Tests) of the protocol: 
• 
Standard hematology 
o Complete blood count [CBC] 


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o WBC differential 
o Hematocrit 
o Hemoglobin 
• 
Clinical chemistry 
o Sodium 
o Potassium 
o Glucose 
o Alanine aminotransferase [ALAT] 
o Aspartate aminotransferase [AST] 
o Lactate dehydrogenase [LDH] 
o Total bilirubin 
o Blood urea nitrogen or blood urea creatinine 
• 
Urinalysis 
o pH 
o Glucose 
o Ketones 
o Leukocytes 
o Hemoglobin 
o Urine pregnancy test (women of childbearing potential) 
All laboratory assessments will be done at the local laboratories according to the site’s standard 
procedures. 
Total serum IgG trough levels will be determined by central laboratories.  
All laboratory data will be converted to standard units during the Data Management process. The 
laboratory data will be listed with suitable flags indicating abnormal values (L=Lower than reference 
range, H=Higher than reference range). 
Summary statistics for the laboratory values as well as their changes from baseline at each time will 
be tabulated for all laboratory parameters. 
10.4. 
Vital Signs 
To evaluate short-term tolerance, monitoring of vital signs including blood pressure, body 
temperature, pulse and respiratory rate will be performed at visits taking place at the clinic/study site 
according to the flow chart of assessments provided in study outline. 
Measurements will be carried out before the infusion of IMP. 
Vital signs parameters will be summarized by visit and measurement time, using the standard set of 
summary statistics for both absolute values and changes from baseline, where the baseline value is 
the pre-infusion measurement. 
10.5. 
Further Safety Evaluations 
10.5.1. 
Physical Examination 
A general physical examination will be performed at the Screening Visit according to routine 
procedures and will be as comprehensive as necessary to detect relevant abnormalities. If any findings 
are abnormal, the Investigator will document the start date and whether or not the abnormal finding 
is still present at the start of treatment. The physical examination will be repeated at subsequent study 


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visits (at 12 week intervals), and finally at the Termination Visit (irrespective of whether termination is 
regular or premature). Clinically relevant worsening from the status at screening will be documented 
as an AE. Summary counts of patients with clinically significant abnormalities will be presented by visit. 
 
 


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11. 
Reporting Conventions 
The following reporting conventions will be adopted for the presentation of study data. These 
conventions will enhance the review process and help to standardize presentation with common 
notations. 
11.1. 
General Reporting Conventions 
• 
All tables and data listings will be developed in landscape orientation, unless presented as 
part of the text in a CSR. 
• 
Figures will in general also be presented in landscape orientation, unless presented as part of 
the text in a CSR. Exceptions are the Trellis plots that will be presented in portrait 
orientation. 
• 
Legends will be used for all figures with more than one variable or item displayed. 
• 
Figures will be in black and white, unless color figures have been identified as useful for 
discriminating presentation in the figure. Lines in figures should be wide enough to view the 
line after being photocopied. 
• 
Specialized text styles, such as bolding, italics, borders, shading, superscripted and 
subscripted text will not be used in tables, figures and data listings unless they add significant 
value to the table, figure, or data listing. 
• 
Only standard keyboard characters should be used in tables and data listings. Special 
characters, such as non-printable control characters, printer specific, or font specific 
characters, will not be used on a table, figure, or data listing. Hexadecimal character 
representations are allowed (e.g., μ, α, β). 
• 
The ICH numbering convention is to be used for all tables, figures and data listings. 
• 
All footnotes will be left justified and placed at the bottom of a page. Footnotes must be 
present on the page where they are first referenced. Footnotes should be used sparingly and 
must add value to the table, figure, or data listing. If more than four footnote lines are 
planned then a cover page may be used to display footnotes. 
• 
Missing values for both numeric and character variables will be presented as blanks in a table 
or data listing. A zero (0) may be used if appropriate to identify when the frequency of a 
variable is not observed. 
• 
All date values will be presented as DDMMMYYYY (e.g., 29AUG2001) format. 
• 
All observed time values will be presented using a 24-hour clock HH:MM format (e.g. 15:26). 
• 
Time durations will be reported in HH:MM notation. The use of decimal notation to present 
(display) time durations should be avoided (e.g. 0.083h = 5min) unless it is necessary to show 
the computation of time differences in a table, figure, or data listing, in which case both 
notations may be used to display the time duration. 
• 
All tables, figures and data listings will have the name of the program, and a date stamp on 
the bottom of each output. 
11.2. 
Population Summary Conventions 
• 
Population(s) represented on the tables or data listings will be clearly identified in the title as 
“Population: <name of population>” where <name of population> is any of the analysis 
population names or abbreviations defined in section 6 (safety analysis set (SAF), full analysis 
set (FAS or ITT), per-protocol set (PP). 


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• 
Sub-population(s) or special population(s) descriptions will provide sufficient detail to ensure 
comprehension of the population (e.g., ITT Females, Per-Protocol Males >60 years of age) 
used for analysis in a table or figure. 
• 
Population sizes may be presented for each treatment or dosing category as totals in the 
column header as (N=xxx), where appropriate. 
• 
Population sizes shown with summary statistics are the samples sizes (n) of patients with 
non-missing values. 
• 
All population summaries for continuous variables will include: N, mean, SD, median, Q1, Q3, 
minimum and maximum. 
• 
All percentages are rounded and reported to a single decimal point (xx.x%). 
 


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12. 
References 
[1]  Kegler SR (2007) Applying the compound Poisson process model to the reporting of injury-
related mortality rates. Epidemiologic Perspectives & Innovations 2007, 4:1 
 


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13. 
 Tables, Listings and Figures 
To be supplied in a separate document later when all feedback from authorities will be available.