An Open-label, Multi-center Study to Evaluate the Safety and Pharmacokinetics of IGSC 20% Administered for 6 Months in Subjects With Primary Immunodeficiency
Phase: PHASE3
Conditions: Primary Immunodeficiency
Sponsor: Grifols Therapeutics LLC

Protocol GTI1502 - Amendment 2 
15 Mar2016 
Clinical Study Protocol 
Protocol Title: 
Investigational Products: 
Sponsor's Name and Address: 
Sponsor's Telephone Number: 
Study Number/Protocol Version 
Number/Date: 
IND Number: 
Development Phase: 
An open-label, multi-center study to evaluate the 
safety and phannacokinetics of IGSC 20% 
administered for 6 months in subjects with 
primary immunodeficiency 
IGSC20% 
Immune Globulin Subcutaneous (Human), 20% 
Caprylate/Chromatography Purified 
Grifols Therapeutics Inc. 
79 TW Alexander Drive 
Research Triangle Park, NC 27709 
 
 
GTl1502Nersion 3.0/15 Mar 2016 
Includes GTl1502Nersion 2.0/20 Aug 2015 and 
GTI1502Nersion 1.0/16 Jun 2015 
16528 
3 
The undersigned confirm that they agree to conduct the study under the conditions 
described in this protocol: 
Medical Monitor:
 
Confidentiality 
Statement: 
COJ\l"FIDENTIAL 
o IC, 
The following confidential information is the property ofGrifols Therapeutics Inc. 
As long as the information contained in this protocol has not been published, it may 
only be used after permission has been obtained from Grifols Therapeutics Inc. It is 
not possible to make reproductions of all or sections of this protocol. Commercial 
use of the information is only possible with the permission of the proprietor and is 
subject to a license fee. 
Page 1 of94 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 2 of 94
Summary of Changes for Amendment 2
Protocol Version
Date of Approval
3.0
Amendment 1 + Integrated Protocol
15 Mar 2016
2.0
Amendment 1 + Integrated Protocol
20 Aug 2015
1.0
Original
16 Jun 2015
Protocol Amendment 2
The protocol for GTI1502 (Version 2.0, dated 20 Aug 2015) has been amended and reissued 
as Protocol Amendment 2, Version 3.0, dated 15 Mar 2016.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 3 of 94
SUMMARY OF CHANGES FOR AMENDMENT 2
Sections
Change From:
(Strikethrough is added to highlight deleted text)
Change To:
(Underline is added to highlight new text)
Rationale:
Global change
Approximately 50 subjects will be enrolled in order to 
have approximately 30 adult subjects and 12 to 15
pediatric subjects (age 2-16 years) completing treatment 
with subcutaneously administered IGSC 20%.  
Approximately 50 subjects will be enrolled in order to 
have approximately 30 adult subjects and 12 to 18
pediatric subjects (age 2-16 years) completing treatment 
with subcutaneously administered IGSC 20%.  
For internal 
consistency.
Global change
Screening Phase: 7 to 28 days 
Screening Phase: up to 28 days 
To clarify that a
minimum 
Screening duration 
is not required.
Protocol 
Synopsis, 
Sections 3.3.2.3,
3.5.4, 3.6.2.4,
and 4.3.1
local infusion site reactions 
infusion site reactions
To provide 
clarification.
Protocol 
Synopsis: 
Inclusion 
Criteria
Section 3.2.1
3. The subject has not had an SBI within the last 3 
months prior to Screening.
4. Currently on IgG replacement therapy (via IV or SC 
infusion) for ≥3 consecutive months. Subjects 
receiving IVIG prior to study must receive a dosage 
of 300 to 800 mg/kg per infusion. 
5. Documented (at least once within previous 3 months) 
IgG trough level of ≥500 mg/dL on current IgG 
replacement therapy regimen.
6. Screening trough IgG levels must be ≥500 mg/dL.
Note: If Screening trough levels are not above this 
threshold, the subjects will be a Screen Failure, but 
may be re-screened following dose adjustment of their 
original IgG replacement therapy regimen and 
maintaining stable dosing for a period of at least 3 
consecutive months prior to Screening a second time.
3. The subject has not had an SBI within the last 3 
months prior to or during Screening.
4. Currently on IgG replacement therapy (via IV or SC 
infusion) for ≥3 months. 
5. Note: This inclusion criterion is removed in protocol 
amendment 2.  
6. Screening trough IgG levels must be ≥500 mg/dL.
Note: If Screening trough levels are not above this 
threshold, the subjects will be a Screen Failure, but 
may be re-screened following dose adjustment of 
their original IgG replacement therapy regimen and 
maintaining stable dosing for a period of at least 3 
months prior to Screening a second time.
(4) IVIG dose 
inclusion 
stipulation 
removed due to 
Run-in Phase
which adjusts to 
the required dose 
range. 
(5) Historical IgG 
trough criterion 
removed since not 
evaluated 
frequently in 
medical practice.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 4 of 94
Sections
Change From:
(Strikethrough is added to highlight deleted text)
Change To:
(Underline is added to highlight new text)
Rationale:
Protocol 
Synopsis: 
Exclusion 
Criteria
Section 3.2.2
7. The subject has significant proteinuria (dipstick 
proteinuria ≥3+ or known urinary protein loss         
>1-2 g/24 h or nephrotic syndrome) and/or has a 
history of acute renal failure and/or severe renal 
impairment (blood urea nitrogen [BUN] or creatinine 
more than 2.5 times the upper limit of normal [ULN]) 
and/or on dialysis
18.The subject has participated in another clinical trial 
within 30 days prior to Screening (observational 
studies without investigative treatments [non-
interventional] are permitted) or has received any 
investigational blood product within the previous 3 
months
20.Mentally challenged subjects who cannot give 
independent informed consent 
7. The subject has significant proteinuria (dipstick 
proteinuria ≥3+ or known urinary protein loss
>1 g/24 h or nephrotic syndrome) and/or has a history 
of acute renal failure and/or severe renal impairment 
(blood urea nitrogen [BUN] or creatinine more than 
2.5 times the upper limit of normal [ULN]) and/or on 
dialysis
18.The subject has participated in another clinical trial 
within 30 days prior to Screening (observational 
studies without investigative treatments [non-
interventional] are permitted) or has received any 
investigational blood product with the exception of 
other IgG products within the previous 3 months
20.Mentally challenged subjects who cannot give 
independent informed consent or assent
(7, 20) To further 
clarify other 
exclusions 
(18) To allow 
patients on 
previous 
investigational IgG 
studies to 
participate without 
a 3 month 
minimum time 
stipulation to avoid
potential treatment 
hiatus. 
Protocol 
Synopsis: 
Determination 
of Sample Size
Section 5.2
…Also a sample size of 42 to 45 with at least 24 
scheduled administrations of IGSC 20% would provide 
the clinical experience data on a total of more than 1008 
to 1080 IGSC 20% dosing administrations for safety 
assessment.
The planned enrollment of 42 subjects should be more 
than adequate to establish that the AUC for total IgG for 
IGSC 20% is non-inferior to that achieved by IGIV-C 
10%.
…Also a sample size of 42 to 48 with at least 24 
scheduled administrations of IGSC 20% would provide 
the clinical experience data on a total of more than 1008 
to 1080 IGSC 20% dosing administrations for safety 
assessment.
The planned minimum enrollment of 42 completing
subjects should be more than adequate to establish that 
the AUC for total IgG for IGSC 20% is non-inferior to 
that achieved by IGIV-C 10%.
To provide 
clarification for the 
requirements for 
number of subjects
Section 3.1.2 
Run-In Phase
Group 2 - Three (3)-month Run-In Phase:
Those subjects who prior to screening are receiving IVIG 
therapy (at a dose between 300 and 800 mg/kg per 
infusion every 3 or 4 weeks) but who are not receiving 
IGIV-C 10% specifically (ie, a different commercially 
available IVIG) will be required to receive IGIV-C 10% 
intravenously (at an equivalent dose and dosing interval 
as in their previous IVIG therapy) for a total duration of a 
3-month Run-In Phase.
Group 2 - Three (3)-month Run-In Phase:
Those subjects who prior to screening are receiving IVIG 
therapy (at a dose between 300 and 800 mg/kg per 
infusion every 3 or 4 weeks) but who are not receiving 
IGIV-C 10% specifically (ie, a different commercially 
available IVIG) will be required to receive IGIV-C 10% 
intravenously (at an equivalent dose and dosing interval 
as in their previous IVIG therapy) for a total duration of a 
3-month Run-In Phase. Subjects receiving infusions 
To add  
clarification

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 5 of 94
Sections
Change From:
(Strikethrough is added to highlight deleted text)
Change To:
(Underline is added to highlight new text)
Rationale:
Group 3 - Four (4)-month Run-In Phase:
Subjects meeting any of the criteria for Groups 2 and 3 
will be scheduled to begin receiving IGIV-C 10% 
intravenously at a dose of 300 to 800 mg/kg every 3 to 4 
weeks (dose and interval to be determined based on the 
investigator’s clinical judgment) for a period of up to 4 
months prior to the IV#1 visit. The number of visits (up 
to 5) during the Run-In Phase will be determined based 
on each subject’s previous IgG treatment regimen.
every 3 weeks will have 4 Run-In visits and subjects 
receiving infusions every 4 weeks will have 3 Run-In 
visits.
Group 3 - Four (4)-month Run-In Phase:
Subjects meeting any of the criteria for Group 3 will be 
scheduled to begin receiving IGIV-C 10% intravenously 
at a dose of 300 to 800 mg/kg every 3 to 4 weeks (dose 
and interval to be determined based on the investigator’s 
clinical judgment) for a period of up to 4 months prior to 
the IV#1 visit. Subjects receiving infusions every 3 
weeks will have 5 Run-In visits and subjects receiving 
infusions every 4 weeks will have 4 Run-In visits. 
Section 3.3.1.4
IGSC 20% and IGIV-C 10% must be stored at 
temperatures of 2°C to 8°C (36°F to 46°F) and protected 
from light. Do not freeze. Investigators, or designees, are 
responsible for maintaining storage temperature records 
and for immediately reporting deviations in temperature 
to the study monitor.
IGSC 20% and IGIV-C 10% must be stored at 
temperatures of 2°C to 8°C (36°F to 46°F) and protected 
from light. Do not freeze or partially freeze. 
Investigators, or designees, are responsible for 
maintaining storage temperature records and for 
immediately reporting deviations in temperature to the 
study monitor.
Wording to be 
consistent with the 
Pharmacy manual
Section 3.3.2.2
The IV and SC dose of study drug will be individualized 
based on each subject’s current IgG regimen which is 
assumed to be an effective dose. Subjects are required to 
have been clinically stable for at least 3 months on this 
pre-determined dose (between 300-800 mg/kg 
administered every 3 or 4 weeks) of an approved IgG 
product. The IV IGIV-C 10% dose will be the same as 
this established dose and dosing interval.  For those 
subjects currently on SCIG, the initial IV IGIV-C 10% 
dose should be between 300 and 800 mg/kg in 
conjunction with investigator judgment. 
The IV and SC dose of study drug will be individualized 
based on each subject’s current IgG regimen which is 
assumed to be an effective dose. Subjects are required to 
have been clinically stable for at least 3 months on an 
IgG product. The IV IGIV-C 10% dose will be between 
300 and 800 mg/kg during the Run-in phase and IV#1 
and IV# 2.  See Table 3-1.
For internal 
consistency and 
simplicity
Section 3.3.2.3
Details regarding infusion rate and infusion 
administration are located in the pharmacy/study manual. 
Subjects may use the same anatomical area or rotate 
Details regarding infusion rate and infusion 
administration are located in the pharmacy/study manual. 
Subjects may use the same anatomical area or rotate 
Corrects 
inconsistency since 
there is allowance 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 6 of 94
Sections
Change From:
(Strikethrough is added to highlight deleted text)
Change To:
(Underline is added to highlight new text)
Rationale:
anatomical areas for SC infusions throughout the study. 
No more than 8 infusion sites per infusion will be used. 
The minimum distance between infusion sites is 
recommended to be no less than 2 inches. The maximum
target infusion rate will be no greater than 25 
mL/hour/site as tolerated by the subject and per the 
Investigator’s discretion; the Investigator will tailor the 
infusion configuration for each subject.
anatomical areas for SC infusions throughout the study. 
No more than 8 infusion sites per infusion will be used. 
The minimum distance between infusion sites is 
recommended to be no less than 2 inches. The target 
infusion rate will be no greater than 25 mL/hour/site as 
tolerated by the subject and per the Investigator’s 
discretion; the Investigator will tailor the infusion 
configuration for each subject.
to increase the 
infusion rate. 
Section 3.3.3.1
Within each study site, subjects in the study will receive 
a consecutive subject number at Screening Visit. Subject 
numbers are generated beginning with the study center 
number (3 digits, assigned by the Sponsor starting at 
100) followed consecutively with a unique number for 
each subject (4 digits, including leading zeros). For 
example, if the Investigator’s center number is 301, 
subject numbers will be 3010001, 3010002, 3010003, 
etc., in consecutive order. Subject numbers, once 
assigned, will not be reused at any center.
Within each study site, subjects in the study will receive 
a consecutive subject number at Screening Visit. Subject 
numbers are generated beginning with the study center 
number (3 digits, assigned by the Sponsor starting at 
100) followed consecutively with a unique number for 
each subject (4 digits). For example, if the Investigator’s 
center number is 301, subject numbers will be 3012001, 
3012002, 3012003, etc., in consecutive order. Subject 
numbers, once assigned, will not be reused at any center.
To reflect the 
actual numbering 
convention used.
Section 3.3.4
All dose calculations will be done by the study clinic 
personnel and the dose preparation procedures will be 
provided to each subject for in-home SC administration.
All dose calculations will be done by the Interactive Web 
Response (IWR) system and the dose preparation 
procedures will be provided to each subject for in-home 
SC administration.
To reflect the 
actual system used.
Section 3.4
Concomitant medications must be recorded in the 
subject’s source documents and in the eCRF, including 
the trade or generic names of the medication, the dose, 
the route of administration, duration, and frequency.
Concomitant medications must be recorded in the 
subject’s source documents and in the eCRF from time of 
consent, including the trade or generic names of the 
medication, the dose, the route of administration, 
duration, and frequency.
To specify the 
starting time for 
concomitant 
medications
recording
Section 3.4.2
Use of the following during the study (from Screening to 
SC Week#25 Final Visit) is prohibited:
• Any IgG replacement therapy other than IGIV-C 10% 
or IGSC 20% provided in this study 
Use of the following during the study (from Screening to 
SC Week#25 Final Visit) is prohibited:
• Any IgG replacement therapy other than IGIV-C 10% 
or IGSC 20% provided in this study once the first dose 
of study treatment is administered
To specify the 
starting point for 
the prohibition of 
any non-study  IgG 
replacement 
therapy

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 7 of 94
Sections
Change From:
(Strikethrough is added to highlight deleted text)
Change To:
(Underline is added to highlight new text)
Rationale:
Section 3.4.3
The medications listed below are not allowed during the 
study as premedication to an infusion; however these 
medications are allowed during the study for general use 
(eg, to treat an AE):
The medications listed below are not allowed during the 
study as premedication to an SC infusion; however these 
medications are allowed during the study for general use 
(eg, to treat an AE):
To provide 
clarification
Section 3.6.2
The following sections describe the 
procedures/assessments to take place at each study visit. 
See the Schedule of Study Procedures table in Appendix 1
for a summary of study visits and the procedures to be 
conducted at each visit. For all visits, a ± 1 day window is 
allowed, with the exception of the serial PK sampling 
visits, and the SC#2 and SC#3 visits which must be 
performed with a +1 day visit window (ie, these 2 visits 
cannot be performed 1 day early). Unscheduled visits may 
be conducted if deemed necessary for the purpose of 
subject safety.
The following sections describe the 
procedures/assessments to take place at each study visit. 
See the Schedule of Study Procedures table in Appendix 1
for a summary of study visits and the procedures to be 
conducted at each visit. For most clinic visits, a ± 1 day 
window is allowed. For the serial PK sampling visits, see 
specific PK windows in Section 3.6.2.3 and 3.6.2.4.  If 
there are logistical issues requiring schedule adjustment 
for weekly subcutaneous IGSC 20% administration, SC#1 
may be scheduled 6 to 9 days after IV#2.  The SC#2 and 
SC#3 visits must be performed with a +1 day visit 
window (ie, these 2 visits cannot be performed 1 day 
early). Unscheduled visits may be conducted if deemed 
necessary for the purpose of subject safety.
To clarify the 
timing of visit 
windows.
Section 3.6.2.1
The subject’s medical records will be reviewed to 
confirm a documented diagnosis of PI. Subjects who are 
interested in participating will undergo the following 
tests and procedures:
• Written informed consent and assent if applicable will 
be obtained prior to initiation of any screening 
procedures
• Eligibility will be checked by careful assessment of the 
inclusion and exclusion criteria
• Demographics and medical history will be recorded 
including age, gender, age at diagnosis of PI, 
previous /current IgG treatments. 
The subject’s medical records will be reviewed to 
confirm a documented diagnosis of PI. Subjects who are 
interested in participating will undergo the following 
tests and procedures:
• Written informed consent and assent if applicable will 
be obtained prior to initiation of any screening 
procedures
• Eligibility will be checked by careful assessment of the 
inclusion and exclusion criteria
• Demographics and medical history will be recorded 
including age, gender, age at diagnosis of PI, and past 
12 months of previous /current IgG treatments. Record 
relevant medical history defined as any history 
impactful on the subject’s condition in terms of current 
functioning, disability, treatment, or management.
To clarify 
requirements for 
medical history 
documentation and 
chest X-ray 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 8 of 94
Sections
Change From:
(Strikethrough is added to highlight deleted text)
Change To:
(Underline is added to highlight new text)
Rationale:
• Chest X-ray (if chest X-ray or CT have not been 
performed within past 6 months prior to screening)
• Total IgG trough level determination: participants will 
be required to have a documented total IgG level of 
≥500 mg/dL to enroll
• Chest X-ray (if chest X-ray or CT have not been 
performed within past 6 months prior to screening) 
Note: at least one radiographic view (anterior-posterior 
[AP] or posterior- anterior [PA] is required.)
• Total IgG trough level determination: participants will 
be required to have a screening total IgG level of ≥500 
mg/dL to enroll
Section 3.6.2.3
IV#1 VISIT & 
PK 
ASSESSMENT 
FOR IV 
DOSING
• Predose urine pregnancy test
• Predose urine pregnancy test (child-bearing  potential 
females only)
To clarify the 
pregnancy test is 
for women of 
child-bearing 
potential
Section 3.6.2.4
SC Week #1 
Clinical Visit
Appendix 1 
footnote m
• Predose virus safety retain samples
Note: For children at the discretion of the Investigator, 
virus safety retain samples may be drawn the day prior 
to SC Week#1 instead of combining with other blood 
draws on a single day.
• Predose virus safety retain samples
Note: For children at the discretion of the Investigator, 
virus safety retain samples may be drawn 1 or 2 days
prior to SC Week#1 instead of combining with other 
blood draws on a single day
To clarify the 
window for virus 
safety retain 
samples
Section 3.6.2.4
Section 3.6.2.5
b.  ……Or any single alarm symptom such as 
hemoptysis or cyanosis (36,37,38).
c. Any single alarm symptom such as hemoptysis or 
cyanosis (36,37,38).
Format change
Section 3.6.2.5 
If the results of the interim PK analysis do not indicate a 
need for a dose adjustment factor change, subjects will 
be brought into the clinic and end of study procedures 
will be performed.
If the results of the interim PK analysis do not indicate a 
need for a dose adjustment factor change, subjects will 
be brought into the clinic (within one week following the 
confirmation of the initial dose adjustment factor) and 
end of study procedures will be performed.
To specify a 
timeframe for 
bringing subjects 
back for end of 
study procedures
Section 3.6.3 
Table 3-2
Additional special 
testsa
DAT, serum free 
hemoglobin, 
haptoglobin
Central 
(central DAT 
if feasible)
Additional special 
testsa
DAT, serum free 
hemoglobin, 
haptoglobin
Central 
To provide 
clarification that 
this testing will be 
performed at the 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 9 of 94
Sections
Change From:
(Strikethrough is added to highlight deleted text)
Change To:
(Underline is added to highlight new text)
Rationale:
central laboratory
Section 3.6.2.3
Note: For pediatric subjects, at the discretion of the 
Investigator, virus safety retain samples may be drawn 
the day prior to SC Week#1 instead of combining with 
other blood draws on a single day.
Note: For pediatric subjects, at the discretion of the 
Investigator, virus safety retain samples may be drawn 1 
or 2 days prior to SC Week#1 instead of combining with 
other blood draws on a single day.
To clarify the 
window for virus 
safety retain 
samples
Section 3.7
Subjects may withdraw or be withdrawn from the study 
for the following reasons:
Also, subjects may be withdrawn from IP/study drug or 
the study for the following reasons:
• Subjects who develop an SBI during the IV Run-In 
Phase or IGIV-C 10% IV Phase prior to the first dose 
of IGSC 20%
If a subject discontinues study after receiving IGIV-C 
10% but prior to receiving the first dose of IGSC 20%, 
an additional subject may be recruited into the study to 
assure that 30 adults and 12 children receive at least one 
dose of IGSC 20%.
Subjects will withdraw or be withdrawn from the study 
for the following reasons:
Also, subjects will be withdrawn from IP/study drug or 
the study for the following reasons:
• Subjects who develop an SBI prior to the first dose of 
IGSC 20%
If a subject discontinues study after receiving IGIV-C 
10% but prior to receiving the first dose of IGSC 20%, 
an additional subject may be recruited into the study to 
assure that 30 adults and 12 children complete IGSC 
20% treatment.
To provide 
clarification for  
subject 
discontinuation and 
subject completion 
target
Section 4.3.1
An AE is defined as any untoward medical occurrence in 
a subject or clinical investigation subject administered a 
medicinal product or study treatment and which does not 
necessarily have a causal relationship with this 
administration. An AE can therefore be any unfavorable 
and unintended sign (including any abnormal laboratory 
finding, for example), symptom, or disease temporally 
associated with the use of a medicinal product, whether 
or not considered related to the medicinal product.
An AE is defined as any untoward medical occurrence in 
a subject or clinical investigation subject administered a 
medicinal product or study treatment and that does not 
necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended 
sign (including any abnormal laboratory finding), 
symptom, or disease temporally associated with the use 
of a medicinal product, whether or not considered related 
to the medicinal product.
To provide 
clarification
Section 4.4.1
Any SAE (see Section 4.3.6) that occurs after signing the 
study ICF through the Final Visit (ie, end of study) must 
be expeditiously reported whether or not considered 
attributable to the study drug. Each SAE must be fully 
Any SAE (see Section 4.3.6) that occurs after signing the 
study ICF through the Final Visit (ie, end of study) must 
be expeditiously reported whether or not considered 
attributable to the study drug. Each SAE must be fully 
To provide 
clarification for 
SAE reporting 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 10 of 94
Sections
Change From:
(Strikethrough is added to highlight deleted text)
Change To:
(Underline is added to highlight new text)
Rationale:
recorded in the subject’s eCRF or SAE Report Form.
SAEs will be reported using the designated SAE Report 
Form. When the Investigator becomes aware of an SAE, 
she/he must submit electronically through the electronic 
data capture (EDC) system or when the EDC system is 
not available submit a completed, signed and dated SAE 
Report Form (in English) within 24 hours to the Sponsor 
by email/fax.
Each SAE must be followed up until resolution or 
stabilization. After the initial report, all relevant 
information for SAE follow up, and for the outcome, 
must also be supplied to the Sponsor in a timely manner 
(within 3 days from its identification or within 24 hours 
for relevant new information) by means of the SAE 
Report Form. In addition, the Sponsor or contract 
research organization (CRO) may request additional 
information and/or reports.
All SAE Report Forms and Pregnancy Report Forms 
must be reported to Grifols electronically through the 
EDC system or when the EDC system is not available, 
reported to:
recorded in the subject’s eCRF and SAE Report Form.
SAEs will be reported using the designated SAE Report 
Form. When the Investigator becomes aware of an SAE, 
she/he must submit a completed, signed and dated SAE 
Report Form (in English) within 24 hours to the Sponsor 
by email/fax.
Each SAE must be followed up until resolution or 
stabilization. After the initial report, all relevant 
information for SAE follow up, and for the outcome, 
must also be supplied to the Sponsor in a timely manner 
(within 3 days from its identification or within 24 hours 
for relevant new information) by means of the SAE 
Report Form. In addition, the Sponsor or contract 
research organization (CRO) may request additional 
information and/or reports.
All SAE Report Forms and Pregnancy Report Forms 
must be reported to:
procedures
Section 4.4.2
(No previous text)
4.4.2
Reporting Pregnancy
Pregnancies occurring during the course of the study will 
not be considered an AE unless a relation to the study 
drug is suspected. In any case, a Pregnancy Report Form 
must be completed and sent as soon as possible to the 
Sponsor for any pregnancies that occur from time of 
consent through the Final Visit (ie, end of study). A copy 
of the form should be filed at the study site for follow-up 
until the end of the pregnancy. Any pregnancy must be 
followed by the Investigator until delivery or to the end 
of pregnancy. Any anomalies, complications, abnormal 
outcomes, or birth defects observed in the child must be 
reported as an SAE (see email address or fax number in 
To provide 
procedures for 
reporting 
pregnancy

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 11 of 94
Sections
Change From:
(Strikethrough is added to highlight deleted text)
Change To:
(Underline is added to highlight new text)
Rationale:
Section 4.4.1) within 24 hours of the Investigator or 
study personnel’s first knowledge.
Appendix 1
Pre-dose laboratory assessments (hematology, chemistry, 
special tests, urinalysis)i
Special tests only (DAT, serum free hemoglobin, 
haptoglobin)
Footnotes:
f Only if chest X-ray or CT have not been performed in 
the past 6 months at Screening 
j Pregnancy testing will be repeated at any time if 
pregnancy is suspected. 
n Weekly SC dosing may be 7 days ± 1 day.  except for
SC#2 and SC#3 which must be performed with a +1 
day window.; the first 3 SC infusions of IGSC 20% 
will be performed in the clinic where site personnel 
will instruct on/observe proper SC dosing technique 
using the pump.  Subsequent monthly SC infusions 
will also occur and be observed in the clinic after labs 
and total IgG trough levels are obtained.  Other SC 
infusions will be performed at home for interim weeks 
starting after the SC Week #3 visit.
Pre-dose laboratory assessments (hematology, chemistry, 
urinalysis)i
Special tests (DAT, serum free hemoglobin, haptoglobin)
Special tests assessment added at Screening, IV#1 
Baseline, SC Week #1, SC Week #9, SC Weeks #17, Final 
Visit (Week #25)/Early Termination, and Monthly 
Extension Visit
Footnotes:
f Only if chest X-ray or CT have not been performed in 
the past 6 months at Screening (Note: at least one 
radiographic view (AP or PA) is required.)
j Pregnancy testing will be repeated at any time if 
pregnancy is suspected. Pregnancy testing including 
serum and urine tests will be performed for child-
bearing potential females only.
n Weekly SC dosing may be 7 days ± 1 day. If there are 
logistical issues requiring schedule adjustment for 
weekly subcutaneous IGSC 20% administration, SC#1 
may be scheduled 6 to 9 days after IV#2.  SC#2 and 
SC#3 visits must be performed with a +1 day window. 
The first 3 SC infusions of IGSC 20% will be 
performed in the clinic where site personnel will 
instruct on/observe proper SC dosing technique using 
the pump.  Subsequent monthly SC infusions will also 
occur and be observed in the clinic after labs and total 
IgG trough levels are obtained.  Other SC infusions 
will be performed at home for interim weeks starting 
after the SC Week #3 visit.
Changes made to 
be consistent with 
the changes in the 
protocol text body
(Note: Administrative changes including minor administrative corrections are not included in Protocol Summary of Changes.)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 12 of 94
Investigator Signature Page
The undersigned confirms that he/she agrees to conduct the study under the conditions 
described in this protocol and comply with International Conference on Harmonization 
Good Clinical Practice (ICH GCP) and all applicable regulatory requirements:
___________________________________
______________________
INVESTIGATOR NAME (Please Print)
LOCATION
___________________________________
______________________
INVESTIGATOR SIGNATURE
DATE

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 13 of 94
Protocol Synopsis
Title of Study:
An open-label, multi-center study to evaluate the safety and pharmacokinetics of IGSC 20% 
administered for 6 months in subjects with primary immunodeficiency
Study Number:
GTI1502
Phase:
3
Number of Subjects Planned:
Approximately 50 subjects
Study Centers Planned:
Approximately 30 study centers
Study Objectives:
Primary Pharmacokinetic (PK) Objective
To determine a dose of weekly subcutaneously administered Immune Globulin Subcutaneous 
(Human), 20% Caprylate/Chromatography Purified (Grifols) (IGSC 20%) that produces 
steady-state AUC of total IgG that is non-inferior to that of the regularly administered IV 
dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified 
(Grifols) (IGIV-C 10%) in primary immunodeficiency (PI) subjects
Secondary Objective
To determine if IGSC 20% replacement therapy maintains mean steady-state trough total IgG 
levels that are comparable to the mean trough total IgG levels with the IGIV-C 10% 
replacement therapy in PI subjects
Safety Objective
To assess the safety and tolerability of IGSC 20% as an IgG replacement therapy in subjects 
with PI
Overall Study Description:
This is a prospective, multi-center, open-label, single-sequence, 6-month, PK and safety and 
tolerability study of IGSC 20% in subjects with PI. Approximately 50 subjects will be 
enrolled in order to have approximately 30 adult subjects and 12 to 18 pediatric subjects (age 
2-16 years) completing treatment with subcutaneously administered IGSC 20%.  Pediatric 
enrollment will be stratified by age category with a target of 4 to 6 children for each group: 
2 to 5 years, >5 to 12 years, and >12 to 16 years of age. The PK profiles of total IgG 
following administration of both IV (IGIV-C 10%) administration and SC (IGSC 20%) 
administration under approximate steady-state conditions will be determined and compared.
This study will include 3 treatment phases: Run-In Phase, IV Phase (IV administration of 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 14 of 94
IGIV-C 10% treatment), and SC Phase (SC administration of IGSC 20%). Before a subject is 
to be enrolled (entering either the Run-In or IV Phase) into the study, the subject will be 
screened during the Screening Phase of up to 28 days (following the first assessment of 
subject eligibility).
Subjects, depending on their current IgG treatment regimen, may be required to enter the 
Run-In Phase to receive IV IGIV-C 10% treatment (Sponsor provided)  to achieve an 
approximately steady-state condition prior to entering the IV Phase. They will then enter the 
IV Phase to determine the AUC profiles of IV infusions of IGIV-C 10%.
Subjects with a qualifying IV IGIV-C 10% treatment regimen (on stable IGIV-C 10% doses
of 300-800 mg/kg) can enter the IV Phase directly where they will receive IGIV-C 10% 
(Sponsor provided). In the IV Phase, steady-state IV PK assessments including AUC will be 
performed.
After completing the IV Phase, subjects will enter the SC Phase to receive weekly SC doses 
of IGSC 20% for at least 24 weeks. The IGSC 20% dose will be determined by using an 
initial IV to SC dose adjustment factor of 1.37. After reaching an approximately steady-state 
condition, the SC PK profiles including AUC at SC Week #13 will be determined.
Comparison of the IV PK profiles and IGSC 20% PK profiles in the first 6 adult/adolescent 
subjects will be performed through an interim PK analysis. If the dose adjustment factor is 
deemed acceptable (SC dose of IGSC 20% is non-inferior to the subject’s IV dose) 
(Section 3.1.5), all subjects will continue to complete treatment and assessments through 
Week#25 (no further monthly extension visits). Otherwise, a new dose adjustment factor will 
be employed for all subjects following the procedures described in Section 3.1.5, and 
subjects will receive 24 weeks of IGSC 20% treatment at the new IGSC 20% dose. In this 
study, the PK profiles will be assessed in all subjects. Subjects aged 2 to 5 years old will be 
assessed using an abbreviated sampling schedule for PK profiles.
The interim serial PK samples (for both the IGIV-C 10% IV and the IGSC 20% SC dosing 
phases) may be obtained at an alternate location.  If an outside agency is utilized for sample 
collection, the samples will be drawn and processed per protocol and laboratory manual 
instructions.
Target Population:
Eligible participants for this study include male or female subjects who are 2 to 75 years of 
age and have a diagnosis of PI requiring IgG replacement treatment. Subjects who initially 
fail to meet eligibility criteria may be re-screened once upon consultation with the Sponsor. 
Subjects who fail to meet eligibility criteria upon re-screen are Screen Failures and will not 
be eligible to participate in the study.
Diagnosis and Main Eligibility Criteria:
Inclusion Criteria:
A subject must meet all the following inclusion criteria to be eligible for participation in this 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 15 of 94
study.
1. Subjects between the ages of 2 and 75 years (inclusive) at Screening.
2. Documented and confirmed pre-existing diagnosis of PI with features of 
hypogammaglobulinemia requiring IgG replacement therapy including but not limited to 
the following humoral-based immunodeficiency syndromes (eg, X-linked 
agammaglobulinemia, common variable immunodeficiency), and combined 
immunodeficiency syndromes without lymphocytopenia (eg, hyper immunoglobulin M 
[IgM] immunodeficiency syndrome). Please also refer to Exclusion Criteria.
3. The subject has not had an SBI within the last 3 months prior to or during Screening.
4. Currently on IgG replacement therapy (via IV or SC infusion) for ≥3 months. 
5. Note: This inclusion criterion is removed in protocol amendment 2. 
6. Screening trough IgG levels must be ≥500 mg/dL.
Note: If Screening trough levels are not above this threshold, the subjects will be a Screen 
Failure, but may be re-screened following dose adjustment of their original IgG 
replacement therapy regimen and maintaining stable dosing for a period of at least 3 
months prior to Screening a second time.
7. The medical records for all subjects should be available to document diagnosis, previous 
infections and treatment.
8. The subject has signed an informed consent.
Note: The subject must sign the informed consent form (ICF) if at least 18 years old; for 
children of younger age, the subject’s parent or legal guardian must sign the ICF and if 
appropriate/applicable, the subject must sign a Child Assent form approved by the 
Institutional Review Board or Ethics Committee (IRB/EC) per their requirements
Exclusion Criteria:
A subject meeting any of the following exclusion criteria is NOT eligible for participation in 
the study.
1. Clinical evidence of any significant acute or chronic disease that, in the opinion of the 
Investigator, may interfere with successful completion of the trial or place the subject at 
undue medical risk
2. The subject has had a known serious adverse reaction to immunoglobulin or any severe 
anaphylactic reaction to blood or any blood-derived product
3. The subject has a history of blistering skin disease, clinically significant 
thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections or other 
disorders where SC therapy would be contraindicated during the study
4. The subject has isolated IgG subclass deficiency, isolated specific antibody deficiency 
disorder, or transient hypogammaglobulinemia of infancy
5. The subject has known selective immunoglobulin A (IgA) deficiency (with or without 
antibodies to IgA)
6. Females of childbearing potential who are pregnant, have a positive pregnancy test at 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 16 of 94
Screening (serum) or IV#1 Baseline (urine) (human chorionic gonadotropin [HCG]-based 
assay), are breastfeeding, or unwilling to practice a highly effective method of 
contraception (oral, injectable or implanted hormonal methods of contraception, 
placement of an intrauterine device [IUD] or intrauterine system [IUS], condom or 
occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or 
true abstinence) throughout the study
Note: True abstinence: When this is in line with the preferred and usual lifestyle of the 
subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation 
methods], declaration of abstinence for the duration of a trial, and withdrawal are not
acceptable methods of contraception.)
7. The subject has significant proteinuria (dipstick proteinuria ≥3+ or known urinary protein 
loss >1 g/24 h or nephrotic syndrome) and/or has a history of acute renal failure and/or 
severe renal impairment (blood urea nitrogen [BUN] or creatinine more than 2.5 times 
the upper limit of normal [ULN]) and/or on dialysis
8. The subject has Screening Visit values of aspartate aminotransferase (AST) or alanine 
aminotransferase (ALT) levels exceeding more than 2.5 times the ULN for the expected 
normal range for the testing laboratory.
9. The subject has hemoglobin <9 g/dL at Screening.
10. The subject has a history of or current diagnosis of deep venous thrombosis or 
thromboembolism (eg, deep vein thrombosis, myocardial infarction, cerebrovascular 
accident or transient ischemic attack); history refers to an incident in the year prior to 
Screening or 2 episodes over lifetime.
11. The subject is currently receiving anti-coagulation therapy which would make SC 
administration inadvisable (vitamin K antagonists, nonvitamin K antagonist oral 
anticoagulants [eg, dabigatran etexilate targeting Factor IIa, rivaroxaban, edoxaban, and 
apixaban targeting Factor Xa], parenteral anticoagulants [eg, fondaparinux]).
12. The subject currently has a known hyperviscosity syndrome.
13. The subject has an acquired medical condition that is known to cause secondary immune 
deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, 
chronic or recurrent neutropenia (absolute neutrophil count less than 1000/µL [1.0 x 
109/L]), or human immunodeficiency virus (HIV) infection/acquired immune deficiency 
syndrome (AIDS).
14. The subject has a known previous infection with or clinical signs and symptoms 
consistent with current hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
15. The subject (if <18 years of age) has non-controlled arterial hypertension at a level of 
greater than or equal to the 90th percentile blood pressure (either systolic or diastolic) for 
their age and height (See Appendix 3) or the adult subject has non-controlled arterial 
hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure 
>100 mmHg)
16. The subject is receiving any of the following medications: (a) immunosuppressants 
including chemotherapeutic agents; (b) immunomodulators; (c) long-term systemic 
corticosteroids defined as daily dose >1 mg of prednisone equivalent/kg/day for 
>30 days.
Note: Intermittent courses of corticosteroids of not more than 10 days would not exclude 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 17 of 94
a subject. Inhaled or topical corticosteroids are allowed.
17. The subject has known substance or prescription drug abuse
18. The subject has participated in another clinical trial within 30 days prior to Screening 
(observational studies without investigative treatments [non-interventional] are 
permitted) or has received any investigational blood product with the exception of other 
IgG products within the previous 3 months
19. The subject/caregiver is unwilling to comply with any aspect of the protocol, including 
the home SC infusions, blood sampling, and completion of a SC infusion diary for the 
duration of the study
20. Mentally challenged subjects who cannot give independent informed consent or assent
21. In the opinion of the Investigator, the subject may have compliance problems with the 
protocol and the procedures of the protocol
Investigational Product, Dose, and Mode of Administration:
Grifols Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified 
(IGSC 20%)
IGSC 20% is a sterile liquid formulation of immunoglobulin that has been purified from 
human plasma via a multi-step process. IGSC 20% is manufactured using the same process 
as for IGIV-C 10% (Immune Globulin Intravenous [Human], 10% 
Caprylate/Chromatography Purified [IGIV-C]), with the addition of a nanofiltration step and 
is further concentrated by ultrafiltration to a higher IgG concentration (20%). IGSC 20% 
vials will be supplied in a 50 mL vial size or smaller containing a 20% solution of 
immunoglobulin, ie, a concentration of 20 g/100 mL, with a nominal 10 grams 
immunoglobulin per vial.
In the current study, the initial IV to SC dose adjustment calculation formula used is:
Reference Therapy, Dose and Mode of Administration:
Grifols Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified
(IGIV-C 10%)
IGIV-C 10% is a sterile liquid formulation of immunoglobulin that has been purified from 
human plasma. IGIV-C 10% is a licensed product. IGIV-C 10% vials may be supplied in the 
vial sizes of 10, 25, 50, 100, and 200 mL.  In this study, administration of IGIV-C 10% will 
be via the IV route only.
The IV IGIV-C 10% dose and dosing interval will be individualized based on the treatment 
each subject is receiving for their PI at screening.
300 to 800 mg/kg (IV dose)
3 or 4 (regular IV dosing interval in week)
× 1.37 (IV to SC dose adjustment factor)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 18 of 94
Duration of Treatment:
Total duration of study participation:  up to 50 weeks
Screening Phase: up to 28 days
Treatment duration:
Run-In Phase:  3 to 4 months
IV Phase:  4 to 5 weeks
SC Phase:  24 weeks
If the initial dose adjustment factor is deemed insufficient at the time of the interim PK 
analysis (please see synopsis section below), a new dose adjustment factor will be calculated 
and implemented. In this case, all subjects will complete 24 weeks of IGSC 20% treatment 
with a dose determined using the new dose adjustment factor.
Study Variables:
Primary PK Variable

AUC in the IV Phase: Steady-state AUC of total IgG over a regular dosing interval (τ), 
either every 3 weeks or every 4 weeks (ie, AUC0- τ,IV or AUC0-21days,IV or AUC0-28 days,IV, 
respectively) in PI subjects

AUC in the SC Phase: Steady-state AUC of total IgG over a weekly SC dosing interval 
(τ) (ie, AUC0- τ,SC or AUC0-7days,SC) in PI subjects
Secondary Variables

Mean steady-state trough (pre-dose) concentration of total IgG following IV 
administration of IGIV-C 10% or SC administration of IGSC 20%
Exploratory Variables

tmax (time to reach Cmax ) and Cmax in PI subjects at steady state

Trough levels of IgG subclasses (IgG1, IgG2, IgG3, IgG4)

Antibody levels for S. pneumoniae, H.influenzae, and C. tetani (tetanus)

Rate of serious bacterial infection (SBI)

All infections of any kind (serious/nonserious including acute sinusitis, exacerbation of 
chronic sinusitis, acute otitis media, pneumonia, acute bronchitis, infectious diarrhea, 
etc.) as determined by the Investigator

Validated infections documented by positive radiograph, fever (>38°C oral or >39°C 
rectal), culture, or diagnostic testing for microorganisms eg, bacterial, viral, fungal, or 
protozoal pathogens (for instance, rapid streptococcal antigen detection test)

Number of days on antibiotics (including oral, parenteral, oral plus parenteral, 
prophylactic and therapeutic). Use of prophylactic antibiotics will be distinguished from 
antibiotics for treatment of acute infection.

Number of hospitalizations due to infection

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 19 of 94

Number of days of work/school/daily activities missed due to infections and their 
treatment

Trough measles antibody titers (functional assay) for informational purposes
Safety Variables

Adverse events (AEs), suspected adverse drug reactions (suspected ADRs), adverse 
reactions (ARs), serious AEs (SAEs), and discontinuations due to AEs and SAEs
Note: All  infusion site reactions will be recorded in the eCRF. For local infusion site 
reactions where the signs/symptoms lead to infusion interruption or discontinuation, 
require concomitant medication, or have an impact on the general condition of the subject 
as judged by the Investigator, they will be considered as AEs.

Vital signs during clinic visits (systolic blood pressure [SBP] and diastolic blood pressure 
[DBP], heart rate [HR], temperature [T], respiratory rate [RR])

Physical assessments: physical examinations will be recorded as normal or abnormal, 
according to the physician's judgment criteria, and findings will be recorded.

Laboratory assessments including chemistry, hematology, and urinalysis.

Total number of non-serious infections and proportion of subjects who experience non-
serious infections of any kind (including acute sinusitis, exacerbation of chronic sinusitis, 
acute otitis media, pneumonia, acute bronchitis, infectious diarrhea, etc.) as determined 
by the Investigator.
Key Assessments and Procedures:
IgG trough levels will be measured for all subjects during the Screening Visit, Run-In Phase, 
IV Phase, and SC Phase as detailed in Appendix 1.
The sampling for determining PK profiles for IV administered IGIV-C 10% will commence 
at the IV#1 (IV Phase) visit for all enrolled subjects.
The sampling for determining PK profiles for the SC administration of IGSC 20% will 
commence at the SC Week #13 visit for all enrolled subjects.
Subjects between the ages of 2 and 5 years of age will undergo serial PK sampling using an 
abbreviated sampling schedule.
SC infusion diary: An IGSC 20% infusion diary will be provided to each subject prior to the 
first IGSC 20% infusion which may be used to record items including but not limited to: 
infusion site reactions, concomitant medications (including antibiotics [prophylactic and 
therapeutic]), and details of study drug administration (location and number of sites, 
date/clock time of start and end of infusion, dose/volume of each SC dose, duration and rates 
of infusion). The SC infusion diary may also be used to record days of missed 
work/school/daily activities due to infections and related treatment.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 20 of 94
Note:  All infusion site reactions will be recorded. For the subset of local infusion site
reactions where the signs/symptoms lead to infusion interruption or discontinuation, require 
concomitant medication, or have an impact on the general condition of the subject as judged 
by the Investigator, these will be considered as AEs.
Statistical Methods:
Study Populations:
Safety Population
The safety population will include all subjects who received any amount of study drugs 
(IGIV-C 10% and/or IGSC 20%) and will be used for safety analysis.
PK Population
The PK population will consist of all subjects who receive study drugs and have sufficient 
and valid total IgG concentration vs. time data for either the IV or SC Phase to allow 
calculation of AUC0-τ,SC or AUC0-τ,IV (the primary PK endpoint).
The validity of total IgG concentrations  will be reviewed and determined before the database 
lock based on consideration of treatment compliance and blood sampling/testing issues (such 
as collection problem). Any invalid total IgG concentrations will be flagged with the reason 
for invalidity in the listing.
IgG Population
The IgG population will consist of all subjects who receive study drugs and have any total 
IgG concentration data. The summary of total IgG concentration data will be based on IgG 
Population.
Demographic and Baseline Characteristics:
The demographic and baseline characteristics will be summarized. For quantitative variables, 
mean, SD, median, and minimum/maximum will be provided. For qualitative variables, the 
frequency and percentage will be provided.
Study Analyses:
Primary PK Analyses
The Primary PK endpoint is the steady-state AUC over a dosing interval defined as follows:

AUC0- τ, SC , the AUC over a weekly dosing interval (τ) at an approximate steady-state 
condition following weekly SC infusion, ie, AUC0-7 days.

AUC0- τ, IV , the AUC over a regular dosing interval (τ) at an approximate steady-state 
condition following the regular IV infusion, either every 3 weeks or every 4 weeks, ie, 
AUC0-21 days or AUC0-28 days, respectively.
AUC0- τ, SC is to be obtained after the 13th SC dose of IGSC 20% at the weekly dose 
calculated using the final dose adjustment factor, and AUC0- τ,IV is to be obtained following 
IV infusion of IGIV-C 10% at the IV#1 visit.  Since the dosing interval (τ) is 7 days for the 
SC dose, AUC0- τ, SC is determined as AUC0-7 days.  For IV dosing, the dosing interval (τ) is 
21 or 28 days for the 3-week or 4-week subjects, AUC0- τ, IV is determined as AUC0-21 days or 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 21 of 94
AUC0-28 days, respectively.
Prior to statistical comparison of AUC0- τ’s between the IV IGIV-C 10% and SC IGSC 20% 
doses, the AUC0-21 days from the IV infusion in subjects on a 3-week IV dosing interval will 
be divided by 3 or the AUC0-28 days from IV dosing in subjects on a 4-week IV dosing 
interval divided by 4 for comparison with AUC0-7 days from the weekly SC infusion.
The hypothesis to be tested is that the weekly SC dose of IGSC 20% will achieve an 
approximate steady-state AUC0- τ, SC of total IgG that is non-inferior to that achieved by a 
regular IV dose of IGIV-C 10% (AUC0- τ, IV divided by 3 or 4 depending on the IV dosing 
intervals).  Non-inferiority of steady-state IgG AUC between SC dose of IGSC 20% and IV 
IGIV-C 10% administration will be tested based on established regulatory guidelines for 
bioequivalence testing. The 90% confidence interval (CI) of the geometric LSM ratio of SC 
AUC to IV AUC will be calculated.  The SC dose is considered to be non-inferior to the IV 
dose if the low bound of the 90% CI for the geometric LSM AUC ratio is above 0.80 based 
on loge-transformed data.
Secondary and Exploratory PK Analysis
Secondary and exploratory PK endpoints include the steady-state mean trough concentration 
of total IgG and the Cmax, tmax of total IgG. Descriptive statistics will be calculated for the 
steady-state mean trough concentration of total IgG and for Cmax and tmax of total IgG.  All 
pre-infusion total IgG concentrations obtained before and at the 13th SC dose of IGSC 20% 
will be evaluated to determine if an approximate steady-state condition has been achieved by 
the 13th SC dose.  The steady-state mean trough concentrations of total IgG following SC 
administrated IGSC 20% will be determined as the average value of Ctrough measurements 
obtained at Weeks#13, #14, #17, and #21. The mean steady-state trough concentrations of 
total IgG following IV administrated IGIV-C 10% will be determined as the average value of 
Ctrough measurements obtained at the IV#1 visit and at 21 or 28 days after the IV#1 IGIV-C 
10% dose (depending on dosing interval), ie, immediately prior to the administration of IV 
dose at IV#2 visit.
Summaries will be provided for trough concentration of total IgG and each of its subclasses 
between IV infusion of IGIV-C 10% and SC administration of IGSC 20%.  Summaries of 
trough level concentration of antibody titers against S. pneumonia, H.influenza, and C. tetani
will also be provided.
Depending on the number of subjects being dosed on IGIV-C 10% at 3- or 4-week dosing 
interval, subgroup analyses may be performed to evaluate PK variables by IV dosing 
interval. Subgroup analyses will additionally include age, sex, race, ethnicity and other 
factors as appropriate.
Additional exploratory variables will be summarized descriptively. The number and 
proportion of subjects having SBI, infections, days on antibiotics, hospitalizations due to 
infection, and days of work/school/daily activities missed due to infections will be calculated 
and summarized. Furthermore, the total number of events or days and corresponding 
annualized rate per subject of SBIs, infections, days on antibiotics, hospitalizations due to 
infection, and days of work/school/daily activities missed due to infections will be calculated 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 22 of 94
and summarized.
Interim PK Analysis
An interim PK analysis will be performed as soon as practical after the first 6
adult/adolescent subjects (age ≥12-75 years) have completed the PK sampling schedule for 
both the IV and SC (after the 13th SC dose) phases of the trial.  PK data from these 
6 adult/adolescent subjects will be analyzed using procedures as described above under 
primary efficacy analysis.  A decision on whether to modify the dose adjustment factor for 
calculating the SC dose will be made based on this interim PK analysis.
Final PK and statistical analysis will be based on the PK data obtained after the final (or 
adjusted, if any) SC dose administered in all completed subjects.
Safety Analysis
The safety analyses are based on the safety population.
All AEs, suspected ADRs, AR, and SAEs, and discontinuations due to AEs and SAEs will be 
summarized by presenting the number of AEs and the number and percentage of subjects 
with AEs. The summaries will be presented by MedDRA system organ class and preferred 
term. AE summaries by severity will also be provided. Local infusion site reactions and non-
serious infections will be similarly summarized.
Subjects with deaths, SAEs, and AEs leading to premature discontinuation from the study 
will be listed and presented in a narrative form.
Adverse events temporally associated with IV or SC administration of study drug will be 
defined as those occurring during or within 72 hours of completion of an infusion. 
Additionally, local infusion site reactions will be tabulated and summarized for the total 
duration of the study and by IGSC 20% infusion week.
For all laboratory tests and vital signs, the original value and the change from Baseline will 
be summarized for numeric results and frequency/percentage will be summarized for 
qualitative results. For laboratory tests with normal ranges, out of normal range values will 
be flagged and shift tables will be provided.
Determination of Sample Size
The planned number of subjects (50 enrolled to provide 30 completing adult subjects and 
12 to 18 completing pediatric subjects). This sample size is primarily based on safety 
assessment consideration. Also a sample size of 42 to 48 with at least 24 scheduled 
administrations of IGSC 20% would provide the clinical experience data on a total of more 
than 1008 to 1080 IGSC 20% dosing administrations for safety assessment.
The planned minimum enrollment of 42 completing subjects should be more than adequate to 
establish that the AUC for total IgG for IGSC 20% is non-inferior to that achieved by 
IGIV-C 10%.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 23 of 94
TABLE OF CONTENTS
SUMMARY OF CHANGES FOR AMENDMENT 2..............................................................3
GLOSSARY AND ABBREVIATIONS..................................................................................27
1
INTRODUCTION ...........................................................................................................30
1.1
Primary Immunodeficiency ...................................................................................30
1.2
Immunoglobulin Replacement Therapy ................................................................30
1.3
Study Rationale......................................................................................................31
1.3.1
Dose Rationale.............................................................................................32
2
STUDY OBJECTIVES....................................................................................................33
2.1
Primary Pharmacokinetic Objective ......................................................................33
2.2
Secondary Objective..............................................................................................33
2.3
Exploratory Objectives ..........................................................................................33
2.4
Safety Objective.....................................................................................................34
3
INVESTIGATIONAL PLAN..........................................................................................34
3.1
Study Design and Plan...........................................................................................34
3.1.1
Screening Phase ...........................................................................................35
3.1.2
Run-In Phase................................................................................................36
3.1.3
IV Phase.......................................................................................................37
3.1.4
SC Phase ......................................................................................................37
3.1.5
Interim PK Analysis.....................................................................................39
3.2
Selection of Study Population................................................................................40
3.2.1
Inclusion Criteria .........................................................................................40
3.2.2
Exclusion Criteria ........................................................................................41
3.3
Treatments..............................................................................................................42
3.3.1
Treatments to Be Administered ...................................................................42
3.3.1.1
IGSC 20% ..........................................................................................43
3.3.1.2
IGIV-C 10%.......................................................................................43
3.3.1.3
Labeling of Investigational Products .................................................43
3.3.1.4
Storage of Investigational Products ...................................................43
3.3.1.5
Preparation .........................................................................................43
3.3.1.6
Accountability for Investigational Products ......................................44
3.3.2
Rationale for Selection of Doses/Timing of Investigational Products.........44
3.3.2.1
Selection of Doses and Timing of Dosing in the Study.....................44
3.3.2.2
Selection and Timing of Dose for Each Subject................................45
3.3.2.3
Subcutaneous Administration Procedures for IGSC 20% .................45
3.3.3
Method of Assigning Subjects to Treatment Groups...................................46
3.3.3.1
Subject Numbering ............................................................................46
3.3.3.2
Randomization...................................................................................46
3.3.3.3
Blinding..............................................................................................46

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 24 of 94
3.3.4
Treatment Compliance.................................................................................46
3.4
Prior and Concomitant Therapy.............................................................................47
3.4.1
Prohibited Medications Prior to Study Participation ...................................47
3.4.2
Prohibited Concomitant Medications during the Study...............................47
3.4.3
Restricted Concomitant Medications during the Study ...............................47
3.4.4
Drug Interactions .........................................................................................48
3.5
Study Variables......................................................................................................48
3.5.1
Primary Pharmacokinetic Variables ............................................................48
3.5.2
Secondary Pharmacokinetic Variables ........................................................48
3.5.3
Exploratory Variables ..................................................................................48
3.5.4
Safety Variables...........................................................................................49
3.6
Assessments...........................................................................................................49
3.6.1
Assessment Periods......................................................................................49
3.6.2
Observations and Measurements .................................................................50
3.6.2.1
Screening Visit...................................................................................50
3.6.2.2
Run-In Phase (If Required) – IV Administration of IGIV-C 10% ....51
3.6.2.3
IV Phase – IV Administration of IGIV-C 10% .................................51
3.6.2.4
SC Phase – SC Administration of IGSC 20% ...................................54
3.6.2.5
Monthly Extension Visits ..................................................................59
3.6.2.6
Final Visit (Week #25)/Early Termination Clinic Visit.....................60
3.6.3
Description of Laboratory Tests and Procedures.........................................61
3.6.3.1
Assessment and Recording of Infections...........................................62
3.6.3.2
Virus Safety Testing ..........................................................................62
3.6.3.3
D-dimer and Wells Score...................................................................63
3.7
Removal of Subjects ..............................................................................................63
3.8
Follow-up of Subjects Withdrawn from Study......................................................64
3.9
Premature Termination of Study/Closure of Center..............................................64
4
ADVERSE EVENTS.......................................................................................................64
4.1
Warnings/Precautions ............................................................................................64
4.2
Adverse Event Monitoring.....................................................................................65
4.3
Adverse Event Definitions.....................................................................................65
4.3.1
Adverse Events ............................................................................................65
4.3.2
Suspected Adverse Drug Reactions/Adverse Reactions..............................65
4.3.3
Causality of Adverse Event .........................................................................65
4.3.4
Severity of Adverse Event or Suspected Adverse Drug Reaction...............66
4.3.5
Expectedness of Adverse Event or Suspected Adverse Drug Reaction ......67
4.3.6
Seriousness of Adverse Event or Suspected Adverse Drug Reaction;  
Serious Adverse Event.................................................................................67
4.3.7
Adverse Event and Pregnancy Documentation............................................68
4.3.8
Type and Duration of the Follow-Up of Subjects after Adverse Events.....69

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 25 of 94
4.4
Reporting of Serious Adverse Events or Pregnancy..............................................69
4.4.1
Reporting Serious Adverse Event................................................................69
4.4.2
Reporting Pregnancy....................................................................................70
5
STATISTICAL METHODS AND DETERMINATION OF SAMPLE  SIZE...............70
5.1
Statistical and Analytical Plans..............................................................................70
5.1.1
Subject Populations for Analysis.................................................................70
5.1.2
Demographic and Baseline Characteristics .................................................71
5.1.3
Pharmacokinetic Analysis............................................................................71
5.1.4
Interim PK Analysis.....................................................................................72
5.1.5
Exploratory Analysis ...................................................................................73
5.1.6
Safety Analysis ............................................................................................73
5.2
Determination of Sample Size ...............................................................................74
6
ADMINISTRATIVE .......................................................................................................74
6.1
Investigator(s), Other Study Personnel and External Committees ........................74
6.2
Data Quality...........................................................................................................74
6.3
Documentation.......................................................................................................74
6.3.1
Record Retention .........................................................................................75
6.3.2
Access to Information for Monitoring.........................................................75
6.3.3
Access to Information for Audits or Inspections.........................................75
7
ETHICAL AND LEGAL ASPECTS...............................................................................76
7.1
Institutional Review Board/Ethics Committee ......................................................76
7.2
Ethical Conduct of the Study.................................................................................76
7.3
Regulatory Authority Approvals/Authorizations...................................................76
7.4
Subject Information and Consent...........................................................................76
7.5
Insurance................................................................................................................77
7.6
Confidentiality .......................................................................................................77
8
USE OF DATA AND PUBLICATION ..........................................................................77
9
REFERENCES ................................................................................................................79
10
APPENDICES .................................................................................................................83
LIST OF IN-TEXT TABLES
Table 3-1 Study entry of subjects ......................................................................................36
Table 3-2 Name, Description, and Location of Laboratory Tests and Procedures............61
LIST OF IN-TEXT FIGURES
Figure 3-1 Overall study design.........................................................................................35

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 26 of 94
Figure 3-2  IV dosing of IGIV-C 10% and SC dosing of IGSC 20% Clinic Visits and 
PK sampling schedules (Also see Sections 3.6.2.3 and 3.6.2.4) .................................38
LIST OF APPENDICES
Appendix 1
Schedule of Study Procedures ...........................................................84
Appendix 2
Diagnostic Criteria for Serious Infection Types ................................88
Appendix 3
Blood Pressure Percentiles for Pediatric Patients ..............................90
Appendix 4
Wells Score ........................................................................................94

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 27 of 94
GLOSSARY AND ABBREVIATIONS
ADR
Adverse drug reaction
AP
Anterior-posterior 
AE
Adverse event
AIDS
Acquired immunodeficiency syndrome
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
AR
Adverse reaction
ARC
Absolute reticulocyte count
AST
Aspartate aminotransferase
AUC
Area under the concentration vs. time curve
AUC0-7days
Area under the concentration-time curve from 0 to 7 days
B19V
Parvovirus B19
BUN
Blood urea nitrogen
Cmax
Maximum concentration
Ctrough
Minimum concentration
CI
Confidence interval
CRO
Contract research organization
CSF
Cerebrospinal fluid
CXR
Chest X-ray
DAT
Direct antiglobulin test
DBP
Diastolic Blood Pressure
DNA
Deoxyribonucleic Acid
DVT
Deep venous thrombosis 
eCRF
Electronic case report form
EDC
Electronic data capture
EMA
European Medicines Agency
FDA
Food and Drug Administration
HAV
Hepatitis A virus
HBV
Hepatitis B virus
HCG
Human Chorionic Gonadotropin

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 28 of 94
HCV
Hepatitis C virus
HIV
Human immunodeficiency virus
HR
Heart rate
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH GCP
International Conference on Harmonization Good Clinical Practice
IgA
Immunoglobulin A
IgG
Immunoglobulin G
IGIV-C 10%
Immune Globulin Injection (Human), 10% Caprylate/Chromatography 
Purified (Grifols)
IgM
Immunoglobulin M
IGSC 20%
Immune Globulin Subcutaneous (Human), 20% 
Caprylate/Chromatography Purified (Grifols)
IM
Intramuscular
IP
Investigational product
IRB/EC
Institutional Review Board/Ethics Committee
IUD
Intrauterine device
IUS
Intrauterine system
IV
Intravenous
IVIG
Intravenous Immune Globulin (generic terminology)
IWR
Interactive Web Response
kg
Kilogram
LDH
Lactate dehydrogenase
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligram
mL
Milliliter
NAT
Nucleic acid amplification technology
PA
Posterior- anterior 
PE
Pulmonary embolus 
pH
Potential of hydrogen; acidity/alkalinity measure
PI
Primary immunodeficiency
PK
Pharmacokinetics

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 29 of 94
RNA
Ribonucleic acid
RR
Respiratory rate
SAE
Serious adverse event
SBI
Serious bacterial infection
SBP
Systolic blood pressure
SC
Subcutaneous
SCIG
Subcutaneously delivered immune globulin or subcutaneous 
immunoglobulin (generic terminology)
SD
Standard deviation
SRC
Safety Review Committee
SSC
Specific Signs/Symptoms Check
T
Temperature
tmax
Time to reach Cmax
TEAE
Treatment-emergent adverse event
US
United States
WBC
White blood cell

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 30 of 94
1
INTRODUCTION
1.1
Primary Immunodeficiency
Primary Immunodeficiency (PI) diseases are a family of congenital disorders of the immune 
system that lead to an increase in frequency of infections, notably, but not limited to, 
bacterial infections of the respiratory tract (1). Results from a recent study suggest that in the 
United States (US) alone 1 in 2,000 children and 1 in 1,200 persons (including adults and 
children) are diagnosed with PI, yielding a total US PI patient population estimate of 
approximately 250,000 adults and children (2). Worldwide upper estimates suggest that six 
million people (638,000 in Europe) may be living with a PI, although orders of magnitude 
fewer patients have been identified in registries (3). Patients with inherited deficiencies 
leading to impaired humoral immunity are highly susceptible to a wide range of infections, 
most commonly bacterial infections. The efficacy of immunoglobulin G (IgG) replacement in 
the treatment of these disorders has been well established (4,5) since 1952 when the use of 
serum globulin fraction was reported to reduce the frequency of infections in a patient with 
agammaglobulinemia. The therapeutic management of PI has been carried out via 
intramuscular (IM), intravenous (IV), and subcutaneous (SC) injections of various IgG 
preparations (6,7).
1.2
Immunoglobulin Replacement Therapy
Despite its widespread use, the infusion of IV immune globulin (IVIG) is problematic in 
some patients, especially those who have poor venous access or develop systemic adverse 
events (AEs), such as headaches, fever, chills, or myalgias from this route of administration 
(8,9). In children, difficulty in obtaining venous access can prevent or delay IVIG therapy 
(7,10,11). Over the last several years subcutaneously delivered immune globulin (SCIG) has 
been developed for administration in the home setting for treatment of PI and has become 
accepted in the clinical setting (10,11,12).
The results of several adult PI studies with SCIG products have shown good efficacy of 
replacement therapy and control of bacterial infections (13,14,15). Additionally, the results 
of several pediatric studies also showed that SC infusion of IgG in children (ages 1-15 years) 
at home was feasible and safe and also resulted in maintenance of the IgG levels above 
500 mg/dL (12,16,17), a level that is considered as sufficient to protect against serious 
bacterial infections (SBIs) in adults and pediatric PI patients. It is now generally accepted 
that repeated SC infusions of IgG cause few, if any, adverse systemic reactions and for some 
patients, including children, the SC route has become a preferred route of administration 
(8,18-29).
Advantages of home-based SCIG infusions in adults and children with PI include treatment 
satisfaction and quality-of-life improvement, specifically, greater independence, better 
control of the therapy situation, and an overall improvement in daily life afforded by home-
based therapy. Moreover, the technique involved is deemed easy to learn by adults and 
children (6,7,24,30).

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 31 of 94
IVIG infusions produce an immediate rise in the IgG levels with marked peak levels which 
gradually decline as the IgG redistributes, equilibration takes place, and the IgG moves into 
the extravascular space over the typical 3 to 4 week IV dosing regimen period. The IgG 
decay occurs with first order kinetics over a period of approximately 3 to 4 weeks (18,31). 
Consequently the patient experiences substantial IgG concentration variations rather than a 
steady IgG level throughout the IV dosing period. Maintenance of higher IgG trough levels 
may benefit patients receiving IgG via the SC route at more frequent intervals (18).
Recent studies with SCIG regimens have documented the SCIG regimen results in much less 
variability in IgG levels, and higher and more consistent trough levels when compared to the 
IVIG regimens (32). One possible reason for the stable blood concentrations is that the SC 
infused IgG probably remains in the SC fat layer as a depot with a slow and continuous 
release into the circulatory system (6) in addition to the increased frequency of dosing. It has 
been reported that the uptake of the antibodies from SC tissue is high and the antibodies are 
not locally destroyed (18,33), which results in IgG reaching the circulation intact.
Several SCIG products, ranging in protein IgG concentrations from 10% to 20%, are 
currently being used to treat PI most commonly by either weekly or biweekly administration. 
IGIV-C 10%, a 10% immunoglobulin product, is licensed in the US and some other countries 
(eg, IGIVnex in Canada) for both IV and SC administration. The advantage of higher 
concentration SCIG products (20%) is primarily reduced infusion volume and shorter 
infusion time thereby significantly increasing ease of administration.
1.3
Study Rationale
The investigational product (IP) in this study is Immune Globulin Subcutaneous (Human), 
20% Caprylate/Chromatography Purified (IGSC 20%), Grifols company designation 
GRF6017. Henceforth in this document, this product will be referred to as IGSC 20%. The 
second study drug is Immune Globulin Injection (Human), 10% Caprylate/Chromatography 
Purified, henceforth referred to as IGIV-C 10% which is approved for the indication of PI
and will be employed in this trial  to standardize IV immune globulin administration during 
the initial Run-In Phase and IV Phase (Section 3.1).
The primary objective of this study is to determine a dose of subcutaneously administered 
IGSC 20% that produces steady-state area under the concentration-time curve (AUC) of total 
IgG by weekly SC administration that is not inferior to that of a regularly administered IV 
dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified 
(Grifols IGIV-C 10%).  IGIV-C 10% is a 10% Grifols immunoglobulin product, licensed in 
the US as GAMUNEX® and some other countries (eg, IGIVnex in Canada) for both IV and 
SC administration.  The additional objective of the trial is to assess the safety of the new 
IGSC 20% formulation.
In addition to the information provided here, please also refer to the Investigator’s Brochure 
(IB) of IGSC 20% and IGIV-C 10%.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 32 of 94
1.3.1
Dose Rationale
AUC-based IVIG to SCIG dose adjustments have historically been in the range of 1.37 to 
1.53 across products (eg, Gamunex-C,  Hizentra, Gammagard), and this study will 
commence with an IVIG:IGSC 20% dose adjustment ratio of 1.37, which is the same ratio 
used for the SC IGIV-C 10%.
For IGSC 20% preclinical data support an IVIG:IGSC 20% dose adjustment factor of 1.37. 
In a single dose study in New Zealand White rabbits, the AUC plasma fractional availability 
was calculated for IGSC 20% vs. IGIV-C 10%. A single 100 mg/kg IV bolus injection was 
compared with IGSC 20% at doses of 1.0, 1.15, 1.3, and 1.5 times the IV dose level. IGSC 
20% produced an AUC that was 74%, 80%, 89%, and 95%, respectively, of the AUC 
produced by 100 mg/kg IV IGIV-C 10%. Thus, it is expected, that an IGSC 20% dose in the 
range of 1.3 to 1.5 times the IGIV-C 10% dose level will produce comparable AUC (see 
IGSC 20% IB).
The new product, IGSC 20%, is manufactured in a similar manner to IGIV-C 10% with an 
additional nanofiltration step and a higher final IgG concentration (20%). As such, it is 
anticipated that the clinical dosing strategy, safety, and efficacy attributes of IGSC 20% will 
be similar to IGIV-C 10% in patients with PI. IGIV-C 10% is currently approved for SC 
administration in PI in various geographic regions. The dose adjustment ratio employed in 
this protocol (1.37) for the transition from IV to SC route has been successfully evaluated 
with IGIV-C 10% in 2 Grifols clinical studies (06001 and T5004-401). Accordingly in this 
study, a 1:1.37 IV to SC dose adjustment factor will be initially employed for the transition 
from IVIG to IGSC 20% treatment and will be evaluated in the interim PK analysis.
Grifols Study 060001 showed that weekly SC administration of IGIV-C 10% in 
32 adult/adolescents PI subjects resulted in a relatively constant steady-state trough 
concentration of total IgG (1140 mg/dL). The steady-state trough levels of IgG following SC 
infusions were found to be 19% higher than those from IV infusions. There were no SBIs 
reported in the 24-week SC treatment phase (34). This study demonstrated that the 1:1.37 IV 
to SC dose adjustment factor produced a point estimate for the geometric least squares mean 
(LSM) ratio of AUCSC vs. AUCIV of 0.888, with a 90% confidence interval (CI) of 0.861 to 
0.917 (analysis of variance [ANOVA]). The lower bound of the 90% CI was above 0.80 
indicating that the SC dose was non-inferior to the IV dose in terms of AUC. In addition, the 
90% CI was within the limit of 0.80 to 1.25, a criterion for concluding “bioequivalence” 
between the 2 treatments (SC and IV doses of IGIV-C 10%).
Additionally, a recently completed pediatric study (Grifols Study T5004-401) of weekly SC 
administration of IGIV-C 10% in 11 pediatric subjects (age range 4-15 years) also resulted in 
no SBI reported in the 12-week SC treatment period. The mean steady-state minimum
concentration (Ctrough) of total IgG was 1325 mg/dL following weekly SC infusion of IGIV-C 
10% which was 31% higher than that of the IV dosing Ctrough (997 mg/dL) (1.37 dose 
adjustment factor relative to IV). The mean of the ratios of SC AUC vs. IV AUC was also 
favorable (mean ± SD: 1.05 ± 0.104).

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 33 of 94
Accordingly in this study, a 1:1.37 IV to SC dose adjustment factor will be initially 
employed for the transition from IVIG to IGSC 20% treatment and will be evaluated in the 
interim PK analysis (Section 3.1.5).
2
STUDY OBJECTIVES
2.1
Primary Pharmacokinetic Objective

To determine a dose of weekly subcutaneously administered IGSC 20% that produces 
steady-state AUC of total IgG that is non-inferior to that of the regularly administered IV
dose of IGIV-C 10% in PI subjects
2.2
Secondary Objective

To determine if IGSC 20% replacement therapy maintains mean steady-state trough total
IgG levels that are comparable to the mean trough total IgG levels with the IGIV-C 10% 
replacement therapy in PI subjects
2.3
Exploratory Objectives

To evaluate tmax (time to reach Cmax) and Cmax in PI subjects at steady state

To evaluate trough levels of IgG subclasses (IgG1, IgG2, IgG3, IgG4)

To evaluate antibody levels for Streptococcus pneumoniae, Hemophilus influenzae, and 
Clostridium tetani (tetanus)

To evaluate the rate of SBIs

To evaluate all infections of any kind (serious/nonserious including acute sinusitis, 
exacerbation of chronic sinusitis, acute otitis media, pneumonia, acute bronchitis, 
infectious diarrhea, etc.) as determined by the Investigator

To evaluate validated infections documented by positive radiograph, fever (> 38°C oral 
or > 39°C rectal), culture, or diagnostic testing for microorganisms, eg, bacterial, viral, 
fungal, or protozoal pathogens (for instance, rapid streptococcal antigen detection test)

To evaluate number of days on antibiotics (including oral, parenteral, oral plus parenteral, 
prophylactic and therapeutic). Use of prophylactic antibiotics will be distinguished from 
antibiotics for treatment of acute infection.

To evaluate number of hospitalizations due to infection

To evaluate number of days of work/school/daily activities missed due to infections and 
their treatment

Trough measles antibody titers (functional assay) are an exploratory variable for 
informational purposes

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 34 of 94
2.4
Safety Objective

To assess the safety and tolerability of IGSC 20% as an IgG replacement therapy in 
subjects with PI
3
INVESTIGATIONAL PLAN
3.1
Study Design and Plan
This is a prospective, multi-center, open-label, single-sequence, 6-month, PK and safety and 
tolerability study of IGSC 20% in subjects with PI. Approximately 50 subjects will be 
enrolled in order to have approximately 30 adult subjects and 12 to 18 pediatric subjects (age 
2-16 years) completing treatment  with subcutaneously administered IGSC 20%.  Pediatric 
enrollment will be stratified by age category with a target of 4 to 6 children for each group: 2
to 5 years, >5 to 12 years, and >12 to 16 years of age. The PK profiles of total IgG following 
administration of both IV (IGIV-C 10%) administration and SC (IGSC 20%) administration 
under approximate steady-state conditions will be determined and compared.  The primary 
objective is to determine a weekly SC dose of IGSC 20% that achieves an AUC of total IgG 
that is non-inferior to that achieved by a subject’s IV dose of immune globulin.
This study will include 3 treatment phases: Run-In Phase, IV Phase (IV administration of 
IGIV-C 10% treatment), and SC Phase (SC administration of IGSC 20%). Before a subject is 
to be enrolled (entering either the Run-In or IV Phase) into the study, the subject will be 
screened during the Screening Phase, which is up to 28 days. The specific inclusion and 
exclusion criteria for this study are described in Section 3.2.
Subjects, depending on their current IgG treatment regimen, may be required to enter the 
Run-In Phase to receive IV IGIV-C 10% treatment (Sponsor provided)  to achieve an 
approximately steady-state condition prior to entering the IV Phase. They will then enter the 
IV Phase to determine the AUC profile of IV infusions of IGIV-C 10%.
Subjects with a qualifying IV IGIV-C 10% treatment regimen (on stable IGIV-C 10% doses
of 300-800 mg/kg) can enter the IV Phase directly where they will receive IGIV-C 10%
(Sponsor provided). In the IV Phase, steady-state IV PK assessments including AUC will be 
performed.
After completing the IV Phase, subjects will enter the SC Phase to receive weekly SC doses 
of IGSC 20% for at least 24 weeks. The IGSC 20% dose will be determined by using an 
initial IV to SC dose adjustment factor of 1.37. After reaching an approximate steady-state 
condition, the SC PK profiles including AUC at SC Week#13 will be determined.
The interim serial PK samples (for both the IGIV-C 10% IV and the IGSC 20% SC dosing 
phases) may be obtained at an alternate location.  If an outside agency is utilized for sample 
collection, the samples will be drawn and processed per protocol and laboratory manual 
instructions.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 35 of 94
Comparison of the IV PK profiles and IGSC 20% PK profiles in the first 6 adult/adolescent 
subjects will be performed through an interim PK analysis. If the dose adjustment factor is 
deemed acceptable (SC dose of IGSC 20% is non-inferior to the subject’s IV dose) 
(Section 3.1.5), all subjects will continue to complete treatment and assessments through 
Week#25 (no further monthly extension visits). Otherwise, a new dose adjustment factor will 
be employed for all subjects following the procedures described in Section 3.1.5, and 
subjects will receive 24 weeks of IGSC 20% treatment at the new IGSC 20% dose. In this 
study, the PK profiles will be assessed in all subjects. Subjects aged 2 to 5 years old will be 
assessed using an abbreviated sampling schedule for PK profiles.
The overall study diagram is depicted in Figure 3-1 and Figure 3-2.  The subject entry criteria 
are described in Table 3-1.
Figure 3-1 Overall study design
3.1.1
Screening Phase
At screening, subjects will be categorized into 3 groups: 1) those subjects who can directly 
enter the IV Phase of the study, 2) those who will require a 3-month Run-In Phase, and 3) 
those who will require a 4-month Run-In Phase (Figure 3-1 and Table 3-1). The Screening 
Phase is up to 28 days long.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 36 of 94
Table 3-1 Study entry of subjects
Subject Populations at Screening Based upon Most 
Recent IgG Treatment History
(All must have confirmed diagnosis of PI)
Required Study 
Entry Point
IGIV-C 10% Dose and 
Interval during Study
1
Receiving stable (≥3 months) dose of IV IGIV-C 10% 
between 300 and 800 mg/kg, every 3 or 4 weeks
IV Phase       
(IV#1)
Same dose and interval as at 
screening.
2
Receiving IVIG other than IGIV-C 10% with doses 
between 300 and 800 mg/kg, every 3 or 4 weeks
Run-In Phase   
(3 month)
Same dose and interval as at 
screening.
3
Receiving IVIG other than IGIV-C 10%, but either 
not on stable dose (≥ 3 months) OR dose is not
between 300 and 800 mg/kg OR interval is not every 3 
or 4 weeks
Run-In Phase   
(4 month)
Dose (300-800 mg/kg) and 
interval (3 or 4 weeks) to be 
determined by Investigator.
Receiving SCIG  
Run-In Phase   
(4 month)
Dose (300-800 mg/kg) and 
interval (3 or 4 weeks) to be 
determined by Investigator.
3.1.2
Run-In Phase
Group 1 - Subjects are eligible for direct entry into the IV Phase:
Subjects who are already receiving a stable (≥3 months) dose of IV IGIV-C 10% between 
300 and 800 mg/kg per infusion every 3 or 4 weeks, do not need to enter the Run-In Phase 
and may proceed directly to the IV Phase. These subjects will have their IV#1 Visit
scheduled to coincide with the date for their next IV infusion according to their regular 
dosing interval. The subjects will come to the clinic for this visit.
Group 2 - Three (3)-month Run-In Phase:
Those subjects who prior to screening are receiving IVIG therapy (at a dose between 300 and 
800 mg/kg per infusion every 3 or 4 weeks) but who are not receiving IGIV-C 10% 
specifically (ie, a different commercially available IVIG) will be required to receive IGIV-C 
10% intravenously (at an equivalent dose and dosing interval as in their previous IVIG 
therapy) for a total duration of a 3-month Run-In Phase. Subjects receiving infusions every 3 
weeks will have 4 Run-In visits and subjects receiving infusions every 4 weeks will have 3 
Run-In visits.
Group 3 - Four (4)-month Run-In Phase:
The following subjects will be required to participate in a 4-month Run-In Phase:

Subjects who are currently receiving IVIG therapy but have not been on a stable dose for 
the 3 months prior to screening OR where the dose is not between 300 and 800 mg/kg 
OR who receive IVIG infusions that are not administered at a frequency of every 3 or 
4 weeks

Subjects who prior to screening are receiving SCIG

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 37 of 94
Subjects meeting any of the criteria for Group 3 will be scheduled to begin receiving IGIV-C 
10% intravenously at a dose of 300 to 800 mg/kg every 3 to 4 weeks (dose and interval to be 
determined based on the investigator’s clinical judgment) for a period of up to 4 months prior 
to the IV#1 visit. Subjects receiving infusions every 3 weeks will have 5 Run-In visits and 
subjects receiving infusions every 4 weeks will have 4 Run-In visits. 
3.1.3
IV Phase
In the IV Phase, subjects will receive 2 IV infusions of IGIV-C 10%. At the IV#1 visit, 
subjects who have at screening entered directly into the IV Phase of the study will receive a 
dose of IV IGIV-C 10% equivalent to their current IgG dose.  Subjects who have been 
required to go through a Run-In Phase will receive the same dose of IV IGIV-C 10% as have 
been administered during that pre-requisite Run-In period.  Blood draws for PK profiling will 
begin just prior to the first IGIV-C 10% infusion (IV#1) and will continue throughout the 
subject’s normal dosing period (3 or 4 weeks total).  At the end of this period and in order to 
ensure that the subjects have adequate total IgG levels prior to initiating study drug by SC, a 
second dose of IV IGIV-C 10% will be administered (IV#2). The SC Phase will begin 1 
week after the IV#2 visit.
3.1.4
SC Phase
One week (7 days) after the second IV dose (IV#2), subjects will return to the clinic to begin 
the weekly SC administrations of IGSC 20%.  The SC Phase will continue for a total of 
24 weeks (6 months).  The initial weekly SC dose is calculated as described in Section 3.3.2.
Briefly, the SC dose is calculated using the following formula:
After 12 weeks (3 months) of weekly SC therapy, determination of PK profiles for total IgG 
during the SC Phase will begin at the blood draw just prior to the 13th SC infusion with the 
last sample collected immediately prior to the 14th SC infusion (7 days total).
The detailed study flow chart and specific time points for PK sampling for IV IGIV-C 10% 
and SC IGSC 20% administration are outlined in Figure 3-2.
300 to 800 mg/kg (IV dose)
3 or 4 (regular IV dosing interval in week)
× 1.37 (IV to SC dose adjustment factor)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 38 of 94
Figure 3-2 IV dosing of IGIV-C 10% and SC dosing of IGSC 20% Clinic Visits and PK sampling schedules (Also 
see Sections 3.6.2.3 and 3.6.2.4)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 39 of 94
3.1.5
Interim PK Analysis
The dosing regimen for SC administration of IGSC 20% is based on literature data of the 
bioavailability of subcutaneous administered IgG and prior experience with SC IGIV-C 10%. 
The weekly IGSC 20% dosing regimen to be evaluated herein (1.37 times the currently stable 
IV IgG dose divided by 4 for subjects on an every-4-week dosing schedule or divided by 
3 for subjects on an every-3-week dosing schedule) is predicted to provide an steady-state 
AUC of total IgG levels not inferior to that of the prior IV dose based on the established 
bioequivalence acceptance data.
While it is believed that a dose adjustment factor of 1.37 for determining an SC dose of 
IGSC 20% (from an IV dose) is suitable, an interim PK analysis is planned to confirm that 
this SC dose adjustment factor calculation is adequate and to allow for potential modification 
of the dose adjustment factor if necessary.  The interim PK analysis will be performed as 
soon as practical after the first 6 adult/adolescent subjects (age ≥12-75 years) have completed 
the steady-state PK sampling schedule for both the IV (IV#2) and SC Phases (SC#14) of the 
trial.  Data from these 6 adult/adolescent subjects will be analyzed using standard PK and 
statistical methodology (Section 5) to evaluate and compare the AUC0-τ’s of total IgG from 
the IV administration of IGIV-C 10% and SC administration of IGSC 20%.
The outcome of this interim analysis will determine whether the dose adjustment factor will 
be modified. If the ratio of geometric LSM for AUC0-7, SC vs. adjusted AUC0-7, IV falls below 
10% of the desired 1.0 (ie, <0.9), and the mean trough concentrations for the SC 
administration of IGSC 20% falls below the target level in more than 3 of the 6 
adult/adolescent subjects, then a dose adjustment factor increase would be implemented to 
ensure that the subjects receive an optimal IGSC 20% and are not susceptible to potential 
bacterial infections.
If the ratio of geometric LSM for AUC0-7, SC vs. adjusted AUC0-7, IV, achieves ≥0.9, there will 
be no change in the dose adjustment factor.
Subjects enrolled early in the trial may complete their regularly scheduled 24 weeks of SC 
therapy on the initial IGSC 20% dose before a decision from the interim analysis is available. 
In this event, these subjects will continue to receive weekly SC infusions of IGSC 20% until 
the interim PK analysis deems whether or not a new dose adjustment factor would be 
required.  Subjects will return to the study center every 4 weeks for evaluation and have the 
same study procedures performed as those at SC Week#21 with (at less frequent intervals)
safety laboratory assessments, IgG subclass levels, and specific antibody titers for S. 
pneumoniae, H. influenzae, and C. tetani (tetanus) every 8 weeks as detailed in 
Section 3.6.2.5.  This will continue until the interim analysis is completed.  If the results of 
the interim analysis do not indicate a need for a dose adjustment factor change, subjects will 
be brought into the clinic and end of study procedures will be performed.
If the need for changing the dose adjustment factor arises, the revised dose adjustment factor 
will be calculated based on the ratio of the geometric LSM for AUC0-7, SC vs. adjusted
AUC0-7, IV with consideration of mean trough levels obtained from the SC administration of 
IGSC 20%.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 40 of 94
The revised dose adjustment factor will be communicated to sites and the revised dose 
adjustment factor would be applied to the subjects’ next SC infusion of IGSC 20% in the 
clinic, which should be scheduled as soon as possible, upon receiving formal notification 
from the Sponsor.  These subjects will re-commence at SC#1 with the new dose adjustment 
factor. All subjects will be required to have a minimum of 24 weekly SC infusions of 
IGSC 20% with the new dose adjustment factor. For subjects currently in the SC Phase or 
who have completed the 24 weeks of the SC Phase and are continuing on treatment until the 
results of the interim PK analysis are available, subjects will be required to continue in the 
SC Phase with the revised dose adjustment factor for 24 weekly SC infusions. In both of the 
above situations, all subjects will have a repeat complete IGSC 20% PK profile after 
12 weeks on the new dose adjustment factor (same assessment as initial SC Week #13). The 
time points for PK blood sample collection will be those outlined in Figure 3-2 and 
Section 3.6.2.4.
3.2
Selection of Study Population
Eligible participants for this study include male or female subjects who are 2 to 75 years of 
age and have a diagnosis of PI requiring IgG replacement treatment. Subjects who initially 
fail to meet eligibility criteria may be re-screened once upon consultation with the Sponsor. 
Subjects who fail to meet eligibility criteria upon re-screen are Screen Failures and will not 
be eligible to participate in the study.
3.2.1
Inclusion Criteria
A subject must meet all the following inclusion criteria to be eligible for participation in this 
study:
1. Subjects between the ages of 2 and 75 years (inclusive) at Screening.
2. Documented and confirmed pre-existing diagnosis of PI with features of
hypogammaglobulinemia requiring IgG replacement therapy including but not limited to
the following humoral-based immunodeficiency syndromes (eg, X-linked
agammaglobulinemia, common variable immunodeficiency), and combined
immunodeficiency syndromes without lymphocytopenia (eg, hyper immunoglobulin M
[IgM] immunodeficiency syndrome). Please also refer to Exclusion Criteria.
3. The subject has not had a SBI within the last 3 months prior to or during Screening.
4. Currently on IgG replacement therapy (via IV or SC infusion) for ≥3 months.
5. Note: This inclusion criterion is removed in protocol amendment 2.
6. Screening trough IgG levels must be ≥500 mg/dL.
Note: If Screening trough levels are not above this threshold, the subjects will be a Screen
Failure, but may be re-screened following dose adjustment of their original IgG
replacement therapy regimen and maintaining stable dosing for a period of at least 3
months prior to Screening a second time.
7. The medical records for all subjects should be available to document diagnosis, previous
infections, and treatment.
8. The subject has signed an informed consent.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 41 of 94
Note: The subject must sign the informed consent form (ICF) if at least 18 years old; for 
children of younger age,  the subject’s parent or legal guardian must sign the ICF and if 
appropriate/applicable, the subject must sign a Child Assent form approved by the 
Institutional Review Board or Ethics Committee (IRB/EC) per their requirements (See 
Section 7.4).
3.2.2
Exclusion Criteria
A subject meeting any of the following exclusion criteria is NOT eligible for participation in 
the study.
1. Clinical evidence of any significant acute or chronic disease that, in the opinion of the
Investigator, may interfere with successful completion of the trial or place the subject at
undue medical risk
2. The subject has had a known serious adverse reaction to immunoglobulin or any severe
anaphylactic reaction to blood or any blood-derived product
3. The subject has a history of blistering skin disease, clinically significant
thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections or other
disorders where SC therapy would be contraindicated during the study
4. The subject has isolated IgG subclass deficiency, isolated specific antibody deficiency
disorder, or transient hypogammaglobulinemia of infancy
5. The subject has known selective immunoglobulin A (IgA) deficiency (with or without
antibodies to IgA)
6. Females of childbearing potential who are pregnant, have a positive pregnancy test at
Screening (serum) or IV#1 Baseline (urine) (human chorionic gonadotropin [HCG]-based
assay), are breastfeeding, or unwilling to practice a highly effective method of
contraception (oral, injectable or implanted hormonal methods of contraception,
placement of an intrauterine device [IUD] or intrauterine system [IUS], condom or
occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or
true abstinence) throughout the study
Note: True abstinence: When this is in line with the preferred and usual lifestyle of the
subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation
methods], declaration of abstinence for the duration of a trial, and withdrawal are not
acceptable methods of contraception.)
7. The subject has significant proteinuria (dipstick proteinuria ≥3+ or known urinary protein
loss > 1 g/24 h or nephrotic syndrome) and/or has a history of acute renal failure and/or
severe renal impairment (blood urea nitrogen [BUN] or creatinine more than 2.5 times
the upper limit of normal [ULN]) and/or on dialysis
8. The subject has Screening Visit values of aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) levels exceeding more than 2.5 times the ULN for the expected
normal range for the testing laboratory.
9. The subject has hemoglobin <9 g/dL at Screening.
10. The subject has a history of or current diagnosis of deep venous thrombosis (DVT) or
thromboembolism (eg, deep vein thrombosis, myocardial infarction, cerebrovascular

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 42 of 94
accident or transient ischemic attack); history refers to an incident in the year prior to 
Screening or 2 episodes over lifetime.
11. The subject is currently receiving anti-coagulation therapy which would make SC
administration inadvisable (vitamin K antagonists, nonvitamin K antagonist oral
anticoagulants [eg, dabigatran etexilate targeting Factor IIa, rivaroxaban, edoxaban, and
apixaban targeting Factor Xa], parenteral anticoagulants [eg, fondaparinux]).
12. The subject currently has a known hyperviscosity syndrome.
13. The subject has an acquired medical condition that is known to cause secondary immune
deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma,
chronic or recurrent neutropenia (absolute neutrophil count less than 1000/µL
[1.0 x 109/L]), or human immunodeficiency virus (HIV) infection/acquired immune
deficiency syndrome (AIDS).
14. The subject has a known previous infection with or clinical signs and symptoms
consistent with current hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
15. The subject (if < 18 years of age) has non-controlled arterial hypertension at a level of
greater than or equal to the 90th percentile blood pressure (either systolic or diastolic) for
their age and height (See Appendix 3) or the adult subject has non-controlled arterial
hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure
>100 mmHg)
16. The subject is receiving any of the following medications: (a) immunosuppressants
including chemotherapeutic agents; (b) immunomodulators; (c) long-term systemic
corticosteroids defined as daily dose >1 mg of prednisone equivalent/kg/day for
>30 days.
Note: Intermittent courses of corticosteroids of not more than 10 days would not exclude
a subject. Inhaled or topical corticosteroids are allowed.
17. The subject has known substance or prescription drug abuse
18. The subject has participated in another clinical trial within 30 days prior to Screening
(observational studies without investigative treatments [non-interventional] are
permitted) or has received any investigational blood product with the exception of other
IgG products within the previous 3 months
19. The subject/caregiver is unwilling to comply with any aspect of the protocol, including
the home SC infusions, blood sampling, and completion of a SC infusion diary for the
duration of the study
20. Mentally challenged subjects who cannot give independent informed consent or assent
21. In the opinion of the Investigator, the subject may have compliance problems with the
protocol and the procedures of the protocol
3.3
Treatments
3.3.1
Treatments to Be Administered
IGSC 20% (IP) and IGIV-C 10% (study drug) are provided by the Sponsor for this study.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 43 of 94
3.3.1.1
IGSC 20%
Grifols Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified 
(IGSC 20%) is a sterile liquid formulation of immunoglobulin that is purified from human 
plasma via a multi-step process. IGSC 20% is manufactured using the same process as for 
IGIV-C 10% (Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography 
Purified [IGIV-C]), with the addition of a nanofiltration step and is further concentrated by 
ultrafiltration to a higher IgG concentration (20%). IGSC 20% vials will be supplied in a 
50 mL vial size or smaller containing a 20% solution of immunoglobulin, ie, a concentration 
of 20 g/100 mL, with a nominal 10 grams immunoglobulin per vial.
3.3.1.2
IGIV-C 10%
IGIV-C 10% is a sterile liquid formulation of immunoglobulin that is purified from human 
plasma via a multi-step process. IGIV-C 10% is a licensed product. IGIV-C 10% vials may 
be supplied in the vial sizes of 10, 25, 50, 100, and 200 mL.  In this study, administration of 
IGIV-C 10% will be via the IV route only.
3.3.1.3
Labeling of Investigational Products
IGSC 20% and IGIV-C 10% will be labeled according to the requirements of local law and 
legislation. Label text will be approved according to agreed Grifols Therapeutics Inc. 
procedures, and a copy of the labels will be made available to the study site upon request.
3.3.1.4
Storage of Investigational Products
IGSC 20% and IGIV-C 10% must be stored in a secure area accessible to study personnel 
authorized by the Investigator, such as the study staff responsible for the preparation and 
dispensing of IP/study drug.
IGSC 20% and IGIV-C 10% must be stored at temperatures of 2°C to 8°C (36°F to 46°F) 
and protected from light. Do not freeze or partially freeze. Investigators, or designees, are 
responsible for maintaining storage temperature records and for immediately reporting 
deviations in temperature to the study monitor.
Details for the storage are located in the pharmacy manual provided to each site and 
instructions will also be provided to participating subjects.
3.3.1.5
Preparation
The volume (ie, total infusion dose administered) of IGSC 20% to be prepared for each SC 
infusion will be individualized for each subject based on an IV to SC dose adjustment factor 
of 1:1.37 using body weight-based dosing. IGIV-C 10% dose will be based on subject’s 
previous IGIV-C 10% or other IVIG product regimen. See Table 3-1.
IGSC 20% and IGIV-C 10% must be inspected visually before being administered. The 
solution must not be used if turbid or if it contains visible particles. Solution which has been 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 44 of 94
frozen should not be used. The Investigator, or designee, is responsible for immediately 
reporting any issues noted with IGSC 20% and IGIV-C 10% to the study monitor.
Reference the pharmacy manual/study manual for detailed instructions for IGSC 20% and 
IGIV-C 10% preparation and administration.
3.3.1.6
Accountability for Investigational Products
IGSC 20% and IGIV-C 10% are to be used only for the study in accordance with the 
directions given in this protocol and pharmacy/study manual. The Investigator, or designee 
such as the study pharmacist, is responsible for the distribution of the IP/study drug in 
accordance with directions given in the protocol and pharmacy manual.
The Investigator, or designee such as the study pharmacist, is responsible for maintaining 
accurate records of IGSC 20% and IGIV-C 10% for his/her site. IP/study drug 
inventory/dispensing documentation, verifying the receipt, dispensing, destruction or return 
must be maintained and kept current by the Investigator or designee. The inventory must be 
made available for inspection by the monitor. IGSC 20% and IGIV-C 10% supplies must be 
accounted for by the monitor and inventory/dispensing logs must be verified by the monitor 
prior to IGSC 20% and IGIV-C 10% return or destruction. Written documentation of all used 
and unused inventory is required. At the end of the study, a copy of the inventory/dispensing 
log(s) will be retrieved by the monitor and returned to Grifols Therapeutics Inc.
3.3.2
Rationale for Selection of Doses/Timing of Investigational Products
3.3.2.1
Selection of Doses and Timing of Dosing in the Study
In the current study, the initial IV to SC dose adjustment calculation formula used is: 
The selection of dosing regimen for SC administration of IGSC 20% is based on literature
data of the bioavailability of SC administered IgG and prior experience with other products 
(Section 1.3.1). The weekly IGSC 20% SC dosing regimen to be evaluated herein 
(1.37 times the currently stable IV IGIV-C 10% dose divided by 4 for subjects on an 
every-4-week dosing interval or divided by 3 for subjects on an every-3-week dosing 
interval) should provide a steady-state AUC of total IgG levels not inferior to that of the 
approved IV dose based on the established bioequivalence acceptance data.
The initial SC dose selected based on a dose adjustment factor of 1.37 will be evaluated in an 
interim PK analysis after the first 6 adult/adolescent subjects have completed both the IV and 
SC PK sampling schedule. If the interim PK analysis suggests that modification of the SC 
dose adjustment factor is needed, a new SC dose adjustment factor will be calculated and the 
procedures in Section 3.1.5 will be followed.
300 to 800 mg/kg (IV dose)
3 or 4 (regular IV dosing interval in week)
× 1.37 (IV to SC dose adjustment factor)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 45 of 94
As described in Section 3.1, the initial IV IGIV-C 10% dose (Run-In or IV Phase) and dosing 
interval will be individualized based on the treatment each subject is receiving for their PI at 
screening (see Table 3-1).
3.3.2.2
Selection and Timing of Dose for Each Subject
The IV and SC dose of study drug will be individualized based on each subject’s current IgG 
regimen which is assumed to be an effective dose. Subjects are required to have been 
clinically stable for at least 3 months on an IgG product. The IV IGIV-C 10% dose will be 
between 300 and 800 mg/kg during the Run-in phase and IV#1 and IV# 2. See Table 3-1.
Subjects currently on stable IV IGIV-C 10% (for at least 3 months) will receive their first IV 
dose of IGIV-C 10% at the IV#1 visit.  Subjects currently on IVIG therapy other than IV 
IGIV-C 10% will receive IV IGIV-C 10% for at least 3 months (during Run-In Phase) prior 
to the IV#1 visit. Subjects currently on SCIG therapy, or whose IVIG dose is not stable for 
the 3 months prior to Screening, or IVIG dose is not between 300 and 800 mg/kg per infusion 
or not receiving infusions every 3 or 4 weeks at Screening will receive IV IGIV-C 10% for at 
least 4 months in Run-In Phase prior to the IV#1 visit. Subjects will return to the clinic at 
their next scheduled IV dosing interval (ie, 3 or 4 weeks later) to receive a 2nd IV IGIV-C 
10% dose (IV#2 Visit).
The first SC administered IGSC 20% will be initiated 7 days after the 2nd IV IGIV-C 10% 
dose (at the SC Week#1 visit).  Weekly (q 7 days ± 1 day) SC administrations of IGSC 20% 
will continue for a total of 24 weeks. The weekly SC dose will be one quarter of the current 
IV monthly dose if the subject is on a 4 week dosing regimen or one third of the current IV 
dose if the subject is on a 3 week dosing regimen multiplied by 1.37 as previously described.
If the interim PK analysis suggests that modification of the SC dose adjustment factor is 
needed, a new SC dose adjustment factor will be calculated and the procedures in 
Section 3.1.5 will be followed.
3.3.2.3
Subcutaneous Administration Procedures for IGSC 20%
The number of injection sites, infusion rate, and the specific times of the day for the SC 
infusion may be individualized by the subject and Investigator. The first 3 SC infusions will 
be given under supervision in the clinic before self-administration at home will be allowed.  
The selected pump specifically designed for SC infusions will be provided for individual use 
to each subject prior to the SC Phase and each subject will be trained thoroughly on its use.  
The PK focus of the study will be emphasized to all the subjects/caregivers. Subjects will be 
instructed to closely adhere to their individualized dosing regimen accurately and cautioned 
not to round-up to the whole vial or to under dose.  The exact IGSC 20% dose (and dose 
volume) based on the predetermined adjustment factor and the stable IV dose of IGIV-C 10% 
will be administered and recorded.
Details regarding infusion rate and infusion administration are located in the pharmacy/study 
manual. Subjects may use the same anatomical area or rotate anatomical areas for SC 
infusions throughout the study. No more than 8 infusion sites per infusion will be used. The 
minimum distance between infusion sites is recommended to be no less than 2 inches. The 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 46 of 94
target infusion rate will be no greater than 25 mL/hour/site as tolerated by the subject and per 
the Investigator’s discretion; the Investigator will tailor the infusion configuration for each 
subject. Once the target infusion rate is achieved, it should not be changed in the middle of 
an infusion unless the subject experiences tolerability issues at that infusion rate. In the event 
that the subject is not able to tolerate the set infusion rate, the rate may be decreased for 
better tolerability. Conversely, if the target infusion rate is well tolerated during 2 infusions,
an increase of 20% in infusion rate and volume per site is allowed at the discretion of the 
Investigator at the time of the clinic visit.
The volume infused, number of infusion sites, infusion start date/time, infusion end 
date/time, the location(s) of infusions, and the initial and final rate of infusion for each 
infusion site, and other SC infusion information will be recorded in the SC Infusion Diary by 
the subject/parents or legal guardians. In addition, SC infusion site reactions may be recorded 
in the diary. Full details regarding the SC Infusion Diary are in Section 3.6.2.4.
3.3.3
Method of Assigning Subjects to Treatment Groups
3.3.3.1
Subject Numbering
Within each study site, subjects in the study will receive a consecutive subject number at 
Screening Visit. Subject numbers are generated beginning with the study center number 
(3 digits, assigned by the Sponsor starting at 100) followed consecutively with a unique 
number for each subject (4 digits). For example, if the Investigator’s center number is 301, 
subject numbers will be 3012001, 3012002, 3012003, etc., in consecutive order. Subject 
numbers, once assigned, will not be reused at any center.
3.3.3.2
Randomization
This is a single-sequence, crossover study with no randomization.
3.3.3.3
Blinding
This is an open-label study with no blinding.
3.3.4
Treatment Compliance
Reasons for any deviation from the administration of less than 100% of all protocol-specified 
doses of IGIV-C 10% or IGSC 20% as prepared by the pharmacist, or designee, must be 
recorded in the eCRF and in the subject’s source documents.
All IV infusions during the Run-In and IV Phases and the first 3 SC infusions will be 
administered in the clinic under the supervision of the treating investigator or designee.  
Subjects will be instructed on SC dosing techniques during the first 3 SC dosing infusions in 
the clinic. All dose calculations will be done by the Interactive Web Response (IWR) system 
and the dose preparation procedures will be provided to each subject for in-home SC 
administration. The actual date/clock time, location of the infusions, number of infusion 
sites, volume, and duration of dosing will be recorded.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 47 of 94
A SC Infusion Diary will be provided to document SC infusions self-administered away from 
the clinic. These data will be used to calculate infusion compliance, dosing compliance, and 
overall drug compliance.
3.4
Prior and Concomitant Therapy
Concomitant medications must be recorded in the subject’s source documents and in the 
eCRF from time of consent, including the trade or generic names of the medication, the dose, 
the route of administration, duration, and frequency.
3.4.1
Prohibited Medications Prior to Study Participation
Use of the following medications, as specified below, would exclude a subject from 
participating in this study:

At the time of Screening, receiving systemic corticosteroids (long-term daily doses
>1 mg of prednisone equivalent/kg/day for >30 days) (intermittent courses of not more
than 10 days would not exclude subject). Note: Inhaled or topical corticosteroids are
allowed.

At the time of Screening, receiving immunosuppressants including chemotherapeutic
agents or immunomodulators

At the time of Screening, receiving anti-coagulation therapy which would make SC
administration inadvisable (vitamin K antagonists, nonvitamin K antagonist oral
anticoagulants [eg, dabigatran etexilate targeting Factor IIa, rivaroxaban, edoxaban, and
apixaban targeting Factor Xa], parenteral anticoagulants [eg, fondaparinux]).
3.4.2
Prohibited Concomitant Medications during the Study
Use of the following during the study (from Screening to SC Week#25 Final Visit) is 
prohibited:

Any IgG replacement therapy other than IGIV-C 10% or IGSC 20% provided in this
study once the first dose of study treatment is administered

Corticosteroids in excess of stipulations delineated in Section 3.4.1

Anti-coagulant therapy as outlined in Section 3.4.1

Immunosuppressants including chemotherapeutic agents or immunomodulators

Investigational products not part of this study
3.4.3
Restricted Concomitant Medications during the Study
For subjects receiving a permissible stable dose of systemic steroids (as defined in 
Section 3.4.1), it is recommended to maintain the same dose throughout the study.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 48 of 94
The medications listed below are not allowed during the study as premedication to an SC
infusion; however these medications are allowed during the study for general use (eg, to treat 
an AE):
Oral medications:

Ibuprofen

Acetaminophen

Antihistamines
Topical medications:

Steroids

Antihistamines
3.4.4
Drug Interactions
In the setting of a PI disease state, live viral vaccines have various contraindications and 
specific risks/degrees of effectiveness dependent on the type/category of the immune 
deficiency (Medical Advisory Committee of the Immune Deficiency Foundation [35]). 
Passive transfer of antibodies from IGIV-C 10% or IGSC 20% may transiently interfere with 
the immune response to live viral vaccines such as measles, mumps, rubella, and varicella in 
the normal host with an intact immune system. Best medical practices should be followed 
regarding immunization requirements, particularly for children during the course of this 
protocol.
3.5
Study Variables
3.5.1
Primary Pharmacokinetic Variables

AUC in the IV Phase: Steady-state AUC of total IgG over a regular dosing interval (τ),
either every 3 weeks or every 4 weeks (ie, AUC0-τ, IV or AUC0-21days,IV or AUC0-28days,IV,
respectively) in PI subjects

AUC in the SC Phase: Steady-state AUC of total IgG over a weekly SC dosing interval
(τ) (ie, AUC0-τ,SC or AUC0-7days,SC) in PI subjects
3.5.2
Secondary Pharmacokinetic Variables

Mean steady-state trough (pre-dose) concentration of total IgG following IV
administration of IGIV-C 10% or SC administration of IGSC 20%
3.5.3
Exploratory Variables

tmax (time to reach Cmax ) and Cmax in PI subjects at steady state

Trough levels of IgG subclasses (IgG1, IgG2, IgG3, IgG4)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 49 of 94

Antibody levels for S. pneumoniae, H.influenzae, and C. tetani (tetanus)

Rate of SBIs

All infections of any kind (serious/nonserious including acute sinusitis, exacerbation of
chronic sinusitis, acute otitis media, pneumonia, acute bronchitis, infectious diarrhea,
etc.) as determined by the Investigator

Validated infections documented by positive radiograph, fever (>38°C oral or >39°C
rectal), culture, or diagnostic testing for microorganisms, eg, bacterial, viral, fungal, or
protozoal pathogens (for instance, rapid streptococcal antigen detection test)

Number of days on antibiotics (including oral, parenteral, oral plus parenteral,
prophylactic and therapeutic). Use of prophylactic antibiotics will be distinguished from
antibiotics for treatment of acute infection.

Number of hospitalizations due to infection

Number of days of work/school/daily activities missed due to infections and their
treatment

Trough measles antibody titers (functional assay) for informational purposes
3.5.4
Safety Variables
The following safety variables will be assessed in this study:

Adverse events (AEs), suspected adverse drug reactions (suspected ADRs), adverse
reactions (ARs), serious AEs (SAEs), and discontinuations due to AEs and SAEs
Note: All infusion site reactions will be recorded in the eCRF. For local infusion site
reactions where the symptoms/signs lead to infusion interruption or discontinuation,
require concomitant medication, or have an impact on the general condition of the subject
as judged by the Investigator, they will be considered as AEs.

Vital signs during clinic visits (systolic blood pressure [SBP] and diastolic blood pressure
[DBP], heart rate [HR], temperature [T], respiratory rate [RR])

Physical Assessments: physical exams will be recorded as normal or abnormal, according
to the physician’s judgment criteria, and findings will be recorded.

Laboratory assessments including chemistry, hematology, and urinalysis.

Total number of non-serious infections and proportion of subjects who experience non-
serious infections of any kind (including acute sinusitis, exacerbation of chronic sinusitis,
acute otitis media, pneumonia, acute bronchitis, infectious diarrhea, etc.) as determined
by the Investigator.
3.6
Assessments
3.6.1
Assessment Periods
Study phases in this study are described in Section 3.1. The study consists of Screening (up 
to 28 days), Run-In (3-4 months), IV (4-5 weeks), and SC Phases (24 weeks). The total 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 50 of 94
duration of study participation may be up to 50 weeks.  If there is a revision to the IV to SC 
dose adjustment factor, there may be an additional 24 weeks added to the study participation.
3.6.2
Observations and Measurements
The following sections describe the procedures/assessments to take place at each study visit. 
See the Schedule of Study Procedures table in Appendix 1 for a summary of study visits and 
the procedures to be conducted at each visit. For most clinic visits, a ± 1 day window is 
allowed. For the serial PK sampling visits, see specific PK windows in Section 3.6.2.3 and 
3.6.2.4. If there are logistical issues requiring schedule adjustment for weekly subcutaneous 
IGSC 20% administration, SC#1 may be scheduled 6 to 9 days after IV#2.  The SC#2 and 
SC#3 visits must be performed with a +1 day visit window (ie, these 2 visits cannot be 
performed 1 day early). Unscheduled visits may be conducted if deemed necessary for the 
purpose of subject safety.
3.6.2.1
Screening Visit
The subject’s medical records will be reviewed to confirm a documented diagnosis of PI. 
Subjects who are interested in participating will undergo the following tests and procedures:

Written informed consent and assent if applicable will be obtained prior to initiation of
any screening procedures

Eligibility will be checked by careful assessment of the inclusion and exclusion criteria

Demographics and medical history will be recorded including age, gender, age at
diagnosis of PI, and past 12 months of previous/current IgG treatments. Record relevant
medical history defined as any history impactful on the subject’s condition in terms of
current functioning, disability, treatment, or management.

A full physical exam will be performed (excluding breast and genitourinary exam)

Wells Score will be performed as a pretreatment benchmark for all subjects (Appendix 4
provides Wells Score and management details; see also Section 3.6.3.3)

Chest X-ray (if chest X-ray or CT have not been performed within past 6 months prior to
screening) Note: at least one radiographic view (anterior-posterior [AP] or posterior-
anterior [PA]) is required)

Vital signs: SBP and DBP, HR, T, RR after 5 minutes at rest

Body weight and height

Blood and urine samples for clinical laboratory assessments (eg, hematology, clinical
chemistry, special tests, urinalysis, pregnancy testing) (see Section 3.6.3).
-
Hematology: Hemoglobin, hematocrit, platelets, red blood cell count including red
blood cell morphology, white blood cell count with differential; absolute reticulocyte 
count (ARC)
-
Clinical chemistry: Sodium, potassium, creatinine, chloride, calcium, BUN, 
bicarbonate, albumin, lactate dehydrogenase (LDH),  AST, ALT, alkaline 
phosphatase (ALP), glucose, total bilirubin, indirect bilirubin
-
Special tests: Direct antiglobulin (DAT), serum free hemoglobin, and haptoglobin
-
D-dimer sample as a pretreatment benchmark for all subjects

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 51 of 94
-
Urinalysis: pH, protein, glucose, ketones, bilirubin, nitrites, urobilinogen, blood, 
leukocyte esterase (with microscopic examination of urine sediment if abnormal)
-
Serum pregnancy test (potential child-bearing females only)

Total IgG trough level determination: participants will be required to have a screening
total IgG level of ≥500 mg/dL to enroll

Prior and concomitant medications

Adverse events and history of serious infections
Subjects who are eligible for study entry will have their first Run-In Phase visit or IV Phase 
(IV#1) visit scheduled to coincide with the date for their next IV or SC infusion according to
their regular dosing interval.
3.6.2.2
Run-In Phase (If Required) – IV Administration of IGIV-C 10%
The following procedures and tests will be completed at each visit (every 3 or 4 weeks) for 
those subjects who are required to enter either the 3-month or 4-month Run-in Phase (see 
Section 3.1.2 and Appendix 1):

Vital signs (pre-infusion: SBP and DBP, HR, T, RR)

Body weight

Predose blood draw for trough total IgG prior to IV infusion (within 0.5 hour prior to the
start of infusion).

IV IGIV-C 10% infusions

Adverse events including SBIs (subjects with an SBI will discontinue from the study)
Note: Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and
non-serious infections (by category*) as detailed in Section 3.6.3.1. (*The site is to
record non-serious infections [by category] which include infections of any kind
including for example acute sinusitis, exacerbation of chronic sinusitis, acute otitis media,
pneumonia, acute bronchitis, infectious diarrhea, etc., which will be recorded as an AE
with the Investigator answering the following question affirmatively in the eCRF: “Is this
an infection? (verbatim term delineating nature of infection). Also record validated
infections documented by positive radiograph, fever [>38°C oral or >39°C rectal],
culture, or diagnostic testing for microorganisms eg, bacterial, viral, fungal, or protozoal
pathogens [for instance, rapid streptococcal antigen test]. The specific evaluations
performed to validate infections must be recorded in the eCRF.)

Concomitant medications

Record days lost from work/school/daily activities due to infections and treatment
3.6.2.3
IV Phase – IV Administration of IGIV-C 10%
IV#1 VISIT & PK ASSESSMENT FOR IV DOSING
The following procedures and tests (Also see Appendix 1) will be completed for all subjects 
at the IV#1 Baseline visit:

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 52 of 94

Vital signs (pre-infusion: SBP, DBP, HR, T, RR)

Body weight and height

Predose laboratory assessments (as outlined in Screening Visit [Section 3.6.2.1] including
hematology, clinical chemistry, special tests, and urinalysis) prior to IV infusion

Predose blood draw for trough total IgG, IgG subclass, and antibody titer levels for
S. pneumoniae, H.influenzae, and C. tetani (tetanus) prior to IV infusion (within 0.5 hour
prior to the start of infusion).

Predose urine pregnancy test (child-bearing potential females only)

IV IGIV-C 10% infusion and initiate serial PK sampling as detailed below

Concomitant medications

Adverse events including SBIs (subjects with an SBI will discontinue from the study)
Note: Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and
non-serious infections (by category as detailed in Section 3.6.3.1.

Record days lost from work/school/daily activities due to infections and treatment
The PK sampling for IV administered IGIV-C 10% will commence at the IV#1 (IV Phase) 
visit for all enrolled subjects.  Subjects who are between 2 and 5 years of age will undergo an 
abbreviated sampling schedule for serial PK sampling. 
IV PK Sampling for subjects >5 years of age: Blood draws for PK assessment will be 
taken at the following time points:

Prior to IV#1 (IV Phase) infusion (within 0.5 hour of the start of infusion)

Immediately at the completion of IV infusion

1 h after completion of infusion

3 to 16 hours post-infusion with a window of 2 hours around the 16-hour time point if
required by site

1 day ± 2 h  post-infusion

2 days ± 2 h post-infusion

3 days ± 4 h post-infusion

5 days ± 4 h post-infusion

7 days ± 1 day post-infusion

14 days ± 1 day post-infusion

21 days ± 1 day post-infusion (last sample for subjects on a 3-week dosing schedule and
is also the pre-dose trough sample for IV#2)

28 days ± 1 day  post-infusion (only for subjects on a 4-week dosing schedule and is also
the pre-dose trough sample for IV#2)
IV PK Sampling for subjects ≤5 years of age: Blood draws for PK assessments will be 
taken at the following time points:

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 53 of 94

Prior to IV #1 (IV phase) infusion (within 0.5 hour of the start of infusion)

1 h after completion of infusion

3 to 16 hours post-infusion with a window of 2 hours around the 16-hour time point if
required by site

2 days ± 2 h post-infusion

7 days ± 1 day post-infusion

21 days ± 1 day post-infusion (last sample for subjects on a 3-week dosing schedule and
is also the pre-dose trough sample for IV#2)

28 days ± 1 day post-infusion (only for subjects on an every-4-week dosing schedule and
is also the pre-dose trough sample for IV#2)
The actual date/clock time of the start and end of the IV infusion, the volume/amount of dose 
infused, and the rate of infusion will be recorded.
All efforts will be made to obtain all PK samples in the time frame specified above.  The 
final PK blood sample will be drawn prior to the subject receiving the next dose of study 
drug (ie, the second IV dose) in the clinic. If an outside agency is utilized in sample 
collection, the sample will be drawn and processed per protocol instructions to ensure sample 
integrity.
IV#2 VISIT
This visit for the second IV infusion (IV#2) will be conducted at the next scheduled dosing 
interval (ie, 3 or 4 weeks from IV#1).  The following procedures and tests will be performed 
at the IV#2 visit:

Vital signs (pre-infusion: SBP and DBP, HR, T, RR)

Predose blood draw for trough total IgG, IgG subclass, and antibody titer levels for S.
pneumoniae, H.influenzae, and C. tetani (tetanus) prior to SC infusion (within 0.5 hour
prior to the start of infusion).
Note: This trough IgG sample is the same one that is used for PK blood draw at the 21 or
28 day post-infusion time points.

Pre-dose measles antibody titer

IV IGIV-C 10% infusion

Concomitant medications

Adverse events including SBIs (subjects with an SBI will discontinue from the study)
Note: Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and
non-serious infections (by category) as detailed in Section 3.6.3.1.

Record days lost from work/school/daily activities due to infections and treatment
Subjects will return to the clinic 7 days after the IV#2 visit to start the SC Phase of the study 
which includes weekly infusions of IGSC 20% that will continue for a total 24 weeks.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 54 of 94
3.6.2.4
SC Phase – SC Administration of IGSC 20%
CONSIDERATIONS FOR SC ADMINISTRATION
The first 3 weekly doses of SC study drug will be administered in the clinic by medical site 
personnel.  During these clinic visits, subjects will be instructed and informed regarding all 
aspects of the techniques and procedures needed for self-administration of study drug (which 
is to begin at SC Week #4).  The SC dose calculations will be performed by study clinic 
personnel and will be verified (double-checked) by another study staff member. The exact 
SC dose volume to be administered and rate of infusion will be provided to each subject by 
the clinic personnel. The number and location of SC infusion sites will be determined by the 
subjects in consultation with the investigator.
SC infusion diary: An IGSC 20% infusion diary will be provided to each subject prior to the 
first IGSC 20% infusion which may be used to record items including but not limited to: 
infusion site reactions, concomitant medications (including antibiotics [prophylactic and 
therapeutic]), and details of study drug administration (location and number of sites, 
date/clock time of start and end of infusion, dose/volume of each SC dose, duration and rates 
of infusion). The SC infusion diary may also be used to record days of missed 
work/school/daily activities due to infections and related treatment.
Note:  All infusion site reactions will be recorded. For the subset of local infusion site
reactions where the symptoms/signs lead to infusion interruption or discontinuation, require 
concomitant medication, or have an impact on the general condition of the subject as judged 
by the Investigator, these will be considered as AEs.
SC WEEK #1 CLINIC VISIT
Subjects with an SBI identified prior to SC#1 administration will discontinue study. The 
following procedures and tests will be completed at the SC Week #1 visit:

A full physical exam prior to IGSC 20% infusion (excluding breast and genitourinary
exam)

Predose Wells Score will be performed as a benchmark prior to first IGSC 20% dose for
all subjects (Appendix 4 provides Wells Score and management details; see also
Section 3.6.3.3)

Vital signs (pre-infusion: SBP, DBP, HR, T, RR)

Body weight (will be used for SC dose calculation)

Predose laboratory assessments (as outlined in Screening Visit [Section 3.6.2.1] including
hematology, clinical chemistry, special tests, and urinalysis)

Predose D-dimer sample as a benchmark prior to first IGSC 20% infusion for all subjects

Predose virus safety retain samples
Collection of virus safety retain samples prior to IGSC 20% infusion as detailed in
Table 3-2. Collect samples but test only if the subject exhibits clinical signs and
symptoms consistent with hepatitis A virus (HAV), HBV, HCV, HIV, or parvovirus B19
(B19V) infection while participating in the study.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 55 of 94
Note: For children at the discretion of the Investigator, virus safety retain samples may be 
drawn 1 or 2 days prior to SC Week#1 instead of combining with other blood draws on a 
single day. Collected samples will be tested only if the subject exhibits clinical signs and 
symptoms consistent with HAV, HBV, HCV, HIV, or B19V infection while participating 
in the study.

SC infusion of IGSC 20%

Concomitant medications

Adverse events including SBIs
Note: Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and
non-serious infections (by category) as detailed in Section 3.6.3.1.

Record days lost from work/school/daily activities due to infections and treatment
IGSC 20% dosage (mg/kg) will be based on the subject’s prior IgG replacement regimen
and current body weight as described in Section 3.3.

Site personnel will train subjects/caregivers how to administer IGSC 20% using an
infusion SC pump

Train and distribute SC Infusion Diary with subjects/caregivers (See Section 3.6.2.4)
POST SC#1 DAY 2-4 BLOOD SAMPLING VISIT ONLY
Obtain a sample for DAT, serum free hemoglobin, and haptoglobin 2-4 days post SC#1.
No other assessments are needed for this blood draw visit.
SC WEEKS #2, #3 CLINIC VISITS
The objective of these 2 visits is for safety monitoring, for the subject/caregiver to self-
administer SC infusions at the clinic, and for additional self-SC administration training and 
support by the clinical site staff to assure capability for full independent home administration.

Abbreviated physical exam defined as targeted to symptoms and to include examination
of heart, lungs, ears/nose/throat, and with inspection of previous injection sites, and
Specific Signs/Symptoms Check for DVT or pulmonary embolus (PE).
If the following specific signs/symptoms are present, perform Wells Score and blood
draw for D-dimer testing (Appendix 4; see also Section 3.6.3.3):
a.
Clinical suspicion of possible DVT with unilateral symptomatic leg swelling,
accompanied by any of the following pain, warmth, and/or redness
b. Medical suspicion of possible PE in a subject presenting with new or worsening
dyspnea, tachypnea, chest pain, syncope, and cough in the appropriate clinical setting
(cough should not be due to infection, lung disease [eg, asthma, emphysema], or
angiotensin-converting enzyme inhibitors)
c.
Any single alarm symptom such as hemoptysis or cyanosis (36,37,38)

Vital signs (pre-infusion: SBP, DBP, HR, T, RR)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 56 of 94

Predose Special tests (DAT, serum free hemoglobin, haptoglobin) will be performed at
both SC Week #2 and SC Week #3 visits. (These visits represent a 7-day time point after
the prior IGSC 20% infusion). Note that additional special tests (DAT, serum free
hemoglobin, haptoglobin) will be performed 2-4 days post SC #2 only (also noted below
as a separate Blood Sampling Visit).

Observe subject/caregiver self-administration of SC infusion of IGSC 20% in the clinic
Note: Site personnel will observe (and re-train if needed)  subjects/caregivers on
administration IGSC 20% using the infusion SC pump

Concomitant medications

Adverse events including SBIs
Note: Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and
non-serious infections (by category) as detailed in Section 3.6.3.1.

Record days lost from work/school/daily activities due to infections and treatment

Review SC infusion diary and infusion details with subjects/caregivers
POST SC#2 DAY 2-4 BLOOD SAMPLING VISIT ONLY
Obtain a sample for DAT, serum free hemoglobin, and haptoglobin 2-4 days post SC#2.
No other assessments are needed for this blood draw visit.
SC WEEKS #5, #9, #17, AND #21 CLINIC VISITS
The following procedures and tests will be completed at the SC Weeks #5, #9, #17, and 
#21visits:

Abbreviated physical exam with inspection of SC injection sites, and Specific
Signs/Symptoms Check.
If the following Specific signs/symptoms are present, perform Wells Score and blood
draw for D-dimer testing (Appendix 4; see also Section 3.6.3.3):
a.
Clinical suspicion of possible DVT with unilateral symptomatic leg swelling,
accompanied by any of the following pain, warmth, and/or redness
b. Medical suspicion of possible PE in a subject presenting with new or worsening
dyspnea, tachypnea, chest pain, syncope, and cough in the appropriate clinical setting
(cough should not be due to infection, lung disease [eg, asthma, emphysema], or
angiotensin-converting enzyme inhibitors)
c.
Any single alarm symptom such as hemoptysis or cyanosis (36,37,38)

Vital signs (pre-infusion: SBP and DBP, HR, T, RR)

Body weight (will be used for SC dose calculation)

Height SC Week #9, SC Week #17, and SC Week #21 only

SC Week #9,  SC Week#17only: Predose laboratory assessments drawn prior to SC
infusion (as outlined in Screening Visit [Section 3.6.2.1] including hematology, clinical
chemistry, special tests, and urinalysis)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 57 of 94

Predose blood draw for trough total IgG (all visits)

SC Week #9, SC Week#17 only: IgG subclass, and antibody titer levels prior to SC
infusion (within 0.5 hour prior to the start of infusion).

Review SC infusion diary and infusion details with subjects/caregivers

Observe subject/caregiver self-administration of SC infusion of IGSC 20% in the clinic

Concomitant medications

Adverse events including SBIs
Note: Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and
non-serious infections (by category) as detailed in Section 3.6.3.1.

Record days lost from work/school/daily activities due to infections and treatment
AWAY FROM CLINIC (SC WEEKS #4, #6, #7, #8, #10, #11, #12, #15, #16, #18, #19, #20,
#22, #23, #24)
Subjects will begin home self-administration of SC infusions of IGSC 20% beginning with 
the 4th SC infusion. If it is felt by the subject or Investigator that the subject requires 
additional educational training for administering the study drug SC, additional clinic visits 
will be scheduled to further train the subject.  Subjects will be directed to adhere closely to 
their individualized dosing regimen and cautioned not to round-up to the whole vial or under 
dose.
SC infusion diary: The IGSC 20% infusion diary may be used to record items including but 
not limited to: infusion site reactions, concomitant medications (including antibiotics 
[prophylactic and therapeutic]), and details of study drug administration (location and 
number of sites, date/clock time of start and end of infusion, dose/volume of each SC dose, 
duration and rates of infusion). The SC infusion diary may also be used to record days of 
missed work/school/daily activities due to infections and related treatment.
SC WEEK #13 CLINIC VISIT & PK ASSESSMENT FOR SC DOSING
The following procedures and tests will be completed at the SC Week #13 visit:

Abbreviated physical exam with inspection of SC injection sites and Specific
Signs/Symptoms Check.
If the following Specific signs/symptoms are present perform Wells Score and blood
draw for D-dimer testing (Appendix 4; see also Section 3.6.3.3):
a.
Clinical suspicion of possible DVT with unilateral symptomatic leg swelling,
accompanied by any of the following pain, warmth, and/or redness
b. Medical suspicion of possible PE in a subject presenting with new or worsening
dyspnea, tachypnea, chest pain, syncope, and cough in the appropriate clinical setting
(cough should not be due to infection, lung disease [eg, asthma, emphysema], or
angiotensin-converting enzyme inhibitors)
c.
Any single alarm symptom such as hemoptysis or cyanosis (36,37,38)

Vital signs (pre-infusion: SBP, DBP, HR, T, RR)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 58 of 94

Predose blood draw for trough total IgG

Body weight

Observe patient/caregiver self-administration of SC infusion of IGSC 20% in the clinic
and initiate serial PK sampling as detailed below

Concomitant medications

Adverse events including SBIs
Note: Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and
non-serious infections (by category) as detailed in Section 3.6.3.1.

Record days lost from work/school/daily activities due to infections and treatment

Review SC infusion diary and infusion details with subjects/caregivers.
PK samples associated with the SC administration of IGSC 20% will commence at the SC 
Week #13 visit for all enrolled subjects including those ≤5 years of age.  Subjects between 
the ages of 2 to 5 years of age will undergo an abbreviated schedule for serial PK sampling.  
Blood draws for PK assessment for subjects >5 years of age will be taken at the following 
times:

Prior to the 13th SC infusion (within 0.5 h of the start of infusion and this is the same
sample for predose trough total IgG level)

1 day ± 4 h  post-infusion

3 days ±  4 h post-infusion

4 days ± 4 h post-infusion

5 days ± 4 h post-infusion

7 days ± 1 day post-infusion (within 0.5 hour prior to the 14th SC dose) for IgG trough
level
Blood draws for PK assessment for subjects ≤5 years of age will be taken at the following 
times:

Prior to the 13th SC infusion (within 0.5 h of the start of infusion and this is the same
sample for predose trough total IgG level)

3 days ±  4 h post-infusion

7 days ± 1 day post-infusion (within 0.5 hour prior to the 14th SC dose) for IgG trough
level
The actual date/clock time of the start and end of the SC infusion, volume/amount of dose 
infused, rate of infusion, and location and number of infusion sites will be recorded.  The 
actual date/clock time for each blood sample for either PK or trough level assessment will be 
collected and recorded. The interim PK samples may be obtained at an alternate location. If 
an outside agency is utilized for sample collection, the sample will be drawn and processed 
per protocol and laboratory manual instructions.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 59 of 94
SC WEEK #14 CLINIC VISIT
The following procedures and tests will be completed at the SC Week #14 visit:

Abbreviated physical exam with inspection of SC injection sites and Specific
Signs/Symptoms Check.
If the following Specific signs/symptoms are present perform Wells Score and blood
draw for D-dimer testing (Appendix 4; see also Section 3.6.3.3):
a.
clinical suspicion of possible DVT with unilateral symptomatic leg swelling,
accompanied by any of the following pain, warmth, and/or redness
b. medical suspicion of possible PE in a subject presenting with new or worsening
dyspnea, tachypnea, chest pain, syncope, and cough in the appropriate clinical setting
(cough should not be due to infection, lung disease [eg, asthma, emphysema], or
angiotensin-converting enzyme inhibitors)
c.
Any single alarm symptom such as hemoptysis or cyanosis (36,37,38)

Vital signs (pre-infusion: SBP, DBP, HR, T, RR)

Predose blood draw for trough total IgG prior to SC infusion (within 0.5 hour prior to the
start of infusion). Note: This trough IgG sample is the same one that is used for PK blood
draw at 7 days post-infusion timepoint (SC Week#13).

Observe subject/caregiver self-administration of SC infusion of IGSC 20% in the clinic

Concomitant medications

Adverse events including SBIs
Note: Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and
non-serious infections (by category) and antibiotic treatment as detailed in
Section 3.6.3.1.

Record days lost from work/school/daily activities due to infections and treatment

Review SC Infusion Diary and infusion details with subjects/caregivers
3.6.2.5
Monthly Extension Visits
The monthly extension visits will occur only for subjects enrolled early in the trial who may 
complete their regularly scheduled 24 weeks of SC therapy on the initial IGSC 20% dose 
before a decision from the interim PK analysis is available. In this event, these subjects will 
continue to receive weekly SC infusions of IGSC 20% until the interim PK analysis deems 
whether or not a new dose adjustment factor would be required.  Subjects will return to the 
study center every 4 weeks for evaluation and have the same study procedures performed as 
those at SC Week#21. At every 8 weeks, safety laboratory assessments, IgG subclass levels, 
and specific antibody titers for S. pneumoniae, H. influenzae, and C. tetani (tetanus) will be 
performed.  This will continue until the interim PK analysis is completed (See Section 3.1.5).
The following procedures and tests will be completed at the Monthly Extension Visit:

Abbreviated physical exam with inspection of SC injection sites and Specific
Signs/Symptoms Check.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 60 of 94
If the following Specific signs/symptoms are present perform Wells Score and blood 
draw for D-dimer testing (Appendix 4; see also Section 3.6.3.3):
a.
Clinical suspicion of possible DVT with unilateral symptomatic leg swelling,
accompanied by any of the following pain, warmth, and/or redness 
b. Medical suspicion of possible PE in a subject presenting with new or worsening
dyspnea, tachypnea, chest pain, syncope, and cough in the appropriate clinical setting 
(cough should not be due to infection, lung disease [eg, asthma, emphysema], or 
angiotensin-converting enzyme inhibitors) 
c.
Any single alarm symptom such as hemoptysis or cyanosis (36,37,38)

Vital signs (pre-infusion: SBP, DBP, HR, T, RR)

Body weight (will be used for SC dose calculation) and height

Every 8 week intervals only: Predose laboratory assessments drawn prior to SC infusion
(as outlined in screening visit [Section 3.6.2.1] including hematology, clinical chemistry,
special tests, and urinalysis) and IgG subclass, and antibody titers for S. pneumoniae,
H. influenzae, and C. tetani (tetanus) prior to SC infusion (within 0.5 hour prior to the
start of infusion)

Predose blood draw for trough total IgG

Observe subject/caregiver self-administration of SC infusion of IGSC 20% in the clinic

Concomitant medications

Adverse events including SBIs
Note: Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and
non-serious infections (by category) as detailed in Section 3.6.3.1.

Record days lost from work/school/daily activities due to infections and treatment

Review SC infusion diary and infusion details with subjects/caregivers
If the results of the interim PK analysis do not indicate a need for a dose adjustment factor 
change, subjects will be brought into the clinic (within one week following the confirmation 
of the initial dose adjustment factor) and end of study procedures will be performed.
3.6.2.6
Final Visit (Week #25)/Early Termination Clinic Visit
The Final Visit (Week #25) visit will be scheduled one week after the final SC infusion.  If a 
subject discontinues at any point during the study after the first Run-In visit or IV#1 for those 
who enter the IV Phase directly, the subject will be requested to return to the Investigator’s 
study site for an Early Termination Visit. The assessments at this visit will be the same as the 
Final Visit in the case a subject who prematurely discontinues the study.
The following procedures and tests will be completed (note that no study-related infusion 
will be scheduled):

Full physical exam (excludes breast and genitourinary exam)

Vital signs (SBP, DBP, HR, T, RR)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 61 of 94

Laboratory assessments (as outlined in Screening Visit [Section 3.6.2.1] including
hematology, clinical chemistry, special tests, and urinalysis)

Blood draw for trough total IgG, IgG subclass, and antibody titers for S. pneumoniae, H.
influenzae, and C. tetani (tetanus)

Serum pregnancy test (for females of childbearing potential)

Measles antibody titer

Concomitant medications

Adverse events including SBIs
Note: Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and
non-serious infections (by category) as detailed in Section 3.6.3.1.

Record days lost from work/school/daily activities due to infections and treatment

Review SC infusion diary and infusion details with subjects/caregivers
3.6.3
Description of Laboratory Tests and Procedures
Detailed descriptions of laboratory test procedures are located in the study Laboratory 
Manual. Table 3-2 provides a summary of the laboratory tests conducted for this study.
Table 3-2 Name, Description, and Location of Laboratory Tests and 
Procedures
Test Panel
Description
Location
Hematologya
Hemoglobin, hematocrit, platelets, red blood cell count including 
red blood cell morphology, white blood cell count with 
differential; ARC
Central
Additional special testsa
DAT, serum free hemoglobin, haptoglobin
Central 
D-dimer
D-dimer
Central
Chemistrya
Sodium, potassium, creatinine, chloride, calcium, BUN, 
bicarbonate, albumin, LDH, AST, ALT, ALP, glucose, total 
bilirubin, indirect bilirubin
Central
IgG levelsa 
Total IgG levels will consist of trough (pre-dose) measurements 
in all subjects, and for PK profiling of IGIV-C 10% (IV Phase) 
and IGSC 20% (SC Phase)
Central
IgG subclass levels and 
antibody titersa
Measurement of IgG subclasses (IgG1, IgG2, IgG3, IgG4). 
Measurement of levels of selected specific antibodies against H. 
influenzae, anti-pneumococcal polysaccharide (S. pneumoniae), 
and C. tetani (tetanus) 
Specialty
Trough measles antibody 
titers (functional assay)a
Trough samples for measles antibody titer will be collected at 
IV#2 (before the first SC infusion of IGSC 20%) and at SC 
Week#25
Specialty
Serum pregnancy testa
Qualitative serum β-HCG for females of child-bearing potential 
will be performed at Screening and Final Visit
Central

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 62 of 94
Table 3-2 Name, Description, and Location of Laboratory Tests and 
Procedures
Test Panel
Description
Location
Urine pregnancy test
Qualitative urine pregnancy test for females of child-bearing 
potential will be performed at IV #1 Baseline
Local
Viral nucleic acid 
amplification technology 
(NAT) testinga, b
SC Week#1 prior to IGSC 20% infusion:
Collect retain samples for hepatitis A virus (HAV) RNA, HBV 
DNA, HCV RNA, HIV RNA, and parvovirus B19 (B19V) DNA 
testing
Central
Viral serology testinga, b
SC Week#1 prior to IGSC 20% infusion:
Collect retain samples for hepatitis A antibody differential 
(IgM/IgG), hepatitis B core antibody differential (IgM/IgG), 
hepatitis C antibody, HIV-1/-2 + Group O antibody, and B19V 
antibody differential (IgM/IgG) testing
Central
Urinalysisa
Microscopic evaluation is done only with cause.
pH, protein, glucose, ketones, bilirubin, nitrites, urobilinogen, 
blood, leukocyte esterase (with microscopic examination of the 
urine if abnormal)
Central
a
Samples collected for laboratory analyses that are non-analyzable due to any factor (ie, lost, quantity 
not sufficient, laboratory error) need to be recollected by contacting the subject and arranging for re-
sampling.
b
See Section 3.6.3.2 for details.
3.6.3.1
Assessment and Recording of Infections
The site is to record non-serious infections (by category), which include infections of any 
kind including for example acute sinusitis, exacerbation of chronic sinusitis, acute otitis 
media, pneumonia, acute bronchitis, infectious diarrhea, etc., which will be recorded as an 
AE with the Investigator answering the following question affirmatively in the eCRF: “Is this 
an infection?” (verbatim term delineating nature of infection). Also record validated 
infections documented by positive radiograph, fever (>38°C oral or >39°C rectal), culture, or 
diagnostic testing for microorganisms eg, bacterial, viral, fungal, or protozoal pathogens (for 
instance, rapid streptococcal antigen test). The specific evaluations performed to validate 
infections must be recorded in the eCRF.
3.6.3.2
Virus Safety Testing
Virus safety (viral NAT and viral serology) retain samples collected at SC Week#1 prior to 
IGSC 20% infusion will be tested only if the subject exhibits clinical signs and symptoms 
consistent with HAV, HBV, HCV, HIV, or B19V infection while participating in the study. 
Virus safety samples will be retained until all analyses in support of the study are complete. 
Additional blood samples for viral NAT and viral serology testing may be collected and 
tested during the study only if the subject exhibits clinical signs and symptoms consistent 
with HAV, HBV, HCV, HIV, or B19V infection while participating in the study. Note: For 
pediatric subjects, at the discretion of the Investigator, virus safety retain samples may be
drawn 1 or 2 days prior to SC Week#1 instead of combining with other blood draws on a 
single day.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 63 of 94
3.6.3.3
D-dimer and Wells Score
The Wells Score for DVT and PE with associated citations is described in Appendix 4 which 
provides full details for assigning point score for each of these individual conditions. At 
Screening and prior to administering IGSC 20% for the first time at the SC Week #1 Clinic 
Visit, Wells Score and blood draw for D-dimer will be performed to establish a pretreatment 
benchmark (prior to receiving IGIV-C 10% and prior to beginning IGSC 20%, respectively).
At subsequent visits during the SC Phase, the Wells Score and blood draw for D-dimer will 
be performed only if the abbreviated physical exam and Specific Signs/Symptoms Check 
(defined in Section 3.6.2.4) raises any clinical/medical concerns regarding possible presence 
of DVT or PE. 
As delineated in Appendix 4, any subject with a total Wells prediction score >1 for the DVT
assessment or >4 for the PE assessment should have further diagnostic testing per study site 
standard of care if medically indicated - unless the D-dimer is negative since this test has a 
high negative predictive value.  If the D-dimer is positive at any time after the Screening time 
point (ie, above Screening value, exceeding cutoff range of the reporting laboratory), redraw 
a blood sample for repeat D-dimer testing at the central laboratory within one week to 
confirm. In all situations, the Investigator should use best medical judgment to evaluate the 
subject as medically indicated.
3.7
Removal of Subjects
Subjects will withdraw or be withdrawn from the study for the following reasons:

At their own request or at the request of their legally acceptable representative

If, in the Investigator's opinion, continuation in the study would be detrimental to the
subject's well-being

At the specific request of the Sponsor
Also, subjects will be withdrawn from IP/study drug or the study for the following reasons:

Subjects with an occurrence of a concomitant disease, or any medical condition which,
either because of its severity or duration or necessary change in treatment, contravenes
the condition of the study or puts the subject at unnecessary risk or harm

Subjects with an occurrence of an AE which in the opinion of the Investigator and/or
subject requires termination of treatment

Subjects who develop an SBI prior to the first dose of IGSC 20%

Subjects who are noncompliant with the protocol per the Investigator’s discretion

Pregnancy
In all cases, the reason for withdrawal must be recorded in the eCRF and in the subject's 
source documentation.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 64 of 94
If a subject discontinues study after receiving IGIV-C 10% but prior to receiving the first 
dose of IGSC 20%, an additional subject may be recruited into the study to assure that 30 
adults and 12 children complete IGSC 20% treatment.
3.8
Follow-up of Subjects Withdrawn from Study
Subjects who receive any amount of IP/study drug and discontinue early from the study will 
be requested to return clinic to have all assessments completed for the Early Termination 
Visit (see Section 3.6.2.6 and Appendix 1) as close as practical to 1 week after their last 
administration of the IP/study drug.
3.9
Premature Termination of Study/Closure of Center
The Sponsor, IRB/EC, and/or regulatory authorities have the right to close this study or a 
study center, and the Investigator/Sponsor has the right to close a center, at any time, 
although this should occur only after consultation among involved parties. The IRB/EC must 
be informed. Should the study/center be closed prematurely, all study materials (except 
documentation that has to remain stored at site) must be returned to the Sponsor. The 
Investigator will retain all other documents until notification given by the Sponsor for 
destruction.
A study center can be closed for the following reasons:

Lack of enrollment

Non-compliance with the requirements of the study protocol

Non-compliance with International Conference on Harmonization Good Clinical Practice
(ICH GCP)
STOPPING RULES FOR THE STUDY AS A WHOLE:
As a conservative measure, if 5 subjects on IGSC 20% develop an SAE of exactly the same 
type (ie, the same MedDRA [Medical Dictionary for Regulatory Activities] preferred term) 
which is not an infection or manifestation of an underlying disorder documented in medical 
history, then this would constitute an unanticipated clustering which could signal a potential 
safety concern. If this situation were to arise, the Sponsor will constitute a Safety Review 
Committee (SRC) whose members (from Grifols) will be impartial and independent of the 
clinical trial team. In cases where there is a clear medical plausibility supporting an 
uncommon clustering of SAEs of the same type (not including infections), and these sentinel 
SAEs are designated as ‘definitely related’, ‘probably related’, or ‘possibly related’ by both 
the Investigator and the SRC, consideration would be given to possibly discontinuing the 
study.
4
ADVERSE EVENTS
4.1
Warnings/Precautions
For complete information on IGSC 20% or IGIV-C 10%, refer to their respective IBs.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 65 of 94
4.2
Adverse Event Monitoring
Subjects must be carefully monitored for AEs. This monitoring includes clinical and 
laboratory tests and physical signs. Adverse events should be assessed in terms of their 
seriousness, severity, and causal relationship to the IP/study drug.
4.3
Adverse Event Definitions
4.3.1
Adverse Events
An AE is defined as any untoward medical occurrence in a subject or clinical investigation 
subject administered a medicinal product or study treatment and that does not necessarily 
have a causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign (including any abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related 
to the medicinal product.
Any AE that occurs at any time between the signature of the ICF and last day of the subject’s 
participation in the clinical trial must be reported and recorded in the AE eCRF.
All infusion site reactions will be recorded. For the subset of local infusion site reactions 
where the symptoms/signs lead to infusion interruption or discontinuation, require 
concomitant medication, or have an impact on the general condition of the subject as judged 
by the Investigator, these will be considered as AEs.
4.3.2
Suspected Adverse Drug Reactions/Adverse Reactions
All noxious and unintended responses to a medicinal product or study treatment related to 
any dose should be considered suspected ADRs. The phrase “responses to a medicinal 
product” means that a causal relationship between a medicinal product or study treatment and 
an AE is at least a reasonable possibility, that is, the relationship cannot be ruled out. In the 
framework of this study, a suspected ADR with a causal relationship of “definite” will be 
labeled as an AR; thus, ARs are a subset of suspected ADRs.
The Sponsor is responsible for assessing the suspected ADR expectedness during the clinical 
trial.
4.3.3
Causality of Adverse Event
The Investigator is required to provide a causality assessment for each AE reported to the 
Sponsor. The Sponsor will consider the Investigator’s causality assessment. Assessment of 
the causal relationship to the study drug will be made according to the following 
classifications based on Karch FE et al. (39):
Definite: An event that follows a reasonable temporal sequence from administration of the 
treatment or in which the treatment level has been established in body fluids or tissues; and 
that is confirmed by improvement on stopping the treatment (dechallenge), and reappearance 
of the event on repeated exposure (rechallenge).

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 66 of 94
Probable: An event that follows a reasonable temporal sequence from administration of the 
treatment; that is confirmed by dechallenge; and that could not be reasonably explained by 
the known characteristics of the subject’s clinical state.
Possible: An event that follows a reasonable temporal sequence from administration of the 
treatment but that could have been produced by the subject’s clinical state or other modes of 
therapy administered to the subject.
Doubtful/Unlikely: An event that follows a reasonable temporal sequence from 
administration of the treatment; but that could not be reasonably explained by the known 
characteristics of the subject’s clinical state.
Unrelated: Any event that does not meet the criteria above.
The operational tool to decide the AE causal relationship is based on algorithms by Karch FE 
et al. and Naranjo CA et al. (40,41).
When an AE is classified, assessing causal relationship by the Investigator, as definitive, ie, 
“probable”, “possible” or “doubtful/unlikely”, the event will be defined as a suspected ADR. 
A suspected ADR with a causal relationship of “definite” will be defined as an AR. When the 
causal relationship is labeled “unrelated”, then it will be considered that the AE is not 
imputable to the study treatment and it is not a suspected ADR.
In addition, when a causal relationship between the study treatment and the AE cannot be 
ruled out by the Investigator and/or Sponsor, it means that the AE cannot be labeled 
“unrelated”.
For any subject, all AEs that occur at any time from the beginning of IP/study drug
administration until the final visit of the clinical trial will be considered as treatment 
emergent AEs (TEAEs).
For AEs that occur during infusions, the infusion rate in effect at the time of onset of the AE, 
the time of onset of the AE and the time of AE change materially in intensity and/or resolve 
will be captured.
4.3.4
Severity of Adverse Event or Suspected Adverse Drug Reaction
AEs and suspected ADRs will be classified depending on their severity according to the 
following definitions:
1. Mild: an AE which is well tolerated by the subject, causing minimum degree of malaise
and without affecting normal activities.
2. Moderate: an AE that interferes with the subject’s normal activities.
3. Severe: an AE that prevents the subject from performing their normal activities.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 67 of 94
AE and suspected ADR severity gradation must be distinguished from AE and suspected 
ADR seriousness gradation, which is defined according to event consequence. For example, 
headache can be mild, moderate or severe but not necessarily serious in all these cases.
The Investigator will be responsible for assessing the AE and suspected ADR intensity 
during the clinical trial, taking into account current criteria included in this section.
4.3.5
Expectedness of Adverse Event or Suspected Adverse Drug Reaction
An AE or suspected ADR is considered “unexpected” if the nature, seriousness, severity or 
outcome of the reaction(s) is not consistent with the reference information. The expectedness 
of an AR shall be determined by the Sponsor according to the reference document (ie, IB).
Events not listed for the particular drug under investigation in the IB are considered 
“unexpected” and those listed are considered “expected.”  When new Serious ADRs 
(potentially related SAEs) are received, it is the Sponsor’s responsibility to determine 
whether the events are “unexpected” for expedited safety reporting purposes.
4.3.6
Seriousness of Adverse Event or Suspected Adverse Drug Reaction; 
Serious Adverse Event
An AE or suspected ADR is considered “serious” if, in the view of either the Investigator or 
Sponsor, it results in any of the following outcomes:
1. Death
2. Life-threatening AE (life-threatening in the definition of “serious” refers to an event in
which the subject was at risk of death at the time of the event; it does not refer to an event
which hypothetically might have caused death if it were more severe)
3. In-patient hospitalization or prolongation of existing hospitalization
4. A persistent or significant incapacity or substantial disruption of the ability to conduct
normal life functions
5. A congenital anomaly/birth defect
6. An important medical event (important medical event in the definition of “serious” refers
to those events which may not be immediately life-threatening, or result in death, or
hospitalization, but from medical and scientific judgment may jeopardize the subject
or/and may require medical or surgical intervention to prevent one of the other outcomes
listed above).
This definition permits either the Sponsor or the Investigator to decide whether an event is 
“serious”. If either the Sponsor or the Investigator believes that the event is serious, the event 
must be considered “serious” and evaluated by the Sponsor for expedited reporting.
A distinction should be drawn between serious and severe AEs. The term “severe” is used to 
describe the intensity (severity) of a specific event; the event itself, however, may be of 
relative minor medical significance (such as severe headache). This is not the same as 
“serious”, which is defined on subject/event outcome or action criteria usually associated 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 68 of 94
with events that pose a threat to a subject’s life or functioning. Seriousness (not severity) is a 
medical term while severity is a subjective term.
According to the medical criteria, an AE or a suspected ADR can be classified as serious, 
although it does not fulfill the conditions fixed in this section, if it is considered important 
from a medical point of view.
4.3.7
Adverse Event and Pregnancy Documentation
All AEs and SAEs occurring after the subject has signed the ICF through the Final Visit (ie, 
end of study) must be fully recorded in the subject’s eCRF or SAE form and medical record. 
If no AE has occurred during the study period, this should also be indicated in the eCRF.
It is the responsibility of the Investigator to ensure that AEs are appropriately recorded.
At each visit, AEs will be elicited by asking the individual a non-leading question such as 
“Do you feel different in any way since the last visit?”  Moreover, AEs will also be collected 
through directly observed events or spontaneously volunteered by the subject. Clearly related 
signs, symptoms and abnormal diagnostic procedures should preferably be grouped together 
and recorded as a single diagnosis or syndrome wherever possible.
The following variables must be recorded in the AE eCRF:
1. the verbatim term (a diagnosis is preferred)
2. date/time of onset
3. date/time of resolution
4. severity (mild, moderate, severe)
5. causality (unrelated, doubtful/unlikely, possible, probable, definite)*
6. seriousness (yes, no)
7. action taken (with regard to IP/study drug)
8. other action (to treat the event)
9. outcome and sequel (follow-up on AE)
*Causality assessment will be made only when the AE occurs after the subject has
initiated at least one infusion of the IP/study drug. An AE occurring before subject's
exposure to IP/study drug will be always labeled as "unrelated".
For AEs that occur during infusions, the infusion rate in effect at the time of onset of the AE, 
the time of onset of the AE and the time of AE change materially in intensity and/or resolve 
will be captured in the eCRF.
In addition to the Investigator’s own description of the AEs, each AE will be encoded 
according to the Medical Dictionary for Regulatory Activities (MedDRA).
For example, a laboratory test abnormality considered clinically relevant, eg, causing the 
subject to withdraw from the study, requiring treatment or causing apparent clinical 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 69 of 94
manifestations, or judged relevant by the Investigator, should be reported as an AE. Each 
event must be described in detail along with start and stop dates, severity, relationship to 
IP/study drug, action taken, and outcome. Each event must be adequately supported by
documentation as it appears in the subject’s medical or case file.
A pregnancy not verified before the screening visit but occurring during the course of the 
study will not be considered an AE unless a relation to the study drug is at least suspected. In 
any case, a Pregnancy Report Form must be completed and sent within 24 hours to the 
Sponsor, and the study treatment must be discontinued. A copy of the form should be filed at 
the study site for follow-up until the end of the pregnancy.
4.3.8
Type and Duration of the Follow-Up of Subjects after Adverse Events
In so far as is possible, all individuals will be followed up until the AE or suspected ADR has 
been resolved. If an AE/suspected ADR/SAE is present when the subject has completed the 
study, the course of the event must be followed until the final outcome is known, or the event 
has been stabilized and no further change is expected and the Investigator decides that no 
further follow-up is necessary.
Any pregnancy must be followed by the Investigator until delivery or to the end of 
pregnancy.
4.4
Reporting of Serious Adverse Events or Pregnancy
4.4.1
Reporting Serious Adverse Event
Any SAE (see Section 4.3.6) that occurs after signing the study ICF through the Final 
Visit (ie, end of study) must be expeditiously reported whether or not considered attributable 
to the study drug. Each SAE must be fully recorded in the subject’s eCRF and SAE Report 
Form.
SAEs will be reported using the designated SAE Report Form. When the Investigator 
becomes aware of an SAE, she/he must submit a completed, signed and dated SAE Report 
Form (in English) within 24 hours to the Sponsor by email/fax.
Each SAE must be followed up until resolution or stabilization. After the initial report, all 
relevant information for SAE follow up, and for the outcome, must also be supplied to the 
Sponsor in a timely manner (within 3 days from its identification or within 24 hours for 
relevant new information) by means of the SAE Report Form. In addition, the Sponsor or 
contract research organization (CRO) may request additional information and/or reports.
All SAE Report Forms and Pregnancy Report Forms must be reported to:
Grifols Global Pharmacovigilance for Reporting SAEs and Pregnancy
Email:
FAX (back-up only): 
 (US/Canada) and 
 (International)

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 70 of 94
When required, and according to local law and regulations, SAEs must be reported to the 
IRB/EC and regulatory authorities.
4.4.2
Reporting Pregnancy
Pregnancies occurring during the course of the study will not be considered an AE unless a 
relation to the study drug is suspected. In any case, a Pregnancy Report Form must be 
completed and sent as soon as possible to the Sponsor for any pregnancies that occur from 
time of consent through the Final Visit (ie, end of study). A copy of the form should be filed 
at the study site for follow-up until the end of the pregnancy. Any pregnancy must be 
followed by the Investigator until delivery or to the end of pregnancy. Any anomalies, 
complications, abnormal outcomes, or birth defects observed in the child must be reported as 
an SAE (see email address or fax number in Section 4.4.1) within 24 hours of the 
Investigator or study personnel’s first knowledge.
5
STATISTICAL METHODS AND DETERMINATION OF SAMPLE 
SIZE
5.1
Statistical and Analytical Plans
Unless otherwise specified, descriptive statistics will include the number of observations, 
mean, standard deviation (SD), median, minimum, and maximum values for the 
continuous/quantitative data or absolute and relative frequency counts and percentages for 
categorical/qualitative data.
Data handling and evaluation procedures will be described as detailed in the Statistical 
Analysis Plan.
5.1.1
Subject Populations for Analysis
Safety Population
The safety population will include all subjects who received any amount of study drugs 
(IGIV-C 10% and/or IGSC 20%) and will be used for safety analysis.
PK Population
The PK population will consist of all subjects who receive study drugs and have sufficient 
and valid total IgG concentration vs. time data for either the IV or SC Phase to allow 
calculation of AUC0-τ,SC or AUC0-τ,IV (the primary PK endpoint).
The validity of total IgG concentrations  will be reviewed and determined before the database 
lock based on consideration of treatment compliance and blood sampling/testing issues (such 
as collection problem). Any invalid total IgG concentrations will be flagged with the reason 
for invalidity in the listing.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 71 of 94
IgG Population
The IgG population will consist of all subjects who receive study drugs and have any total 
IgG concentration data. The summary of total IgG concentration data will be based on IgG 
Population.
5.1.2
Demographic and Baseline Characteristics
The demographic and baseline characteristics will be summarized. For quantitative variables, 
mean, SD, median, and minimum/maximum will be provided. For qualitative variables, the 
frequency and percentage will be provided.
5.1.3
Pharmacokinetic Analysis
All subjects in the PK Population as defined above will be included in the PK analysis.  Total 
IgG concentrations will be summarized for IV and SC by each timepoint.  Individual and 
mean total IgG concentrations vs. time curves will be plotted.  PK parameters of total IgG 
will be determined by noncompartmental PK methods using WinNonlin Professional version 
6.4 or above (Pharsight Corporation, Cary, NC).  Steady-state PK parameters to be 
calculated, as appropriate, or as permitted by data, will include AUC, Cmax, and tmax.  All PK 
parameters will be calculated separately for IV and SC administration and will be tabulated 
and summarized descriptively.  The mean and the lower and upper bounds of the 90% CI will 
be calculated on ln-transformed AUC parameters.  These mean and lower and upper bounds 
will be back-transformed (exponentiated) to provide the geometric mean and 90% CI on the 
original scale.
The Primary PK endpoint is the steady-state AUC over a dosing interval defined as follows:

AUC0- τ,SC , the AUC over a weekly dosing interval (τ) at an approximate steady-state
condition following weekly SC infusion, ie, AUC0-7 days.

AUC0- τ,IV , the AUC over a regular dosing interval (τ) at an approximate steady-state
condition following the regular IV infusion, either every 3 weeks or every 4 weeks, ie,
AUC0-21 days or AUC0-28 days, respectively.
AUC0- τ,SC is to be obtained after the 13th SC dose of IGSC 20% at the weekly dose 
calculated using the final dose adjustment factor, and AUC0- τ,IV is to be obtained following 
IV infusion of IGIV-C 10% at the IV#1 visit.  Since the dosing interval (τ) is 7 days for the 
SC dose, AUC0- τ,SC is determined as AUC0-7 days.  For IV dosing, the dosing interval (τ) is 
21 or 28 days for the 3-week or 4-week subjects, AUC0- τ,IV is determined as AUC0-21 days or 
AUC0-28 days, respectively.
Prior to statistical comparison of AUC0- τ’s between the IV IGIV-C 10% and SC IGSC 20% 
doses, the AUC0-21 days from the IV infusion in subjects on a 3-week IV dosing interval will be 
divided by 3 or the AUC0-28 days from IV dosing in subjects on a 4-week IV dosing interval 
divided by 4 for comparison with AUC0-7 days from the weekly SC infusion.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 72 of 94
The hypothesis to be tested is that the weekly SC dose of IGSC 20% will achieve an 
approximate steady-state AUC0- τ,SC of total IgG that is non-inferior to that achieved by a 
regular IV dose of IGIV-C 10% (AUC0- τ,IV divided by 3 or 4 depending on the IV dosing 
intervals).  Non-inferiority of steady-state IgG AUC between SC dose of IGSC 20% and IV 
IGIV-C 10% administration will be tested based on established regulatory guidelines for 
bioequivalence testing. The 90% CI of the geometric LSM ratio of SC AUC to IV AUC will 
be calculated.  The SC dose is considered to be non-inferior to the IV dose if the low bound 
of the 90% CI for the geometric LSM AUC ratio is above 0.80 based on loge-transformed 
data.
Secondary and Exploratory PK Analysis
Secondary and exploratory PK endpoints include the steady-state mean trough concentration 
of total IgG and the Cmax, tmax of total IgG.  Descriptive statistics will be calculated for the 
steady-state mean trough concentration of total IgG and for the Cmax, and tmax of total IgG.  
All pre-infusion total IgG concentrations obtained before and at the 13th SC dose of IGSC 
20% will be evaluated to determine if an approximate steady-state condition has been 
achieved by the 13th SC dose.  The steady-state mean trough concentrations of total IgG 
following SC administrated IGSC 20% will be determined as the average value of Ctrough
measurements obtained at Weeks#13, #14, #17, and #21. The average steady-state trough 
concentrations of total IgG following IV administrated IGIV-C 10% will be determined as 
the average value of Ctrough measurements obtained at the IV#1 visit and at 21 or 28 days 
after the IV#1 IGIV-C 10% dose (depending on dosing interval), ie, immediately prior to the 
administration of IV dose at IV#2 visit.
Summaries will be provided for trough concentration of total IgG and each of its subclasses 
between IV infusion of IGIV-C 10% and SC administration of IGSC 20%.  Summaries of 
trough level concentration of antibody titers against S. pneumonia, H.influenza, and C. tetani 
will also be provided.
Depending on the number of subjects being dosed on IGIV-C 10% at 3- or 4-week dosing 
intervals, subgroup analyses may be performed to evaluate PK variables by IV dosing 
interval. Subgroup analyses will additionally include age, sex, race, ethnicity and other  
factors as appropriate.
5.1.4
Interim PK Analysis
An interim PK analysis will be conducted as described in Section 3.1.5.  This analysis will be 
performed as soon as practical after the first 6 adult/adolescent subjects (aged ≥12-75 years) 
have completed the PK sampling schedule for both the IV and SC (after the 13th SC dose) 
Phases of the trial.  PK data from these 6 adult/adolescent subjects will be analyzed using 
procedures as described in Section 5.1.3 above.  A decision on whether to modify the dose 
adjustment factor for calculating the SC dose will be made based on this interim PK analysis.
Final PK and statistical analysis will be based on the PK data obtained after the final (or 
adjusted, if any) SC dose administered in all completed subjects.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 73 of 94
5.1.5
Exploratory Analysis
Other exploratory variables include the following:

Serious bacterial infections

All infections of any kind (serious/nonserious including acute sinusitis, exacerbation of
chronic sinusitis, acute otitis media, pneumonia, acute bronchitis, infectious diarrhea,
etc.) which will be recorded as an AE with the Investigator answering the following
question affirmatively in the eCRF: “Is this an infection? (verbatim term delineating
infection).

Validated infections documented by positive radiograph, fever (>38°C oral or >39°C
rectal), culture, or diagnostic testing for microorganisms, eg, bacterial, viral, fungal or
protozoal pathogens (for instance, rapid streptococcal antigen detection test).

Number of days on antibiotics (including oral, parenteral, oral plus parenteral,
prophylactic and therapeutic). Use of prophylactic antibiotics will be distinguished from
antibiotics for treatment of acute infection.

Number of hospitalizations due to infection

Number of days of work/school/daily activities missed due to infections and their
treatment.
These parameters will be summarized descriptively. The number and proportion of subjects 
having any SBI, infections, days on antibiotics, hospitalizations due to infection, and days of 
work/school/daily activities missed due to infections will be calculated and summarized. 
Furthermore, the total number of events or days and corresponding annualized rate per 
subject of SBIs, infections, days on antibiotics, hospitalizations due to infection, and days of 
work/school/daily activities missed due to infections will be calculated and summarized.
5.1.6
Safety Analysis
The safety analyses are based on the safety population.
All AEs, suspected ADRs, ARs, SAEs, and discontinuations due to AEs and SAEs will be 
summarized by presenting the number of AEs and the number and percentage of subjects 
with AEs. The summaries will be presented by MedDRA system organ class and preferred 
term. AE summaries by severity will also be provided. Local infusion site reactions will be 
similarly summarized. Non-serious infections of any kind (including acute sinusitis, 
exacerbation of chronic sinusitis, acute otitis media, pneumonia, acute bronchitis, infectious 
diarrhea, etc.) as determined by the Investigator will also be considered a safety endpoint and 
will be similarly summarized.
Subjects with deaths, SAEs, and AEs leading to premature discontinuation from the study 
will be listed and presented in a narrative form.
Adverse events temporally associated with IV or SC administration of study drug will be 
defined as those occurring during or within 72 hours of completion of an infusion. 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 74 of 94
Additionally, local infusion site reactions will be tabulated and summarized for the total 
duration of the study and by IGSC 20% infusion week.
For all laboratory tests and vital signs, the original value and the change from Baseline will 
be summarized for numeric results and frequency/percentage will be summarized for 
qualitative results. For laboratory tests with normal ranges, out of normal range values will 
be flagged and shift tables will be provided.
5.2
Determination of Sample Size
The planned number of subjects is 50 enrolled to provide 30 completing adult subjects and 
12 to 18 completing pediatric subjects. This sample size is primarily based on safety 
assessment consideration. Also a sample size of 42 to 48 with at least 24 scheduled 
administrations of IGSC 20% would provide the clinical experience data on a total of more 
than 1152 to 1080 IGSC 20% dosing administrations for safety assessment.
The planned minimum enrollment of 42 completing subjects should be more than adequate to 
establish that the AUC for total IgG for IGSC 20% is non-inferior to that achieved by IGIV-
C 10%.
6
ADMINISTRATIVE
6.1
Investigator(s), Other Study Personnel and External Committees
Information regarding additional key personnel involved in the conduct of the study, 
including names and contact details of participating Investigators, monitors, clinical 
laboratories, technical departments and/or institutions, as well as information on members of 
additional study committees, will be found in the study files of the Sponsor and at the 
Investigator sites within the study reference manual/file.
Investigators and staff will receive training via an Investigators meeting, site initiation visit,
or other appropriate individual site training session(s).
6.2
Data Quality
Monitoring and auditing procedures defined/agreed by the Sponsor will be followed in order 
to comply with ICH GCP guidelines. Each center will be visited at regular intervals by a 
monitor to ensure compliance with the study protocol, ICH GCP, and legal aspects. The 
on-site verification of the eCRF for completeness and clarity will include cross checking with 
source documents and clarification of administrative matters. Query verification of data will 
be described in the Data Management Plan.
6.3
Documentation
The study data will be recorded and kept current in the eCRF by the site study personnel 
directly responsible for the information. Entries made in the eCRF must be verifiable against 
source documents, or have been directly entered into the eCRF, in which case the entry in the 
eCRF will be considered the source data.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 75 of 94
The data in the eCRF will be monitored at the site by Grifols Therapeutics Inc. 
representatives at regular intervals and reviewed for completeness and compared with the 
source documents. Examples of source documents include individual subject medical 
records, which are separate from the eCRFs.
All AEs and SAEs must be recorded. All SAEs must be recorded on the SAE form. The SAE 
form must be kept in the site records with a copy provided to the designated person as 
detailed in the study file.
6.3.1
Record Retention
At study completion, all study data will be transferred to Grifols Therapeutics Inc. according 
to ICH GCP guidelines, local laws, regulations, and Grifols Therapeutics Inc. requirements. 
The study file and all source data should be retained until notification is given by the Sponsor 
for destruction.
An Investigator is required by ICH GCP guidelines to retain the study files. If an Investigator 
moves, withdraws from an investigation or retires, the responsibility for maintaining the 
records may be transferred to another person (eg, other Investigator). Grifols Therapeutics 
Inc. must be notified in writing of the person responsible for record retention and the 
notification will be retained in the Sponsor study file and the Investigator site file.
6.3.2
Access to Information for Monitoring
The data will be recorded and kept current in eCRFs by the study site personnel directly 
responsible for the information and reviewed for completeness by the monitor. Grifols 
Therapeutics Inc. personnel or designee can review the records.
In accordance with ICH GCP guidelines, the monitor must have direct access to the 
Investigator’s source documentation in order to verify the data recorded in the eCRFs for 
consistency, to verify adherence to the protocol, and to verify the completeness, consistency, 
and accuracy of data entered. “Source documentation” includes individual subject files, 
separate from the eCRFs, which should be maintained and include visit dates, laboratory 
results, concomitant treatment, vital signs, medical history, examinations, AEs, IP/study drug
dispensing logs, and other notes as appropriate. The Investigator agrees to cooperate with the 
monitor to ensure that any problems noted during the course of these monitoring visits are 
resolved.
6.3.3
Access to Information for Audits or Inspections
Representatives of regulatory authorities or of Grifols Therapeutics Inc. may conduct audits 
or inspections of the Investigator study site. If the Investigator is notified of an audit or 
inspection by a regulatory authority, the Investigator agrees to notify the Grifols Therapeutics 
Inc. Medical Monitor immediately. The Investigator agrees to provide to representatives of a 
Regulatory Agency or Grifols Therapeutics Inc. access to records, facilities, and personnel 
for the effective conduct of an audit or inspection.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 76 of 94
7
ETHICAL AND LEGAL ASPECTS
7.1
Institutional Review Board/Ethics Committee
Documented approval from appropriate IRBs/ECs will be obtained for all participating 
centers/countries prior to study start, according to ICH GCP guidelines, local laws, 
regulations and organizations. When necessary, an extension, amendment or renewal of the 
IRB’s/EC’s approval must be obtained and also forwarded to the Sponsor. The IRB/EC must 
supply to the Sponsor, upon request, a list of the IRBs/ECs members involved in the vote and 
a statement to confirm that the IRB/EC is organized and operates according to ICH GCP 
guidelines and applicable laws and regulations.
7.2
Ethical Conduct of the Study
The procedures set out in this protocol, pertaining to the conduct, evaluation, and 
documentation of this study, are designed to ensure that the Sponsor and Investigator abide 
by ICH GCP guidelines. The study will also be carried out in keeping with applicable local 
law(s) and regulation(s). This may include an audit by the Sponsor representatives and/or an 
inspection by Regulatory Authority representatives at any time. The Investigator must agree 
to the audit or inspection of study-related records by the Sponsor representatives and/or 
Regulatory Authority representatives, and must allow direct access to source documents to 
the Sponsor and/or Regulatory Authority representatives.
Modifications to the study protocol will not be implemented by either the Sponsor or the 
Investigator without agreement by both parties. However, the Investigator may implement a 
deviation from, or a change to, the protocol to eliminate an immediate hazard(s) to the study 
subjects without prior IRB/EC/Sponsor approval/favorable opinion. As soon as possible, the 
implemented deviation or change, the reasons for it, and, if appropriate, the proposed 
protocol amendment should be submitted to the IRB/EC/Sponsor. Any deviations from the 
protocol must be fully explained and documented by the Investigator.
7.3
Regulatory Authority Approvals/Authorizations
Regulatory Authority approvals/authorizations/notifications, where required, must be in place 
and fully documented prior to study start. Study information including contact information 
for Investigator sites responsible for conducting the study will be posted on a publicly 
accessible clinical registry(ies) as required by local law.
7.4
Subject Information and Consent
Subject information, ICF, and Assent Form will be provided to Investigator sites. Prior to the 
beginning of the study, the Investigator must have the IRB/EC written approval/favorable 
opinion of the written ICF, Assent Form, and any other written information to be provided to 
subjects. The written approval of the IRB/EC together with the approved subject 
information/Assent Form/ICF must be filed in the study files and a copy of the documents 
must also be provided to Sponsor by the Investigator site.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 77 of 94
Written ICF by the subject or a parent and/or legal guardian along with subject assent, if 
applicable, must be obtained before any study specific procedure takes place. Participation in 
the study and date of ICF given by the subject should be documented appropriately in the 
subject's files. A signed copy of the subject ICF and Assent Form, if applicable, will be 
provided to the subject or subject's authorized representative (ie, parent or legal guardian).
7.5
Insurance
Sponsor shall maintain comprehensive general liability insurance or self-insurance in 
amounts adequate to cover any damage, demand, claim, loss or liability caused or incurred 
by Sponsor, or as otherwise required by applicable laws and/or regulations.
7.6
Confidentiality
All records identifying the subject will be kept confidential and, to the extent permitted by 
the applicable laws and/or regulations, will not be made publicly available.
Subject names will not be supplied to the Sponsor. Only the subject number and subject 
initials where it is permitted will be recorded in the eCRF, and if the subject’s name appears 
on any other document (eg, pathologist report), it must be obliterated before a copy of the 
document is supplied to the Sponsor. Study findings stored on a computer will be stored in 
accordance with local data protection laws. Subjects will be informed in writing that 
representatives of the Sponsor, IRB/EC, or Regulatory Authorities may inspect their medical 
records to verify the information collected, and that all personal information made available 
for an audit or inspection will be handled in strictest confidence and in accordance with local 
data protection laws.
If the results of the study are published, the subject’s identity will remain confidential. 
The Investigator will maintain a list to enable subjects’ records to be identified.
8
USE OF DATA AND PUBLICATION
Sponsor is committed to honoring the principles of academic freedom while, at the same 
time, protecting its confidential information, the subjects, and the integrity of the study, and 
the study documentation all in compliance with applicable law. Institution and/or Investigator 
recognize that, with respect to any study that is part of a multi-site study, there is a need for a 
coordinated approach to any publication or presentation of results from the sites. 
Accordingly, the Institution/Investigator shall not publish or present any results from this 
study to any third parties until: (1) Sponsor publishes the results; (2) Institution and/or 
Investigator receives written notification from Sponsor that publication of the results is no 
longer planned; or (3) twelve (12) months following the close of Study, whichever occurs 
first.
Institution and/or Investigator shall submit to Sponsor for its review a copy of any proposed 
publication at least thirty (30) calendar days prior to the planned date of submission for 
publication or presentation. Institution and Investigator shall consider in good faith all 

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 78 of 94
comments received from Sponsor during the review period and shall delete Sponsor’s 
confidential information (other than study results).
If Sponsor determines that the publication contains patentable subject matter which requires 
protection, Sponsor may require the delay of submission for publication or presentation for 
an additional period of time for the purpose of filing patent applications or otherwise take 
measures to protect such information.
Institution and/or Investigator shall acknowledge Sponsor’s support in all publications and 
presentations.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 79 of 94
9
REFERENCES
1. Rosen F. Primary immunodeficiency diseases report of an IUIS Scientific Committee.
Clinical & Experimental Immunology. 1999;118(S1):1-28.
2. Boyle J, Buckley R. Population prevalence of diagnosed primary immunodeficiency
diseases in the United States. Pharmaceuticals Policy and Law. 2008;10:99-108.
3. Bousfiha AA, Jeddane L, Ailal F, Benhsaien I, Mahlaoui N, Casanova J-L et al. Primary
immunodeficiency diseases worldwide: more common than generally thought. J Clin
Immunol. 2013;33: 1-7.
4. Buckley R, Schiff RI. The use of intravenous immune globulin in immunodeficiency
diseases. N Engl J Med. 1991;11(2):110-7.
5. Sacher RA. Intravenous immunoglobulin consensus statement. J Allergy Clin Immunol.
2001;(4 Suppl):S139-S146.
6. Gardulf A. Immunoglobulin treatment for primary antibody deficiencies advantages of
the subcutaneous route. Biodrugs. 2007;21(2):105-16.
7. Helbert M, Farragher A. Subcutaneous immunoglobulin for patients with antibody
deficiency. British Journal of Hospital Medicine. 2007;68(4):206-10.
8. Ochs H, Gupta S, Kiessling P, Nicolay U, Berger M, the Subcutaneous IgG Study Group.
Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with
primary immunodeficiency diseases. Journal of Clinical Immunology. 2006;26(3):265-
73.
9. Boyle ML, Scalchunes C. Impact of intravenous immunoglobulin (IVIG) treatment
among patients with primary immunodeficiency diseases. Pharmaceuticals Policy and
Law. 2008;10:133–146.
10. Stiehm E, Casillas A, Finkelstein J, Gallagher K, Groncy P, Kobayashi R et al. Slow
subcutaneous human intravenous immunoglobulin in the treatment of antibody
immunodeficiency: Use of an old method with a new product. J Allergy Clin Immunol.
1998;101:848-9.
11. Radinsky S, Bonagura V. Subcutaneous immunoglobulin infusion as an alternative to
intravenous immunoglobulin. J Allergy Clin Immunol. 2003;112 (3):630-3.
12. Thomas M, Brennan V, Chapel H. Rapid subcutaneous immunoglobulin infusions in
children. The Lancet. 1993;342:1432-3.
13. Hagan JB, Fasano M, Spector S, Wasserman R, Melamed I, Rojavin M  et al.  Efficacy
and safety of a new 20% immunoglobulin preparation for subcutaneous administration,
IgPRo20, in patients with Primary Immunodeficiency.  J Clin Immunol 2010;30(5): 734-
45.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 80 of 94
14. Jolles S, Bernatowska E, de Gracia J, Borte M, Cristea V, Peter HH et al. Efficacy and
safety of Hizentra® in patients with primary immunodeficiency after a dose-equivalent
switch from intravenous or subcutaneous replacement therapy. Clinical Immunology.
2011a;141:90–102.
15. Jolles S, Borte M, Nelson RP, Rojavin M, Bexon M, Lawo J-P at el. Long-term efficacy,
safety, and tolerability of Hizentra® for treatment of primary immunodeficiency disease.
Clinical Immunology. 2014;150:161-169.
16. Abrahamsen TG, Sandersen H, Bustnes A. Home therapy with subcutaneous
immunoglobulin infusions in children with congenital immunodeficiencies. Pediatrics.
1996;6:1127-1131.
17. Gaspar J. Gerritsen B, Jones A. Immunoglobulin replacement treatment by rapid
subcutaneous infusion. Arch Dis Child. 1998;79:48-51.
18. Berger M. Subcutaneous immunoglobulin replacement in primary immunodeficiencies.
Clin Immunol. 2004;112:1-7.
19. Chapel HM, Spickett GP, Ericson D, Engl W, Eibl MM et al. The Comparison of the
Efficacy and Safety of Intravenous Versus Subcutaneous Immunoglobulin Replacement
Therapy. Journal of Clinical Immunology. 2000;20(2):94-100.
20. Chinen J, Shearer WT. Subcutaneous immunoglobulins: Alternative for the
hypogammaglobulinemic patient? J Allergy Clin Immunol. 2004;114:934-5.
21. Chouksey A, Duff K, Wasserbauer N, Berger M. Subcutaneous immunoglobulin-G
replacement therapy with preparations currently available in the United States for
intravenous or intramuscular use: reasons and regimens. Allergy, Asthma, and Clinical
Immunology. 2005;1(3):120-30.
22. Gardulf A, Björvell H, Gustafson R, Hammarström L, Smith CI. Safety of rapid
subcutaneous gammaglobulin infusions in patients with primary antibody deficiency.
Immunodeficiency. 1993;4:81-4.
23. Gardulf A, Björvell H, Gustafson R, Hammarström L, Smith CI. The life situations of
patients with primary antibody deficiency untreated or treated with subcutaneous
gammaglobulin infusions. Clin Exp Immunol. 1993;92(2):200-4.
24. Gardulf A, Andersen V, Björkander J, Ericson D, Frøland S, Gustafson R et al.
Subcutaneous immunoglobulin replacement in patients with primary antibody
deficiencies: safety and costs. The Lancet. 1995;345:365-9.
25. Gardulf A, Nicolay U, Math D, Asensio O, Bernatowska E, Böck A et al. Children and
adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-
infusions at home. J Allergy Clin Immunol. 2004;114 (4):936-42.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 81 of 94
26. Gardulf A, Nicolay U. Replacement IgG therapy and self-therapy at home improve the
health-related quality of life in patients with primary antibody deficiencies. Curr Opin
Allergy Clin Immunol. 2006;6:434-42.
27. Gardulf A, Nicolay U, Asensio O, Bernatowska E, Böck A, Carvalho BC et al. Rapid
subcutaneous IgG replacement therapy is effective and safe in children and adults with
primary immunodeficiencies — a prospective, multi-national study. J Clin Immunol.
2006;26(2):177-85.
28. Hansen S, Gustafson R, Smith CI, Gardulf A. Express subcutaneous IgG infusions:
decreased time of delivery with maintained safety. Clin Immunol. 2002;104 (3):237-41.
29. Nicolay U, Haag S, Eichmann F, Herget S, Spruck D, Gardulf A. Measuring treatment
satisfaction in patients with primary immunodeficiency diseases receiving lifelong
immunoglobulin replacement therapy. Qual Life Res. 2005;14:1683-91.
30. Nicolay U, Kiessling P, Berger M, Gupta S, Yel L, Roifman CM et al. Health-related
quality of life and treatment satisfaction in North American patients with primary
immunodeficiency diseases receiving subcutaneous IgG self-infusions at home. J Clin
Immunol. 2006;26(1):65-72.
31. Waldmann TA, Strober W, Blaese RM. Metabolism of immunoglobulins. Prog Immunol.
1972;891-903.
32. Orange JS, Belohradsky BH, Berger M, Borte M, Hagan J, Jolles S, et al. Evaluation of
correlation between dose and clinical outcomes in subcutaneous immunoglobulin
replacement therapy. Clinical and Experimental Immunology. 2012;169:172–181.
33. Wanieski J,  Gardulf A, Hammarstrom L. Bioavailability of gamma-globulin after
subcutaneous infusions in patients with common variable immunodeficiency.J Clin.
Immunology. 1994;14:90-97.
34. Wasserman RL, Irani A-M, Tracy J, Tsoukas C, Stark D, Levy R, et al. Pharmacokinetics
and safety of subcutaneous immune globulin (human), 10% caprylate/chromatography
purified in patients with primary immunodeficiency disease.  British Society for
Immunology, Clinical and Experimental Immunology. 2010;161:518–526.
35. Shearer WT, Fleisher TA, Buckley RH, Ballas Z, Ballow M, Blaese RM et al.
Recommendations for live viral and bacterial vaccines in immunodeficient patients and
their close contacts. J Allergy Clin Immunol. 2014;133(4):961-966.
36. Levin D. Seo JB, Kiely DG, Hatabu H, Gefter W, van Beek EJR, Schiebler ML on behalf
of the 2013 International Workshop for Pulmonary Functional Imaging (IWPFI). Triage
for suspected acute pulmonary embolism: think before opening Pandora’s box. European
Journal of Radiology 2015; 84: 1202-1211.
37. Wilbur J, Shian B. Diagnosis of deep venous thrombosis and pulmonary embolism. Am
Fam Physician 2012; 86(10):913-919.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 82 of 94
38. Oudega R, Moons KGM, Hoes AW. Ruling out deep venous thrombosis in primary care.
Thromb Haemost 2005; 94: 200-205.
39. Karch FE, Lasagna L. Adverse drug Reactions. A critical review. JAMA. 1975;234:
1236-1241.
40. Karch FE, Lasagna L. Toward the operational identification of adverse drug reactions.
Clin Pharmacol Ther. 1977;21:247-54.
41. Naranjo CA, Busto U, Sellers EM et al. A method for estimating the probability of
adverse drug reactions. Clin Pharmacol Ther. 1981;30:239-45.
42. Levy MM, Fink MP, Marshall JC et al. 2001 SCCM/ESICM/ACCP/ATS/SIS
International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250-1256.
43. International Consensus Conference on Pediatric Sepsis. Pediatric Crit Care Med. 2005;
6:2-8.
44. FDA Guidance for Industry “Acute Bacterial Meningitis – Developing Antimicrobial
Drugs for Treatment,” Draft Guidance, July 1998.
http://www.fda.gov/downloads/Drugs/.../Guidances/ucm070937.pdf. Last checked: 13
Feb 2015.
45. FDA Guidance for Industry “Community Acquired Pneumonia – Developing
Antimicrobial Drugs for Treatment,” Draft Guidance, July 1998.
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/u
cm123686.pdf. Last checked: 13 Feb 2015.
46. Anderson DR, Kovacs MJ, Kovacs G, et al. Combined use of clinical assessment and D-
dimer to improve the management of patients presenting to the emergency department
with suspected deep vein thrombosis (the EDITED Study). J Thromb Haemost
2003;1(4):645-51.
47. Wells PS, Anderson, DR, Rodger M, et al. Evaluation of D-dimer in the Diagnosis of
Suspected Deep-Vein Thrombosis. N Engl J Med 2003;349:1227-35.
48. Wells PS. Integrated strategies for the diagnosis of venous thromboembolism. J Thromb
Haemost 2007; 5 Suppl 1: 41-50.
49. Adam SS, Key NS, Greenberg CS.  D-dimer antigen: current concepts and future
prospects. Blood 2009; 113(13): 2878-2887.
50. Wells PS, Anderson, DR, Rodger M, et al. Derivation of a simple clinical model to
categorize patients probability of pulmonary embolism: increasing the models utility with
the SimpliRED D-dimer. Thromb Haemost 2000;83(3):416-20.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 83 of 94
10 APPENDICES

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 84 of 94
Appendix 1
Schedule of Study Procedures
Phase
Clinic Visits
Procedures and 
Evaluation
Screening
(up to 28 
days)
Run-In   
(if 
required)
(IGIV-C 
10%)
(3 to 4 
months)
IV Phasea
(IGIV-C 10%)
SC Phaseb
(IGSC 20%)
IV#1
Baseline
IV#2
SC  
Week   
#1
+2-4 
days 
post 
SC#1
SC  
Week 
#2
+2-4 
days 
post 
SC#2
SC  
Week
#3
SC    
Week   
#5
SC
Week  
#9
SC  
Week 
#13
SC  
Week  
#14
SC  
Week  
#17
SC 
Week
#21p
Final 
Visit 
(Week 
#25)/
Early 
Term
Monthly 
Extension 
Visitc
Informed consent/assent (if 
applicable)
X
Inclusion and exclusion 
criteria (confirm eligibility)
X
Medical history, 
demographics
X
Full physical examd
X
X
X
Abbreviated  physical exam 
and Specific Signs/Symptoms 
Check (SSC)e
X
X
X
X
X
X
X
X
X
Pre-dose Wells Score and D-
dimer testing (at subsequent 
visits only if indicated per 
Specific SSC)e
X
X
SSCe
SSCe
SSCe
SSCe
SSCe
SSCe
SSCe
SSCe
SSCe
Chest X-rayf
X
Vital signsg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight h
X
X
X
X
X
X
X
X
X
X
Height
X
X
X
X
X
X
Pre-dose laboratory 
assessments (hematology, 
chemistry, urinalysis)i
X
X
X
X
X
X
Xc
Special tests (DAT, serum
free hemoglobin, haptoglobin)
X
X
X
X
X
X
X
X
X
X
Xc
Serum pregnancy testj
X
X
Urine pregnancy testj
X
Pre-dose sample for total IgG 
levelk
X
X
X
X
X
X
X
X
X
X
X
X

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 85 of 94
Phase
Clinic Visits
Procedures and 
Evaluation
Screening
(up to 28 
days)
Run-In   
(if 
required)
(IGIV-C 
10%)
(3 to 4 
months)
IV Phasea
(IGIV-C 10%)
SC Phaseb
(IGSC 20%)
IV#1
Baseline
IV#2
SC  
Week   
#1
+2-4 
days 
post 
SC#1
SC  
Week 
#2
+2-4 
days 
post 
SC#2
SC  
Week
#3
SC    
Week   
#5
SC
Week  
#9
SC  
Week 
#13
SC  
Week  
#14
SC  
Week  
#17
SC 
Week
#21p
Final 
Visit 
(Week 
#25)/
Early 
Term
Monthly 
Extension 
Visitc
Pre-dose sample for IgG 
subclass levels and antibody 
titersl
X
X
X
X
X
Xc
Pre-dose measles antibody 
titer samples
X
X
Pre-dose virus safety retain 
samplesm
X
IGIV-C 10% infusions
X
X
X
IGSC 20% infusionsn & 
infusion number
X
q
weekly 
#2
  q 
weekly 
#3
q
weekly 
#4-8
q
weekly 
#9-12
q
weekly 
#13
q
weekly
#14-16
q
weekly
#17-20
q
weekly 
#21-24
q
weekly
Serial PK sampling (subjects 
age ≤5 years, abbreviated 
schedule)
Xo
Xp
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE Assessments including 
SBIsq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Record days lost from 
work/school/daily activities 
due to infections and 
treatment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject SC Infusion Diary 
review and infusion details
X
X
X
X
X
X
X
X
X
X
X
a
Time between IV#1 and #2 visits (IV Phase) will be dependent upon subject’s IV dosing interval (3 or 4 weeks) upon entering the IV Phase.
b
SC week number = SC infusion number with the exception of Week#25 which is the Final Visit/Early Termination Visit. 
c
In the event that subjects complete their regularly scheduled 24 weeks of SC infusions prior to the results of the interim PK analysis, they will continue to 
receive weekly SC infusions of IGSC 20% and return to the clinic for monthly (every 4 weeks) visits which will have the same assessments as SC Week#21 
visit  including (at less frequent intervals) safety laboratory assessments, IgG subclass levels, and specific antibody titers for S. pneumoniae, H. influenzae, 
and C. tetani (tetanus) every 8 weeks. They will continue to be followed monthly until the results of the interim PK analysis are available.  If a dose 
adjustment modification is not required, subjects will return to the clinic for a final visit.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 86 of 94
d
A full physical exam will be performed (excluding breast and genitourinary exam) 
e
Abbreviated physical exam (targeted to symptoms and to include examination of heart, lungs, ears/nose/throat, and inspection of previous injection sites.). 
Specific Signs/Symptoms Check: If the following Specific Signs/Symptoms are present, perform Wells Score and blood draw for D-dimer testing (Appendix 
4; see also Section 3.6.3.3): (a) clinical suspicion of possible DVT with unilateral symptomatic leg swelling, accompanied by any of the following pain,
warmth, and/or redness; (b) medical suspicion of possible PE in a subject presenting with new or worsening dyspnea, tachypnea, chest pain, syncope, and 
cough in the appropriate clinical setting (cough should not be due to infection, lung disease [eg, asthma, emphysema], or angiotensin-converting enzyme 
inhibitors), (c) Any single alarm symptom such as hemoptysis or cyanosis (36,37,38).
f
Only if chest X-ray or CT have not been performed in the past 6 months at Screening (Note: at least one radiographic view (AP or PA) is required.)
g
Vital signs (systolic blood pressure, diastolic blood pressure, heart rate, temperature, and respiration rate) will be measured prior to infusion.
h
Body weight is measured to determine the IV or SC study drug dose.
i
Laboratory assessments to be obtained prior to infusion of any study drug (IV IGIV-C 10% or IGSC 20%) at all specified visits. Additional special tests 
include DAT, serum free hemoglobin, and haptoglobin. Laboratory testing includes Hematology: Hemoglobin, hematocrit, platelets, red blood cell count 
including red blood cell morphology, white blood cell count with differential; ARC. Chemistry: Sodium, potassium, creatinine, chloride, calcium, BUN, 
bicarbonate, albumin, LDH, AST, ALT, ALP, glucose, total bilirubin, indirect bilirubin. Urinalysis: pH, protein, glucose, ketones, bilirubin, nitrites, 
urobilinogen, blood, leukocyte esterase (with microscopic examination of urine sediment if abnormal).
j
Pregnancy testing will be repeated at any time if pregnancy is suspected. Pregnancy testing including serum and urine tests will be performed for child-
bearing potential females only.
k
Blood samples for total IgG trough level to be obtained prior to infusion of study drug (IGIV-C 10% or IGSC 20%) where indicated.   
l
IgG subclasses IgG1, IgG2, IgG3, IgG4, and antibody levels for S. pneumoniae, H. influenzae, and C. tetani (tetanus).
m
Collect virus safety retain samples at SC Week#1 prior to IGSC 20% infusion but test only if the subject exhibits clinical signs and symptoms consistent with 
HAV, HBV, HCV, HIV, or B19V infection while participating in the study.  See Section 3.6.3.2 and Table 3-2 for details. Note: For children at the 
discretion of the investigator,  virus safety retain samples may be drawn 1 or 2 days prior to SC Week #1 instead of combining with other blood draws on a 
single day.
n
Weekly SC dosing may be 7 days ± 1 day. If there are logistical issues requiring schedule adjustment for weekly subcutaneous IGSC 20% administration, 
SC#1 may be scheduled 6 to 9 days after IV#2. SC#2 and SC#3 visits must be performed with a +1 day window. The first 3 SC infusions of IGSC 20% will 
be performed in the clinic where site personnel will instruct on/observe proper SC dosing technique using the pump.  Subsequent monthly SC infusions will 
also occur and be observed in the clinic after labs and total IgG trough levels are obtained.  Other SC infusions will be performed at home for interim weeks 
starting after the SC Week #3 visit.
o
Blood samples for IV#1 (IV Phase) PK assessments are at the following time points for subjects >5 years of age: prior to the IV#1 IGIV-C 10%  infusion 
(within 0.5 hour of the start of infusion); immediately at the completion of the IV# 1 infusion; 1 hour after completion of infusion; 3 to 16 hours with a 
window of 2 hours around the 16-hour time point if required by site; 1 day ± 2 hours  post infusion; 2 days ± 2 hours  post infusion; 3 days ± 4 hours post 
infusion; 5 days ± 4 hours post infusion; 7 days ± 1 day post infusion; ; 14 days ± 1 day post infusion; 21 days ± 1 day post infusion; 28 days ± 1 day post 
infusion (only for subjects on a 4-week dosing schedule; within 0.5 hour prior to the IV#2  dose) for total IgG trough level. Subjects who are between 2 to 
5 years of age will undergo abbreviated serial PK sampling: Prior to IV #1 IGIV-C 10% infusion (within 0.5 hour of the start of infusion); 1 hour after 
completion of infusion; 3 to 16 hours with a window of 2 hours around the 16-hour time point if required by site; 2 days±2 hours post infusion;7 days±1 day
post infusion; 21 days±1 day post infusion; 28 days±1 day post infusion (only for subjects on a 4-week dosing schedule; within 0.5 hour prior to the IV#2 
dose).

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 87 of 94
p
Blood samples for SC Week#13 PK assessments are at the following time points for subjects >5 years of age: prior to the 13th IGSC 20% infusion (within 
0.5 hour of the start of infusion); 1 day ± 4 hours post 13th  infusion; 3 days ± 4 hours post 13th  infusion; 4 days ± 4 hours post 13th  infusion; 5 days ± 4 
hours post 13th  infusion and 7 days ± 1 day post 13th  infusion (within 0.5 hour prior to the 14th IGSC 20% dose) for total IgG trough level. Subjects who 
are between 2 to 5 years of age will undergo abbreviated serial PK sampling: prior to the 13th IGSC 20% infusion (within 0.5 hour of the start of 
infusion); 3 days± 4 hours post 13th infusion; 7 days ± 1 day post 13th infusion (within 0.5 hour prior to the 14th IGSC 20% dose).
q
Record any SBIs (defined in Appendix 2), hospitalizations due to infections, and non-serious infections (by category) as detailed in Section 3.6.3.1.

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 88 of 94
Appendix 2
Diagnostic Criteria for Serious Infection Types
Infection:  Bacteremia/sepsisa

Symptoms:  chills, rigors

Physical findings: fever, hypothermia, tachycardia, tachypnea, hypocarbia, hypotension 
(systolic blood pressure <90 mmHg or a reduction of >40 mmHg 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.) 

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 
(MRI) scan, or computed tomography (CT) scan showing bony destruction with radiolucent 
areas; for chronic osteomyelitis: sequestra, involucra
Note: 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 mmHg; WBC count >12,000/mm3, <4,000/mm3, or >10% immature (band) forms (42). For 
pediatric subjects, we recommend you employ the definition of sepsis using age-specific criteria as 
recommended by the International Consensus Conference on Pediatric Sepsis (43).
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 subjects without indwelling 
catheters or vascular access devices, a single blood culture positive for a pathogenic organism will meet the 
diagnostic criteria for bacteremia. (Multiple blood cultures are typically obtained in cases of suspected 
bacteremia/sepsis, as per standard medical practice, and the finding of a single positive culture should prompt 
additional confirmatory cultures). Subjects 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 S. pneumoniae, Neisseria meningitides, or H. influenzae, in 
combination with CSF leukocytosis and/or decrease in CSF glucose, can serve to confirm the diagnosis of 
acute bacterial meningitis (44).

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 89 of 94
Infection: Bacterial Pneumoniad

Symptoms:  productive cough/change in character of sputum, dyspnea or tachypnea, 
chills, chest pain, rigors, headache, fatigue, sweats, anorexia, myalgias

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 sputume, 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 (CXR) 
(new in comparison with Baseline CXR)
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, CT scan, MRI scan, or 
radionuclide scan
Note: Items in bold are considered essential diagnostic features.
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 infection episodes in a clinical trial of IVIG, the finding of a new pulmonary 
infiltrate with consolidation on CXR 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 (45).
e We recommend 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 
(45).

Protocol GTI1502 – Amendment 2
CONFIDENTIAL
Appendix 3
Blood
2
Page 90 of 94
d Pressure Percentiles for Pediatric P
15 Mar 2016
Patients

Protocol GTI1502 – Amendment 2
CONFIDENTIAL
2
Page 91 of 94
15 Mar 2016

Protocol GTI1502 – Amendment 2
CONFIDENTIAL
2
Page 92 of 94
15 Mar 2016

Protocol GTI1502 – Amendment 2
CONFIDENTIAL
2
Page 93 of 94
15 Mar 2016

Protocol GTI1502 – Amendment 2
15 Mar 2016
CONFIDENTIAL
Page 94 of 94
Appendix 4
Wells Score
Deep Vein Thrombosis (46,47)
Clinical Characteristic
Score
Active cancer (treatment ongoing, within previous 6 months or palliative)
1
Paralysis, paresis, or recent plaster immobilization of the lower extremities
1
Recently bedridden >3 days or major surgery within previous 12 weeks 
requiring general or regional anesthesia
1
Previously documented DVT
1
Localized tenderness along distribution of deep venous system
1
Entire leg swollen
1
Calf Swelling 3 cm larger than asymptomatic side (measured 10 cm below 
tibial tuberosity)
1
Pitting edema confined to the symptomatic leg
1
Collateral superficial veins (non-varicose)
1
Alternative diagnosis at least as likely as DVT
-2
Total Score:
Any subject with a total Wells prediction score >1 for DVT assessment should have further 
diagnostic testing per study site standard of care if medically indicated - unless the D-dimer 
is negative since this test has a high negative predictive value.  If the D-dimer is positive at 
any time after the Screening time point (ie, above Screening value, exceeding cutoff range of 
the reporting laboratory), redraw a blood sample for repeat D-dimer testing at the central 
laboratory within one week to confirm. In all situations, the investigator should use best 
medical judgment to evaluate the subject as medically indicated (48,49).
Pulmonary Embolism (50)
Clinical Characteristic
Score
Previous DVT or PE 
1.5
Surgery or bedridden for 3 days during past 4 weeks
1.5
Active cancer (treatment within 6 months or palliative)
1
Hemoptysis
1
Heart rate > 100 beats/min
1.5
Clinical signs of DVT
3
Alternative diagnosis less likely than PE
3
Total Score:
Any subject with a total Wells prediction score >4 for the PE assessment should have further 
diagnostic testing per study site standard of care if medically indicated - unless the D-dimer 
is negative since this test has a high negative predictive value.  If the D-dimer is positive at 
any time after the Screening time point (ie, above Screening value, exceeding cutoff range of 
the reporting laboratory), redraw a blood sample for repeat D-dimer testing at the central 
laboratory within one week to confirm. In all situations, the investigator should use best 
medical judgment to evaluate the subject as medically indicated (48,49).