A Phase 3, Prospective, Randomized, Controlled, Open-label, Multicenter, 2 Period Crossover Study With a Single Arm Continuation Evaluating the Safety And Efficacy of BAX 930 (rADAMTS13) in the Prophylactic And On-demand Treatment of Subjects With Severe Congenital Thrombotic Thrombocytopenic Purpura (cTTP, Upshaw-Schulman Syndrome [USS], Hereditary Thrombotic Thrombocytopenic Purpura [hTTP])
Phase: PHASE3
Conditions: Thrombotic Thrombocytopenic Purpura (TTP)
Sponsor: Baxalta now part of Shire

For non-commercial use only

TAKEDA PHARMACEUTICALS
PROTOCOL:
281102
TITLE:
A phase 3, prospective, randomized, controlled, open-label, multicenter, 
2 period crossover study with a single arm continuation evaluating the 
safety and efficacy of BAX 930 (rADAMTS13) in the prophylactic and 
on-demand treatment of subjects with severe congenital thrombotic 
thrombocytopenic purpura (cTTP, Upshaw-Schulman Syndrome [USS], 
hereditary thrombotic thrombocytopenic purpura [hTTP])
SHORT TITLE:
A phase 3, randomized, controlled study of prophylactic and on-demand 
treatment of cTTP with BAX 930 (rADAMTS13)
STUDY PHASE:
Phase 3
DRUG:
BAX 930 / SHP655 / TAK-755 / rADAMTS13
IND NUMBER:
015219
EUDRACT NUMBER:
2017-000858-18
SPONSOR:
Takeda Development Center Americas, Inc. 
95 Hayden Avenue, Lexington, MA 02421, USA and
Baxalta Innovations GmbH, Industriestrasse 67, A-1221 Vienna
PROTOCOL HISTORY:
AMENDMENT 15 (Global): 18-NOV-2021
Replaces All Versions:
Amendment 14 (Germany): 2021 APR 30
Amendment 13 (Global): 2021 APR 28
Amendment 12 (Germany): 2021 MAR 25
Amendment 11 (Global): 2021 FEB 24
Amendment 10 (Germany): 2020 JUN 25
Amendment 9 (Global): 2020 MAR 06
Amendment 8 (UK): 2019 DEC 19
Amendment 7 (Switzerland): 2019 SEP 12
Amendment 6 (Germany): 2019 JUL 18
Amendment 5: 2018 DEC 06
Amendment 4 (UK): 2018 APR 11
Amendment 3 (UK): 2017 AUG 21
Amendment 2: 2017 MAY 09
Amendment 1: 2017 MAR 15
Original: 2017 FEB 13
Confidentiality Statement
This document contains confidential and proprietary information of Takeda and is disclosed pursuant 
to confidentiality and non-disclosure obligations. This information should be used solely for the 
purposes for which it was provided and should not be copied, shared with, or disclosed to any third 
party without the express written consent of Takeda.
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Page 3
BAX 930 (rADAMTS13)
TAK-755-281102 Protocol Amendment 15 (Global)
18 Nov 2021
1. STUDY PERSONNEL
1.1 Authorized Representative (Signatory) / Responsible Party
, MD
 
Takeda Development Center Americas, Inc.
1.2 Study Organization
The name and contact information of the responsible party and individuals involved with the 
study ( eg, investigator[s], sponsor’s medical expert and study monitor, sponsor’s 
representative[s], laboratories, steering committees, and oversight committees [including ethics 
committees {ECs}], as applicable) will be maintained by the sponsor and provided to the 
investigator.
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BAX 930 (rADAMTS13)
TAK-755-281102 Protocol Amendment 15 (Global)
18 Nov 2021
2. SERIOUS ADVERSE EVENT REPORTING
The investigator will comply with applicable laws/requirements for reporting serious adverse 
events (SAEs), including suspected unexpected serious adverse reactions (SUSARS), to the ECs. 
ALL SAEs, INCLUDING SUSARs, ARE TO BE REPORTED ON THE 
SERIOUS ADVERSE EVENT REPORT FORM AND 
TRANSMITTED TO THE SPONSOR 
WITHIN 24 HOURS AFTER BECOMING AWARE OF THE EVENT
Drug Safety contact information: see SAE Report form.
Refer to SAE Protocol Sections and the study team roster for further information.
For definitions and information on the assessment of these events, refer to the following:

Adverse event (AE), Section 13.1

SAE, Section 13.1.1.1

SUSARs, Section 13.1.1.2

Assessment of AEs, Section 13.1.2
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BAX 930 (rADAMTS13)
TAK-755-281102 Protocol Amendment 15 (Global)
18 Nov 2021
3. SUMMARY OF CHANGES FROM PREVIOUS VERSION
An overview of the updates incorporated into Amendment 15 is presented below.
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
Sponsor name was updated to Takeda Development Center 
Americas, Inc.
Legal entity name 
change
Title page and 
throughout the 
document
Study completion dates updated as follows:

Study Primary Completion date changed from Feb 
2023 to Nov 2023

Study Completion from Jan 2024 to Mar 2024
Adjusted to account for 
enrollment of pediatric 
subjects.
Section 4, Synopsis
Footnote ‘a’ was added to the Table of TTP Definitions in 
the synopsis and body of the protocol:
a In this instance, a laboratory measure refers to platelet 
counts or an LDH measurement
Added for clarity
Section 4, Synopsis
Table 2
Terminology was aligned across document: 

acute episodes of thrombotic thrombocytopenic 
purpura (TTP), and acute clinical events now 
thrombotic thrombocytopenic purpura (TTP) events

acute events or acute TTP events now acute TTP 
events throughout document

subacute events or subacute manifestations now 
subacute TTP events throughout document

Outcome measure or endpoint now outcome measure 
throughout document

Allergic manifestations now allergic reactions 
throughout the document
Clarification and 
alignment of 
terminology across the 
text
Throughout document
The definition of acute TTP event resolution was added to 
the synopsis
Language was reiterated 
for clarity
Section 4, Synopsis
Exploratory objective 2 was revised to the following:
To assess the relationship between ADAMTS13 activity 
levels (measured and/or estimated from PK parameters) and 
time of occurrence of acute TTP events, subacute TTP 
events, and a composite of TTP manifestations in the 
prophylactic group
Revised for clarity
Section 4, Synopsis
Section 8.4
Secondary Outcome Measure/ Efficacy #10 was updated 
(new text in bold):
Incidence of acute TTP events while subjects are on their 
final dose and dosing regimen in the study
Language reverted to 
original for clarity
Section 4, Synopsis
Section 9.4.2.1
Section 14.4.2.1
Added “Isolated TTP manifestations” definition to 
definitions tables; note that the definition did not change 
but it was summarized from other locations in the protocol 
and added to the table
Clarification of 
terminology and 
completeness of the table
Section 4, Synopsis
Table 2
The following Health Related Quality of Life and Resource 
Utilization objective was moved to Efficacy Objectives: 
To evaluate the incidence of dose modification and 
supplemental dose for each treatment in the 
prophylactic cohort. 
To align with general 
objectives of the study
Section 4, Synopsis
Section 8.3.1
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TAK-755-281102 Protocol Amendment 15 (Global)
18 Nov 2021
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
The following clarifying language was added;
A PK-II evaluation is not applicable to subjects who 
received BAX930 SIN in Period 1 or Period 2
Language was reiterated
for clarity
Section 9.2.2
New text added to sentence (in bold):
ADAMTS13-mediated VWF cleavage products will be 
analyzed using mass spectrometry or visualized by 
SDS-poly-acrylamide gel electrophoresis followed by 
Western blot staining and quantitative densitometry.
Removed specificity to 
increase assay technique 
flexibility
Section 13.7.5.5
Reporting of TTP manifestations was clarified:
For the purpose of this study the TTP manifestations 
listed below, with an onset date after the first IP 
exposure, should be reported on the Adverse Event 
eCRF regardless of severity. Relationship to cTTP or to 
BAX 930 must be indicated. The TTP manifestations 
should be captured even if they were experienced as 
part of an acute or subacute event.
The bulleted list of TTP events was reorganized to match 
those presented in Table 3.

Ensure TTP
manifestations are 
reported and 
categorized on AE 
eCRF Ensured list 
of TTP symptoms 
matched those 
presented in the 
Definitions table
Section 13.1.2
Revised Secondary Outcome Measure Efficacy # 2 as 
follows (new and removed text):
2. Time to resolution of acute TTP events clinical 
symptomatology, if present, and normalization of 
laboratory parameters (platelet count ≥150,000/µL; 
LDH ≤1.5×ULN) following initiation of treatment in 
acute TTP episodes with BAX 930 or SoC agent
Clarification of the 
terminology and 
alignment with present 
eCRF since clinical 
symptoms start and end 
time not tracked, only 
the start and end time of 
the TTP event.
Section 4, Synopsis
Section 9.4.2.1
Section 14.4.2.1
Wording in secondary PK/PD outcome measure #4 was 
deleted and/or updated for clarity: 
#4 Data allowing Assessment of the impact of 
immunogenicity (immunogenicity status, time of onset) on 
ADAMTS13 antigen and activity PK parameters. will be 
evaluated. Additionally, impact of immunogenicity 
(incidence, time of onset) on PD time profiles including 
VWF:RCo, VWF:Ag, VWF multimers and VWF cleavage 
products may be evaluated.
Prior wording was vague 
and was updated for 
clarity. Also, vWF:Ag, 
vWF multimers, and 
vWF cleavage products 
are exploratory outcome 
measures so should be 
removed from this 
section.
Section 4, Synopsis
Section 9.4.2.3
Purpose of Protocol Amendment 15 was added:

provide clarification and alignment of various 
terms and definition throughout the text

include suggestions and options to reduce volume 
of blood samples collected from pediatric subjects 
to ensure the blood volume is within 
recommended limits

Other items listed in Summary of Changes
To provide a rationale 
for the changes included 
in Protocol Amendment 
15
Section 9.1
Subjects who enroll into the TAK-755-3002 continuation 
study will complete the TAK-755-3002 
Screening/Enrollment visit on the same day as the 281102 
last IP infusion of Period 3. 
To reduce the gap in 
treatment for cTTP 
subjects enrolled in both 
Phase 3 cTTP studies
Section 9.2.1.4
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TAK-755-281102 Protocol Amendment 15 (Global)
18 Nov 2021
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
Sentence was removed: "Subjects who switch from the on-
demand to the prophylaxis cohort upon resolution of the 
acute event will be excluded from the primary efficacy 
analysis."
The primary efficacy 
analysis will include all 
subjects that were treated 
in prophylaxis cohort, 
regardless of prior 
participation in the on-
demand cohort.
Section 14.4
Clarified wording in PK/PD Secondary Objective 
#3/Secondary Outcome Measure #2 adding terms in bold:
#3 To assess ADAMTS13 activity (pre-infusion 
ADAMTS13 levels) and select VWF parameters prior to 
each PK infusion of SoC or BAX 930 and at the time of 
acute TTP event presentation in the prophylactic cohort
#2 Assessment of PD markers, such as VWF:Ag, and 
VWF: RCo, at baseline and following infusion of the 
SoC agent and BAX 930 treatment during the initial PK 
assessment
To provide clarification 
and consistency with the 
schedule of assessments.
Section 4, Synopsis
Throughout document
Secondary outcome measure 8 was revised to (new text in 
bold):
8.
Incidence of supplemental doses prompted by 
subacute TTP events isolated TTP manifestations
Updated to reflect new 
definitions of TTP 
events.
Section 4, Synopsis
Section 9.4.2.1
General editing made throughout document to ensure 
alignment of wording/phrasing across the document.
Ensure alignment and 
reduce ambiguity.
Throughout document
Sentence regarding dose calculation was added:
Note that the weight from the subject’s previous visit can 
be used to calculate the dose as long as the weight was 
collected less than 6 weeks prior for adult subjects (>12 
years of age) and less than 4 weeks prior for pediatric 
subjects (<12 years of age).
To provide more 
flexibility to the sites 
while ensuring the 
patient receives the 
correct dose per weight. 
A weight measurement 
taken at a prior visit falls 
within a reasonable 
timeframe in which 
weight is not expected to 
change significantly 
enough to adversely 
affect the dose delivered 
in the study
Section 9.7.3
Revised wording so that pediatric PK sample blood 
collection schedules for pediatric subjects <6 years old may 
be optimized by the Investigator and Sponsor to 
accommodate for local blood collection volume 
considerations. The timing of related assessments to be 
modified in accordance with the optimized schedule. 
To address blood volume 
limitations in young 
pediatric subjects.
Section 9.2.1.1.1, 
Section 9.2.1.1.3, 
Section 9.7.2, 
Section 11.3.1, 
Section 12.2, 
Section 12.2.1, 
Section 13.7.1, 
Section 13.7.2, 
Section 13.7.6.2, 
Section 13.8, 
Table 7, Table 9, 
Table 10, Table 12
Table 13, Table A1
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BAX 930 (rADAMTS13)
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18 Nov 2021
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
The interim assessment was eliminated (note that the 
interim analysis is retained).
Study timing is such that 
the interim assessment is 
no longer feasible
Section 4, Synopsis
Section 14
Statistical analyses wording was refined to:

Update wording as needed in regard to the elimination 
of the interim assessment

Provide clarification of the summary statistics

The timing of the 
interim analysis was 
changed.

To align with 
changes in the SAP.
Section 4, Synopsis
Section 14
Direct-to-Patient shipments of Investigational Product will 
be permitted for subjects having infusions at home, 
additional information will be provided in the Pharmacy 
Manual and Home Nursing documentation.
To accommodate for 
subjects receiving IP in a 
home setting.
Section 9.7.5
Withdrawal and discontinuation criteria was updated to 
reflect the follow-up procedures for subjects experiencing 
allergic reactions upon exposure, and ongoing AEs
Updated for clarity
Section 10.3
Study assessments were updated to indicate that, for 
subjects 0-<6 years old (prophylactic subjects only), if 
available and at the discretion of the Investigator, growth, 
development, and cognitive performance metrics may be 
recorded and reviewed from a subject’s medical record at 
the Screening/Enrollment Visit, the start of every Treatment 
Period or annually, and at the Final Visit.
DMC recommendation 
to include key pediatric 
outcomes such as the 
child’s growth, 
development, and 
cognitive performance. 
Section 11.3.2
Realigned format of Secondary Objectives in synopsis to 
match the presentation in the body of the document.
In prior version (13), the 
Secondary Objectives 
were listed in numerical 
order in Synopsis but 
subcategorized by topic 
(eg., Efficacy, Safety, 
etc) in the body of the 
document. Now they are 
aligned.
Section 4, Synopsis
Germany-specific requirements, which were formally 
presented in a Germany-specific protocol, are now 
presented in the current Global version and are addressed in 
a German-specific Appendix 1, Table A1 that (for German 
sites only) replaces Table 8. Notes were added throughout 
the text accordingly.
Allow for elimination of 
a country-specific 
protocol by including all 
country-specific relevant 
text in the Global 
protocol.
Section 13.6, 
Section 13.8
Table A1
The second bullet of the statistical efficacy analysis section 
were revised, and the third bullet was removed (new text in 
bold):
• For acute TTP events, a Kaplan-Meier curve for each 
treatment group will be drawn based on each subject's 
time to resolution of the acute TTP event, defined as the 
time from initial treatment of the event to the end of the 
acute TTP event for pooled prophylactic and on-
demand cohort data, and separately. Only the first acute 
TTP event for each subject will be included in the 
analysis. The median time to resolution will be 
presented for each treatment, along with the 
corresponding 95% CI.
Text was revised and 
condensed for clarity
Section 14.4.2.1
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18 Nov 2021
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
Footnote ‘v’ (Table 10) and footnote ‘q’ (Table 11) was 
added to clarify cardiac marker measurement procedures: 
a.
Testing is only applicable if available at local 
laboratory.
To allow flexibility at 
sites where local cardiac 
marker testing is not 
available
Table 9 and Table 10)
Figure 2 was updated
Updated for visual 
clarity of study flow
Section 20.1
(Figure 2)
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18 Nov 2021
4. SYNOPSIS
INVESTIGATIONAL PRODUCT
Name of Investigational 
Product (IP)
BAX 930 / SHP655 / TAK-755
Name(s) of Active 
Ingredient(s)
rADAMTS13
CLINICAL CONDITION(S)/INDICATION(S)

Congenital thrombotic thrombocytopenic purpura (cTTP) (Upshaw-Schulman Syndrome) 
(hereditary thrombotic thrombocytopenia purpura) (hTTP)
PROTOCOL ID
281102
PROTOCOL TITLE
A phase 3, prospective, randomized, controlled, open-label, multicenter, 
2-period crossover study with a single arm continuation evaluating the safety 
and efficacy of BAX 930 (rADAMTS13) in the prophylactic and on-demand 
treatment of subjects with severe congenital thrombotic thrombocytopenic 
purpura (cTTP, Upshaw-Schulman Syndrome [USS], hereditary thrombotic 
thrombocytopenic purpura [hTTP])
Short Title
A phase 3, randomized, controlled study of prophylactic and on-demand 
treatment of cTTP with BAX 930 (rADAMTS13)
STUDY PHASE
Ph3
PLANNED STUDY PERIOD
Initiation
2017 OCT
Primary Completion
2023 NOV
Study Completion
2024 MAR
Duration
approximately 70 months
STUDY OBJECTIVES AND PURPOSE
Study Purpose
To assess safety and efficacy of BAX 930 in the prevention and treatment of acute thrombotic thrombocytopenic 
purpura (TTP) events in subjects with severe congenital deficiency of ADAMTS13 (cTTP; defined as plasma 
ADAMTS13 <10%, as measured by the fluorescent resonance energy transfer-VWF73 [FRETS] assay)
Primary Objective
1. To determine the incidence of acute TTP events in subjects with severe cTTP receiving either standard of 
care (SoC) or BAX 930 as a prophylactic treatment.
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Secondary Objectives
Efficacy
1. To evaluate the efficacy of BAX 930 in the treatment of acute TTP events as measured by the 1) number 
of acute TTP events responding to treatment and 2) time to resolution in both the prophylactic and the 
on-demand cohorts
2. To evaluate the incidence of isolated TTP manifestations including thrombocytopenia, microangiopathic 
hemolytic anemia, renal dysfunction, neurologic signs and symptoms, and abdominal pain in the 
prophylactic cohort 
3. To evaluate the incidence of dose modification and supplemental dose for each treatment in the 
prophylactic cohort
Safety
1. To evaluate the safety and tolerability of BAX 930 in terms of related AEs and SAEs in both the 
prophylactic and the on-demand cohorts
2. To assess the immunogenicity of BAX 930 as measured by the incidence of binding and inhibitory 
antibodies to ADAMTS13 in both the prophylactic and the on-demand cohorts
Pharmacokinetics/Pharmacodynamics
1.
For both adult and pediatric subjects two crossover PK evaluations and an end-of-study ADAMTS13 PK 
evaluation (PK-III) may be performed for up to 288 hours post-infusion in the prophylactic cohort 
1) PK-I: To characterize the baseline PK of ADAMTS13 activity after administration of BAX 930 ORT 
or BAX 930 SIN and SoC prior to Period 1 
2) PK-II: To assess the PK comparability between BAX 930 SIN and BAX 930 ORT, in subjects who 
received BAX 930 ORT in PK-I.
3) PK-III: To assess if any time dependent PK changes occur due to long-term exposure to BAX 930 
SIN at the end of period 3.
2.
To assess VWF:antigen (VWF:Ag), and VWF:ristocetin cofactor activity (RCo) at baseline and following 
infusion of the SoC agent and BAX 930 treatment during the initial PK assessment in the prophylactic 
cohort.
3.
To assess ADAMTS13 activity (pre-infusion ADAMTS13 levels) and select VWF parameters prior to 
each PK infusion of SoC or BAX 930 in the prophylactic cohort.
4.
To evaluate the effect of immunogenicity on the PK profile of ADAMTS13 
Health Related Quality of Life and Resource Utilization
1. To evaluate Health Related Quality of Life (HRQoL), treatment satisfaction, and health resources 
utilization in each of the treatment periods in both the prophylactic and the on-demand cohorts.
Exploratory Objectives
1. To evaluate the incidence of subacute TTP events in subjects receiving the respective prophylactic 
treatment.
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2. To assess the relationship between ADAMTS13 activity levels (measured and/or estimated from PK 
parameters) and time of occurrence of acute TTP events, subacute TTP events, and a composite of TTP 
manifestations in the prophylactic group
3. To assess shifts in biomarkers of organ damage, including troponin T (cTnT) and I (cTnI) (cardiac), 
creatine kinase myocardial band (CK-MB) fraction (cardiac), neuron-specific enolase (NSE) (brain), 
S100B (brain), and serum creatinine (kidney), during routine prophylaxis with the SoC treatment and 
BAX 930 as well as during acute TTP events in the prophylactic cohort.
4. To characterize the PK profile of ADAMTS13 activity at the end of the study.
5. To evaluate additional exploratory PD biomarkers, including but not limited to VWF multimer patterns, 
ADAMTS13 mediated VWF cleavage products and coagulation readouts, at baseline and following 
infusion of the SoC agent and BAX 930.
STUDY DESIGN
This is a prospective, randomized, controlled, open-label, multicenter, 2-period crossover study with a single arm 
continuation evaluating the safety and efficacy of BAX 930 in the prophylactic and on-demand treatment of 
subjects with severe cTTP.
The bulk drug substance (BDS) manufacturing location in Orth, Austria will move to the manufacturing facility 
located in Singapore in the middle of Phase 3 study. A PK comparability between BAX 930 ORT and BAX 930 
SIN will be conducted.
Prophylaxis Treatment Cohort
The principal part of the study involves the prophylactic treatment of cTTP. There are 3 periods, 2 crossover PK 
assessments and 1 end-of-study PK assessment. 
After informed consent has been obtained, all subjects will undergo a minimum washout period of 1 week from 
their last prophylactic infusion. Upon completion of the washout period, subjects will undergo screening 
procedures for the determination of eligibility. Subjects who meet eligibility criteria based on the 
inclusion/exclusion criteria and consent to treatment in the prophylaxis cohort will be randomized equally to 1 of 
2 treatment orders: BAX 930-SoC or SoC-BAX 930. Subjects randomized into the SoC treatment arm for Period 
1 will receive a single dose of BAX 930 to evaluate PK (i.e., PK dose) followed by a PK dose of their current 
SoC product 14 days [±2 days] later. Subjects randomized into the BAX 930 treatment arm for Period 1 will 
receive a PK dose of their current SoC product followed by a PK dose of BAX 930 14 days [±2 days] later. This 
crossover PK evaluation is PK-I. Subjects will then receive either BAX 930 or SoC for the first 6 months (one 
month=28 days) treatment period (Period 1) as randomized. For each subject, the SoC regimen will be 
determined by the investigator and defined by their treatment product and dosing regimen at the time of entry into 
the study. After completing Period 1 with either BAX 930 or SoC, subjects will enter Period 2 and crossover to 
the alternative treatment (BAX 930 for subjects who start on the SoC and SoC for subjects who start on 
BAX 930) and remain on that treatment for another 6 months during Period 2. Once Period 2 is completed, 
subjects will enter Period 3. 
Availability of BAX 930 SIN material and the date (before or after 30 September 2021), will guide the specific 
study design each subject will follow. For adult and pediatric subjects starting on BAX 930 ORT, following the 
first randomized crossover PK evaluation of both the subject’s SoC product and BAX 930 ORT, which is PK-I, 
subjects will receive 6 months (one month=28 days) of prophylaxis treatment with SoC product and 6 months of 
prophylaxis treatment with BAX 930 ORT. Once Period 2 is completed, subjects will enter Period 3. 
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TTP-related Clinical 
Signs/Symptoms
Not required to meet 
criteria but to be 
recorded if observed
Organ-specific signs and 
symptoms, including but not 
limited to:
• Renal signs, as defined by 
increase of serum 
creatinine >1.5 × baseline 
• Neurological symptoms 
(eg, headache, confusion, 
memory issues, irritability, 
paresthesia, dysarthria, 
dysphonia, visual 
disturbances, focal or 
general motor symptoms 
including seizures)
• Fever (≥100.4°F/38°C)
• Fatigue/lethargy 
• Abdominal pain
Organ-specific signs and 
symptoms, including but not 
limited to:
• Renal signs, as defined by 
increase of serum 
creatinine >1.5 × baseline 
• Neurological symptoms 
(eg, headache, confusion, 
memory issues, 
irritability, paresthesia, 
dysarthria, dysphonia, 
visual disturbances, focal 
or general motor 
symptoms including 
seizures) 
• Fever (≥100.4°F/38°C)
• Fatigue/lethargy 
• Abdominal pain
a In this instance, a laboratory measure refers to platelet counts or an LDH measurement

Standard of care treatment (6 monthsi) (Period 1 or 2, depending on randomization)

Subjects will receive the investigator-recommended standard prophylaxis treatment regimen for 
6 months
o
Dose modifications to increase the dose or frequency of SoC therapy, to the extent possible, is 
recommended if any of the following conditions are met:

One acute TTP event

Two separate occurrences of any laboratory deviations:

Drop in platelet count ≥25% of baseline or a platelet count <150,000/μL; OR

Elevation of LDH >1.5× of baseline or >1.5× ULN

Three separate occurrences of any organ-specific signs or symptoms, with or without 
changes in platelet count or LDH 
o
Neurological symptoms ( eg, confusion, dysphonia, dysarthria, focal or general motor 
symptoms including seizures) as per the opinion of the investigator; OR
o
Abdominal pain; OR
o
Increase of serum creatinine >1.5×baseline 

Subjects will receive the investigator-recommended standard treatment and dosing regimen during 
the acute TTP event

Acute management:
o
Subjects experiencing an acute TTP event during the prophylaxis period will receive the 
investigator-recommended standard treatment and dosing regimen during the acute TTP event
o
Subjects will continue prophylaxis therapy 1 week after their last acute treatment dose 
                                                
i The length of Period 1 and Period 2 is 6 months each. If a subject cannot switch to the next period at the end of 
month 6, for either logistical or medical reasons, the length of Period 1 and Period 2 can be extended to up to 
7 months total. For subjects enrolled before November 2017, Period 1 can be extended until the global amendment 
to lift the temporary study halt is approved.
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Acute TTP events are considered resolved when:

Platelet count is >150,000/ μL or platelet count is within 25% of baseline 

Elevation of LDH <1.5 x baseline or <1.5 x ULN

Subacute management:
o
Investigators may elect to treat a subacute TTP event with 1 or 2 additional daily doses of SoC

BAX 930 treatment (6 monthsii) (Period 1 or 2, depending on randomization and Period 3)

Subjects will receive BAX 930 prophylactically for 6 months 
o
Initial prophylactic dose and dosing regimen:

Subjects currently treated Q1W with fresh frozen plasma (FFP) or a solvent/detergent (S/D) 
treated plasma replacement product will start BAX 930 treatment with 40 IU/kg [±4 IU/kg] 
Q1W

All other subjects will receive a starting prophylaxis dose of 40 IU/kg [±4 IU/kg] every 
2 weeks (Q2W)
o
Dose modification based on clinical response:

Dose modifications to 40 IU/kg [±4 IU/kg] Q1W will be required if any of the following 
conditions is met:

One acute TTP event

Two separate occurrences of laboratory deviations:
o
Drop in platelet count ≥25% of baseline or a platelet count <150,000/µL; OR
o
Elevation of LDH >1.5× of baseline or >1.5× ULN

Three separate occurrences of organ-specific signs or symptoms, with or without 
changes in platelet count or LDH 
o
Neurological symptoms ( eg, confusion, dysphonia, dysarthria, focal or general 
motor symptoms including seizures) as per the opinion of the investigator; OR
o
Abdominal pain; OR
o
Increase of serum creatinine >1.5×baseline 

Acute management:
o
Subjects experiencing an acute TTP event during the prophylaxis period will receive the following 
dose and dosing regimen:

Subjects will receive an initial dose of 40 IU/kg [±4 IU/kg] BAX 930

Subjects will receive a subsequent dose of 20 IU/kg [±2 IU/kg] BAX 930 on Day 2

Subjects will receive an additional daily dose of 15 IU/kg [±1.5 IU/kg] BAX 930 until 
2 days after the acute TTP event is resolved
                                                
ii The length of Period 1 and Period 2 is 6 months each. If a subject cannot switch to the next period at the end of 
month 6, for either logistical or medical reasons, the length of Period 1 and Period 2 can be extended to up to 
7 months. For subjects enrolled before November 2017, Period 1 can be extended until the global amendment to 
lift the temporary study halt is approved. The length of Period 3 is approximately 6 months or when the 
continuation study has opened at the subject’s site.
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o
Subjects will continue prophylactic therapy 1 week after their last acute treatment dose

Subacute management:
o
Investigators may elect to treat a subacute TTP event- with 1 or 2 additional daily doses of 
40 IU/kg BAX 930.
On-Demand Treatment Cohort
Subjects experiencing an acute TTP event, meeting all other inclusion criteria, and entering and consenting to 
treatment in the study through the on-demand cohort will be randomized to receive urgent treatment with either 
the SoC or BAX 930. Upon resolution of the acute TTP event, subjects may choose to move to the prophylaxis 
cohort of the study and continue with assigned treatment or discontinue entirely. Subjects electing to move to the 
prophylaxis cohort will move directly to Period 1 and PK-I will not be conducted. Re-enrollment of an 
on-demand subject who has finished the study into the on-demand treatment cohort is allowed if he/she 
experiences a new acute TTP event.
Switching to BAX 930 SIN: Beginning on 1 October 2021, subjects entering the study will no longer receive 
BAX 930 ORT in Period 1, or any subsequent period thereafter. At this point, all subjects will receive BAX 930 
SIN or SoC only, depending on randomization, beginning with PK-I, and continuing throughout the study. For 
subjects randomized to receive BAX 930 in the on-demand arm will receive treatment with BAX 930 ORT until 
BAX 930 SIN becomes available. If a subject is randomized to receive BAX 930 ORT and BAX 930 SIN 
becomes available prior to Period 1, subjects will continue to receive BAX 930 ORT until completion of Period 1 
or Period 2, depending on randomization. Once BAX 930 SIN is available, on-demand subjects will receive 
BAX 930 SIN or SoC per their randomization schedule. Subjects who move to prophylactic treatment will 
continue with treatment assigned during their on-demand treatment and receive BAX 930 SIN in either Period 1 
or Period 2, per randomization schedule.in other per randomization schedule during Period 1. 
Pediatric subjects: Pediatric subjects (<12 years old) will be able to switch to BAX 930 SIN material after the 
cut-off date of 30 September 2021. At sites where BAX 930 SIN becomes available prior to the cut-off date, 
pediatric subjects who initiate the study with BAX 930 ORT, will not switch to BAX 930 SIN if or until initiation 
of prophylactic treatment.

Standard of care treatment:

Subjects will receive the investigator-recommended standard treatment and dosing regimen during 
the acute TTP event

BAX 930 treatment:

Subjects will receive an initial dose of 40 IU/kg [±4 IU/kg] BAX 930

Subjects will receive a subsequent dose of 20 IU/kg [±2 IU/kg] BAX 930 on Day 2

Subjects will receive an additional daily dose of 15 IU/kg [±1.5 IU/kg] BAX 930 until 2 days after 
the acute TTP event is resolved

Enrollment:
o
Subjects with a confirmed diagnosis of cTTP may provisionally enroll in the on-demand treatment 
cohort if a clinician believes the subject is undergoing an acute TTP event, based on platelet count 
and LDH irrespective of clinical symptomatology. Continuation in the study will be dependent on 
the confirmation of an acute TTP episode and compliance with all inclusion criteria and a 
determination that no exclusion criteria apply. 
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Efficacy data from such subjects will be excluded from the efficacy analysis if subsequent 
laboratory tests provide evidence that the subject did not experience an acute TTP event or was 
ineligible to participate in the study. All investigational product (IP)-related safety data will be 
included in the final study analysis.
Safety

Enrollment will be paused pending Data Monitoring Committee (DMC) evaluation if there are ≥3 product 
related SAEs, including the development of inhibitory antibodies to BAX 930

The study will be stopped if 2 or more subjects develop confirmed ADAMTS13 inhibitory antibodies 
defined as ≥0.6 BU in the central laboratory on 2 separate assays performed within a 1-month period.
Study Type/ Classification/ 
Discipline
Bioavailability, Efficacy, Pharmacodynamics, Pharmacoeconomics, 
Pharmacokinetic, Safety ( eg, Immunogenicity)
Control Type
Concurrent (Active)
Study Indication Type
Prevention, Treatment
Intervention model 
2-period crossover with a single arm continuation
Blinding/Masking
Open-label
Study Design
This is a Phase 3, prospective, randomized, controlled, prospective, 
open-label, multicenter, 2-period crossover study with a single arm 
continuation evaluating the safety and efficacy of BAX 930 in a total of 
approximately 57 subjects (48 subjects starting in the prophylaxis cohort, and 
9 subjects in the on-demand cohort) with severe cTTP.
Planned Duration of Subject 
Participation
Approximately 22 months in the prophylaxis cohort and approximately 
1 month in the on-demand cohort. 
Primary Outcome Measure
1. Incidence of acute TTP events among subjects receiving either BAX 930 or SoC prophylactically during the 
corresponding treatment periods.
Secondary Outcome Measures
Efficacy
1. Proportion of acute TTP events responding to BAX 930, defined as not requiring the use of another 
ADAMTS13-containing agent
2. Time to resolution of acute TTP events following initiation of treatment with BAX 930 or SoC agent
3. Incidence of thrombocytopenia defined as a drop in platelet count ≥25% of baseline or a platelet count 
<150,000/µL
4. Incidence of microangiopathic hemolytic anemia defined as an elevation of LDH >1.5× of baseline or >1.5× 
ULN
5. Incidence of neurological symptoms ( eg, confusion, dysphonia, dysarthria, focal or general motor 
symptoms including seizures)
6. Incidence of renal dysfunction defined as an increase in serum creatinine >1.5×baseline
7. Incidence of abdominal pain
8. Incidence of supplemental doses prompted by subacute TTP events 
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9.
Incidence of dose modification not prompted by an acute TTP event
10. Incidence of acute TTP events while subjects are on their final dose and dosing regimen in the study
Safety/Immunogenicity
1. Incidence of product-related and unrelated AEs and SAEs during each treatment period
2. Incidence of binding and inhibitory antibodies to ADAMTS13 
3. Clinically relevant changes in vital signs, clinical chemistry, and hematology
4. Estimated total quantity of ADAMTS13 administered during the treatment of acute TTP events
Pharmacokinetics/Pharmacodynamics
1. Assessment of the PK parameters (incremental recovery [IR], area under the plasma curve [AUC], terminal 
half-life [t1/2], mean residence time [MRT], systemic clearance [CL], steady state volume of distribution 
[Vss], and maximum concentration following infusion [Cmax]) for ADMATS13 activity and ADMATS13 
antigen for both the SoC agent and BAX 930 
2. Assessment of PD markers, such as VWF:Ag and VWF:RCo, at baseline and following infusion of the SoC 
agent and BAX 930 treatment during the initial PK assessment
3. Assessment of ADAMTS13 activity (pre-infusion ADAMTS13 levels) and select VWF parameters prior to 
each PK infusion of SoC or BAX 930 
4. Assessment of the impact of immunogenicity (immunogenicity status, time of onset) on ADAMTS13 
antigen and activity PK parameters
Health Related Quality of Life and Resource Utilization
1. Assessment of HRQoL including chronic TTP-related symptoms and disabilities, including cognitive 
function, using the following instruments:

cTTP-specific patient reported outcomes (PROs)

36-Item Short Form Health Survey (SF-36)

Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9)

EuroQol 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) and EQ-5D-youth (EQ-5D-Y)

Pediatric Quality of Life (Ped QL) Inventory 
2. Assessment of health care resource utilization, including hospital length of stay for acute TTP events, 
resource utilization during prophylaxis, and days missed from school/work due to TTP-related illness
Exploratory Outcome Measures
Efficacy
1.
Incidence of TTP manifestations, defined as a compositea of secondary outcome measures (secondary 
efficacy outcome measures 3 to 7), while receiving prophylactic treatment with BAX 930 or SoC during 
the 6 months of the corresponding treatment
2.
Incidence of TTP manifestations, defined as a compositea of secondary outcome measures (secondary 
efficacy outcome measures 3 to 7), while receiving the final prophylactic treatment regimen with 
BAX 930 or SoC.
3.
Incidence of TTP manifestations, defined as a compositea of secondary outcome measures (secondary 
efficacy outcome measures 3 to 7), requiring supplemental dose treatment.
4.
Incidence of the subacute TTP events in subjects receiving prophylactic treatment.
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5.
Assessment of additional exploratory PD biomarkers including but not limited to VWF multimer 
patterns, ADAMTS13 mediated VWF cleavage products, and coagulation readouts, at baseline and 
following infusion of the SoC agent and BAX 930 treatment during the initial PK assessment.
a composite of the secondary outcome measure is defined as the occurrence of at least one of the secondary 
outcome measures (3 to 7).
INVESTIGATIONAL PRODUCT(S), DOSE AND MODE OF ADMINISTRATION
Active Product
BAX 930
Dosage form: Lyophilized formulation 
Dosage frequency: Daily (on-demand cohort) or once every 1-2 weeks (Q1W or Q2W) 
(prophylaxis cohort)
Mode of Administration: Intravenous (i.v.)
Standard of Care
FFP, pooled solvent/detergent (S/D) treated plasma, or factor VIII (FVIII): VWF 
concentrates 
Dosage form: Liquid
Dosage frequency: Daily (on-demand cohort) or once every 1-2 weeks (Q1W or Q2W) 
(prophylaxis cohort)
Mode of Administration: i.v.
SUBJECT SELECTION 
Targeted Accrual
Approximately 57 subjects; including approximately 36 adult (≥18 years old) subjects 
and 12 adolescent (>12-≤17 years old) or pediatric (0-<12 years old) subjects starting in 
the prophylaxis cohort, and approximately 6 adult (≥18 years old) subjects and 
3 adolescent (>12-≤17 years old) or pediatric (0-<12 years old) subjects in the 
on-demand cohort.
Enrollment will conclude following enrollment of:

The last dosing visit of the fourth pediatric subject in the 0- to <6-year 
pediatric cohort; and

At least 30 adult subjects in the prophylaxis cohort
Number of Cohorts
2 (prophylaxis and on-demand)
Inclusion Criteria
1. Subject or legally authorized representative has provided signed informed consent (≥18 years of age) and/or 
assent form (signed by legal representative if subject is <18 years of age).
2. Subject is 0 to 70 years of age, inclusive, at the time of screening. (Subjects <18 years of age will be 
enrolled only after at least 5 adults (≥18 years of age) each have at least 10 exposures with BAX 930 and 
reviewed by the DMC. In France, no subjects younger than 18 years of age will be enrolled into the study 
before the first adult subject has been treated with BAX 930 for a minimum of 6 months.).
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3. Subject has a documented diagnosis of severe hereditary ADAMTS13 deficiency, defined as:

Confirmed by molecular genetic testing, documented in subject history or at screening, and 

ADAMTS13 activity <10% as measured by the FRETS-VWF73 assay, documented in subject history or 
at screening (subjects currently receiving SoC prophylactic therapy may exceed 10% ADAMTS13 
activity at screening).
Note: Subjects currently receiving prophylactic therapy will be screened immediately prior to their usual 
prophylactic infusion
4. Subject does not display any severe TTP signs (platelet count <100,000/µL and elevation of LDH >2× 
ULN) at screening. (prophylactic cohort only).
5. Subject is currently on a prophylactic dosing regimen or has a documented history of at least 1 TTP event 
and an ability to tolerate SoC prophylactic dosing (prophylactic cohort only).
6. Subjects ≥16 years of age must have a Karnofsky score ≥70% and subjects <16 years of age must have a 
Lansky score ≥80%.
7. Subject is hepatitis C virus (HCV)-negative as confirmed by antibody or polymerase chain reaction testing 
OR HCV-positive if their disease is chronic but stable.
8. If female of childbearing potential, subject presents with a negative blood or urine pregnancy test, 
confirmed no more than 7 days before the first administration, and agrees to employ adequate birth control 
measures for the duration of the study and to undergo quarterly pregnancy testing.
9. Sexually active males must use an accepted and effective method of contraception during the treatment and 
until a minimum of 16 days after the last dose administered.
10. Subject is willing and able to comply with the requirements of the protocol.
Exclusion Criteria
1. Subject has been diagnosed with any other TTP-like disorder (microangiopathic hemolytic anemia), 
including acquired TTP.
2. Subject has known hypersensitivity to hamster proteins.
3. Subject has experienced an acute TTP episode less than 30 days prior to screening (prophylactic cohort 
only).
4. Subject has a medical history or presence of a functional ADAMTS13 inhibitor at screening.
5. Subject has a medical history of a genetic or acquired immune deficiency that would interfere with the 
assessment of product immunogenicity, including subjects who are human immunodeficiency virus 
(HIV)-positive with an absolute cluster of differentiation 4 (CD4) count <200/mm3 or who are receiving 
chronic immunosuppressive drugs.
6. Subject has been diagnosed with severe cardiovascular disease (New York Heart Association classes 3 to 4).
7. Subject with end stage renal disease requiring chronic dialysis.
8. Subject has been diagnosed with hepatic dysfunction, as evidenced by, but not limited to, any of the 
following:
a. Serum alanine aminotransferase (ALT) ≥2xULN
b. Severe hypoalbuminemia <24 g/L
c. Portal vein hypertension ( eg, presence of otherwise unexplained splenomegaly, history of esophageal 
varices)
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9. In the opinion of the investigator, the subject has another clinically significant concomitant disease that may 
pose additional risks for the subject.
10. Subject has been treated with an immunomodulatory drug, excluding topical treatment ( eg, ointments, nasal 
sprays), within 30 days prior to enrollment. Use of corticosteroids in conjunction with administration of FFP 
to prevent allergic reactions is permitted.
11. Subject has an acute illness ( eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, bronchial 
asthma) at the time of screening (prophylaxis cohort only).
12. Subject is receiving or anticipates receiving another investigational drug and/or interventional drug within 
30 days before enrollment.
13. Subject has a history of drug and/or alcohol abuse within the last 2 years.
14. Subject has a progressive fatal disease and/or life expectancy of less than 3 months.
15. Subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.
16. Subject suffers from a mental condition rendering him/her unable to understand the nature, scope, and 
possible consequences of the study and/or evidence of an uncooperative attitude.
17. Subject is a family member or employee of the sponsor or investigator.
18. If female, subject is pregnant or lactating at the time of enrollment.
19. Any contraindication to standard of care medicinal product(s) as per local prescribing information.
STATISTICAL ANALYSIS
Sample Size Determination
In total, approximately 42 adult (≥18 years old) subjects and 15 adolescent (>12-≤17 years old) or pediatric 
(<12 years old) subjects will be enrolled in this study, including approximately 36 adult subjects and 
12 adolescent or pediatric subjects starting in the prophylaxis cohort, and approximately 6 adult subjects and 
3 adolescent or pediatric subjects, in the on-demand cohort. The sample size is limited by the extremely low 
prevalence of the disease (0.5 to 4 per million) (Mansouri Taleghani et al., 2013). The updated approximate 
number of subjects reflects the current, observed enrollment patterns and accounts for a 10% dropout rate. The 
number of subjects starting enrollment in the prophylactic cohort should allow an overall assessment of efficacy 
and safety of BAX 930, including immunogenicity, and PK.
The sample size of approximately 36 adult (≥18 years old) subjects and 12 adolescent (4 subjects age >12-≤17) or 
pediatric subjects (4 subjects age >6-<12, and 4 subjects age 0-< 6) in the prophylaxis cohort, will be evaluated 
for the safety and efficacy of the investigational product. 
If 15 of the 30 adult and adolescent prophylaxis subjects receive FFP and each subject receiving FFP will have at 
least 14 infusions per treatment period, there will be 210 total FFP infusions. With 210 FFP infusions, there is a 
>99% probability that at least 1 SAE will be observed, if as reported in the literature, the rate of serious adverse 
reactions (SARs) is 6% (Huisman et al., 2014). 
The sample size for the on-demand cohort will be approximately 6 adult subjects, if enrollment allows, and 
3 pediatric or adolescent subjects.
The sample size is not selected as a result of a power calculation and the primary outcome measure will not 
be assessed by a formal significance test.
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Planned Statistical Analysis
Efficacy
The overall treatment effect of BAX 930 will be assessed on the totality of evidence provided by efficacy, safety, 
PRO, and PK data. The statistical analysis for the prophylactic cohort will be carried out in 2 steps: (a) an 
interim analysis (with interim clinical study report) will be performed after 30 adults and adolescent subjects in 
the prophylactic cohort, complete the study; (b) a final analysis will be done at the end of the study when all 
efficacy, safety, PRO and PK data collected become available for both adult and pediatric subjects. 
The interim analysis will be performed on a cleaned snapshot of the study database. The interim analysis results 
will be used in regulatory submissions and scientific manuscripts. An efficacy analysis for the on-demand cohort 
based on available data at the time of the snapshot will also be included in the interim analysis.
Analyses will be performed separately for the prophylaxis and on-demand cohorts on applicable outcome 
measures and will be presented by treatment group for each cohort, unless otherwise stated.
Details on the specific analyses to be performed will be provided in the Statistical Analysis Plan.
Prophylaxis cohort
The primary efficacy analysis will provide the number and incidence rate of acute TTP events for each treatment 
arm in the prophylactic cohort, with the corresponding 95%, 2-sided confidence intervals (CIs). The ratio of the 
2 treatment incidence rates and a 95%, 2-sided CI will be estimated using a generalized linear mixed-effects 
model with the negative binomial distribution as a family and with a logarithmic link function (the default), if 
data facilitate convergence of the model; this approach will utilize the paired counts for each subject obtained 
under each of the 2 treatments. Summaries of the numbers and incidence rates of the two treatments will be 
provided also by period and by age groups.
The number and incidence rates of the following: (a) thrombocytopenia, defined as a drop in platelet count ≥25% 
of baseline or a platelet count <150,000/µL; (b) microangiopathic anemia defined as an elevation of LDH >1.5× 
of baseline or >1.5× ULN; (c) neurological symptoms (TTP related); (d) renal disfunction defined as an increase 
in serum creatinine >1.5×baseline and (e) abdominal pain (TTP related) will be tabulated by treatment arm for 
the prophylactic cohort. The number and incidence rate of (a) dose modification and (b) supplemental dose while 
on either the BAX 930 or SoC treatment arm will be reported by treatment arm for the prophylactic cohort.
For acute TTP events, the number and the proportion of acute TTP events responding to treatment will be 
summarized, for the pooled prophylactic and on-demand cohort data, and separately. A Kaplan-Meier curve for 
each treatment group will be drawn based on each subject's time to resolution of the acute TTP event, defined as 
the time from the initial treatment to resolution of the acute TTP event. Only the first acute TTP event for each 
subject will be included in the analysis.
Safety
The number and percentage of treatment-emergent adverse events will be calculated overall, by system organ 
class, by preferred term, and by treatment group for each cohort. Treatment-emergent adverse events will be 
further summarized by seriousness, severity, and relationship to IP. Adverse events related to IP, AEs leading to 
withdrawal, SAEs, and deaths will be similarly summarized/listed.
Incidence of binding and inhibitory antibody formation will be tabulated and summarized. 
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Vital signs and clinical laboratory results (clinical chemistry, hematology, and urinalysis), observed and change 
from baseline, will be summarized by study visit, treatment, and age group (as applicable) using descriptive 
statistics.
For the laboratory safety data, out of range values will be flagged in the data listings and a list of clinically 
significant abnormal values will be presented.
The estimated total quantity of ADAMTS13 administered during the treatment of acute TTP events will be listed 
by subject and summarized by treatment cohort (prophylactic or on-demand) using descriptive statistics.
Pharmacokinetics/Pharmacodynamics
Standard PK parameters for ADAMTS13 activity and ADAMTS13:Ag including IR, AUC, MRT, systemic CL, 
Vss, and Cmax after single infusions of BAX 930 will be estimated for each subject utilizing a non-compartmental 
approach. Plasma VWF:RCo, VWF:Ag, and VWF multimer structure analysis prior to and following a single 
infusion (PK studies) and following each subsequent infusion (treatment periods) of BAX 930, FFP, or other 
ADAMTS13 replacement product will also be measured. Additional summary statistics like median, coefficient 
of variation, geometric mean, and the corresponding 90% CIs will be reported.
Health Related Quality of Life
Health related quality of life and resource utilization will be tabulated by treatment group.
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5. TABLE OF CONTENTS
PROTOCOL SIGNATURE PAGE..............................................................................................2
1. STUDY PERSONNEL ..............................................................................................................3
1.1 Authorized Representative (Signatory) / Responsible Party ..........................................3
1.2 Study Organization.............................................................................................................3
2. SERIOUS ADVERSE EVENT REPORTING........................................................................4
3. SUMMARY OF CHANGES FROM PREVIOUS VERSION...............................................5
4. SYNOPSIS................................................................................................................................10
5. TABLE OF CONTENTS ........................................................................................................24
LIST OF IN-TEXT TABLES .....................................................................................................29
LIST OF IN-TEXT FIGURES ...................................................................................................29
LIST OF APPENDICES .............................................................................................................29
6. LIST OF ABBREVIATIONS .................................................................................................30
7. BACKGROUND INFORMATION .......................................................................................34
7.1 Description of Investigational Product ...........................................................................34
7.2 Clinical Condition/Indication...........................................................................................34
7.3 Population to be Studied...................................................................................................37
7.4 Findings from Nonclinical and Clinical Studies.............................................................37
7.4.1 Nonclinical Studies .....................................................................................................37
7.4.1.1 Nonclinical Pharmacology ..................................................................................38
7.4.1.2 Nonclinical Pharmacokinetics ............................................................................39
7.4.1.3 Nonclinical Toxicology.........................................................................................41
7.4.2 Clinical Studies ...........................................................................................................44
7.4.2.1 Safety.....................................................................................................................44
7.4.2.2 Immunogenicity....................................................................................................44
7.4.2.3 Pharmacokinetics.................................................................................................44
7.4.2.4 Pharmacodynamics..............................................................................................45
7.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) to 
Human Subjects ................................................................................................................46
7.6 Compliance Statement......................................................................................................47
8. STUDY PURPOSE AND OBJECTIVES ..............................................................................48
8.1 Study Purpose....................................................................................................................48
8.2 Primary Objective.............................................................................................................48
8.3 Secondary Objectives........................................................................................................48
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8.3.1 Efficacy........................................................................................................................48
8.3.2 Safety ...........................................................................................................................48
8.3.3 Pharmacokinetics/Pharmacodynamics.....................................................................48
8.3.4 Health Related Quality of Life and Resource Utilization .......................................49
8.4 Exploratory Objectives.....................................................................................................49
9. STUDY DESIGN......................................................................................................................50
9.1 Brief Summary and Amendment Rationale ...................................................................50
9.2 Overall Study Design ........................................................................................................50
9.2.1 Prophylaxis Treatment Cohort and PK Assessments .............................................53
9.2.1.1 Pharmacokinetic Assessments ............................................................................53
9.2.1.2 Switching to BAX 930 SIN ..................................................................................56
9.2.1.3 Standard of Care Treatment Arm (6 Months) (Period 1 or 2, Depending 
on Randomization)...............................................................................................57
9.2.1.4 BAX 930 Treatment Arm (6 Months) (Period 1 or 2, Depending on 
Randomization and Period 3) .............................................................................58
9.2.2 On-Demand Treatment Cohort.................................................................................60
9.2.2.1 BAX 930................................................................................................................60
9.2.3 Safety ...........................................................................................................................61
9.3 Duration of Study Period(s) and Subject Participation ................................................62
9.4 Outcome Measures............................................................................................................62
9.4.1 Primary Outcome Measures......................................................................................62
9.4.2 Secondary Outcome Measures ..................................................................................62
9.4.2.1 Efficacy..................................................................................................................62
9.4.2.2 Safety.....................................................................................................................63
9.4.2.3 Pharmacokinetics/Pharmacodynamics..............................................................63
9.4.2.4 Health Related Quality of Life and Resource Utilization ................................63
9.4.3 Exploratory Outcome Measures ...............................................................................64
9.5 Randomization and Blinding ...........................................................................................64
9.6 Study Stopping Rules........................................................................................................64
9.7 Investigational Product(s) ................................................................................................65
9.7.1 Packaging, Labeling, and Storage.............................................................................65
9.7.2 Administration............................................................................................................65
9.7.3 Description of Treatment...........................................................................................66
9.7.4 Dosing Justification ....................................................................................................68
9.7.5 Investigational Product Accountability....................................................................68
9.8 Source Data........................................................................................................................68
10. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION .....................70
10.1 Inclusion Criteria ............................................................................................................70
10.2 Exclusion Criteria ...........................................................................................................71
10.3 Withdrawal and Discontinuation ..................................................................................72
11. STUDY PROCEDURES .......................................................................................................74
11.1 Informed Consent ...........................................................................................................74
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11.2 Subject Identification Code............................................................................................74
11.3 Screening and Study Visits.............................................................................................74
11.3.1 Screening and Study Visits for Pediatric Subjects................................................74
11.3.2 Pediatric Development Assessments.......................................................................75
11.4 Medications and Non-Drug Therapies..........................................................................75
11.5 Subject Reported Outcomes...........................................................................................76
11.6 Subject Completion/Discontinuation.............................................................................76
11.7 Procedures for Monitoring Subject Compliance .........................................................77
11.8 Acute TTP events During PK Assessment....................................................................77
12. ASSESSMENT OF EFFICACY, PHARMACOKINETICS, AND 
PHARMACODYNAMICS.....................................................................................................78
12.1 Assessment of Efficacy: Acute TTP Events ..................................................................78
12.2 Assessment of Pharmacokinetics and Pharmacodynamics.........................................78
12.2.1 Pediatric Subjects (<6 Years Old)...........................................................................79
13. ASSESSMENT OF SAFETY................................................................................................80
13.1 Adverse Events ................................................................................................................80
13.1.1 Definitions .................................................................................................................80
13.1.1.1 Serious Adverse Event.......................................................................................80
13.1.1.2 Suspected Unexpected Serious Adverse Reaction (SUSAR)..........................81
13.1.1.3 Non-Serious Adverse Event ..............................................................................81
13.1.1.4 Unexpected Adverse Events..............................................................................81
13.1.1.5 Preexisting Diseases ...........................................................................................82
13.1.2 Assessment of Adverse Events.................................................................................82
13.1.2.1 Severity................................................................................................................84
13.1.2.2 Causality .............................................................................................................84
13.2 Urgent Safety Measures..................................................................................................85
13.3 Untoward Medical Occurrences....................................................................................86
13.4 Non-Medical Complaints................................................................................................86
13.5 Medical, Medication, and Non-Drug Therapy History ...............................................86
13.6 Physical Examinations....................................................................................................87
13.7 Clinical Laboratory Parameters....................................................................................87
13.7.1 Hematology and Clinical Chemistry.......................................................................87
13.7.2 Biomarkers of Organ Damage ................................................................................88
13.7.2.1 Cardiac Troponin...............................................................................................89
13.7.3 Creatine Kinase Myocardial Band Fraction..........................................................89
13.7.3.1 Neuron-specific Enolase ....................................................................................89
13.7.3.2 S100 Calcium-binding Protein B......................................................................89
13.7.4 Urinalysis...................................................................................................................89
13.7.5 Pharmacokinetics and Pharmacodynamic Tests...................................................89
13.7.5.1 ADAMTS13 Activity..........................................................................................90
13.7.5.2 ADAMTS13 Antigen (ADAMTS13:Ag) ..........................................................90
13.7.5.3 VWF Ristocetin Cofactor Activity (VWF:RCo) .............................................90
13.7.5.4 VWF Antigen (VWF:Ag) ..................................................................................90
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13.7.5.5 VWF Multimer Analysis and ADAMTS13 mediated VWF cleavage 
products ................................................................................................................90
13.7.6 Immunogenicity ........................................................................................................90
13.7.6.1 Anti-ADAMTS13 Antibodies............................................................................91
13.7.6.2 Anti-CHO Protein Antibodies ..........................................................................91
13.7.7 Viral Serology ...........................................................................................................92
13.7.8 Genetic Testing .........................................................................................................92
13.7.9 Pregnancy Test..........................................................................................................92
13.7.10 Assessment of Laboratory Values.........................................................................93
13.7.10.1 Assessment of Abnormal Laboratory Values................................................93
13.7.11 Backup Samples and Biobanking..........................................................................93
13.8 Vital Signs and 12-lead Electrocardiogram..................................................................93
13.9 Health-related Quality of Life........................................................................................94
14. STATISTICS..........................................................................................................................97
14.1 Sample Size Determination ............................................................................................97
14.2 Analysis Sets ....................................................................................................................97
14.2.1 All Subjects Enrolled Set .........................................................................................97
14.2.2 Full Analysis Set (FAS) ............................................................................................97
14.2.3 Modified Full Analysis Set (MFAS)........................................................................98
14.2.4 Per-protocol Analysis Set.........................................................................................98
14.2.5 Safety Analysis Set....................................................................................................98
14.2.6 Pharmacokinetic and Pharmacodynamic Analysis Sets.......................................98
14.3 Handling of Missing, Unused, and Spurious Data .......................................................98
14.4 Methods of Analysis........................................................................................................99
14.4.1 Primary Outcome Measure .....................................................................................99
14.4.1.1 Incidence of Acute TTP Events ......................................................................100
14.4.2 Secondary Outcome Measures ..............................................................................100
14.4.2.1 Efficacy..............................................................................................................100
14.4.2.2 Safety.................................................................................................................101
14.4.2.3 Pharmacokinetics/Pharmacodynamics..........................................................101
14.4.2.4 Health Related Quality of Life and Resource Utilization ............................103
14.4.3 Exploratory Outcome Measures ...........................................................................103
14.4.4 Other Analyses........................................................................................................104
14.4.4.1 Planned Interim Analyses of the Study: ........................................................104
14.5 Direct Access to Source Data/Documents ...................................................................104
15. QUALITY CONTROL AND QUALITY ASSURANCE.................................................105
15.1 Investigator’s Responsibility........................................................................................105
15.1.1 Final Clinical Study Report...................................................................................105
15.2 Training..........................................................................................................................105
15.3 Monitoring .....................................................................................................................105
15.4 Safety Monitoring .........................................................................................................105
15.5 Auditing..........................................................................................................................106
15.6 Non-Compliance with the Protocol .............................................................................106
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15.7 Laboratory and Reader Standardization....................................................................106
16. ETHICS ................................................................................................................................107
16.1 Subject Privacy..............................................................................................................107
16.2 Ethics Committee and Regulatory Authorities ..........................................................107
16.3 Informed Consent .........................................................................................................107
17. DATA HANDLING AND RECORD KEEPING..............................................................109
17.1 Confidentiality Policy....................................................................................................109
17.2 Study Documentation and Case Report Forms..........................................................109
17.3 Document and Data Retention.....................................................................................109
18. FINANCING AND INSURANCE......................................................................................110
19. PUBLICATION POLICY...................................................................................................111
20. SUPPLEMENTS..................................................................................................................112
20.1 Study Flow Chart..........................................................................................................112
20.2 Pediatric Subjects..........................................................................................................114
20.2.1 Prophylactic Cohort ...............................................................................................114
20.2.2 On-demand Cohort ................................................................................................115
20.3 Schedule of Study Procedures and Assessments ........................................................116
20.4 Clinical Laboratory Assessments ................................................................................122
20.5 Contraceptive Methods for Female Subjects of Childbearing Potential .................130
20.6 Contraceptive Method for Male Subjects...................................................................131
21. REFERENCES.....................................................................................................................132
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LIST OF IN-TEXT TABLES
Table 1. Overview of Nonclinical Studies for BAX 930............................................................38
Table 2. TTP Event Definitions ..................................................................................................52
Table 3. Composition of BAX 930 FDP .....................................................................................67
Table 4. Patient Reported Outcome (PRO) Instruments.........................................................95
Table 5. Pediatric Enrollment (Prophylactic Cohort)............................................................114
Table 6. Pediatric Enrollment (On-demand Cohort) .............................................................115
Table 7. Schedule of Study Procedures and Assessments for Subjects on Prophylaxis
Cohort.....................................................................................................................................116
Table 8. Schedule of Study Procedures and Assessments for Subjects on On-Demand 
Cohort ....................................................................................................................................120
Table 9. Clinical Laboratory Assessments: Prophylaxis Treatment (Prophylaxis 
Cohort)* .................................................................................................................................122
Table 10. Clinical Laboratory Assessments: Acute Treatment (On-Demand Cohort)*.....125
Table 11. Adult and Adolescent Subjects (≥12 Years of Age) PK Laboratory 
Assessments............................................................................................................................127
Table 12. Pediatric (<12 Years of Age) PK Laboratory Assessment Adolescent 
Subjects* ................................................................................................................................128
Table 13. End of Study, PK-III Assessment, PK Laboratory Assessments by Age.............129
LIST OF IN-TEXT FIGURES
Figure 1. Study Design for Subjects Entering Study with BAX 930 ORT ...........................112
Figure 2. Study Design for Subjects Entering Study with BAX 930 SIN .............................113
LIST OF APPENDICES
Appendix 1 Country-Specific Information..............................................................................135
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6. LIST OF ABBREVIATIONS
Abbreviation
Definition
z
apparent terminal rate constant
ADAMTS13
a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13
AE
adverse event
Ag
antigen
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the plasma curve
AUC(0-inf)
area under the plasma-time concentration curve from zero to infinity
AUC(0-last)
area under the plasma-time concentration curve from zero to the last measured timepoint
AUMC(0-inf)
area under the moment curve from zero to infinity
B19V
parvovirus B19
BAX 930
rADAMTS13
BAX 930 ORT
rADAMTS13 manufactured in Orth
BAX 930 SIN
rADAMTS13 manufactured in Singapore
BW
body weight
°C
degree Celsius
CBC
complete blood count
CD4
cluster of differentiation 4
CFR
Code of Federal Regulations
CHO
Chinese hamster ovary
CI
confidence interval
CK-MB
creatine kinase myocardial band
CL
clearance
Cmax
maximum concentration (following infusion)
CNS
central nervous system
CRF
case report form
CTA
Clinical Trial Agreement
cTnI
cardiac troponin I
cTnT
cardiac troponin T
cTTP
congenital thrombotic thrombocytopenic purpura
DMC
data monitoring committee
EC
ethics committee
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Abbreviation
Definition
ECG
electrocardiogram
eCRF
electronic case report form 
ELISA
enzyme-linked immunosorbent assay
EQ-5D-3L
EuroQol 5 Dimensions Questionnaire 3-Level
EQ-5D-Y
EuroQol 5 Dimensions Questionnaire Youth version
EU
European Union
oF
degree Fahrenheit
FAS
full analysis set
FDP
Final Drug Product
FFP
fresh frozen plasma
FRET
fluorescent resonance energy transfer
FVIII
factor VIII
GCP
good clinical practice
GLP
good laboratory practice
GmbH
Gesellschaft mit beschränkter Haftung − German term for a company that does not trade 
its shares on the stock market
hr
hour(s)
HAV
hepatitis A virus
HBc
hepatitis B core
HBV
hepatitis B virus
HCV
hepatitis C virus
HEV
hepatitis E virus
HIV
human immunodeficiency virus
HRQoL
health-related quality of life
hTTP
hereditary thrombotic thrombocytopenic purpura; congenital thrombotic 
thrombocytopenic purpura
i.a.
intra-arterial
IB
investigator’s brochure
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use
IP
investigational product 
IR
incremental recovery
i.v.
intravenous(ly)
IVR
in vivo recovery
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Abbreviation
Definition
ko
knockout
LDH
lactate dehydrogenase
LLOQ
lower levels of quantification
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
min
minute(s)
MRT
mean residence time
NMC
non-medical complaint
NOAEL
no-observed-adverse-effect-level
NSE
neuron-specific enolase
PD
pharmacodynamic(s)
PedsQL
Pediatric Quality of Life Inventory
PK
pharmacokinetic(s)
PP
per-protocol
PRO
patient reported outcome
Q1W
every week
Q2W
every 2 weeks
rADAMTS13
a recombinant human disintegrin and metalloprotease with a thrombospondin type 1 
motif, member 13
RBC
red blood cell
RCo
ristocetin cofactor activity
RSI
Reference Safety Information
S100B
S100 calcium-binding protein B
S/D
solvent/detergent
SAE
serious adverse event 
SAP
statistical analysis plan
SD
Sprague-Dawley
SDS
sodium dodecyl sulfate
SF-36
36-Item Short Form Health Survey
SIC
subject identification code
SoC
standard of care
SUSAR
suspected unexpected serious adverse reactions
t1/2
terminal half-life
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Abbreviation
Definition
TBD
to be determined
TEAE
treatment emergent adverse event (s)
tmax
time to maximum concentration
TSQM-9
abbreviated 9-item Treatment Satisfaction Questionnaire for Medication
TTP
thrombotic thrombocytopenic purpura
U
unit(s)
UL VWF
ultra-large von Willebrand Factor
ULN
upper limit of normal
US
United States
Vss
steady state volume of distribution
VWF
von Willebrand factor 
VWF:Ag
von Willebrand factor: antigen
VWF:RCo
von Willebrand factor: ristocetin cofactor activity
w/w
weight-to-weight ratio
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7. BACKGROUND INFORMATION
7.1 Description of Investigational Product
Baxalta Innovations GmbH/Baxalta US Inc (later Shire and now Takeda, hereafter referred to as 
Takeda or sponsor) has developed a recombinant ADAMTS13 (a disintegrin and 
metalloproteinase with a thrombospondin type 1 motif, member 13) named BAX 930, which is 
synthesized by a genetically engineered Chinese hamster ovary (CHO) cell line that expresses 
the human ADAMTS cDNA. To address concerns regarding the risk of transmission of 
blood-borne pathogens that may be introduced by human plasma, no exogenously added raw 
materials of human or animal origin are employed in the cell culture, purification, or formulation 
of the final product. A plasma-protein-free method and 2 virus inactivation steps are used in this 
process. This process virtually eliminates any risk of transmission of human blood-borne viruses 
or other adventitious agents that could, in theory, be introduced by the use of animal- or human-
derived raw materials. The only proteins present in the final product other than BAX 930 are 
trace quantities of host cell (i.e., CHO) protein. The biologic product is a lyophilized formulation 
of human rADAMTS13 for intravenous (i.v.) injection intended for use as on-demand and 
prophylactic treatment of patients with thrombotic thrombocytopenic purpura (TTP).
See Section 9.7 for further information on the investigational product (IP) and its usage 
in this study. A detailed description of BAX 930 is also provided in the investigator’s 
brochure (IB).
7.2 Clinical Condition/Indication
Thrombotic thrombocytopenic purpura is a rare, life-threatening microvascular disease 
characterized by single or recurrent episodes of thrombocytopenia, microangiopathic hemolytic 
anemia, and widespread microvascular thrombosis, which leads to the ischemic damage of 
multiple organs (mainly kidney, heart, and brain) (George, 2006).
Defective processing of von Willebrand factor (VWF), a large plasma glycoprotein that plays a 
central role in both primary and secondary hemostasis, is central to the pathophysiology of TTP. 
Patients with TTP display abnormally large VWF multimers in their plasma; the thrombi in TTP 
are enriched in VWF and platelets; and VWF is present on the surface of platelets in patients 
with TTP (Tsai, 2003).
Two forms of TTP are recognized: congenital and acquired. The distinction is clinically
important because of the different mechanisms of disease and treatment protocols.
The congenital form of TTP (cTTP) comprises no more than 5% of all TTP cases. The exact 
prevalence of cTTP is not known but is estimated to be less than 1/1,000,000 patients. 
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It exhibits an autosomal recessive mode of inheritance caused by homozygous or double 
heterozygous mutations in both ADAMTS13 alleles on chromosome 9. The nature of these 
mutations is quite diverse and includes missense, nonsense, and splice site mutations as well as 
deletions and insertions less commonly (Lotta et al., 2010). A severe deficiency of ADAMTS13 
results in the accumulation of VWF multimers of ultra-large molecular weight (UL VWF), a 
characterizing feature of TTP (Moake and McPherson, 1989).
The clinical presentation of cTTP is quite variable. Although symptoms develop soon after birth 
in approximately 50% of patients, in others, symptoms do not occur until the second or third 
decade of life. Moreover, while some patients present with relatively asymptomatic anemia and 
thrombocytopenia, progressive organ dysfunction is frequently encountered and rapidly 
progressive life-threatening organ failure may also be encountered (Furlan and Lämmle, 2001; 
Schneppenheim et al., 2003; Schneppenheim et al., 2006). Among patients presenting soon after 
birth, severe neonatal jaundice requiring exchange transfusion is commonly encountered. Often, 
the disease is initially misdiagnosed as idiopathic thrombocytopenia purpura and the initiation of 
appropriate therapy is delayed. A highly sensitive detection system (surface-enhanced laser 
desorption/ionization time-of-flight mass spectrometry) has demonstrated that residual 
ADAMTS13 activity correlates with the genotype of the disease and the severity of the clinical 
phenotype (Lotta et al., 2012).
Often, conditions that are associated with increases in circulating VWF levels, such as second or 
third trimester pregnancy and infection, are triggers for acute TTP events. These observations 
suggest that while only very low levels of circulating ADAMTS13 activity are generally required 
to maintain an appropriate VWF multimer size distribution, the increased release of endothelial 
stores of VWF can overwhelm this limited capacity and result in a clinically apparent syndrome.
Plasma therapy was proposed empirically in patients with TTP long before its logic was 
demonstrated. Two preparations are presently in use: quarantine-stored fresh frozen plasma 
(FFP) and solvent/detergent (S/D)-treated plasma. Both contain normal levels of ADAMTS13, 
i.e., approximately 1 µg/mL (Allford et al., 2000; Furlan et al., 1999; Heger et al., 2007; 
Kentouche et al., 2002; Rock et al., 2006).
Fresh frozen plasma is a single donor plasma preparation produced by whole blood fractionation 
or by automated plasmapheresis. The plasma units are rapidly frozen within 6 hours (hr) after 
donation. 
The residual risk of transmitting human immunodeficiency virus (HIV), hepatitis B virus (HBV), 
and hepatitis C virus (HCV) is reduced by quarantine storage for 6 months and adjacent second 
donor screening for these blood-borne viruses. The FFP contains physiologic levels of 
functionally active plasma proteins according to their respective intra-individual variations. 
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The FFP involves a very small but not negligible risk of transmitting blood-borne viruses 
(Hellstern et al., 2002). The FFP units contain all clotting factors and inhibitors of hemostasis 
and fibrinolysis, with average activities of 100 U/dL and considerable variations corresponding 
to inter-individual variability (Heim et al., 2009).
For treating TTP episodes, 10 to 20 mL/kg FFP rescues acute episodes, with cessation of 
hemolysis within 24 hr and improvement of platelet count within a few days. Nevertheless, 
rescue infusions may not prevent central nervous system (CNS) and renal involvement. In 
neonates, exchange transfusion is generally indicated because of the severe hyperbilirubinemia. 
Platelet infusions are contraindicated, as they may trigger thrombotic complications.
The general use of prophylaxis in cTTP has been proposed as rescue infusions may not prevent 
CNS and renal involvement (Loirat et al., 2006). In prophylactic treatment, 10 mL/kg FFP every 
2 or 3 weeks (80% of patients), or in some patients (about 10%) only every 4 weeks, are 
necessary to maintain remission (Allford et al., 2003; Barbot et al., 2001). Approximately 10% 
of patients require prophylactic treatment every week to maintain remissioniii. 
Low levels of ADAMTS13, generally <10%, are sufficient to prevent clinical manifestations 
(Kiss, 2010). The half-life of ADAMTS13 in FFP is 2 to 4 days (Furlan et al., 1999; 
Kovarova et al., 2018), and its protective effect persists for at least 14 days (George, 2007). A 
proposed explanation to this long-lasting effect, even at low plasma concentrations, has been that 
ADAMTS13 may “dock” to the endothelium where it is able to cleave UL VWF over a longer 
period of time (Loirat et al., 2006).
In practice, the interval between 2 FFP infusions is typically decided based upon clinical 
symptomatology and laboratory parameters such as platelet count and lactate dehydrogenase 
(LDH) levels. Pharmacokinetic modeling suggests that currently employed regimens maintain 
ADAMTS13 levels above most or all of the treatment period.
In order to cover triggering events, intensification of plasma therapy (10 mL/kg FFP infusion 
even if the interval since last infusion is <1 to 2 weeks) is typically considered any time 
an infection occurs. Close monitoring of LDH and hemoglobin levels have been proposed 
as an indication to administer FFP when the platelet count drops below 150 ×109/L 
(Willis and Bandarenko, 2005). A similar approach has been recommended for vaccinations. In 
case of surgery, prophylactic administration of FFP is justified. Lastly, it is recommended that 
plasma therapy is intensified during pregnancy. 
                                                
iii
Kremer J. Personal Communication, Clinical Trial Identifier NCT01257269.
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Whether the intensification (eg, weekly infusions of FFP) needs to be started at the beginning of 
the third trimester or earlier has not been established.
7.3 Population to be Studied
A total of approximately 57 eligible subjects diagnosed with severe congenital ADAMTS13 
deficiency (cTTP; defined as plasma ADAMTS13 activity <10%) between 0 and 70 years of age, 
inclusive, as applicable at time of enrollment, are planned to be enrolled. Approximately 36 adult 
(≥18 years old) subjects and 12 adolescent (>12-≤17 years old) or pediatric (0-<12 years old) 
subjects will be enrolled in the prophylactic cohort. A total of approximately 6 adult subjects 
(≥18 years old) and 3 adolescent (>12-≤17 years old) or pediatric (0-<12 years old) subjects will 
be enrolled in the on-demand cohort, as applicable, and depending on the minimum age 
permitted in each individual country. 
Enrolled subjects (i.e., subjects who have signed the informed consent form [ICF] or provided 
assent [<18 years of age]) will be eligible to participate in the study if they meet all of the 
inclusion criteria (see Section 10.1) and none of the exclusion criteria (see Section 10.2).
7.4 Findings from Nonclinical and Clinical Studies
The current investigational product BAX 930 consists of a mixture of the native protein and a 
protein variant Q97R (A single nucleotide change of “A” to “G” in the ADAMTS13 nucleotide 
sequence leads to a change of amino acid glutamine “Q” to arginine “R” at position 97 at the 
protein level, resulting in the sequence variant Q97R). 
All nonclinical studies and the Phase 1 clinical study were performed with the two-variant 
product. No safety concerns were raised in the nonclinical toxicology studies or among subjects 
participating in the Phase 1 clinical study. Refer to the BAX 930 IB for information on findings 
from nonclinical and clinical studies. Potential risks and efficacy of BAX 930 are summarized in 
the following sections.
7.4.1 Nonclinical Studies
Nonclinical studies have been performed in vitro and in vivo to characterize the safety, efficacy, 
pharmacokinetics (PK), and toxicity of BAX 930.
An overview of the nonclinical studies is summarized in Table 1.
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Table 1. Overview of Nonclinical Studies for BAX 930
Study Number
Study
Species
527739
Repeat Dose Toxicity (5 days)a
SD Rat
PV2511001
Repeat Dose Toxicity (4 weeks)a
SD Rat
523430
Repeat Dose Toxicity (26 weeks)a
Rat
8234215
Escalating Dose and Repeat Dose Toxicity (4 weeks)a
Cynomolgus monkey
8243420
Repeat Dose Toxicity (4 weeks) including cardiovascular 
investigationsa
Cynomolgus monkey
PV2541101
Local Tolerancea
Rabbit
495388
Placental Transfer Feasibility
SD Rat
496821
Pre- and Post-natal Developmenta
SD Rat
497081
Female Fertility and Embryo-fetal Developmenta
SD Rat
PV2521007
PKa
ADAMTS13 ko mouse
PV2531005
PKa
Rat
8234215
PKa
Cynomolgus monkey
WH0610
Efficacy of prophylactic administration
ADAMTS13 ko mouse
WH0211
Efficacy of prophylactic administration over time
ADAMTS13 ko mouse
WH0710
Efficacy of therapeutic administration
ADAMTS13 ko mouse
248.220.5098
Efficacy of therapeutic administration at different doses
ADAMTS13 ko mouse
ATS0007101
In Vitro Functional Activity
Plasma from ADAMTS13 ko 
mouse, SD rat, guinea pig, minipig, 
and cynomolgus monkey
ko=knockout; PK=pharmacokinetics; SD=Sprague-Dawley.
a.
GLP compliant according to the following: US Code of Regulations, 21 CFR 58 – GLP for Nonclinical 
Laboratory Studies; Organisation de Coopération et de Développement Economiques - Principles of GLP, 
ENV/MC/CHEM(98)17 (as revised in 1997); Austrian Federal Law Gazette II No. 450/2006 – Regulation of 
the Minister of Health and Women on GLP; Austrian Federal Law Gazette II No. 211/2000 - Regulation of the 
Minister of Agriculture, Forestry, Environment and Water Management on the Application of Principles of 
GLP and the monitoring of compliance (Chemicals GLP Inspection Regulation – GLP-V); Austrian Federal 
Law Gazette No. 501/1989 - Animal Experiments Act; and Japanese Ordinance No. 21/1997, GLP Standard 
for Conduct of Nonclinical Safety Studies of Drugs.
7.4.1.1 Nonclinical Pharmacology
Primary pharmacodynamics studies were performed to evaluate the efficacy of both prophylactic
and therapeutic administration of BAX 930 in ADAMTS13 knockout (ko) mice using a TTP 
model developed by (Schiviz et al., 2012). 
Briefly, TTP like symptoms are induced in ADAMTS13 ko mice by injecting a high dose of a 
recombinant human von Willebrand factor (rVWF) preparation containing UL VWF multimers. 
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These mice are not able to cleave human high-molecular weight VWF multimers; therefore, 
rVWF triggers TTP-like symptoms.
Efficacy of the test item was defined as the degree of prevention of platelet drop and prevention 
of increase in LDH, both parameters being markers of TTP. In addition, organ damage was 
assessed histologically. In all 4 efficacy studies (WH0610, WH0710, WH0211, 248.220.5098iv), 
body weight loss, severe thrombocytopenia, increase in serum LDH, and thrombotic changes in 
the heart were present in all animals in the negative control groups, confirming that the induction 
of TTP like symptoms is homogeneous, stable, and reproducible.
In all 4 studies, animals treated with buffer and challenged with a high dose of rVWF served as 
negative controls. Untreated animals served as background controls.
Both prophylactic and therapeutic treatment with BAX 930 was efficacious in the rVWF-induced 
TTP model in ADAMTS13 ko mice. The efficacy of BAX 930 was interval- and dose-dependent 
when administered before or after induction of TTP. Treatment with BAX 930 showed similar or 
slightly improved efficacy to treatment with fresh frozen human plasma, the current standard of 
care.
Regarding safety pharmacology, the influence of administration of BAX 930 on vital functions 
(cardiovascular and respiratory parameters) was tested in the repeat dose toxicity study in 
cynomolgus monkeys (Study 8243429). Treatment with BAX 930 was well-tolerated and did not 
result in any adverse effect on the cardiovascular or respiratory system in cynomolgus monkeys 
up to a dose of 400 U/kg body weight (BW), which was the highest dose tested and which is 
10 times the maximum anticipated human dose in the Phase 3 clinical trial.
7.4.1.2 Nonclinical Pharmacokinetics
Pharmacokinetic studies were performed in 3 animal species (ADAMTS13 ko mice, 
Sprague-Dawley [SD] rats and cynomolgus monkeys). Citrated plasma samples were analyzed 
for ADAMTS13 activity by a validated ADAMTS13 activity assay (FRETS-VWF73 assay). 
ADAMTS13 antigen was measured using a validated antigen ELISA.
7.4.1.2.1 Pharmacokinetic Study in ADAMTS13 ko Mice 
The pharmacokinetic profile of BAX 930 was evaluated in ADAMTS13 ko mice after 
intravenous bolus administration of 40, 80, or 200 U/kg BW. 
                                                
iv
Studies WH0610, WH0710, WH0211, and 248.220.5098 data on file at Takeda
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The study followed a serial sacrifice design. For each arm, 10 animals (5 male/5 female) at each 
of 9 timepoints were bled by cardiac puncture under anesthesiav.
Similar dose-adjusted values (average) of area under the plasma-time concentration curve from 
zero to infinity (AUC(0-inf)) were observed for all 3 doses, for both the ADAMTS13 activity 
and the ADAMTS13 antigen (approximately 0.13 hr* U/mL / U/kg and approximately 
0.13 hr*μg/mL/μg/kg). Both the ADAMTS13 activity and antigen values showed similar 
results for in vivo recovery (IVR), incremental recovery (IR), clearance (CL), and also for 
mean residence time (MRT), terminal half-life (t1/2), and steady state volume of distribution 
(Vss).
7.4.1.2.2 Pharmacokinetic Study in Rats 
The pharmacokinetics and dose proportionality of BAX 930 were evaluated in SD rats 
(Study PV2531005vi) after single intravenous (bolus) administration of 80, 200, or 400 U/kg 
BW. A single animal design was used with 10 animals in each dose group.
The geometric means, following analysis for ADAMTS13 activity, for dose-adjusted area under 
the plasma-time concentration curve from zero to the last measured timepoint (AUC(0-last)) 
(hr*U/mL/U/kg) were 0.326, 0.384, and 0.458 for the low, mid, and high doses, respectively. 
The geometric means for antigen for dose-adjusted AUC(0-last) (hr*μg/mL/μg/kg) were 0.301, 
0.285, and 0.283, respectively. The ratios of AUC(0-last) and AUC(0-inf) for both activity and 
antigen indicated good coverage of the drug exposure for all doses during the observational 
period of the study. Terminal half-lives ranged from 16.7 to 25.6 hr and 23.5 to 24.0 hr for 
activity and antigen, respectively. 
Mean residence times ranged from 22.8 to 30.8 hr and 28.3 to 29.7 hr for activity and antigen, 
respectively, and IVR ranged from 60% to 66%, and 49% to 57% for activity and antigen, 
respectively.
7.4.1.2.3 Pharmacokinetic Study in Cynomolgus Monkeys
Pharmacokinetics of BAX 930 in cynomolgus monkeys was assessed in Study 8234215vii. 
Three males and 3 females received the test (800 U/kg BW) and control item by slow bolus i.v. 
injection once weekly during the repeated dose phase of this study.
                                                
v
Study PV251007 data on file at Takeda
vi
Study PV2531005 data on file at Takeda
vii Study 8234215 data on file at Takeda
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The geometric mean of dose-adjusted AUC(0-last) [hr* U/mL/U/kg] for combined sexes was 0.377 
(95% confidence interval [CI]: 0.357 to 0.398) and 0.401 (95% CI: 0.379 to 0.423) at Days 1 and 
15, respectively. This slight increase was also observed with antigen: geometric mean of 
dose-adjusted AUC(0-last) [hr*μg/mL / μg/kg] for combined sexes. Further, t1/2 and MRTs were 
comparable between Days 1 and 15 for combined sexes for both analytes.
7.4.1.3 Nonclinical Toxicology
Sprague-Dawley rats and cynomolgus monkeys were selected as suitable species for evaluation 
of safety and toxicity of BAX 930. Species suitability was shown by demonstrating that 
(BAX 930 can cleave endogenous monkey and rat VWF in vitro and in vivo. Only one species 
(SD rat) was used for long-term toxicity assessment and DART (developmental and reproductive 
toxicity) assessment based on the following reasons:

In the 1-month repeat-dose toxicity studies, the safety profile of BAX 930 in SD rats and 
cynomolgus monkeys was comparable

In the 1-month repeat-dose toxicity study in the cynomolgus monkey, formation of 
neutralizing anti-drug antibodies was observed which resulted in a decrease in exposure 
and in development of TTP-like symptoms after repeated dosing. Cynomolgus monkeys 
are therefore not considered suitable for long-term studies with BAX 930.
7.4.1.3.1 Repeat Dose Toxicity Study in Rats
In Study 527739viii, the toxicity and toxicokinetics of BAX 930 were evaluated in SD rats when 
intravenously dosed for 5 consecutive days. Treatment with BAX 930 at 80, 200, or 400 U/kg 
BW for 5 consecutive days was well tolerated in rats and did not cause any adverse treatment 
related effects. The NOAEL for BAX 930 in this study was 400 U/kg, which was the highest 
dose tested.
Study PV2511001ix assessed the toxicity of BAX 930 in rats after repeated i.v. administration 
every third day over a 28-day period (10 applications) and a 2-week recovery phase. 
Treatment with 80, 400, and 800 U/kg BAX 930 every third day for 28 days was well-tolerated 
and did not cause any adverse treatment related effects. The NOAEL for BAX 930 for this study 
in rats was 800 U/kg, which was the highest dose tested.
                                                
viii Study 527739 data on file at Takeda
ix
Study PV2511001 data on file at Takeda
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7.4.1.3.2 Escalating Dose- and Repeat Dose Toxicity Study in Cynomolgus Monkeys
Study 8234215x was conducted to assess the PK profile of BAX 930 and to determine the 
NOAEL and a suitable dose level for repeated application in the cynomolgus monkey following 
i.v. administration (4 males and 4 females for the escalating dose phase and 3 males and 
3 females for the repeated dose phase).
Treatment with BAX 930 at 800 U/kg i.v. once a week for a total of 5 weeks (repeat dose phase) 
was well-tolerated and did not reveal any adverse treatment related changes in general. The 
formation of antibodies against BAX 930 is an expected immune response after repeated 
application of heterologous proteins to cynomolgus monkeys and was not regarded as adverse. 
The NOAEL was the high dose of 800 U/kg under the conditions of this repeated dose phase 
study. Based on data available from the escalating dose phase, the NOAEL for this phase of 
study was the high dose of 1790 U/kg.
7.4.1.3.3 Repeat Dose Toxicity Study in Cynomolgus Monkeys
Study 8243420xi aimed to determine the toxicity of the test item BAX 930, following i.v. 
administration to the cynomolgus monkey for 4 weeks and to assess the reversibility of effects 
observed during a 2-week recovery phase.
BAX 930 was administered i.v. to 3 groups (5/sex/group) of cynomolgus monkeys by bolus 
injection at doses of 0, 80, 200, and 400 U/kg every 7 days (weekly) for 29 days (5 doses). 
Another group of cynomolgus monkeys (5/sex) received vehicle (buffer for BAX 930) at the 
highest dosing volume of 1.117 mL/kg. Two animals per sex in each group were maintained on 
study for a 2-week recovery period. 
Treatment with BAX 930 was well-tolerated at either dose and did not reveal any adverse 
clinical symptoms or findings that could be clearly attributed to the test item. The formation of 
antibodies against BAX 930 is an expected immune reaction after repeated application of 
heterologous proteins to cynomolgus monkeys. The NOAEL was the high dose of 400 U/kg.
7.4.1.3.4 Reproductive and Developmental Toxicity and Placental Transfer Feasibility 
Study in Rats 
Study 495388xii was performed to assess the potential of BAX 930 to cross the placenta. 
Sprague-Dawley rats received a single i.v. (bolus) injection of BAX 930 of a dose level of 
0 (vehicle control group) and 3200 U/kg (test group) on Day 21 gestation, via the lateral tail vein 
at a dose volume of 5 mL/kg. 
                                                
x
Study 8234215 data on file at Takeda
xi
Study 8243420 data on file at Takeda
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Incomplete placental transfer of BAX 930 was detected in SD rats following a single 
administration on Day 21 of gestation at a level of 3200 U/kg. ADAMTS13 antigen 
concentration was measured up to only 0.6% of the concentration detected in maternal serum.
In Study 497081xiii, the effect of BAX 930 on female fertility and pregnancy was assessed in SD 
rats after intravenous administration every third day for 2 weeks before mating, throughout 
mating, and up to approximately day 16 of gestation. BAX 930 was administered at doses of 80, 
200, or 400 U/kg BW (20 females per group). The formulation buffer of BAX 930 served as 
vehicle control. In conclusion, treatment with BAX 930 at 80, 200, and 400 U/kg BW in female 
rats was not associated with any adverse maternal findings or treatment related effects on 
fertility, pregnancy performance, or fetal development. In addition, no binding anti-drug 
antibodies were detected in any animals during the study. The highest dose tested, 400 U/kg BW, 
was therefore considered to be the maternal and fetal NOAEL in this study.
In Study 496821xiv, the effects of BAX 930 on pregnant/parturient/lactating rats and on the 
development of the conceptus and offspring to sexual maturity was assessed after repeated 
intravenous administration. BAX 930 was administered at doses of 80, 200, or 400 U/kg BW 
(24 females per group). The formulation buffer of BAX 930 served as vehicle control. There was 
no effect on the physical or functional development of the F1 generation or their reproductive 
function. Both the maternal and the reproductive NOAEL were determined to be 400 U/kg which 
was the highest dose tested.
7.4.1.3.5 Local Tolerance in Rabbits
Study PV2541101xv investigated the local tolerance of BAX 930 after i.v. (clinical application 
route), intra-arterial (i.a.), and paravenous (possible misapplication routes) application in rabbits 
in comparison with buffer for BAX 930 (vehicle control) and saline (negative control). Each 
item was injected i.v. or i.a. at a volume of 5 mL per animal (within 2 minutes), or paravenously 
at a volume of 0.5 mL per animal (bolus injection), into the right ear of each of 4 rabbits (2 male, 
2 female; total of 24 tested animals). The animals’ behavior was observed, and the injection sites 
examined macroscopically for possible changes in the first 30 minutes after treatment and 
thereafter intermittently up to 6 hours and again at 24, 48, and 72 hours.
No changes in behavior and no macroscopic changes at the injection sites were observed after 
administration of BAX 930 for any of the administration routes tested. Histopathologically, no 
adverse lesions regarding local tissue tolerability of the test item were detected.
                                                
xiii Study 497081 data on file at Takeda
xiv Study 496821 data on file at Takeda
xv Study PV2541101 data on file at Takeda
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BAX 930 was well-tolerated after i.v. (intended clinical administration route), i.a., and 
paravenous administration.
7.4.2 Clinical Studies
A first in man, Phase 1, prospective, open-label, multicenter, dose-escalation studyxvi to evaluate 
safety including immunogenicity and PK of BAX 930 in a total of at least 14 subjects diagnosed 
with severe cTTP (plasma ADAMTS13 activity <6%) assigned to either 1 of 3 dose cohorts (i.e., 
5, or 20, or 40 U/kg) has been completed. Overall, 16 subjects were enrolled, of whom 
15 received the IP and completed the study.
7.4.2.1 Safety
No severe treatment emergent adverse events (TEAEs), deaths, serious AEs (SAEs), or TEAEs 
leading to discontinuation from the study or from the investigational product, or breakthrough 
TEAEs were observed in the study. Although most of the subjects in the study reported TEAEs, 
a greater proportion of the TEAEs were mild in severity and assessed as not related to the IP or 
study procedure. The most commonly reported TEAEs were in the system organ class nervous 
system disorders, gastrointestinal disorders, and infections and infestations. All the TEAEs 
reported in the study resolved. 
No safety signals were evident by shifts in laboratory values. After BAX 930 infusion, platelet
counts increased and LDH levels decreased before returning to baseline levels, consistent with 
ADAMTS13 activity.
7.4.2.2 Immunogenicity
All subjects tested negative at all scheduled timepoints for neutralizing anti-ADAMTS13 
antibodies, anti-CHO protein antibodies, and anti-BAX 930 binding antibodies.
7.4.2.3 Pharmacokinetics
Low levels below the limit of quantification (quantified using FRETS-VWF73) of 
ADAMTS13:antigen (Ag) and limited ADAMTS13 activity were measured in most subjects at 
predose baseline. Following single-dose administration of BAX 930 at 5, 20, and 40 U/kg to 
adults, dose-related increases in individual ADAMTS13:Ag and activity were observed and 
reached a maximum at approximately 1 hour or earlier. Similar ADAMTS13:Ag and 
ADAMTS13 FRETS-VWF73, profiles notwithstanding some differences due to different lower 
levels of quantification (LLOQs), suggested a good correlation between protein concentrations 
(ADAMTS13:Ag) and activity. ADAMTS13:Ag and activity coverage was higher than baseline 
(predose) value for most data points over the 288-hour sample collection window.
                                                
xvi Full Clinical Study Report 281101, BAX 930 (rADAMTS13). 
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The most robust PK data were derived from the 40 U/kg dose cohort, in which the greatest 
number of subjects (9 subjects, including 7 adults) were enrolled and values above the LLOQ 
observed. The protein antigen and activity PK parameters of BAX 930 were comparable to those 
estimated from previous FFP studies (Furlan et al., 1999; Fujimura et al., 2015). In the 40 U/kg 
cohort, the geometric mean of IR was 0.0232 (U/mL x kg/U) and mean half-life was 59.2 hours
for ADAMTS13 FRETS-VWF73.
The geometric mean of ADAMTS13:Ag CL was 61.5 mL/h and of Vss was 5300 mL (at 40 U/kg 
dose level), suggesting the protein distributed primarily within the intravascular compartment. 
There was approximate dose proportionality with respect to the maximum concentration 
following infusion (Cmax; geometric means of 0.323 µg/mL after 20 U/kg infusion and 
0.672 µg/mL after 40 U/kg infusion) and AUC(0-inf) (geometric means of 18.3 µg∙h/mL after 
20 U/kg infusion and 36.0 µg∙h/mL after 40 U/kg infusion). Likewise, ADAMTS13 activity 
(FRETS-VWF73) Cmax and total exposures increased approximately in proportion to the dose 
escalations. The geometric mean Cmax was 0.398 U/mL after 20 U/kg infusion and 0.948 U/mL 
after 40 U/kg infusion; and geometric mean AUC(0-inf) was 19.1 U∙h/mL after 20 U/kg infusion 
and 53.1 U∙h/mL after 40 U/kg infusion.
No apparent differences were observed for ADAMTS13 activity and ADAMTS13:Ag between 
adolescents (N=2) and adults (N=7), where data were available. Pediatric PK parameters could 
not be accurately estimated due to insufficient data from the sparse sampling scheme of 
2 adolescent subjects and the absence of younger pediatric subjects to support parameter 
calculations.
7.4.2.4 Pharmacodynamics
Detectable ADAMTS13-mediated VWF cleavage products were present in all subjects (100%) 
up to 3, 24, and 48 hours postdose at 5, 20, and 40 U/kg, respectively. A trend for decreasing 
large multimers, a fraction of which also included ultra-large multimers, and increasing levels of 
the intermediate fraction was observed over the first 24 hours post-infusion in individual profiles 
at BAX 930 doses of 20 or 40 U/kg. In addition, the function of VWF to bind platelet GP1b, as 
measured by the VWF:RCo assay, decreased by almost 30% in the first 9 hours. 
There was an increase in the platelet count in all dosing groups and a decrease of LDH in the 
first 96 hours. Taken together, these findings provide evidence of in vivo ADAMTS13 activity 
following BAX 930 IP administration.
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7.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) to 
Human Subjects
Currently, acute TTP events are treated with FFP infusions, typically 10 to 20 mL/kg BW for 
3 or more days or until the platelet count rises to above 150,000 per μL. There is currently no 
approved treatment for cTTP, therefore BAX 930 represents a new therapeutic to improve 
current treatment (Plaimauer and Scheiflinger, 2004; Plaimauer et al., 2011). Takeda intends to 
evaluate BAX 930 as replacement therapy in a fashion analogous to the use of FFP, the current 
standard clinical therapy for TTP.
Based on the retrospective analysis of available peptide mapping data, the composition of 
Q97 native and Q97R variant protein appears to have been consistent throughout development. 
The evaluation further confirmed no differences in the structure/function relationship of the 
native and variant protein in the composition observed and demonstrated consistency of the 
product throughout preclinical and clinical development with a Q97R protein abundance of 
between 52% and 72%.
Evaluation of biochemical, enzymatic and pharmacokinetic characteristics of BAX 930 which 
contains both the native dominant Q97 and variant Q97R proteins, concluded (1) no differences 
in the structure/function relationship of the native vs. variant protein and (2) that they closely 
reflect the properties of plasma-derived ADAMTS13. The amino acid exchange position is 
located away from the proposed VWF binding sites that are critical for cleavage and metal ion 
binding, significantly reducing the possibility of any effect it may have on regulation of these 
binding domains.
No safety concerns were raised in the nonclinical toxicology studies or among subjects 
participating in the Phase 1 clinical study - none of the study subjects developed antibodies to 
ADAMTS13 following treatment with BAX 930. An in silico assessment of immunogenicity has
been performed (utilizing the Immune Epitope Database), indicating no generation of novel 
immune-dominant MHC II T cell epitopes as result of the Q97R amino acid exchange. 
Over the course of evaluation of ADAMTS13 variability in the human population, the 
ADAMTS13 protein variant identified in BAX 930 resembles a benign missense mutation, 
which was also supported by an immunogenicity assessment based on non-clinical study results 
as well as an in-silico assessment which did not provide any data pointing to new immune 
epitopes formed by the variant.
BAX 930 is therefore expected to behave in the same way as endogenous ADAMTS13, as 
demonstrated in several non-clinical in vitro and in vivo studies. Replacement therapy with 
BAX 930 promotes increased plasma levels of ADAMTS13, which are absent or greatly reduced 
in subjects with cTTP. 
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The temporary correction of the enzyme deficiency results in improvement of VWF cleaving 
activity and prevention of the clinical symptoms. Due to the lack of clinical experience with 
BAX 930, there is no known risk of formation of inhibitors to ADAMTS13.
There is no experience with the therapeutic use of Takeda’s BAX 930 in pediatric or geriatric 
TTP subjects; however, with respect to the anticipated efficacy and safety of BAX 930, no 
differences are expected between adults and children as treatment with current SoC replacement 
products is similar in the 2 populations. It is now well established that FFP and virus-inactivated 
plasma replace active ADAMTS13 in subjects with TTP (Loirat et al., 2006). There is only 
1 example of a subject developing an inhibitor to ADAMTS13 reported in the literature 
(Raval et al., 2015).
While the treatment of TTP via plasma infusions is effective, the therapy can cause 
complications such as allergic reaction (i.e., urticaria and anaphylaxis). Plasma infusions also 
carry the following risks: infection associated with exposure to blood-borne pathogens; volume 
overload, and hyperviscosity associated with rapid infusion of plasma volumes that are required 
in order to increase the plasma ADAMTS13 levels significantly (Hellstern et al., 2002); and in 
subjects undergoing long-term prophylaxis, hemorrhage related to the insertion of a central 
venous catheter, venous thrombosis, and systemic infection (Howard et al., 2006). Furthermore, 
an additional risk involves the availability of FFP, which can fluctuate due to its use in market as 
a source material for plasma protein preparations (Hellstern et al., 2002).
BAX 930 should be administered with caution in subjects with known hypersensitivity to any of 
the components of rADAMTS13. As with any i.v. protein product, allergic-type hypersensitivity 
reactions are possible. Subjects must be closely monitored for any symptoms throughout the 
infusion period. 
Subjects should be informed of the early signs of hypersensitivity reactions including hives, 
generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. If these 
symptoms occur, the administration should be discontinued immediately. In case of shock, 
standard medical treatment for shock should be implemented.
Please refer to the BAX 930 IB for further details on benefits and risks of the IP.
7.6 Compliance Statement
This study will be conducted in accordance with this protocol, the International Council for 
Harmonisation Guideline for Good Clinical Practice E6 (ICH GCP, April 1996), Title 21 of the 
US Code of Federal Regulations (US CFR), the European Union (EU) Directives 2001/20/EC 
and 2005/28/EC, and applicable national and local regulatory requirements.
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8. STUDY PURPOSE AND OBJECTIVES
8.1 Study Purpose
The purpose of the study is to assess safety and efficacy of BAX 930 in the prevention and 
treatment of acute TTP events in subjects with severe congenital deficiency of ADAMTS13 
(cTTP; defined as plasma ADAMTS13 <10%, as measured by the FRETS-VWF73 assay).
8.2 Primary Objective
The primary objective of the study is:
1. To determine the incidence of acute TTP events in subjects with severe cTTP receiving 
either standard of care (SoC) or BAX 930 as a prophylactic treatment.
8.3 Secondary Objectives
8.3.1 Efficacy
1. To evaluate the efficacy of BAX 930 in the treatment of acute TTP events as measured by 
the 1) number of acute TTP events responding to treatment and 2) time to resolution in both 
the prophylactic and the on-demand cohorts
2. To evaluate the incidence of isolated TTP manifestations including thrombocytopenia, 
microangiopathic hemolytic anemia, renal dysfunction, neurologic signs and symptoms, and 
abdominal pain in the prophylactic cohort 
3. To evaluate the incidence of dose modification and supplemental dose for each treatment in 
the prophylactic cohort
8.3.2 Safety
1. To evaluate the safety and tolerability of BAX 930 in terms of related AEs and SAEs in 
both the prophylactic and the on-demand cohorts
2. To assess the immunogenicity of BAX 930 as measured by the incidence of binding and 
inhibitory antibodies to ADAMTS13 in both the prophylactic and the on-demand cohorts
8.3.3 Pharmacokinetics/Pharmacodynamics
1. For both adult and pediatric subjects two crossover PK evaluations and an end-of-study 
ADAMTS13 PK evaluation (PK-III) may be performed for up to 288 hours post-infusion 
in the prophylactic cohort 
1) PK-I: To characterize the baseline PK of ADAMTS13 activity after administration of 
BAX 930 ORT or BAX 930 SIN and SoC prior to Period 1 
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2) PK-II: To assess the PK comparability between BAX 930 SIN and BAX 930 ORT, in 
subjects who received BAX 930 ORT in PK-I.
3) PK-III: To assess if any time dependent PK changes occur due to long-term exposure 
to BAX 930 SIN at the end of period 3.
2.
To assess VWF:antigen (VWF:Ag), and VWF:ristocetin cofactor activity (RCo) at baseline 
and following infusion of the SoC agent and BAX 930 treatment during the initial PK 
assessment in the prophylactic cohort.
3.
To assess ADAMTS13 activity (pre-infusion ADAMTS13 levels) and select VWF 
parameters prior to each PK infusion of SoC or BAX 930 in the prophylactic cohort.
4.
To evaluate the effect of immunogenicity on the PK profile of ADAMTS13 
8.3.4 Health Related Quality of Life and Resource Utilization
1.
To evaluate Health Related Quality of Life (HRQoL), treatment satisfaction, and health 
resources utilization in each of the treatment periods in both the prophylactic and the 
on-demand cohorts.
8.4 Exploratory Objectives
1.
To evaluate the incidence of subacute TTP events in subjects receiving the respective 
prophylactic treatment.
2.
To assess the relationship between ADAMTS13 activity levels (measured and/or estimated 
from PK parameters) and time of occurrence of acute TTP events, subacute TTP events, 
and a composite of TTP manifestations in the prophylactic group.
3.
To assess shifts in biomarkers of organ damage, including troponin T (cTnT) and I (cTnI) 
(cardiac), creatine kinase myocardial band (CK-MB) fraction (cardiac), neuron-specific 
enolase (NSE) (brain), S100B (brain), and serum creatinine (kidney), during routine 
prophylaxis with the SoC treatment and BAX 930 as well as during acute TTP events in 
the prophylactic cohort.
4.
To characterize the PK profile of ADAMTS13 activity at the end of the study
5.
To evaluate additional exploratory PD biomarkers, including but not limited to VWF 
multimer patterns, ADAMTS13 mediated VWF cleavage products and coagulation 
readouts, at baseline and following infusion of the SoC agent and BAX 930.
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9. STUDY DESIGN
9.1 Brief Summary and Amendment Rationale
This is a Phase 3, prospective, randomized, controlled, open-label, multicenter, 2-period 
crossover study with a single arm continuation evaluating the safety and efficacy of BAX 930 in 
the prophylactic and on-demand treatment of subjects with severe cTTP.
The primary purpose of Protocol Amendment 15 is to 1) provide clarification and alignment of 
various terms and definition throughout the text and 2) include suggestions and options to reduce 
volume of blood samples collected from pediatric subjects to ensure the blood volume is within 
recommended limits. Refer to Section 3 for a summary of all changes from the prior version. 
9.2 Overall Study Design 
The overall study design is illustrated in Figure 1. The principal part of the study involves the 
prophylactic treatment of cTTP. There are 3 periods, 2 crossover PK and one end-of-study PK 
assessment. Adult, adolescent, and pediatric subjects, who are screened prior to 01 October 2021, 
will initiate the study with BAX 930 ORT. Following the first randomized crossover PK 
evaluation (PK-I) of both the subject’s SoC product and BAX 930 ORT, subjects will receive 
6 months of prophylaxis treatment with SoC product and 6 months of prophylaxis treatment with 
BAX 930 ORT. Once Period 2 is completed, subjects will enter Period 3. Subjects will receive 
treatment with BAX 930 ORT in Period 3 until BAX 930 SIN is available at their site. Once 
BAX 930 SIN is available, subjects randomized to the study after the temporary study halt will 
initiate a crossover PK evaluation, which is PK-II (see Section 9.2.1.1.2 for PK-II exceptions), 
and then initiate an additional 6 months of prophylaxis treatment with BAX 930 SIN in Period 3. 
To briefly describe PK-1, after informed consent has been obtained, all adult and pediatric 
subjects will undergo a minimum washout period of 1 week from their last prophylactic infusion. 
For subjects receiving factor VIII (FVIII):VWF concentrates, the minimum required SoC PK 
dose washout period may be reduced to 5 days. Upon completion of the washout period, subjects 
will undergo screening procedures for the determination of eligibility. Subjects who meet all 
eligibility criteria based on the inclusion/exclusion criteria (see Section 10.1 and Section 10.2, 
respectively) and consent to treatment in the prophylactic cohort will be randomized equally to 
1 of 2 treatment orders: BAX 930-SoC or SoC-BAX 930. Subjects randomized into the SoC 
treatment arm for Period 1 will receive a single dose of BAX 930 to evaluate pharmacokinetics 
(i.e., PK dose) followed by a PK dose of their current SoC product 14 days [±2 days] later. 
An exception will be permitted for subjects on Q1W dosing if the investigator is concerned that 
delaying an infusion would impact subject safety. These subjects will be permitted to receive 
their current SoC product 7 days [±0.5 days] after the BAX 930 PK dose. 
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Subjects randomized into the BAX 930 treatment arm for Period 1 will receive a PK dose of 
their current SoC product followed by a PK dose of BAX 930 14 days [±2 days] later. 
Following PK-I, subjects will then receive either BAX 930 ORT or SoC for the first 6-month 
treatment period (Period 1) as randomized. For each subject, the SoC regimen will be determined 
by the investigator and defined by their treatment product and dosing regimen at the time of 
entry into the study.
After completing Period 1 with either BAX 930 ORT or SoC, subjects will enter Period 2 and 
crossover to the alternative treatment (BAX 930 ORT for subjects who start on the SoC and SoC 
for subjects who start on BAX 930 ORT) and remain on that treatment for another 6 months 
during Period 2. Once Period 2 is completed, subjects will enter Period 3. Subjects will receive 
treatment with BAX 930 ORT in Period 3 until BAX 930 SIN is available at their site. Once 
BAX 930 SIN is available, adult and adolescent (≥12 years old) subjects randomized to the study 
after the temporary study halt will initiate a crossover PK evaluation, which is PK-II (see 
Section 9.2.1.1.2 for PK-II exceptions). Then, subjects will start Period 3 and receive an 
additional 6 months of treatment with BAX 930 SIN. Subjects randomized to the study prior to 
the temporary study halt, will receive prophylactic treatment with BAX 930 ORT in Period 3. 
After the last IP infusion of Period 3, an end-of-study, PK-III assessment may be implemented 
for a subset of subjects including; 1.) Any subject in the prophylactic cohort, including any 
subject who switches from on-demand treatment to prophylactic treatment, who initiates the 
study with BAX 930 SIN, and 2.) A minimum of 4 adults (≥18 years old), and a minimum of 
2 pediatric or adolescent subjects (age 0-17 years) who receive BAX 930 SIN in Period 3. 
Pediatric subjects (<12 years old) and subjects who receive weekly (Q1Week) dosing regimen 
will undergo the PK-III assessment. Subjects will be allowed to remain in the 281102 study until 
the continuation study is open for enrollment. Dosing, visits and assessments will be continued 
unchanged and as per protocol description of Period 3 (See Section 9.2.1.4), until their transfer to 
the continuation study.
Subjects who are screened for Study 281102 after 30 September 2021, will follow the same 
design principles as with BAX 930 ORT with two exceptions: 1) that subjects will initiate the 
study with BAX 930 SIN instead of BAX 930 ORT and 2) an end-of-study PK-III may be 
conducted in lieu of the aforementioned PK-II assessment. These subjects will first undergo PK-I 
as a randomized crossover between BAX 930 SIN and SoC. After completing Period 1 with 
either BAX 930 SIN or SoC, subjects will enter Period 2 and crossover to the alternative 
treatment (BAX 930 SIN for subjects who start on the SoC and SoC for subjects who start on 
BAX 930 SIN) and remain on that treatment for another 6 months during Period 2. Once 
Period 2 is completed, subjects will enter Period 3 with BAX 930 SIN (Figure 2). Subjects may 
then undergo an end-of-study, PK-III assessment.
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During prophylactic treatment, and if deemed necessary and acceptable by the investigator, 
subjects will be given the option to have at-home infusion of BAX 30 by a healthcare provider. 
Subjects will be required to come to the clinic for an acute/subacute TTP event. Subjects will 
also be required to have in-clinic visits periodically throughout the trial, further details regarding 
at-home visits can be found in the Home Nursing Manual. 
An interim analysis will be performed after 30 adult or adolescent subjects in the prophylactic
cohort, who were randomized to the prophylactic cohort, complete the study. The interim 
analysis will be performed on a cleaned snapshot of the study database. The interim analysis will 
include final data from at least 30 subjects in the prophylactic cohort who have completed the 
study. The interim analysis data will be used in regulatory submissions and scientific 
manuscripts.
It is anticipated that TTP-related events will occur during the study. These events will be 
classified as acute TTP events, isolated TTP manifestations, or subacute TTP events according to 
the following classifications (refer also to Section 13.1.2 regarding the reporting of TTP-related 
events and adverse events):
Table 2. TTP Event Definitions
Acute TTP Event
Subacute TTP Event
Isolated TTP Manifestations
Criteria
Both of the 
following laboratory 
measuresa
At least 2 of the following; at least 1 
of which must include a laboratory 
measurea
Any of the following
Thrombocytopenia
Drop in platelet 
count ≥50% of 
baseline or a platelet 
count <100,000/μL
Drop in platelet count ≥25% of 
baseline or a drop in platelet count 
<150,000/μL
Drop in platelet count ≥25% of 
baseline or a drop in platelet count 
<150,000/μL
Microangiopathic 
Hemolytic 
Anemia
Elevation of LDH 
>2 x of baseline or 
>2 x ULN
Elevation of LDH >1.5 x of baseline 
or >1.5 x ULN
Elevation of LDH >1.5 x of baseline 
or > 1.5 x ULN
TTP-related 
Clinical 
Signs/Symptoms
Not required to meet 
criteria but to be 
recorded if observed
Organ-specific signs and symptoms, 
including but not limited to:
• Renal signs, as defined by 
increase of serum creatinine 
>1.5 × baseline 
• Neurological symptoms ( eg, 
headache, confusion, memory 
issues, irritability, paresthesia, 
dysarthria, dysphonia, visual 
disturbances, focal or general 
motor symptoms including 
seizures)
•
Fever (≥100.4°F/38°C)
• Fatigue/lethargy 
• Abdominal pain
Organ-specific signs and symptoms, 
including but not limited to:
• Renal signs, as defined by 
increase of serum creatinine 
>1.5 × baseline 
• Neurological symptoms ( eg, 
headache, confusion, memory 
issues, irritability, paresthesia, 
dysarthria, dysphonia, visual 
disturbances, focal or general 
motor symptoms including 
seizures) 
• Fever (≥100.4°F/38°C)
• Fatigue/lethargy 
• Abdominal pain
a In this instance, a laboratory measure refers to platelet counts or an LDH measurement
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Acute TTP events will be managed by intensification of the replacement regimen using the same 
therapeutic agent (SoC or BAX 930) as employed for prophylaxis at that time. The occurrence of 
these events may also necessitate a change in the prophylactic regimen according to 
pre-specified criteria.
Subjects experiencing an acute TTP event, meeting all other inclusion criteria, and entering and 
consenting to treatment in the study through the on-demand cohort will be randomized to receive 
urgent treatment with either the SoC or BAX 930. Upon resolution of the acute TTP event, 
subjects may choose to move to the prophylaxis cohort of the study or discontinue entirely. 
Subjects electing to move from on-demand cohort to the prophylaxis cohort will move directly to 
Period 1 and will not receive PK-I infusions. Subjects switching from on-demand treatment 
cohort to prophylaxis cohort will receive the same treatment in Period 1 as the randomized 
on-demand treatment, and alternative in Period 2. 
Re-enrollment of on-demand subjects who has finished the study into the on-demand treatment 
cohort is allowed if he/she experiences a new acute TTP event.
9.2.1 Prophylaxis Treatment Cohort and PK Assessments
9.2.1.1 Pharmacokinetic Assessments 
Three PK evaluations of ADAMTS13 will be performed: 1) PK-I: To characterize the baseline 
PK of ADAMTS13 activity after administration of BAX 930 and SoC prior to Period 1; 2) 
PK-II: To assess the PK comparability between BAX 930 SIN and BAX 930 ORT at the 
beginning of Period 3 for those subjects treated with BAX 930 ORT during Period 1 or 2; 3) 
PK-III: To characterize the PK profile of ADAMT13 activity at the end of the study following 
long term exposure to BAX 930.
In case of an acute TTP event occurring during the PK study, PK sampling should be redone for 
PK-I and PK-II, if there are less than 7 post-dose PK timepoints collected up to the time of the 
acute TTP event and the last time point is shorter than 168 hr [±12 hr].
For PK-I, for subjects receiving weekly treatment as part of their SoC prophylaxis regimen, all 
washout periods can be reduced to 1 week at the discretion of the investigator. Due to lower 
content of ADAMT13 in factor VIII (FVIII):VWF concentrates (Peyvandi et al., 2013), subjects 
receiving factor VIII (FVIII):VWF concentrates or who are undergoing weekly prophylactic 
treatment, the minimum required SoC PK dose washout period may be reduced to 5 days. For 
PK-II, samples from subjects on prophylaxis treatment will be collected and included in the PK 
analysis.
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For PK-III, a subset of subjects may undergo ADAMTS13 activity PK assessments after the last 
dose with BAX 930 SIN in Period 3.
9.2.1.1.1 PK-I
PK-I is a randomized two-way crossover PK evaluation. Depending upon the availability of 
BAX 930 SIN material, either BAX 930 ORT or BAX 930 SIN will be administered in PK-I. 
When BAX 930 SIN is not available, prior to the cut-off date of 01 Oct 2021, subjects in the 
prophylaxis treatment cohort randomized into the SoC treatment arm for Period 1 will receive a 
single infusion of 40 IU/kg BAX 930 ORT, no less than 1 week after their previous prophylactic 
dose (washout period during screening). For subjects receiving factor VIII (FVIII):VWF 
concentrates, the minimum required SoC PK dose washout period may be reduced to 5 days. 
After subjects receive their BAX 930 ORT PK dose, they will then receive a single infusion of 
their current SoC product at their usual prophylactic dose 14 days [±2 days] later. See exceptions 
in Section 9.2.
Similarly, all subjects randomized into the BAX 930 ORT treatment arm for Period 1 will 
receive a single infusion of their current SoC product at their usual prophylactic dose, no less 
than 1 week after their previous prophylactic dose (washout period). For subjects receiving 
FVIII:VWF concentrates, the minimum required BAX 930 ORT PK dose washout period may be 
reduced to 5 days. Subjects will then receive a PK dose of 40 IU/kg BAX 930 ORT 14 days 
[±2 days] later. See exceptions in Section 9.2.
PK assessments will be conducted at the timepoints described in Table 11 (adult and adolescent 
subjects ≥12 years) and Table 12 (pediatric subjects <12 years). Note that, subject to discussion 
and agreement with the Sponsor, blood collection timepoints for pediatric subjects <6 years of 
age may be adjusted and/or omitted and the timing of assessments associated with blood 
collections will be adjusted accordingly; refer also to Section 11.3.1 and Section 12.2.1.
9.2.1.1.2 PK-II
PK-II is applicable to all subjects who received BAX 930 ORT in PK-I, Period 1 or Period 2. It
is not applicable to subjects who received BAX 930 SIN in PK-I, Period 1 or Period 2. After 
Period 2, before study subjects are switched from BAX 930 ORT to BAX 930 SIN, a 
1:1 randomized, single-dose, crossover PK assessment of 40 IU/kg BAX 930 ORT and 40 IU/kg 
BAX 930 SIN will be conducted in subjects that received BAX 930 ORT during Period 1 or 
Period 2. 
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Subjects on weekly treatment at the end of period 2, pediatric subjects <12 years of age, subjects 
randomized to the study prior to the temporary study halt, and on-demand subjects that were 
treated with BAX 930 SIN and continue into the prophylactic cohort are to be excluded from the 
PK-II assessments. 
Once the PK sampling is completed, subjects randomized to the study after the temporary 
study halt will start treatment of BAX 930 SIN for 6 months in Period 3. The amount of 
time between the two PK infusions (washout) will be 14 days [±2 days]. For subjects 
receiving FVIII:VWF concentrates or undergoing weekly prophylactic treatment during Period 1 
and Period 2, the minimum required BAX 930 PK dose washout period may be reduced to 
5 days.
PK assessments will be conducted at the timepoints described in Table 11 (adult and adolescent 
subjects ≥12 years). 
9.2.1.1.3 PK-III
An end-of-study PK-III assessment of ADAMTS13 activity will be conducted after the last 
BAX 930 SIN dose in Period 3. PK-III assessments will be conducted for any subject in the 
prophylactic cohort who initiates the study with BAX 930 SIN, including any subject who 
switches from on-demand treatment to prophylactic treatment. 
All subjects who receive BAX 930 SIN in Period 3 may voluntarily receive an end-of-study 
PK-III assessment, with a total study minimum of 4 adult subjects (≥18 years old), and 
2 pediatric or adolescent subjects (age 0-17 years). 
Pediatric subjects (<12 years old), subjects who receive a weekly (Q1Week) dosing regimen, and 
on-demand subjects that were treated with BAX 930 SIN and continue into the prophylactic 
cohort, will undergo a PK-III assessment. PK-III assessments will be conducted at the timepoints 
described in Table 13. Note that, subject to discussion and agreement with the Sponsor, blood 
collection timepoints for pediatric subjects <6 years of age may be adjusted and/or omitted and 
the timing of assessments associated with blood collections will be adjusted accordingly; refer 
also to Section 11.3.1 and Section 12.2.1.
For subjects that consent to PK-III, the assessments will occur at the last IP Infusion of 
Period 3. Subjects will not need to come back for a separate infusion visit to participate in 
PK-III. 
For subjects who decide to enroll in the TAK-755-3002 continuation study, they will complete 
the TAK-755-3002 Screening/Enrollment visit on the same day as the 281102 last IP infusion of 
Period 3. 
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Their 281102 Study Completion date will be documented as the last day of PK-III assessments 
(i.e. 72-hr PK sample for Q1W subjects >12 years old, 168-hr PK sample for Q1W subjects 
<12 years old, and 288-hr PK sample for all Q2W subjects). All adverse events that occur 
through the final PK-III assessment will be reported in the 281102 EDC.
If the last PK-III assessment occurs on the same day as the first dosing visit for TAK-755-3002:

The 281102 PK-III assessments (blood-draw and vital signs) must occur pre-infusion. 

Adverse events that occur prior to IP infusion will be reported in 281102.

Adverse events that occur at the time of IP infusion or after, will be reported in the 
TAK-755-3002.
As detailed in Section 13.1.2, any reported adverse events that are ongoing at the Study 
Completion date will remain ongoing in 281102 database and imported to the TAK-755-3002 
continuation study and followed within the TAK-755-3002 eCRF.
9.2.1.2 Switching to BAX 930 SIN
Adult Subjects
Beginning after 30 September 2021, subjects entering the study will no longer receive BAX 930 
ORT in Period 1, or any subsequent period thereafter. At this point, all subjects will receive 
BAX 930 SIN or SoC only, depending on randomization, beginning with PK-I, and continuing 
throughout the study. Prior to 01 October 2021, subjects who have entered Period 1 on BAX 930 
ORT, will continue to receive BAX 930 ORT until the end of Period 2. Thereafter, subjects will 
switch to BAX 930 SIN in Period 3. 
Pediatric Subjects
Pediatric subjects (<12 years old) will initiate the study with BAX 930 SIN after 
30 September 2021. Prior to 01 October 2021, pediatric subjects who have entered Period 1 on 
BAX 930 ORT, will continue to receive BAX 930 ORT until the end of Period 2. Thereafter, 
subjects will switch to BAX 930 SIN in Period 3. 
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9.2.1.3 Standard of Care Treatment Arm (6 Monthsxvii) (Period 1 or 2, Depending on 
Randomization)
Subjects will receive the investigator-recommended standard treatment regimens for 6 months. 
We strongly suggest investigators follow SoC treatment at intervals of Q1W or Q2W. 
Q3W will be accepted but not encouraged. Subjects experiencing an acute TTP event during 
the prophylaxis period will receive the investigator-recommended standard treatment and 
dosing regimen during the acute TTP event. Subjects will resume the previous prophylactic 
regimen 1 week after their last acute treatment dose. Subjects requiring a vaccination during 
treatment should schedule the vaccination administration within 72 hours after a prophylactic 
treatment dose.
Subjects receiving a COVID-19 vaccination during the study period should be monitored 
frequently by telephonic health checks and for thrombocytopenia for 14 consecutive days 
following vaccination, as deemed appropriate by the investigator. Elective surgeries should be 
scheduled 24 hours after the last prophylactic dose and ADAMTS13 levels should be obtained 
daily for up to 7 days or until hospital discharge post-surgery after surgery.
Dose modifications to increase the dose or frequency of SoC therapy, to the extent possible, is 
recommended if any of the following conditions are met: 

One acute TTP event or,

Two separate occurrences of any laboratory deviations:

Drop in platelet count ≥25% of baseline, or a platelet count <150,000/μL; OR

Elevation of LDH >1.5× of baseline or >1.5 x ULN

Three separate occurrences of any organ-specific signs or symptoms, with or without 
changes in platelet count or LDH

Neurological symptoms ( eg, confusion, dysphonia, dysarthria, focal or general motor 
symptoms including seizures) as per the opinion of the investigator; OR 

Abdominal pain; OR

Increase of serum creatinine >1.5×baseline
Subjects experiencing an acute TTP event during the SoC prophylaxis period will receive the 
investigator-recommended SoC treatment and dosing regimen during the acute TTP event. 
                                                
xvii The length of Period 1 and Period 2 is 6 months each. If a subject cannot switch to the next period at the end of 
month 6, for either logistical or medical reasons, the length of Period 1 and Period 2 can be extended to up to 
7 months. For subjects enrolled before November 2017, Period 1 can be extended until the global amendment 
to lift the temporary study halt is approved. 
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Although not required, investigators may also elect to treat subacute TTP events (refer to Table 2
for definitions) with 1 or 2 additional daily doses of SoC; these treatments will be tabulated 
separately in the statistical analysis.
9.2.1.4 BAX 930 Treatment Arm (6 Monthsxviii) (Period 1 or 2, Depending on 
Randomization and Period 3)
Most of the subjects will receive BAX 930 ORT prophylactically for 6 months for Period 1 or 2; 
BAX 930 SIN will replace BAX 930 ORT during Period 3. Subjects randomized after the 
temporary study halt will receive BAX 930 SIN prophylactically for 6 months for Period 3.
After the last IP infusion of Period 3, subjects will be enrolled and followed in the continuation 
study. Subjects will be allowed to remain in the 281102 study until the continuation study is 
open for enrollment. Dosing, visits and assessments will be continued according to the protocol / 
visits in period 3 until their transfer to the continuation study. 
Subjects who enroll into the TAK-755-3002 continuation study will complete the 
TAK-755-3002 Screening/Enrollment visit on the same day as the 281102 last IP infusion of 
Period 3. 
Subjects requiring a vaccination during treatment should schedule the vaccination administration 
within 72 hours after a prophylactic treatment dose. Subjects receiving a COVID-19 vaccination 
during the study period should be monitored frequently by telephonic health checks and for 
thrombocytopenia for 14 consecutive days following vaccination, as deemed appropriate by the 
investigator. 
Elective surgeries should be scheduled 24 hours after the last prophylactic dose and ADAMTS13 
levels should be obtained daily for up to 7 days or until hospital discharge post-surgery. 
Although not required, investigators may also elect to treat subacute TTP events with 1 or 
2 additional daily doses of BAX 930; these treatments will be tabulated separately in the 
statistical analysis.
                                                
xviii The length of Period 1 and Period 2 is 6 months each. If a subject cannot switch to the next period at the end of 
month 6, for either logistical or medical reasons, the length of Period 1 and Period 2 can be extended to up to 
7 months. For subjects enrolled before November 2017, Period 1 can be extended until the global amendment 
to lift the temporary study halt is approved. The length of Period 3 is approximately 6 months or when the 
continuation study has opened at the subject’s site.
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9.2.1.4.1 Initial BAX 930 Prophylactic Dose and Dosing Regimen
Subjects currently treated Q1W with FFP or S/D treated plasma replacement product will start 
BAX 930 treatment with 40 IU/kg [±4 IU/kg] Q1W. All other subjects will receive a starting 
prophylaxis dose of 40 IU/kg [±4 IU/kg] every 2 weeks (Q2W).
9.2.1.4.2 Dose Modification Based on Clinical Response
Dose modifications to 40 IU/kg Q1W will be required if any of the following conditions -are 
met: 

One acute TTP event or,

Two separate occurrences of laboratory deviations: Drop in platelet count ≥25% of 
baseline, or a platelet count <150,000/µL; OR

Elevation of LDH >1.5× of baseline or >1.5 × ULN

Three separate occurrences of organ-specific signs or symptoms, with or without changes 
in platelet count or LDH

Neurological symptoms ( eg, confusion, dysphonia, dysarthria, focal or general motor 
symptoms including seizures) as per the opinion of the investigator; OR

Abdominal pain; OR

Increase of serum creatinine >1.5×baseline 
9.2.1.4.3 Acute Management
Subjects experiencing an acute TTP event during the prophylaxis period will receive the 
following dose and dosing regimen:

Subjects will receive an initial dose of 40 IU/kg [±4 IU/kg] BAX 930

Subjects will receive a subsequent dose of 20 IU/kg [±2 IU/kg] BAX 930 on Day 2

Subjects will receive an additional daily dose of 15 IU/kg [±1.5 IU/kg] BAX 930 until 
2 days after the acute TTP event is resolved
Subjects in Q1W and Q2W will recommence their prophylaxis therapy 1 week after their last 
acute treatment dose and receive BAX 930 40 IU/kg Q1W. 
Acute TTP events are considered resolved when:

Platelet count is >150,000/ μL or platelet count is within 25% of baseline 

Elevation of LDH <1.5 x baseline or <1.5 x ULN
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Investigators may elect to treat subacute TTP events (refer to Table 2 for definitions) with 1 or 
2 additional daily doses of 40 IU/kg BAX 930.
9.2.2 On-Demand Treatment Cohort
Subjects experiencing an acute TTP event, meeting all other inclusion criteria, and entering and 
consenting to treatment in the study through the on-demand cohort will be randomized to receive 
urgent treatment with either the SoC or BAX 930. Upon resolution of the acute TTP event, 
subjects may choose to move to the prophylaxis cohort of the study or discontinue entirely. 
Re-enrollment of on-demand subject who has finished the study into the on-demand treatment
cohort is allowed if he/she experiences a new acute TTP event. Subjects electing to move to the 
prophylaxis cohort will move directly to Period 1 and will not go through PK-I assessment but 
will be subject to PK-II evaluation later after completion of Period 2.A PK-II evaluation is not 
applicable to subjects who received BAX930 SIN in Period 1 or Period 2. Subjects randomized 
to receive SoC in the on-demand cohort will receive SoC in Period 1 of the prophylaxis cohort 
and BAX 930 in Period 2 and 3. Subjects randomized to receive BAX 930 in the on-demand arm 
will receive BAX 930 in Period 1, SoC in Period 2, and BAX 930 in Period 3. If a subject is 
randomized to BAX 930 and BAX 930 SIN is available at the time of enrollment, that subject 
will receive BAX 930 SIN during prophylactic treatment. Subjects who initiate on-demand 
treatment with BAX 930 SIN may voluntarily receive prophylactic treatment with BAX 930 SIN 
following resolution of an acute TTP event, and will undergo an end-of-study, PK-III evaluation.
Standard of Care On-demand Treatment
Subjects will receive the investigator-recommended standard treatment and dosing regimen 
during the acute TTP event. Standard of care treatment should contain ADAMTS13 in a 
quantifiable amount for each administered dose.
9.2.2.1 BAX 930
On-demand Treatment
During acute TTP events:

Subjects will receive an initial dose of 40 IU/kg [±4 IU/kg] BAX 930

Subjects will receive a subsequent dose of 20 IU/kg [±2 IU/kg] BAX 930 on Day 2

Subjects will receive an additional daily dose of 15 IU/kg [±1.5 IU/kg] BAX 930 until 
2 days after the acute TTP event is resolved
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Acute TTP events are considered resolved when:

Platelet count is ≥150,000/ μL or platelet count is within 25% of baseline 
And 

Elevation of LDH ≤1.5× of baseline or ≤1.5× ULN
Switching to BAX 930 SIN
Adult subjects randomized to receive BAX 930 will receive on-demand treatment with BAX 930 
ORT until BAX 930 SIN becomes available. Once BAX 930 SIN is available, subjects 
randomized to receive BAX 930 will start on-demand treatment with BAX 930 SIN and continue 
treatment with BAX 930 SIN during prophylactic treatment. 
Pediatric subjects
Pediatric subjects (<12 years old) may initiate the study with BAX 930 SIN beginning on 
01 October 2021. At sites where BAX 930 SIN becomes available prior to the cut-off date, 
pediatric subjects who initiate the study with BAX 930 ORT in the on-demand cohort, will not 
switch until completing Period 2.
Enrollment
Subjects with a confirmed diagnosis of cTTP may provisionally enroll in the on-demand 
treatment cohort if a clinician believes the subject is undergoing an acute TTP event, based on 
platelet count and LDH irrespective of clinical symptomatology. 
Continuation in the study will be dependent on the confirmation of an acute TTP episode and
compliance with all inclusion criteria and no exclusion criteria apply. Efficacy data will be 
excluded from the analysis if subsequent laboratory tests provide evidence that the subject did 
not experience an acute TTP event or was ineligible to participate in the study. All IP-related 
safety data will be included in the final study analysis. 
9.2.3 Safety
Enrollment will be paused pending Data Monitoring Committee (DMC) evaluation (see 
Section 15.4) if there are ≥3 product-related SAEs, including the development of inhibitory 
antibodies to BAX 930.
The study will be stopped if 2 or more subjects develop confirmed ADAMTS13 inhibitory 
antibodies defined as ≥0.6 BU in the central laboratory on 2 separate assays within a 1-month 
period.
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9.3 Duration of Study Period(s) and Subject Participation
The overall duration of the study is approximately 70 months from study initiation (i.e., first 
subject enrolled) to study completion (i.e., last subject last visit). The recruitment period is 
approximately 24 months.
Depending on date of subject enrollment and treatment regimen, the subject participation period 
is approximately 22 months (1 month=28 days) from enrollment to subject completion (i.e., last 
study visit), unless prematurely discontinued.
9.4 Outcome Measures
9.4.1 Primary Outcome Measures
The primary outcome measure is:
1.
The incidence of acute TTP events among subjects receiving either BAX 930 or SoC 
prophylactically during the corresponding treatment periods
9.4.2 Secondary Outcome Measures
9.4.2.1 Efficacy
1.
Proportion of acute TTP events responding to BAX 930, defined as not requiring the use of 
another ADAMTS13-containing agent
2.
Time to resolution of acute TTP events following initiation of treatment with BAX 930 or 
SoC agent
3.
Incidence of thrombocytopenia defined as a drop in platelet count ≥25% of baseline or a 
platelet count <150,000/µL
4.
Incidence of microangiopathic hemolytic anemia defined as an elevation of LDH >1.5× of 
baseline or >1.5 x ULN
5.
Incidence of neurological symptoms ( eg, confusion, dysphonia, dysarthria, focal or 
general motor symptoms including seizures)
6.
Incidence of renal dysfunction defined as an increase in serum creatinine >1.5×baseline
7.
Incidence of abdominal pain
8.
Incidence of supplemental doses prompted by subacute TTP events
9.
Incidence of dose modification not prompted by an acute TTP event
10. Incidence of acute TTP events while subjects are on their final dose and dosing regimen in 
the study
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9.4.2.2 Safety
1.
Incidence of product-related and unrelated AEs and SAEs during each treatment period
2.
Incidence of binding and inhibitory antibodies to ADAMTS13
3.
Clinically relevant changes in vital signs, clinical chemistry, and hematology
4.
Estimated total quantity of ADAMTS13 administered during the treatment of acute TTP 
events
9.4.2.3 Pharmacokinetics/Pharmacodynamics
1.
Assessment of the PK parameters (incremental recovery [IR], area under the plasma curve 
[AUC], terminal half-life [t1/2], mean residence time [MRT], systemic clearance [CL], 
steady state volume of distribution [Vss], and maximum concentration following infusion 
[Cmax]) for ADMATS13 activity and ADMATS13 antigen for both the SoC agent and 
BAX 930 
2.
Assessment of PD markers, such as VWF:Ag and VWF:RCo, at baseline and following 
infusion of the SoC agent and BAX 930 treatment during the initial PK assessment
3.
Assessment of ADAMTS13 activity (pre-infusion ADAMTS13 levels) and select VWF 
parameters prior to each PK infusion of SoC or BAX 930 
4.
Assessment of the impact of immunogenicity (immunogenicity status, time of onset) on 
ADAMTS13 antigen and activity PK parameters
9.4.2.4 Health Related Quality of Life and Resource Utilization
1.
Assessment of HRQoL including chronic TTP-related symptoms and disabilities, including 
cognitive function, using the following instruments:

cTTP-specific patient reported outcomes (PROs)

36-Item Short Form Health Survey (SF-36)

Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9)

EuroQol 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) and EQ-5D-youth 
(EQ-5D-Y)

Pediatric Quality of Life Inventory (PedsQL)
2.
Assessment of health care resource utilization, including hospital length of stay for acute 
TTP events, resource utilization during prophylaxis, and days missed from school/work 
due to TTP-related illness
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9.4.3 Exploratory Outcome Measures
1. Incidence of TTP manifestations, defined as a compositea of secondary outcome measures 
(secondary efficacy outcome measures 3 to 7), while receiving prophylactic treatment with 
BAX 930 or SoC during the 6 months of the corresponding treatment
2.
Incidence of TTP manifestations, defined as a compositea of secondary outcome measures 
(secondary efficacy outcome measures 3 to 7), while receiving the final prophylactic 
treatment regimen with BAX 930 or SoC
3.
Incidence of TTP manifestations, defined as a compositea of secondary outcome measures 
(secondary efficacy outcome measures 3 to 7), requiring supplemental dose treatment
4.
Incidence of the subacute TTP events in subjects receiving prophylactic treatment.
5.
Assessment of additional exploratory PD biomarkers including but not limited to VWF 
multimer patterns, ADAMTS13-mediated VWF cleavage products, and coagulation 
biomarkers, at baseline and following infusion of the SoC agent and BAX 930 treatment 
during the initial PK assessment.
a composite of the secondary outcome measure is defined as the occurrence of at least one of the 
secondary outcome measures (3 to 7).
9.5 Randomization and Blinding
This is a randomized, open-label, active-controlled clinical study. Subjects in the prophylaxis 
cohort will be randomized equally using a permuted block algorithm to randomly assign 
treatment order (BAX 930 – SoC or SoC – BAX 930). Subjects in the on-demand cohort will be 
randomized equally using a permuted block algorithm to either BAX 930 or SoC. 
After the Period 2, subjects in the prophylaxis cohort will be randomized to the infusion 
sequence for PK-II (BAX 930 ORT followed by BAX 930 SIN, or BAX 930 SIN followed by 
BAX 930 ORT) in a 1:1 ratio stratifying for the sequence for PK-I.
9.6 Study Stopping Rules 
Enrollment will be paused pending DMC evaluation (see Section 15.4) if there are 
≥3 product-related SAEs, including the development of inhibitory antibodies to BAX 930.
This study will be stopped if 2 or more subjects develop confirmed ADAMTS13 inhibitory 
antibodies defined as ≥0.6 BU in the central laboratory on 2 separate assays within a 1-month 
period.
If this study is halted for reasons listed in this section, restarting the trial will require a substantial 
amendment.
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9.7 Investigational Product(s)
9.7.1 Packaging, Labeling, and Storage
BAX 930 will be packaged in single boxes with 2 glass vials, 1 vial containing the lyophilized 
BAX 930, the other containing the diluent. Further details are provided in the Pharmacy Manual. 
BAX 930 must not be used beyond the expiration date printed on the vial. Freezing should be 
avoided at all times to prevent damage to the diluent vial. The recommended storage condition 
for BAX 930 is 2 to 8°C. The expiration date for BAX 930 is included on the IP label. The 
stability of the clinical lots will be monitored throughout the period of use in clinical studies.
For additional information please refer to the BAX 930 IB and/or other specific instructions 
provided by the sponsor.
9.7.2 Administration
BAX 930 is administered by i.v. injection.
The reconstituted solution of BAX 930 should be clear and colorless in appearance. BAX 930 
should be administered at room temperature and within 3 hr of reconstitution.
Prior to administration of the IP, it should be ensured that the solution is clear and free of 
particles. In addition, it should be ensured that venous access via an i.v. cannula is available; 
however, for the IP infusion, the butterfly needle may be inserted immediately prior to the 
infusion.
A tourniquet should be applied, and the injection site prepared by wiping the skin well with an 
alcohol swab.
The supplied butterfly infusion set should be used if possible, or an i.v. catheter, if available. The 
butterfly needle should be placed into a vein of the opposite forearm to that used for blood 
draws. Samples for PK analysis should be drawn from the opposite arm to that used for 
BAX 930 or SoC infusion during the first 24 hours post-infusion of BAX 930 or SoC. Either arm 
can be used for blood draw of samples upon completing 24 hours post-infusion. The butterfly 
needle or i.v. catheter should be secured as suggested by standard medical care.
Following removal of the tourniquet, placement of the needle/i.v. catheter should be ensured and 
BAX 930 slowly infused (between 2 to 4 mL per minute [min]). Syringes should be changed 
according to medical practice.
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For adult and adolescent subjects (≥12 years of age), vital signs should be recorded within 1 hr 
before PK infusion and at the following timepoints post-infusion: 15±5 min, 60±5 min, 
3±0.5 hr, 9±2 hr, 24±2 hr, 72±4 hr, 120±12 hr, 168±12 hr, 216±24 hr, and 288±24 hr. For 
pediatric subjects (<12 years of age), vital signs should be recorded within 1 hr before PK 
infusion and at the following timepoints post infusion: 30±5 min, 12±2 hr, 24±2 hr, 48±2 hr,
96±2 hr and 168±4 hr. Refer to the Schedule of Study Procedures and Assessments in 
Section 20.3 for the overall timing of vital signs collection.
Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for 
pediatric subjects <6 years of age may be adjusted and/or omitted and the timing of assessments 
associated with blood collections will be adjusted accordingly; refer also to Section 11.3.1 and 
Section 12.2.1.
Should a significant increase in pulse rate occur or a significant drop in blood pressure, as 
determined by the investigator, the rate of administration should be reduced or the injection 
temporarily halted, which usually allows the symptoms to disappear promptly. If symptoms are 
progressive for 15 min, despite discontinuation of the infusion, emergency measures should be 
considered.
Upon completion of the infusion, the butterfly catheter should be flushed with at least 1 mL 
saline solution prior to removal of the needle. In case of a (central) venous access device, the 
flush should be with at least 10 mL of saline solution.
Finally, the butterfly should be removed but the i.v. catheter left, if placed on the same site 
(optional).
9.7.3 Description of Treatment
BAX 930 is formulated as a sterile, highly purified protein preparation appearing as a compact 
white lyophilized cake. The active drug substance is a fully glycosylated BAX 930 protein 
produced in a CHO cell line. For reconstitution and administration of the product as i.v. solution, 
a vial of diluent (5 mL sterilized Water for Injections), a butterfly infusion set with Luer Lock 
syringes (B.Braun Omnifix, 3, 5, 10, and 20 mL) and a needleless transfer device (BAXJECT II 
Hi-Flow) are provided. BAXJECT II Hi-Flow system is a needleless transfer device with the 
primary function of transferring diluent from its vial into an evacuated vial containing 
lyophilized product requiring reconstitution prior to infusion. 
Upon reconstitution with sterile water for injection, the final drug product (FDP) contains 
purified BAX 930 together with excipients (mannitol, L-histidine, Tween 80 [polysorbate80],
sodium chloride, calcium chloride, and sucrose). The reconstituted solution has a nominal 
strength of 300 U/mL.
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Dose for administration should be calculated based on the subject’s BW as measured at each 
dosing visit. Note that the weight from the subject’s previous visit can be used to calculate the 
dose as long as the weight was collected less than 6 weeks prior for adult subjects (>12 years of 
age) and less than 4 weeks prior for pediatric subjects (<12 years of age). For most subjects, the 
final volume of infusion after reconstitution of FDP will be between 5 and 14 mL, to be 
calculated by subject weight and the required number of units.
A list of all the components of BAX 930 FDP is shown in Table 3.
Table 3. Composition of BAX 930 FDP
Name of Constituent
Unit 
(and/or Percentage Formula)
Function
Reference to 
Standards
rADAMTS13
300 IU/mL reconstituted
Active ingredient
Takeda specification
Sodium chloride
30 mM
Tonicity modifier
USP, EP, JP
Calcium chloride
2 mM
Stabilizing Agent
USP, EP, JP
L-Histidine
20 mM
Buffer
USP, EP, JP
Mannitol
3% (w/w)
Bulking agent
USP, EP, JP
Sucrose
1% (w/w)
Bulking Agent
USP, EP
Polysorbate 80 (Tween 
80)
0.05% (w/w)
Surfactant
USP, EP, JP
EP=European Pharmacopeia; JP=Japanese Pharmacopeia; USP=United States Pharmacopeia; w/w=weight-to-
weight ratio
For those subjects who are randomized to receive SoC in the prophylactic cohort (see 
Section 9.2.1.3 and Figure 1), SoC will be provided with their routine prophylactic dose of either 
FFP, pooled S/D treated plasma, or FVIII: VWF concentrates. Subjects switching from the 
on-demand treatment cohort to the prophylaxis cohort will receive the same treatment in Period 1 
as the randomized on-demand treatment, and alternative in Period 2. In the on-demand treatment 
cohort, subjects will receive investigator-recommended standard treatment and dosing regimen 
during the acute TTP event. Investigator-recommended standard treatment should contain 
ADAMTS13 as a measurable and quantifiable administered dose. SoC treatment type and dose 
will be recorded in subject CRFs. The SoC treatments will be in liquid form and administered 
intravenously.
For those subjects randomized to receive BAX 930 in the prophylactic cohort, subjects will 
receive BAX 930 40 IU/kg prophylactically (see Section 9.2.1.4 and Figure 1). For the 
on-demand treatment cohort, subjects will receive an initial dose of 40 IU/kg BAX 930 followed 
by treatment with 20 IU/kg on Day 2, then 15 IU/kg BAX 930 until 2 days after the acute TTP 
event is resolved (see Section 9.2.2.1).
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Most subjects in the prophylactic cohort will receive BAX 930 SIN treatment during Period 3.
9.7.4 Dosing Justification
As cTTP may be considered a classical deficiency disease and BAX 930 represents a substitution 
therapy with a well characterized mechanism of action. There was no safety concern with 
infusions between 5 to 40 U/kg BAX 930 observed during the Phase 1 clinical study 281101. 
The pharmacokinetic parameters for BAX 930 were like FFP, specifically, a mean incremental 
recover of approximately 2.4 U/dL per U/kg infused and a mean plasma half-life of 
approximately 2.5 days (60 hours).
Recognizing that the ADAMTS13 content of FFP is approximately 1U/ mL, the dose exceeds 
current replacement strategies and would provide both a higher Cmax and AUC level than is 
currently employed with SoC agents.
Based on data from Study 281101, the proposed dosing regimen of BAX 930 for acute TTP 
events should result in complete normalization of ADAMTS13 levels with mean ADAMTS13 
levels between approximately 90 and 125 IU/dL (90% and 125% of normal). In a low case 
assumption of both an IR and t1/2 of 50% of the means, the range of ADAMTS13 levels expected 
is predicted to be between approximately 50% of normal throughout the treatment period. 
9.7.5 Investigational Product Accountability
The investigator will ensure that the IP(s) is stored as specified in the protocol and that the 
storage area is secured, with access limited to authorized study personnel. The investigator 
will maintain records that the IP(s) was received, including the date received, drug identity code, 
date of manufacture or expiration date, amount received, and disposition. IP(s) must be 
dispensed only at the study site or other suitable location ( eg, infusion center). Direct-to-Patient 
shipments of Investigational Product will be permitted for subjects having infusions at home, 
additional information will be provided in the Pharmacy Manual and Home Nursing 
documentation. Records will be maintained that include the subject identification code (SIC), 
dispensation date, and amount dispensed. All remaining partially used and/or unused IP(s) will 
be returned to the sponsor or sponsor’s representative after study completion/termination or 
destroyed with the permission of the sponsor in accordance with applicable laws and study site 
procedures. If IP(s) is to be destroyed, the investigator will provide documentation in accordance 
with sponsor’s specifications.
9.8 Source Data
Per ICH GCP, source data are defined as all information in original records and certified copies 
of original records of clinical findings, observations, or other activities in a clinical trial that are 
necessary for the reconstruction and evaluation of the trial. 
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Source data are contained in source documents (original records or certified copies), which may 
be in paper and/or electronic format. Source data for this study comprise the following: hospital 
records, medical records, clinical and office charts, laboratory notes, memoranda, subjects' 
diaries or evaluation checklists, outcomes reported by subjects, pharmacy dispensing records, 
recorded data from automated instruments, copies or transcriptions certified after verification as 
being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, 
x-rays, subject files, and records kept at the pharmacy, at the laboratories and at 
medico-technical departments involved in the clinical study.
No data will be entered directly onto the case report form (CRF). 
For additional information on study documentation and CRFs, see Section 17.2. The use of 
subject diaries is described in Section 11.5.
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10. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION
10.1 Inclusion Criteria
Subjects who meet ALL the following criteria are eligible for this study:
1.
Subject or legally authorized representative has provided signed informed consent 
(≥18 years of age) and/or assent form (signed by legal representative if subject is <18 years 
of age)
2.
Subject is 0 to 70 years of age, inclusive, at the time of screening. (Subjects <18 years of 
age will be enrolled only after at least 5 adults (≥18 years of age) each have at least
10 exposures with BAX 930 and reviewed by the DMC. In France, no subjects younger 
than 18 years of age will be enrolled into the study before the first adult subject has been 
treated with BAX 930 for a minimum of 6 months.
3.
Subject has a documented diagnosis of severe hereditary ADAMTS13 deficiency, defined 
as:

Confirmed by molecular genetic testing, documented in subject history or at screening, 
and 

ADAMTS13 activity <10% as measured by the FRETS-VWF73 assay, documented in 
subject history or at screening (subjects currently receiving SoC prophylactic therapy 
may exceed 10% ADAMTS13 activity at screening)
Note: Subjects currently receiving prophylactic therapy will be screened immediately 
prior to their usual prophylactic infusion
4.
Subject does not display any severe TTP signs (platelet count <100,000/µL and elevation 
of LDH >2 x ULN) at screening. (prophylactic cohort only).
5.
Subject is currently on a prophylactic dosing regimen or has a documented history of at 
least 1 TTP event and an ability to tolerate SoC prophylactic dosing (prophylactic cohort 
only).
6.
Subjects ≥16 years of age must have a Karnofsky score ≥70% and subjects <16 years of 
age must have a Lansky score ≥80%
7.
Subject is HCV-negative as confirmed by antibody or polymerase chain reaction testing 
OR HCV-positive if their disease is chronic but stable
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8.
If female of childbearing potential, subject presents with a negative blood or urine 
pregnancy test, confirmed no more than 7 days before the first administration, and agrees 
to employ adequate birth control measures for the duration of the study and to undergo 
quarterly pregnancy testingxix
9.
Sexually active males must use an accepted and effective method of contraception during 
the treatment and until a minimum of 16 days after the last dose administered.
10. Subject is willing and able to comply with the requirements of the protocol
10.2 Exclusion Criteria
Subjects who meet ANY of the following criteria are not eligible for this study:
1.
Subject has been diagnosed with any other TTP-like disorder (microangiopathic hemolytic 
anemia), including acquired TTP
2.
Subject has known hypersensitivity to hamster proteins
3.
Subject has experienced an acute TTP episode less than 30 days prior to screening 
(prophylactic cohort only)
4.
Subject has a medical history or presence of a functional ADAMTS13 inhibitor at 
screening
5.
Subject has a medical history of genetic or acquired immune deficiency that would 
interfere with the assessment of product immunogenicity, including subjects who are 
HIV-positive with an absolute cluster of differentiation 4 (CD4) count <200/mm3 or who 
are receiving chronic immunosuppressive drugs. 
6.
Subject has been diagnosed with severe cardiovascular disease (New York Heart 
Association classes 3 to 4)
7.
Subject with end stage renal disease requiring chronic dialysis
8.
Subject has been diagnosed with hepatic dysfunction, as evidenced by, but not limited to, 
any of the following: 
a. Serum alanine aminotransferase (ALT) ≥2×ULN
b. Severe hypoalbuminemia <24 g/L
c. Portal vein hypertension ( eg, presence of otherwise unexplained splenomegaly, history 
of esophageal varices)
9.
In the opinion of the investigator, the subject has another clinically significant concomitant 
disease that may pose additional risks for the subject
                                                
xix See Section 20.5 for a list of adequate contraceptive methods for females of childbearing potential
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10. Subject has been treated with an immunomodulatory drug, excluding topical treatment (
eg, ointments, nasal sprays), within 30 days prior to enrollment. Use of corticosteroids in 
conjunction with administration of FFP to prevent allergic reactions is permitted.
11. Subject has an acute illness ( eg, influenza, flu-like syndrome, allergic 
rhinitis/conjunctivitis, bronchial asthma) at the time of screening (prophylaxis cohort only)
12. Subject is receiving or anticipates receiving another investigational drug and/or 
interventional drug within 30 days before enrollment
13. Subject has a history of drug and/or alcohol abuse within the last 2 years
14. Subject has a progressive fatal disease and/or life expectancy of less than 3 months
15. Subject is identified by the investigator as being unable or unwilling to cooperate with 
study procedures
16. Subject suffers from a mental condition rendering him/her unable to understand the nature, 
scope, and possible consequences of the study and/or evidence of an uncooperative attitude 
17. Subject is a family member or employee of the sponsor or investigator
18. If female, subject is pregnant or lactating at the time of enrollment
19. Any contraindication to standard of care medicinal product(s) as per local prescribing 
information.
10.3 Withdrawal and Discontinuation
Enrollment will be paused pending DMC evaluation (see Section 15.4) if there 
are ≥3 product-related SAEs, including the development of inhibitory antibodies to BAX 930.
The study will be stopped if 2 or more subjects develop confirmed ADAMTS13 inhibitory 
antibodies defined as ≥0.6 BU in the central laboratory on 2 separate assays within a 1-month 
period.
Any subject may voluntarily withdraw (i.e., reduce the degree of participation in the study) 
consent for continued participation and data collection. The reason for withdrawal will be 
recorded on the End of Study CRF. Assessments to be performed at the termination visit 
(including in cases of withdrawal or discontinuation) are described in Section 11.5 and 
Section 20.3.
Discontinuation (i.e., complete withdrawal from study participation) may be due to dropout (i.e., 
active discontinuation by subject) or loss to follow-up (i.e., discontinuation by subject without 
notice or action). 
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Additionally, the investigator and sponsor have the discretion to discontinue any subject from the 
study if, in their judgment, continued participation would pose an unacceptable risk for the 
subject. 
Subjects also will be withdrawn from treatment or discontinued from further study participation 
for the following reasons:
1.
The subject becomes pregnant. IP exposure will be discontinued. Attempts will be made to 
follow the subject through completion of the pregnancy and up to 1 year post-delivery, if 
feasible. The investigator will record a narrative description of the course of the pregnancy 
and its outcome.
2.
The subject frequently misses administration of IP. The subject will be discontinued from 
further participation in the study.
3.
Subjects who experience allergic reactions (eg, for anaphylaxis) upon exposure to 
BAX 930 and subjects who develop an inhibitory antibody to ADAMTS13 or any other 
safety issue will be discontinued from study treatment. Recovering/resolving AEs will be 
followed until resolution, medically stabilized, or 30 days after the study 
completion/termination visit, whichever comes first; follow-up information is to be 
documented in the CRF. 
Subjects who develop allergic reactions to their standard of care treatment will be 
discontinued from the study. Recovering/resolving AEs will be followed until resolution, 
medically stabilized, or 30 days after the study completion/termination visit, whichever 
comes first; follow-up information is to be documented in the CRF.
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11. STUDY PROCEDURES
11.1 Informed Consent
Any subject who provides informed consent (i.e., signs and dates the ICF and assent form, if 
applicable) is considered as a subject in the study.
11.2 Subject Identification Code
The following series of numbers will comprise the SIC: protocol identifier (eg, 281102) to be 
provided by the sponsor, 3-digit study site number (eg, 002) to be provided by the sponsor, and 
3-digit subject number (eg, 003) reflecting the order of providing informed consent. For 
example, the third subject who signed an ICF at study site 002 will be identified as 
Subject 281102-002003. All study documents (eg, CRFs, clinical documentation, sample 
containers, drug accountability logs, etc.) will be identified with the SIC. 
11.3 Screening and Study Visits
The study site is responsible for maintaining a screening log that includes all subjects who 
provided informed consent. The log also will serve to document the reason for screening failure. 
All screening data will be collected and reported in CRFs, regardless of screening outcome. If a 
subject is re-screened, the End of Study CRF should be completed, and a new ICF (or assent, if 
applicable), new SIC, and new CRF are required for that subject.
The overall study design is illustrated in the Figure 1 and Figure 2. Details on the procedures to 
be performed at each study visit, including screening, can be found in Section 20.3 Schedule of 
Study Procedures and Assessments and Section 20.4 Clinical Laboratory Assessments. For study 
sites in Germany only, please refer to the complete Schedule of Assessments in Table A1.
11.3.1 Screening and Study Visits for Pediatric Subjects
For pediatric subjects up to 12 years of age, the screening visits may be spread to several days 
to limit the amount of the blood drawn in one day. Since PK tests, immunogenicity (tiered 
approach for antibody testing), and genetic testing have the longest turnaround time, these tests 
should be performed first. Other tests can be done afterwards. Below is a suggested lab 
assessments order:
Day 1: Blood sampling for PK tests (without back-up samples), immunogenicity (total binding 
ABs only), genetic testing (if applicable)
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Day 2: Immunogenicity (neutralizing Abs only); blood sampling for PK tests (back-up samples 
only), 
Day 3: Blood sampling for Clinical Chemistry and CBC
Day 4: Blood sampling for Viral Serology
For pediatric subjects 0 to <6, if additional considerations are needed to not exceed the 
country-specific EC and applicable regulatory guidelines for daily and monthly limits, the 
following options (based on the subject weight at screening) to be discussed and, if agreed upon 
with the Sponsor, may be applied: 

Allowing pre-infusion samples to be collected up to 72 hours prior to infusion

Omitting some PK/PD time points

Not collecting samples that would be used for exploratory analysis

Only collecting certain back-up samples
Refer to the Laboratory Manual for further information.
11.3.2 Pediatric Development Assessments
For subjects 0 to <6 years old (prophylactic subjects only), if available and at the discretion of 
the Investigator, growth, development and cognitive performance metrics may be collected from 
a subject’s medical record and reviewed at the Screening/Enrollment Visit, the start of every 
Treatment Period or annually, and at the Final Visit.
11.4 Medications and Non-Drug Therapies 
The following medications and non-drug therapies are not permitted within 30 days before study 
entry and during the study:
1.
Medications:
Immunomodulatory drugs
Corticosteroids with an equivalent to hydrocortisone greater than 10 mg/day, excluding 
topical treatment ( eg, ointments, nasal spray) are not permitted except as part of an 
established pre-medication regimen during the Standard of Care period of the study
Another IP or interventional drug A subject who has taken any of these medications or 
received any of these non-drug therapies will be considered a protocol deviation.
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The following medications and non-drug therapies are permitted within 30 days before study 
entry and during the study:
1.
Medications:
FFP or any other ADAMTS13-containing products interfering with ADAMTS13 PK 
will have to be paused at least 14 days [±2 days] prior to the IP infusion for PK 
assessment. However, for PK-I, if subjects are receiving weekly treatment as part of 
their SoC prophylaxis regimen, washout periods can be reduced to 1 week at the 
discretion of the investigator. For subjects receiving factor VIII (FVIII):VWF 
concentrates, the minimum required SoC PK dose washout period may be reduced to 
5 days. 
Use of corticosteroids in conjunction with administration of FFP to prevent allergic 
reactions is permitted
11.5 Subject Reported Outcomes
Subject (patient) reported outcomes, based on relevant questionnaires, will be captured at 
screening and at the end of each period visit (i.e., end of Period 1 visit, end of Period 2 visit, and 
end of Period 3 visit), and if subjects have an early termination, during the termination visit, in 
an electronic subject diary to assess chronic TTP-related symptoms and disabilities, including 
cognitive function. In the eventuality of nonfunctional electronic diaries, a web back-up option 
will be available for temporary use. Lower scores indicate worse HRQoL. The PRO instruments 
to be measured in this study are described in Table 4.
Subjects and/or their legally authorized representatives will be trained on use of the diary. The 
diary will be provided in electronic format and will remain at the site for the duration of the 
study. In the eventuality of non-functional electronic diaries, a web back-up option will be 
available for temporary use. The investigator will review the diary for completeness and request 
missing information periodically and in a timely manner. Subject entries in the diary will serve 
as source records. During study participation the investigator has access to the database holding 
the subject diary data. After study closure, the investigator will receive the diary records for their 
subjects, including audit trail records, in an archive disk. The data will be transmitted to the CRF 
by a validated transfer.
11.6 Subject Completion/Discontinuation
A subject is considered to have completed the study when he/she ceases active participation in 
the study because the subject has, or is presumed to have, completed all study procedures 
according with the protocol (with or without protocol deviations).
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Reasons for completion/discontinuation will be reported on the Completion/Termination CRF, 
including: completed, screen failure, AE ( eg, death), discontinuation by subject ( eg, lost to 
follow-up [defined as 3 documented unsuccessful attempts to contact the subject], dropout), 
physician decision ( eg, pregnancy, progressive disease, non-compliance with IP/protocol 
violation[s], recovery), study terminated by sponsor, or other (reason to be specified by the 
investigator, eg, technical problems). Regardless of the reason, all data available for the subject 
up to the time of completion/discontinuation should be recorded on the appropriate CRF. 
Every effort will be made to have discontinued subjects complete the study 
completion/termination visit. If the completion/termination visit is done as an additional, 
unscheduled visit, the assessment results shall be recorded with the completion/termination visit. 
If a subject terminates participation in the study and does not return for the 
completion/termination visit, their last recorded assessments shall remain recorded with their last 
visit. The reason for discontinuation will be recorded, and the data collected up to the time of 
discontinuation will be used in the analysis and included in the clinical study report. If additional 
assessments are required, the assessments shall be recorded separately. Assessments to be 
performed at the termination visit (including in cases of withdraw or discontinuation) can be 
found in Section 20.3 Schedule of Study Procedures and Assessments and Section 20.4 Clinical 
Laboratory Assessments.
In the event of subject discontinuation due to an AE, clinical, and/or laboratory investigations 
that are beyond the scope of the required study observations/assessments may be performed as 
part of the evaluation of the event. These investigations will take place under the direction of the
investigator in consultation with the sponsor, and the details of the outcome may be reported to 
the appropriate regulatory authorities by the sponsor. 
11.7 Procedures for Monitoring Subject Compliance
All study procedures are to be performed under the direct supervision of the investigator/a 
licensed healthcare professional at home or at the study site, and thus, no separate procedures 
will be used to monitor subject compliance.
11.8 Acute TTP events During PK Assessment
Acute TTP events occurring during PK-I should be treated with the agent the subject is 
receiving. If less than 7 PK timepoint assessments have been collected at the time of the acute 
TTP event, PK assessments should be repeated. Acute TTP events occurring during PK-II should 
be treated with BAX 930 ORT. 
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12. ASSESSMENT OF EFFICACY, PHARMACOKINETICS, AND 
PHARMACODYNAMICS
12.1 Assessment of Efficacy: Acute TTP Events
The efficacy of BAX 930 will be assessed by the number and incidence of acute TTP events, 
where an acute TTP event is defined as having both:
1.
Reduction in platelet count ≥50% of baseline, or a platelet count <100,000/µL;
and
2.
Elevation of LDH by >2× of baseline or >2 x ULN 
Laboratory (see Section 13.7) and vital sign measurements (see Section 13.8) will be used to 
identify acute TTP events.
12.2 Assessment of Pharmacokinetics and Pharmacodynamics
The date and time of the infusion start and stop, as well as start/stop of any infusion interruptions 
and restart of the infusion, and the actual volume infused (and lot number as applicable) will be 
recorded for all infusions. 
The time and date of collection for each sample and any missing blood draws will be recorded. 
The details regarding sample processing are described in the Laboratory Manual.
The PK and PD assessments will be performed in adult and pediatric subjects for the prophylaxis 
cohort at screening during the initial SoC or BAX 930 infusions of Period 1 and after Period 3, 
and at each dosing visit as shown in Section 20.4. Additional details regarding PK sampling can 
be found in Section 9.2.1. 
The PK, PD assay panel (PK: ADAMTS13 activity [see Section 13.7.5], 
ADAMTS13:Ag [see Section 13.7.5.2]; PD: VWF:RCo [see Section 13.7.5.3], 
VWF:Ag [see Section 13.7.5.4], and VWF multimer analysis and ADAMTS13 mediated VWF 
cleavage products [see Section 13.7.5.5]) will be assessed in a central laboratory. 
Blood samples will be drawn at the following standardized timepoints for adult and adolescent 
subjects (≥12 years of age): pre-infusion (within 60 min prior to the start of the infusion), and 
relative to the end of the infusion for all following timepoints, at 15±5 min, 60±5 min, 
3 hr±0.5 hr, 9 hr±2 hr, 24 hr±2 hr, 72 hr±4 hr, 120 hr±12 hr, 168 hr±12hr, 216 hr±24 and 
288 hr±24 hr. 
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PK Post-Infusion Laboratory Assessments for subjects undergoing Q1W dosing should not be 
performed at 168±12 hrs, 216±12 hrs and 288±12 hrs timepoints, after PK Infusion #1. However, 
PK assessments up to 168±12 hrs timepoint should be performed after PK Infusion #2. Please 
refer to Table 11 to see the assessment schedule for subjects undergoing Q1W dosing. PK 
assessments for subjects on Q3W SoC treatment, are to be performed at the same timepoints as 
the subjects undergoing Q2W SoC treatment.
Timepoints for pediatric subjects (<12 years of age) include: pre-infusion (within 60 min prior to 
the start of the infusion) and, relative to the end of the infusion for all following timepoints, at 
30 min±5 min, 12 hr±2 hr, 24 hr±2 hr, 48 hr±2 hr, 96 hr±2 hr, and 168 hr±4 hr. 
Timepoints for subjects who undergo PK-III include: pre-infusion (within 60 min prior to the 
start of the infusion) and, relative to the end of infusion for all following timepoints, at 15±5 min, 
30±5 min, 60 min±5 min, 9 hr±2 hr, 72 hr±8 hr, 168 hr±12 hr, and 288 hr±24 hr.
Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for 
pediatric subjects <6 years of age may be adjusted and/or omitted and the timing of assessments 
associated with blood collections will be adjusted accordingly; refer also to Section 11.3.1 and 
Section 12.2.1.
See Section 14.4.2.3.1 for PK parameters to be calculated.
12.2.1 Pediatric Subjects (<6 Years Old)
If additional considerations are needed to not exceed the country-specific EC and applicable 
regulatory guidelines for daily and monthly limits that are based on the subject weight at 
screening, the following options to be discussed and, if agreed upon with the Sponsor, may be 
applied: 

Allowing pre-infusion samples to be collected up to 72 hours prior to infusion

Omitting some PK/PD time points as agreed upon with the Sponsor

Not collecting samples that would be used for exploratory analysis

Only collecting certain back-up samples.
This list is not all inclusive; further information will be provided in the Laboratory Manual and 
recommendations tailored to the subject's weight will be provided prior to Screening.
Note that the timing of the collection of vital signs or other assessments associated with sample 
collections mentioned throughout this protocol will be adjusted accordingly. 
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13. ASSESSMENT OF SAFETY
13.1 Adverse Events
13.1.1 Definitions
An AE is defined as any untoward medical occurrence in a subject administered an IP that does 
not necessarily have a causal relationship with the treatment. An AE can therefore be any 
unfavorable and unintended sign ( eg, an abnormal laboratory finding), symptom ( eg, rash, pain, 
discomfort, fever, dizziness, etc.), disease ( eg, peritonitis, bacteremia, etc.), or outcome of death 
temporally associated with the use of an IP, whether or not considered causally related to the IP.
13.1.1.1 Serious Adverse Event 
An SAE is defined as an untoward medical occurrence that at any dose meets 1 or more of the 
following criteria:
1.
Outcome is fatal/results in death (including fetal death)
2.
Is life-threatening – defined as an event in which the subject was, in the judgment of the 
investigator, at risk of death at the time of the event; it does not refer to an event that 
hypothetically might have caused death had it been more severe
3.
Requires inpatient hospitalization or results in prolongation of an existing hospitalization –
inpatient hospitalization refers to any inpatient admission, regardless of length of stay
4.
Results in persistent or significant disability/incapacity (i.e., a substantial disruption of a 
person’s ability to conduct normal life functions)
5.
Is a congenital anomaly/birth defect
6.
Is a medically important event – a medical event that may not be immediately 
life-threatening or result in death or require hospitalization but may jeopardize the subject 
or may require medical or surgical intervention to prevent 1 of the other outcomes listed in 
the definitions above. Examples of such events are:
Intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias, or convulsions that do not result in hospitalization, or development of drug 
dependence or drug abuse 
Reviewed and confirmed seroconversion for HIV, hepatitis A virus (HAV), HBV, 
HCV,xx hepatitis E virus (HEV), or parvovirus B19 (B19V)
Severe hypersensitivity/allergic reactions to BAX 930
                                                
xx
Patients with HCV can be included if the disease is chronic and stable. These subjects will have already 
seroconverted so will have anti-HCV antibodies detectable in the blood.
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Uncomplicated pregnancies, following maternal or paternal exposure to IP are not considered an 
(S)AE; however, any pregnancy complication or pregnancy termination by therapeutic, elective, 
or spontaneous abortion shall be considered an SAE.
13.1.1.2 Suspected Unexpected Serious Adverse Reaction (SUSAR)
Any suspected adverse reaction to study treatment (i.e., including active comparators) that is 
both serious and unexpected. 
The event(s) must meet all of the following:

Suspected adverse reaction

Serious

Unexpected

Assessed as related to study treatment
Once determined to meet the criteria for a SUSAR, an SAE should be submitted to regulatory 
agencies expeditiously.

The sponsor will notify country’s regulatory authorities (wherever the trial has been 
initiated) and all participating investigators regarding all serious and unexpected suspected 
adverse reactions within 15 days.

All unexpected fatal or life threatening suspected adverse reactions must be reported in 
under 7 days.
13.1.1.3 Non-Serious Adverse Event
A non-serious AE is an AE that does not meet the criteria of an SAE.
13.1.1.4 Unexpected Adverse Events
An unexpected adverse event is an AE whose nature, severity, specificity, or outcome is not 
consistent with the term, representation, or description used in the Reference Safety Information 
(RSI). “Unexpected” also refers to the AEs that are mentioned in the IB and/or prescribing 
information as occurring with a class of drugs or as anticipated from the pharmacological 
properties of the product but are not specifically mentioned as occurring with the particular 
product under investigation. The expectedness of AEs will be determined by the sponsor using 
the IB and/or prescribing information as the RSI. This determination will include considerations 
such as the number of AEs previously observed, but not on the basis of what might be 
anticipated form the pharmacological properties of a product.
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13.1.1.5 Preexisting Diseases
Preexisting diseases that are present before entry to the study are described in the medical 
history, and those that manifest with the same severity, frequency, or duration after IP exposure, 
will not be recorded as AEs. However, when there is an increase in the severity, duration, or 
frequency of a preexisting disease after IP exposure, the event must be described on the AE CRF.
13.1.2 Assessment of Adverse Events
For the purpose of this study the TTP manifestations listed below, with an onset date after the 
first IP exposure, should be reported on the Adverse Event eCRF regardless of severity. 
Relationship to cTTP or to BAX 930 must be indicated. The TTP manifestations should be 
captured even if they were experienced as part of an acute or subacute event.
TTP manifestations, including but not limited to:

Renal signs, as defined by increase of serum creatinine >1.5 × baseline 

Neurological symptoms, such as:
o
headache 
o
confusion 
o
memory issues 
o
irritability 
o
paresthesia 
o
dysarthria 
o
dysphonia
o
visual disturbances
o
focal or general motor symptoms including seizures

Fever (≥100.4°F/38°C)

Fatigue/lethargy 

Abdominal pain
All other AEs from the first IP exposure until study completion/discontinuation will be described 
on the AE CRF using the medical diagnosis (preferred), or, if no diagnosis could be established 
at the time of reporting the AE, a symptom or sign, in standard medical terminology in order to 
avoid the use of vague, ambiguous, or colloquial expressions (see definition in Section 13.1). 
Each AE will be evaluated by the investigator for:
1.
Seriousness as defined in Section 13.1.1.1
2.
Severity as defined in Section 13.1.2.1
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3.
Causal relationship to IP exposure or study procedure as defined in Section 13.1.2.2
For each AE, the outcome (i.e., recovering/resolving, recovered/resolved, recovered/resolved 
with sequelae, not recovered/not resolved, fatal, unknown) and if applicable action taken (i.e., 
dose increased, dose not changed, dose reduced, drug interrupted, drug withdrawn, not 
applicable, or unknown) will also be recorded on the AE CRF. Recovering/resolving AEs will be 
followed until resolution, medically stabilized, or 30 days after the study completion/termination 
visit, whichever comes first); follow-up information is to be documented in the CRF. 
Subjects with reported ongoing AEs at the study completion date (date of last IP infusion or last 
date of PK-III assessments) who move on to the continuation study prior to the end of the 30-day 
AE follow up period will have all AE-related information captured and locked in the eCRF of 
Study 281102. At the time of enrollment into the continuation study, details surrounding an 
ongoing AE will be imported from Study 281102 into the subject’s eCRF for Study 
TAK-755-3002. Resolution of an AE that occurs in 281102, but is resolved in TAK-755-3002, 
will be captured in the subject’s eCRF for TAK-755-3002 only. If the severity rating for an 
ongoing AE changes before the event resolves, the original AE report will be revised (i.e., the 
event will not be reported as separate AE). During the course of any AE, the highest severity
rating will be reported.
Deviations from the protocol-specified dosage (including overdosing, underdosing, abuse, and 
withdrawal), treatment errors (including incorrect route of administration, use of an incorrect 
product, and deviations from the protocol-defined dosing schedule), failures of expected 
pharmacological actions, and unexpected therapeutic or clinical benefits will be followed with 
regard to occurrence of AEs, lack of efficacy, and/or other observations because these events 
may be reportable to regulatory authorities.
Any pregnancy that occurs after administration of IP will be reported on a Pregnancy Report 
Form to the Takeda Global Drug Safety Department and followed-up at estimated date of 
delivery and 1 year post-delivery, if feasible.
If an investigator becomes aware of an SAE occurring in a subject within 2 weeks after study 
completion, the SAE must be reported on the provided SAE Report Form within 24 hr after 
awareness; no additional reporting on CRFs is necessary.
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13.1.2.1 Severity
The investigator will assess the severity of each AE using his/her clinical expertise and judgment 
based on the most appropriate description below:
1.
Mild

The AE is a transient discomfort and does not interfere in a significant manner with 
the subject’s normal functioning level

The AE resolves spontaneously or may require minimal therapeutic intervention
2.
Moderate

The AE produces limited impairment of function and may require therapeutic 
intervention

The AE produces no sequela/sequelae
3.
Severe

The AE results in a marked impairment of function and may lead to temporary 
inability to resume usual life pattern

The AE produces sequela/sequelae, which require (prolonged) therapeutic intervention
These severity definitions will also be used to assess the severity of an AE with a study-related 
procedure(s), if necessary.
13.1.2.2 Causality
Causality is a determination of whether there is a reasonable possibility that the IP is 
etiologically related to/associated with the AE. Causality assessment includes, eg, assessment of 
temporal relationships, dechallenge/rechallenge information, association (or lack of association) 
with underlying disease, presence (or absence) of a more likely cause, and physiological 
plausibility. For each AE, the investigator will assess the causal relationship between the IP and 
the AE using his/her clinical expertise and judgment according to the following most appropriate 
algorithm for the circumstances of the AE:
1.
Not related (both circumstances must be met)

Is due to underlying or concurrent illness, complications, concurrent treatments, or 
effects of concurrent drugs

Is not associated with the IP (i.e., does not follow a reasonable temporal relationship to 
the administration of IP or has a much more likely alternative etiology). 
2.
Unlikely related (either 1 or both circumstances are met)

Has little or no temporal relationship to the IP 

A more likely alternative etiology exists
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3.
Possibly related (both circumstances must be met)

Follows a reasonable temporal relationship to the administration of IP

An alternative etiology is equally or less likely compared to the potential relationship 
to the IP
4.
Probably related (both circumstances must be met)

Follows a strong temporal relationship to the administration of IP, which may include 
but is not limited to the following:
Reappearance of a similar reaction upon re-administration (positive rechallenge)
Positive results in a drug sensitivity test (skin test, etc.)
Toxic level of the IP as evidenced by measurement of the IP concentrations in the 
blood or other bodily fluid

Another etiology is unlikely or significantly less likely
For events assessed as not related or unlikely related, the investigator shall provide the 
alternative etiology. These causality definitions will also be used to assess the relationship of an 
AE with a study-related procedure(s), if necessary.
13.2 Urgent Safety Measures
An urgent safety measure is an immediate action taken, which is not defined by the protocol, in 
order to protect subjects participating in a clinical trial from immediate harm. Urgent safety 
measures may be taken by the sponsor or clinical investigator, and may include any of the 
following: 
1.
Immediate change in study design or study procedures
2.
Temporary or permanent halt of a given clinical trial or trials
3.
Any other immediate action taken in order to protect clinical trial participants from 
immediate hazard to their health and safety
The investigator may take appropriate urgent safety measures in order to protect subjects against 
any immediate hazard to their health or safety. The measures should be taken immediately and 
may be taken without prior authorization from the sponsor. In the event(s) of an apparent 
immediate hazard to the subject, the investigator will notify the sponsor immediately by phone 
and confirm notification to the sponsor in writing as soon as possible, but within 1 calendar day 
after the change is implemented. The sponsor will also ensure the responsible ethics committees 
(ECs) and relevant competent authority(s) are notified of the urgent safety measures taken in 
such cases according to local regulations.
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13.3 Untoward Medical Occurrences
Untoward medical occurrences occurring before the first exposure to IP are not considered AEs 
(according to the definition of AE, see Section 13.1). However, each serious untoward medical 
occurrence experienced before the first IP exposure (i.e., from the time of signed informed 
consent up to but not including the first IP exposure) will be described on the AE CRF and on 
the SAE Report Form. These events will not be considered as SAEs and will not be included in 
the analysis of SAEs. 
13.4 Non-Medical Complaints
A non-medical complaint (NMC) is any alleged product deficiency that relates to identity, 
quality, durability, reliability, safety and performance of the product but did not result in an 
AE. Non-medical complaints include but are not limited to the following:
1.
A failure of a product to exhibit its expected pharmacological activity and/or design 
function, eg, reconstitution difficulty
2.
Missing components
3.
Damage to the product or unit carton
4.
A mislabeled product ( eg, potential counterfeiting/tampering)
5.
A bacteriological, chemical, or physical change or deterioration of the product causing it 
to malfunction or to present a hazard or fail to meet label claims
Any NMCs of the product will be documented on an NMC form and reported to the sponsor 
within 1 business day. If requested, defective product(s) will be returned to the sponsor for 
inspection and analysis according to procedures.
13.5 Medical, Medication, and Non-Drug Therapy History
At screening (and during Period 1 of the on-demand cohort only), the subject’s medical history 
will be described for the following body systems including severity (defined in Section 13.1.2.1) 
or surgery and start and end dates, if known: eyes, ears, nose, and throat; respiratory; 
cardiovascular; gastrointestinal; musculoskeletal; neurological; endocrine; 
hematopoietic/lymphatic; dermatological; and genitourinary.
All medications taken and non-drug therapies received from providing informed consent until 
completion/termination will be recorded on the concomitant medications and non-drug therapies 
CRFs.
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13.6 Physical Examinations
At screening and study completion/termination (see Section 20.3), a physical examination
will be performed on the following body systems: general appearance, head and neck, eyes 
and ears, nose and throat, chest, lungs, heart, abdomen, extremities and joints, lymph nodes, 
skin, and neurological. At screening, if an abnormal condition is detected, the condition 
will be described on the medical history CRF. At study visits, if a new abnormal or 
worsened abnormal pre-existing condition is detected, the condition will be described on 
the AE CRF.
If the abnormal value was not deemed an AE because it was due to an error, due to a preexisting 
disease (described in Section 13.1.1.5), not clinically significant, a symptom of a new/worsened 
condition already recorded as an AE, or due to another issue that will be specified, the 
investigator will record the justification on the source record.
For study sites in Germany only, refer to Appendix 1.1: Country-Specific Information for 
physical examination frequency and Table A1 Germany-specific Schedule of Assessments.
13.7 Clinical Laboratory Parameters
Clinical laboratory assessments are presented in Section 20.4, Table 9, and Table 10.
13.7.1 Hematology and Clinical Chemistry
The hematology panel will consist of a complete blood count (CBC): red blood cell (RBC) 
count, hemoglobin, hematocrit, haptoglobin, reticulocyte count, mean corpuscular volume 
(MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration 
(MCHC), leukocytes (i.e., white blood cell count) with differential (i.e., basophils, eosinophils, 
lymphocytes, monocytes, neutrophils) and platelet counts:

In adult and adolescent subjects (≥12 years of age), samples for CBC analysis will be 
taken within 1 hr prior to infusion and, relative to the end of the infusion for all following 
timepoints, at 15±5 min, 9±1 hr, 24±2 hr, 72±4 hr, 216±24 hr, and 288±24 hr 
post-infusion (see Section 20.4).

In pediatric subjects (<12 years of age), samples for CBC analysis will be taken within 
1 hr prior to infusion and at 48±2 hr post-infusion (see Section 20.4, Table 12).
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The clinical chemistry panel will consist of sodium, potassium, chloride, ALT, aspartate 
aminotransferase (AST), LDH, bilirubin, albumin (only at screening), alkaline phosphatase, 
blood urea nitrogen, creatinine, and glucose:

In adult and adolescent subjects (≥12 years of age), samples for clinical chemistry 
analysis will be taken within 1 hr prior to infusion and, relative to the end of the infusion 
for all following timepoints, at 9±1 hr, 24±2 hr, 72±4 hr, 216±24 hr, and 288±24 hr 
post-infusion (see Section 20.4).

In pediatric subjects (<12 years of age), samples for clinical chemistry analysis will be 
taken within 1 hr prior to infusion and at 48 ±2 hr post-infusion (see Section 20.4, 
Table 12).
Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for 
pediatric subjects <6 years of age may be adjusted and/or omitted; refer also to Section 11.3.1
and Section 12.2.1. 
Blood will be obtained for assessment of hematology and clinical chemistry parameters at 
screening, within 60 min of the start of the initial infusions of Period 1 and Period 2, interval 
study visits (i.e., every 3 months during SoC and BAX 930 treatment phases of Period 1 and 
Period 2), and at study completion/termination (see Section 20.4, Table 9 and Table 10). 
Hematology and clinical chemistry assessments will be performed on ethylenediaminetetraacetic 
acid-anticoagulated whole blood and serum, respectively, at the central laboratory (all 
assessments) and the local laboratory. 
Blood group will be determined at screening only if not available in subject’s medical history.
13.7.2 Biomarkers of Organ Damage
The biomarkers panel will consist of cTnT and cTnI, CK-MB, NSE, S100B:

In adult and adolescent subjects (≥12 years of age), samples for biomarker analysis will 
be taken within 1 hr prior to infusion and, relative to the end of the infusion for all 
following timepoints, at 9±1 hr, 24±2 hr, 72±4 hr, 120±12 hr, 168±12 and 288±24 hr 
post-infusion (see Section 20.4, Table 10, and Table 13).

In pediatric subjects (<12 years of age), samples for biomarker analysis will be taken 
within 1 hr prior to infusion and at 48±2 hr, and 168±4 hr post-infusion (see Section 20.4, 
Table 12 and Table 13).
Blood samples collected from subjects <18 years of age, for exploratory outcome measures, can 
be collected at the discretion of the investigator and are not to exceed the local EC and applicable 
regulatory guidelines for daily and monthly maximum blood volume limits.
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Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for 
pediatric subjects <6 years of age may be adjusted and/or omitted; refer also to Section 11.3.1
and Section 12.2.1.
13.7.2.1 Cardiac Troponin
Cardiac troponin T and I are sensitive biochemical markers of myocardial cell necrosis; these 
markers are superior to classical enzyme markers of necrosis due to their cardio-specificity.
13.7.3 Creatine Kinase Myocardial Band Fraction
Creatine kinase is a biochemical marker used as an indicator of organ damage. This parameter 
will also be measured at the local laboratory at specified timepoints further described in 
Section 20.4 (see Table 9 and Table 10) to look for signs of an acute TTP relapse.
13.7.3.1 Neuron-specific Enolase
Neuron-specific enolase is a glycolytic enzyme and a brain-specific biochemical seromarker for 
neuronal integrity, thus indicative for brain impairment.
13.7.3.2 S100 Calcium-binding Protein B
S100B is a calcium-binding protein, localized in astroglial and Schwann cells. Detectable serum 
levels of S100B are indicative for the acute phase of brain damage.
13.7.4 Urinalysis
Urinalysis dipstick assessments will be performed at screening and will consist of erythrocytes, 
specific gravity, urobilinogen, ketones, glucose, protein, bilirubin, nitrite, and pH.
13.7.5 Pharmacokinetics and Pharmacodynamic Tests
ADAMTS13 activity, ADAMTS13 antigen, VWF:RCo, VWF:Ag, VWF multimer analysis, and 
ADAMTS13 mediated VWF cleavage products will be measured at specified timepoints. For the 
adult sampling scheme, see Section 12.2, Section 20.4, and Table 11; for the pediatric sampling 
scheme see Section 12.2, Section 20.4, and Table 12.
Blood samples collected from subjects <18 years of age, for exploratory outcome measures, can 
be collected at the discretion of the investigator and are not to exceed the local EC and applicable 
regulatory guidelines for daily and monthly maximum blood volume limits.
Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for 
pediatric subjects <6 years of age may be adjusted and/or omitted; refer also to Section 11.3.1
and Section 12.2.1.
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13.7.5.1 ADAMTS13 Activity
ADAMTS13 activity will be measured by the FRETS-VWF73 assay. Results for samples with 
hemoglobin and bilirubin levels above the acceptable limit will be invalidated and excluded from 
reporting (not reportable).
13.7.5.2 ADAMTS13 Antigen (ADAMTS13:Ag)
ADAMTS13 antigen detects the status of total ADAMTS13 protein that may include free 
protein, protein in complex with antibody inhibitor, and ADAMTS13 bound to other carrier 
proteins, and will be measured using a commercial ADAMTS13 ELISA.
13.7.5.3 VWF Ristocetin Cofactor Activity (VWF:RCo)
The VWF:RCo provides a measure of the ability of VWF to bind platelet glycoprotein Ib, a key 
step in primary hemostasis. Stabilized platelets are agglutinated in the presence of VWF and the 
antibiotic Ristocetin.
13.7.5.4 VWF Antigen (VWF:Ag)
The VWF:Ag, a measure of total VWF protein, will be assessed using a sandwich ELISA 
employing anti-human-VWF antibodies.
13.7.5.5 VWF Multimer Analysis and ADAMTS13 mediated VWF cleavage products
The relative distribution of VWF multimers pattern (small, intermediate, large, and ultra large) 
over time will be assessed using low-resolution sodium dodecyl sulfate (SDS)-agarose gel 
electrophoresis. These analyses will employ Western blot with luminescence video imaging. 
In addition, the same high resolution SDS-agarose gel electrophoresis will be used to 
qualitatively determine the satellite band structure of VWF. ADAMTS13-mediated 
VWF cleavage products will be analyzed using mass spectrometry or visualized by 
SDS-poly-acrylamide gel electrophoresis followed by Western blot staining and quantitative 
densitometry.
13.7.6 Immunogenicity
Plasma will be assayed for the presence of antibodies against ADAMTS13 and CHO protein 
using validated immunoassays at the timepoints presented in Section 20.4, Table 9, and Table 10. 
The date/time of sample collection will be recorded in the eCRF.
Antibody-containing samples will be identified in a screening assay followed by a confirmatory 
assay to exclude false positive results.
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A tiered approach for antibody testing will be followed:

Total binding (total Ig) antibodies to ADAMTS13 (BAX 930) (screening and 
confirmation) will be tested initially. Absence of total binding antibodies to ADAMTS13 
is an indication of the absence of neutralizing (activity inhibition) antibodies to 
ADAMTS13 and no further antibody assessments will be conducted on the sample.

If total binding (total Ig) antibodies to ADAMTS13 are positive, binding Ab titer and the 
presence and levels of neutralizing (activity inhibition) antibodies to both plasma-derived 
ADAMTS13 and BAX 930 will be tested.
13.7.6.1 Anti-ADAMTS13 Antibodies
Caution is advised in interpreting positive results. Any clinical association, changes in the natural 
history of the disease, effect of therapy, etc. need to be considered for final judgement. 
The sponsor’s Medical Director should be consulted for additional advice. As part of the AE 
follow-up, any sample testing positive needs to be confirmed after 2 to 4 weeks and documented 
for AE follow-up. Only confirmed neutralizing anti-ADAMTS13 antibodies (biological assays) 
are considered inhibitors. 
Subjects who develop an inhibitory antibody to ADAMTS13, will not receive any further IP 
infusion, however, will be followed until study completion and all remaining study procedures 
such as clinical and laboratory assessments will be completed. As an additional safety measure, 
ADAMTS13 specific IgE antibodies will only be assessed in case of allergic reactions.
13.7.6.1.1 Total Binding Antibodies to ADAMTS13
Total binding antibodies to ADAMTS13 will be measured by an ELISA-based assay, detecting 
total immunoglobulins (IgG, IgA, and IgM).
13.7.6.1.2 Neutralizing Antibodies to ADAMTS13
Neutralizing antibodies to ADAMTS13 will be measured by a Bethesda method with Nijmegen 
modification using the ADAMTS13 FRETS-VWF73 activity assay. Test plasma will be mixed 
and incubated with equal volume of test control at approximately 1 IU/mL, and the residual
ADAMTS13 activity in the mixed samples will be determined by the FRETS-VWF73 assay.
13.7.6.2 Anti-CHO Protein Antibodies 
Total immunoglobulin antibodies (Immunoglobulin G [IgG], A [IgA], and M [IgM]) against 
CHO protein will be analyzed. For this assay (ELISA), CHO protein derived from cultures of 
untransfected cells and propagated under the identical cell culture conditions used for 
recombinant antihemophilic factor-protein-free method production will be coated onto a 
microtiter plate, then incubated with dilutions of the positive control, negative control, or test 
sample. 
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Antibodies against CHO protein that are present in the samples bind to the coated antigen and 
will be detected with a horseradish peroxidase-coupled goat anti-human antibody (secondary 
antibody). A positive result without known hypersensitivity to hamster proteins, such as a history 
of anaphylactic or anaphylactoid reactions or other severe allergic reactions upon exposure to 
hamster-derived substances, will not constitute an exclusion criteria for randomization.
For subjects <6 years of age, anti-CHO protein Ab assessments may be omitted to not exceed 
local EC and applicable regulatory guidelines for daily and monthly maximum blood volume 
limits. 
13.7.7 Viral Serology
Virus serology will be established during the screening period and at completion of standard of 
care treatment.
The following viral seromarkers will be assessed:
1.
HIV: anti-HIV 1, HIV 2
2.
Hepatitis A virus: anti-HAV (IgG and IgM)
3.
HBV: hepatitis B surface antigen, anti-Hepatitis B core, anti-hepatitis B surface antibody
4.
HCV: Chemiluminescence anti-HCV 
5.
HEV: anti-HEV
6.
Parvovirus B19: anti-B19V (IgG and IgM)
7.
CD4 levels (at screening in HIV-positive subjects)
13.7.8 Genetic Testing
A cell pellet (buffy coat and erythrocytes) will be retained for ADAMTS13 gene mutational 
analysis at Screening if the information is not already available in the subject’s medical history.
13.7.9 Pregnancy Test
A blood or urine pregnancy test for females of child-bearing potential will be performed at 
screening, within 7 days prior to first dosing with BAX 930, interval study visits (i.e., every 
3 months during SoC and BAX 930 treatment phases of Period 1, Period 2 and Period 3), and at 
study completion/termination (see Section 20.4, Table 9 and Table 10). 
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13.7.10 Assessment of Laboratory Values
13.7.10.1 Assessment of Abnormal Laboratory Values 
The investigator’s assessment of each abnormal laboratory value will be recorded on the CRF 
(note: there is no need for recording of normal local laboratory values on the CRF, with 
four exceptions: a) Coombs test, and b) the evaluation of schistocytes, c) platelet count, and d) 
LDH for which normal laboratory values should be reported). For each hematology and 
chemistry abnormal laboratory value, the investigator will determine whether the value is 
considered clinically significant or not. For clinically significant values, the investigator will 
indicate if the value constitutes a new AE (see definition in Section 13.1, and record the sign, 
symptom, or medical diagnosis on the AE CRF), is a symptom or related to a previously 
recorded AE, is due to a pre-existing disease (described in Section 13.1.1.5), or is due to another 
issue that will be specified. If the abnormal value was not clinically significant, the investigator 
will indicate the reason, i.e., because it is due to a preexisting disease, due to a lab error, or due 
to another issue that will be specified. Additional tests and other evaluations required to establish 
the significance or etiology of an abnormal value, or to monitor the course of an AE should be 
obtained when clinically indicated. Any abnormal value that persists should be followed at the 
discretion of the investigator.
Any seroconversion result for HIV, HAV, HBV, HCV, HEV, or B19V shall be re-tested.
13.7.11 Backup Samples and Biobanking
Backup samples taken and stored short-term may be used, for example, for re-testing, follow-up 
of an AE(s) or other test results, and/or assay development. After study testing is completed, the 
remaining samples may be stored in a coded form for no more than 2 years after the final study 
report has been completed and then the samples will subsequently be destroyed.
For this study, no samples will be taken or stored long-term in a biobank for future analyses.
13.8 Vital Signs and 12-lead Electrocardiogram
Vital signs will be collected at each dosing visit within 1 hour before and after IP infusion, and 
will include body temperature (°C or °F), respiratory rate (breaths/min), pulse rate (beats/min), 
and systolic and diastolic blood pressure (mmHg). Height (in or cm) and weight (lb or kg) will 
also be collected.
For adult and adolescent subjects (≥12 years of age), vital signs should be recorded within 1 hr 
before PK infusion and at the following timepoints post-infusion: 15±5 min, 60±5 min, 
3±0.5 hr, 9±2 hr, 24±2 hr, 72±4 hr, 120±12 hr, 168±12 hr, 216±24 hr, and 288±24 hr, as well as 
at each dosing visit. 
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For pediatric subjects (<12 years of age), vital signs should be recorded within 1 hr before PK 
infusion and at the following timepoints post infusion: 30±5 min, 12±2 hr, 24±2 hr, 48±2 hr, 
96±2 hr and 168±4 hr, and as well as at each dosing visit. 
Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for 
pediatric subjects <6 years of age may be adjusted and/or omitted and the timing of assessments, 
such as vital signed, associated with blood collections will be adjusted accordingly; refer also to
Section 11.3.1 and Section 12.2.1.
Blood pressure will be measured when subjects are in the supine position.
Height will be measured at screening only for subjects >=12 years of age. Height will be 
measured at screening, Day 1, dosing visits and at study completion/termination, for subjects 
<12 years of age. Weight will be measured for all subjects at screening, Day 1, PK 2 infusion (if 
BAX 930 is being administered for this infusion), PK 3 infusion, PK 4 infusion, dosing visits and 
at study completion/termination.
A 12-lead electrocardiogram (ECG) will be measured at screening and at study 
completion/termination.
Vital signs and 12-lead ECG are to be recorded on the CRF. For each assessment, the 
investigator will determine whether or not to report an AE (see definition in Section 13.1) and 
record the medical diagnosis (preferably), symptom, or sign on the AE CRF.
Additional tests and other evaluations required to establish the significance or etiology of an 
abnormal value, or to monitor the course of an AE should be obtained when clinically indicated. 
Any abnormal value that persists should be followed at the discretion of the investigator.
For study sites in Germany only, refer to Appendix 1.2: Country-Specific Information for 
12-lead ECG frequency and Table A1 Germany-specific Schedule of Assessments.
13.9 Health-related Quality of Life
Patient reported outcomes, based on relevant questionnaires, will be captured at screening and at 
the end of each period visit (i.e., end of Period 1 visit, end of Period 2 visit, and end of Period 3 
visit), and if subjects have an early termination, during the termination visit, to assess chronic 
TTP-related symptoms and disabilities, including cognitive function. Lower scores indicate 
worse HRQoL.
The PRO instruments to be measured in this study are described in Table 4.
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Table 4. Patient Reported Outcome (PRO) Instruments
PRO
Assessment
Time of Measurement
SF-36v2
Self-administered, validated questionnaire. This 36-item 
questionnaire measures 8 domains, including: 

Physical functioning

Role-physical

Bodily pain

General health

Vitality

Social functioning

Role emotional

Mental health. 
Two summary scores can be calculated:

Physical Component Score

Mental Component Score
Additionally, scores can be calculated for each of the 
8 domains.

Screening

Prophylactic cohort: 
Period 1, and end of 
Periods 1, 2, and 3, 
and at early 
termination visit, if 
applicable.

On-demand cohort: 
End of Period 1 and at 
early termination visit, 
if applicable.
EQ-5D-3L or EQ-5D-Y
The EQ-5D-3L is a generic measure of health, 
consisting of a descriptive system. It captures the 
following domains:

Mobility

Self-care

Usual activities

Pain/discomfort

Anxiety/depression
Self-rated health is captured using a visual analog scale.
The youth version contains the same features but uses 
more child-friendly wording.

Screening

Prophylactic cohort: 
end of Periods 1, 2, 
and 3, and at early 
termination visit, if 
applicable. 

On-demand cohort: 
End of Period 1
PedsQLa:
Age 2-4 
(Parent proxy, 21 items)
Age 5-7 
(Parent proxy, 23 items)
Age 8-12
(Child version, 23 items)
Age 13-18 (Child 
version, 23 items)—It 
will only be 
administered to subjects 
aged 13-17 years
The PedsQL is a generic HRQoL instrument designed 
specifically for a pediatric population. It captures the 
following domains:

Physical functioning

Emotional functioning

School functioning

Social functioning

Psychosocial summary

Physical health

Total score

Screening

Prophylactic cohort: 
end of Periods 1, 2, 
and 3, and at early 
termination visit, if 
applicable.

On-demand cohort: 
End of Period 1
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Table 4. Patient Reported Outcome (PRO) Instruments
PRO
Assessment
Time of Measurement
TSQM-9 
(Bharmal et al., 2009)
The TSQM-9 questionnaire is a validated measure 
consisting of 3 domains (efficacy, convenience, and 
overall satisfaction) and 9 questions

Screening

Prophylactic cohort: 
end of Periods 1, 2, 
and 3, and at early 
termination visit, if 
applicable.

On-demand cohort: 
End of Period 1
Health resource use 
items
This information will be gathered by the sites as part of 
the eCRF. It assesses:

Number of hospitalizations and length of stay

Number of acute care visits

Number of emergency room visits

Number of days missed from school, daycare or 
work (i.e., grade school, kindergarten, daycare)

Via eCRF after 
randomization
cTTP PRO assessment
The cTTP PRO assessment is focused on measuring the 
symptoms and impacts of the disease. It is a 26-item 
questionnaire assessing several concepts, including the 
following:

Fatigue

Pain (joint, muscle, abdominal, chest)

Neuro-cognitive impairment

Vision difficulties

Headaches

Bruising

Emotional functioning

Impact on daily activities

Screening

Prophylactic cohort: 
end of Periods 1, 2, 
and 3, and at early 
termination visit, if 
applicable.

On-demand cohort: 
End of Period 1
eCRF, electronic case report form; EQ-5D-3L, EuroQol 5 Dimensions Questionnaire 3 Level; EQ 5D Y, EQ-5D-
youth; HRQoL, health-related quality of life; cTTP, congenital thrombotic thrombocytopenic purpura; PedsQL, 
Pediatric Quality of Life Inventory; PRO (patient reported outcome); SF 36v2, 36 Item Short Form Health Survey 
version 2; TSQM-9, Treatment Satisfaction Questionnaire for Medication.
a
Subjects should be given the same questionnaire at follow-up that they were given at Screening, even if they 
move up an age range during the study.
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14. STATISTICS
14.1 Sample Size Determination
In total, approximately 42 adult (≥18 years old) subjects and 15 adolescent (>12-≤17 years old) 
or pediatric (<12 years old) subjects will be enrolled in this study, including approximately 
36 adult subjects and 12 adolescent or pediatric subjects starting in the prophylaxis cohort, and 
approximately 6 adult subjects and 3 adolescent or pediatric subjects, in the on-demand cohort. 
The sample size is limited by the extremely low prevalence of the disease (0.5 to 4 per million) 
(Mansouri Taleghani et al., 2013). The updated approximate number of subjects reflects the 
current, observed enrollment patterns and accounts for a 10% dropout rate. The number of 
subjects starting enrollment in the prophylactic cohort should allow an overall assessment of 
efficacy and safety of BAX 930, including immunogenicity, and PK following infusion.
The sample size of approximately 36 adult (≥18 years old) subjects and 12 adolescent (4 subjects 
age >12-≤17) or pediatric subjects (4 subjects age >6-<12, and 4 subjects age 0-<6) in the 
prophylaxis cohort, will also provide an estimate of the safety and efficacy of the IP. 
If 15 of the 30 enrolled adult and adolescent prophylaxis subjects receive FFP and each subject 
receiving FFP will have at least 14 infusions per treatment period, there will be 210 total FFP 
infusions. With 210 FFP infusions, there is a >99% probability that at least 1 SAE will be 
observed, if as reported in the literature, the rate of serious adverse reactions (SARs) is 6% 
(Huisman et al., 2014). 
The sample size for the on-demand cohort will be approximately 6 adult subjects, if enrollment 
allows, and 3 pediatric or adolescent subjects.
The sample size is not selected as a result of a power calculation and the primary outcome 
measure will not be assessed by a formal significance test.
14.2 Analysis Sets 
14.2.1 All Subjects Enrolled Set
The all subjects enrolled set will comprise all subjects for whom informed consent has been 
obtained.
14.2.2 Full Analysis Set (FAS)
The full analysis set (FAS) will include all subjects with a confirmed cTTP diagnosis receiving 
at least 1 dose of BAX 930 or SoC treatment after randomization. 
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14.2.3 Modified Full Analysis Set (MFAS)
The modified full analysis set (MFAS) is based on the FAS, with the following modifications: 

For subjects enrolled prior to the study hold in November 2017, if BAX 930 was the 
randomized treatment for period 1 and were treated on SoC because BAX 930 was not 
available, the subjects will be excluded from the MFAS.

For subjects enrolled prior to the study hold in November 2017, if SoC was the 
randomized treatment for period 1 and were treated on SoC because BAX 930 was not 
available, only the primary efficacy data for period 1 collected prior to the Month 6 visit 
will be used in the MFAS-based primary efficacy analysis.
14.2.4 Per-protocol Analysis Set
The per-protocol (PP) analysis set will include all subjects in the MFAS who have no major 
protocol deviations from the protocol affecting the efficacy outcome or treatment of the subject. 
Further information on major protocol deviations will be provided in the Statistical Analysis Plan 
(SAP).
14.2.5 Safety Analysis Set
The safety analysis set will include all subjects treated with at least 1 dose of BAX 930 or SoC 
treatment after randomization. All safety analyses will be performed on the safety analysis set.
14.2.6 Pharmacokinetic and Pharmacodynamic Analysis Sets
The PK Full Analysis Set (PKFAS) will be a subset of the FAS and will contain all subjects who 
receive at least 1 dose of investigational product and provide adequate postdose PK 
measurements for at least 1 of the PK analytes and have no major protocol deviations or events 
that may affect the integrity of the PK data. Subjects in this population will be used for all 
respective PK concentration and parameter summaries. 
The PD analysis set will be a subset of FAS and will contain all subjects who receive at least 
1 dose of investigational product and provide at least 1 valid data point postdose of the respective 
infusion for at least 1 PD measurement for any of the PD outcome measures, and have no major 
protocol deviations or events that may affect the integrity of the PD data. Subjects in this 
population will be used for all respective PD concentration summaries.
14.3 Handling of Missing, Unused, and Spurious Data
In general, missing data will not be imputed. However, if body weight at the time of infusion is 
missing for a subject then the last available body weight measurement will be carried forward in 
order to compute weight-adjusted BAX 930 consumption. 
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For PK data, if any concentration data are considered spurious ( eg, lack of biological 
plausibility), they will be excluded from the analysis, and the reason for exclusion from the 
analysis will be documented.
Regarding missing data in AE records:

Handling of unknown causality assessment:
If a subject experiences an AE with missing causality assessment, the relationship of 
the AE will be counted as “related.” However, all efforts will be made to discuss with 
the investigator for a causality assessment. 

Handling of unknown severity grades:
If a subject experiences more than 1 AE categorized under the same preferred term, 
1 of them is categorized as “severe” and 1 of them is categorized as “unknown”, the 
severity of this AE will be counted as “severe”
If a subject experiences more than 1 AE categorized under the same preferred term, 
1 of them is categorized as “mild” or “moderate” and 1 of them is categorized as 
“unknown,” the severity of this AE will be counted as “unknown”
14.4 Methods of Analysis
The overall assessment of BAX 930 treatment will be based on the totality of evidence provided 
by efficacy, safety, PRO, and PK data. The statistical analysis for the prophylactic cohort will be 
carried out in 2 steps: (a) an interim analysis (with an interim clinical study report) will be 
performed after 30 adults and adolescent subjects in prophylactic cohort complete the study; (b) 
a final analysis will be done at the end of the study when all efficacy, safety, PRO and PK data 
collected become available for both adult and pediatric subjects. 
Analyses will be performed separately for the prophylaxis and on-demand cohorts on applicable 
outcome measures and will be presented by treatment group for each cohort, unless otherwise 
stated.
Details on the specific analyses to be performed for this study will be provided in the SAP.
14.4.1 Primary Outcome Measure
The primary outcome measure is:
The incidence of acute TTP events among subjects receiving either BAX 930 or SoC 
prophylactically during the corresponding treatment periods.
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14.4.1.1 Incidence of Acute TTP Events
The number of acute TTP events and the incidence rate of acute TTP events will be summarized 
by treatment group (BAX 930 or SoC) and treatment period.
The acute TTP event annualized rate will be assumed to have a negative binomial distribution, 
and the mean acute TTP rate will be estimated using a generalized linear mixed-effects model 
with a negative binomial distribution as a family and a logarithmic link function (the default) 
with treatment as a fixed effect, subject as a random effect, and the logarithm of follow-up time 
(in years) as an offset. The model-based mean annual rate and corresponding 95% CI will be 
presented for each treatment for the prophylactic cohort, as well as the ratio of the two treatment 
incidence rates, accompanied by a two-sided, 95% CI. If the model fails to converge, descriptive 
statistics on event rates will be reported without a statistical model.
Additional summaries of the number of acute TTP events and incidence rates of the 
two treatments will be provided by treatment group, treatment period and age group.
Efficacy analysis for the pediatric subjects will be performed separately.
The primary efficacy analysis will be based on the MFAS for the prophylactic cohort. A 
sensitivity analysis will be performed based on the FAS for the prophylactic cohort. 
14.4.2 Secondary Outcome Measures 
14.4.2.1 Efficacy
The methods of analysis for the secondary efficacy outcome measures (see Section 9.4.2.1) are:

The proportion of acute TTP events responding to BAX 930 will be summarized including 
95% CI by treatment for both the prophylactic and on-demand cohorts 

For acute TTP events, a Kaplan-Meier curve for each treatment group will be drawn based 
on each subject's time to resolution of the acute TTP event, defined as the time from initial 
treatment of the event to the end of the acute TTP event for pooled prophylactic and 
on-demand cohort data, and separately. Only the first acute TTP event for each subject will 
be included in the analysis. The median time to resolution will be presented for each 
treatment, along with the corresponding 95% CI.

Incidence of thrombocytopenia defined as a drop in platelet count ≥25% of baseline, or a 
platelet count <150,000/µl, will be reported by treatment arm for the prophylactic cohort

Incidence of microangiopathic hemolytic anemia defined as an elevation of LDH >1.5× 
baseline or >1.5×ULN, will be reported by treatment arm for the prophylactic cohort
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
Incidence of neurological symptoms (TTP related) ( eg, confusion, dysphonia, dysarthria, 
focal or general motor symptoms including seizures), will be reported by treatment arm for 
the prophylactic cohort

Incidence of renal dysfunction, defined as an increase in serum creatinine >1.5×baseline, 
will be reported by treatment arm for the prophylactic cohort

Incidence of abdominal pain (TTP related) will be reported by treatment arm for the 
prophylactic cohort

The incidence of supplemental doses prompted by subacute TTP events will be 
summarized by treatment for the prophylactic cohort

The incidence of dose modifications not prompted by an acute TTP event will be 
summarized by treatment for the prophylactic cohort

The incidence of acute TTP events while subjects are on their final dose and dosing 
regimen in the study will be summarized by treatment for the prophylactic cohort 
14.4.2.2 Safety
Safety outcome measures (see Section 9.4.2.2) are:

The number and percentage of treatment-emergent adverse events will be calculated 
overall, by system organ class, by preferred term, and by treatment group for each cohort. 
Treatment-emergent adverse events will be further summarized by seriousness, severity, 
and relationship to IP. Adverse events related to IP, AEs leading to withdrawal, SAEs, and 
deaths will be similarly summarized/listed. 

Incidence of binding and inhibitory antibody will be tabulated and summarized.

Vital signs and clinical laboratory results (clinical chemistry, hematology, and urinalysis), 
observed and change from baseline, will be summarized by study visit, treatment, and age 
group (as applicable) using descriptive statistics.

For the laboratory safety data, out of range values will be flagged in the data listings and a 
list of clinically significant abnormal values will be presented.

The estimated total quantity of ADAMTS13 administered during the treatment of acute 
TTP events will be listed by subject and summarized by treatment cohort (prophylactic or 
on-demand) using descriptive statistics.
14.4.2.3 Pharmacokinetics/Pharmacodynamics
The methods for analysis of PK and PD outcome measures (see Section 9.4.2.3) are outlined in 
Section 14.4.2.3.1, Section 14.4.2.3.2, and Section 14.4.2.3.3. 
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14.4.2.3.1 Pharmacokinetics
Pharmacokinetic parameters for ADAMTS13 activity and ADAMTS13:Ag following SoC or 
BAX 930 infusion will be derived for adults using non compartmental methods, including, where 
estimable:

IR

Cmax

Time to reach Cmax (tmax) 

Apparent terminal rate constant (z)

t1/2

MRT

Area under the plasma concentration/activity/time curve (AUC) including:
AUC from time zero to the time of the last concentration (AUC(0-last))
AUC from time zero to infinity (AUC(0-inf))

Area under the moment curve from time zero to infinity (AUMC(0-inf))

Systemic CL

Vss
Potency of ADAMTS13 activity and ADAMTS13:Ag in the SoC or BAX 930 dosing solutions 
will be used to derive actual dose amount for calculating IR, CL, and Vss.
For BAX 930 and SoC activity, FRETS-VWF73 will be used to measure potency. 
For PK parameter calculations, should the measurement at pre-infusion of the respective PK 
infusion be above the lower limit of quantitation, baseline may be subtracted from post infusion 
measurements, or used as a covariate as applicable if other analysis methods are employed.
Pharmacokinetic parameters for pediatric subjects will be assessed separately. An attempt will be 
made to determine PK parameters using a non-compartmental method for pediatric subjects 
based on the reduced sampling schedule and may include Cmax, tmax, and appropriate estimates of 
AUC over the sampling period. Other analysis methods may be used to analyze pediatric data. 
The PK levels and PK parameters for adult and pediatric subjects will be listed and summarized 
by age group, treatment cohort (prophylaxis or on-demand), treatment arm, and study visit (and 
by scheduled time for PK levels). Individual and mean PK profiles over time will be presented. 
Impact of immunogenicity on ADAMTS13 antigen and activity time profiles and PK parameters 
will be assessed. 
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Immunogenicity status, time of onset of immunogenicity for both binding and inhibitory 
antibodies will be used to assess this impact. Additional figures may be generated as applicable. 
Additional details will be provided in the SAP and Clinical Pharmacology Analysis Plan.
A nonlinear mixed effects model approach will be used to derive a population PK model for 
ADAMTS13. The modeling report will be reported separately.
14.4.2.3.2 Pharmacodynamics
The PD measurement of plasma VWF:RCo and VWF:Ag will be listed and summarized by age 
group, treatment cohort (prophylaxis or on-demand), treatment arm, study visit, and scheduled 
time. Individual and mean PD profiles over time will be presented. Data allowing impact of 
immunogenicity (immunogenicity status, time of onset) on VWF:RCo and VWF:Ag may be 
evaluated. Additional figures may be generated as applicable.
14.4.2.3.3 Pharmacokinetic/Pharmacodynamic
The relationship between ADAMTS13 activity levels and/or PK parameters and the presence of 
and/or time of occurrence of acute TTP events and subacute TTP events will be explored. 
14.4.2.4 Health Related Quality of Life and Resource Utilization
The methods of analysis for the secondary HRQoL and resource utilization outcome measures 
(see Section 9.4.2.4) are:

HRQoL and resource utilization will be tabulated by treatment period and treatment cohort 
(prophylaxis or on-demand)

Differences observed between treatments will be assessed for each treatment cohort 
(prophylactic or on-demand) by significance tests
14.4.3 Exploratory Outcome Measures
Exploratory outcome measures based on incidence of events, where applicable, will be assessed 
using a generalized linear mixed-effects model assuming a negative binomial distribution and a 
logarithmic link function (the default) with treatment as a fixed effect, subject as a random 
effect, and the logarithm of follow-up time (in years) as an offset. The model-based mean annual 
rate and corresponding 95% CI will be presented for each treatment for the prophylactic cohort, 
as well as the ratio of the two treatment incidence rates, accompanied by a two-sided, 95% CI. If 
the model fails to converge, descriptive statistics on event rates will be reported without a 
statistical model.
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The PD measurement of ADAMTS13 mediated VWF cleavage products (if available) will be 
listed and summarized by age group, treatment cohort (prophylaxis or on-demand), treatment 
arm, study visit, and scheduled time. Individual and mean PD profiles over time will be 
presented. Additional figures may be generated as applicable.
14.4.4 Other Analyses
All other analyses, including analyses on subject disposition, demographics, disease 
characteristics, medications, histories etc. will be further defined in the SAP.
14.4.4.1 Planned Interim Analyses of the Study: 
An interim analysis will be performed after 30 adult or adolescent subjects in the prophylactic 
treatment group complete the study. All data collected by that time point will be included in the 
statistical analysis. 
The interim analysis will be performed on a cleaned snapshot of the study database and will 
include all data for adults, adolescent, and pediatric subjects in the study.
The interim analysis data will be used in regulatory submissions and scientific manuscripts. The 
interim analysis will include all analyses outlined in Section 14.4.1, Section 14.4.2, 
Section 14.4.3, and Section 14.4.4. Further details will be provided in the SAP.
14.5 Direct Access to Source Data/Documents
The investigator/study site will cooperate and provide direct access to study documents and data, 
including source documentation for monitoring by the study monitor, audits by the sponsor or 
sponsor’s representatives, review by the EC, and inspections by applicable regulatory authorities, 
as described in the Clinical Trial Agreement (CTA). If contacted by an applicable regulatory 
authority, the investigator will notify the sponsor of contact, cooperate with the authority, 
provide the sponsor with copies of all documents received from the authority, and allow the 
sponsor to comment on any responses, as described in the CTA.
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15. QUALITY CONTROL AND QUALITY ASSURANCE
15.1 Investigator’s Responsibility
The investigator will comply with the protocol (which has been approved/given favorable 
opinion by the EC), ICH GCP, and applicable national and local regulatory requirements as 
described in the CTA. The investigator is ultimately responsible for the conduct of all 
aspects of the study at the study site and verifies by signature the integrity of all data transmitted 
to the sponsor. The term “investigator” as used in this protocol as well as in other study 
documents, refers to the investigator or authorized study personnel that the investigator has 
designated to perform certain duties. Sub-investigators or other authorized study personnel are 
eligible to sign for the investigator, except where the investigator’s signature is specifically 
required.
15.1.1 Final Clinical Study Report 
The investigator, or coordinating investigator(s) for multicenter studies, will sign the clinical 
study report. The coordinating investigator will be selected before study start.
15.2 Training
The study monitor will ensure that the investigator and study site personnel understand all 
requirements of the protocol, the investigational status of the IP, and his/her regulatory 
responsibilities as an investigator. Training may be provided at an investigator’s meeting, at the 
study site, and/or by instruction manuals. In addition, the study monitor will be available for 
consultation with the investigator and will serve as the liaison between the study site and the 
sponsor.
15.3 Monitoring
The study monitor is responsible for ensuring and verifying that each study site conducts the 
study according to the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable national and local regulatory 
guidelines/requirements. The investigator will permit the study monitor to visit the study site at 
appropriate intervals, as described in the CTA. Monitoring processes specific to the study will be 
described in the clinical monitoring plan.
15.4 Safety Monitoring
The safety of the subjects in this study shall be monitored by an external DMC.
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The DMC is a group of individuals with pertinent expertise that reviews on a regular basis 
accumulating data from an ongoing clinical study. For this study, the DMC will be composed of 
recognized experts in the field of hemophilia clinical care and research who are not actively 
recruiting subjects. The DMC can stop a trial if it finds toxicities or if treatment is proven to be 
not beneficial.
Enrollment will be paused pending DMC evaluation if there are ≥3 product-related SAEs, 
including the development of inhibitory antibodies to BAX 930. In addition, the DMC will 
review the enrollment of pediatric subjects in line with Table 5.
The study will be stopped if 2 or more subjects develop confirmed ADAMTS13 inhibitory 
antibodies defined as ≥0.6 BU in the central laboratory on 2 separate assays within a 1-month 
period.
This trial will also include a safety evaluation after first 6 subjects each have at least 3 BAX 930 
SIN infusions (including PK infusions) to evaluate the ADAMTS13 activity.
15.5 Auditing
The sponsor and/or sponsor’s representatives may conduct audits to evaluate study conduct and 
compliance with the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable national and local regulatory 
guidelines/requirements. The investigator will permit auditors to visit the study site, as described 
in the CTA. Auditing processes specific to the study will be described in the audit plan.
15.6 Non-Compliance with the Protocol
The investigator may deviate from the protocol only to eliminate an apparent immediate hazard 
to the subject. In the event(s) of an apparent immediate hazard to the subject, the investigator 
will notify the sponsor immediately by phone and confirm notification to the sponsor in writing 
as soon as possible, but within 1 calendar day after the change is implemented. Takeda will also 
ensure the responsible EC and relevant competent authority is notified of the urgent measures 
taken in such cases according to local regulations.
If monitoring and/or auditing identify serious and/or persistent non-compliance with the 
protocol, the sponsor may terminate the investigator’s participation. The sponsor will notify the 
EC and applicable regulatory authorities of any investigator termination.
15.7 Laboratory and Reader Standardization
Not applicable; a central laboratory/reader will be used for all clinical assessments.
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16. ETHICS
16.1 Subject Privacy
The investigator will comply with applicable subject privacy regulations/guidance as described 
in the CTA.
16.2 Ethics Committee and Regulatory Authorities
Before subjects participate in this study, the protocol, ICF, any promotional 
material/advertisements, and any other written information will be reviewed and approved/given 
favorable opinion by the EC and applicable regulatory authorities. The IB will be provided for 
review. The EC’s composition or a statement that the EC’s composition meets applicable 
regulatory criteria will be documented. The study will commence only upon the sponsor’s receipt 
of approval/favorable opinion from the EC and, if required, upon the sponsor’s notification of 
applicable regulatory authority(s) approval, as described in the CTA. 
If the protocol or any other information given to the subject is amended, the revised documents 
will be reviewed and approved/given favorable opinion by the EC and applicable regulatory 
authorities, where applicable. The protocol amendment will only be implemented upon the 
sponsor’s receipt of approval and, if required, upon the sponsor’s notification of applicable 
regulatory authority(s) approval.
16.3 Informed Consent
Investigators will choose subjects for participation considering the study eligibility criteria. The 
investigator will exercise no selectivity so that no bias is introduced from this source. 
All subjects and/or their legally authorized representative must sign an ICF before entering the 
study according to applicable national and local regulatory requirements and ICH GCP. An 
assent form may be provided and should be signed by the legally authorized representative for 
subjects less than 18 years of age. Before use, the ICF will be reviewed by the sponsor and 
approved by the EC and regulatory authority(s), where applicable, (see Section 16.2). The ICF 
will include a comprehensive explanation of the proposed treatment without any exculpatory 
statements, in accordance with the elements required by ICH GCP and applicable national and 
local regulatory requirements. subjects or their legally authorized representative(s) will be 
allowed sufficient time to consider participation in the study. By signing the ICF, subjects or 
their legally authorized representative(s) agree that they will complete all evaluations required by 
the study, unless they withdraw voluntarily or are terminated from the study for any reason.
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The sponsor will provide to the investigator in written form any new information that 
significantly bears on the subjects’ risks associated with IP exposure. The informed consent will 
be updated, if necessary. This new information and/or revised ICF, approved by the applicable 
EC and regulatory authorities where applicable, will be provided by the investigator to the 
subjects who consented to participate in the study.
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17. DATA HANDLING AND RECORD KEEPING
17.1 Confidentiality Policy
The investigator will comply with the confidentiality policy as described in the CTA. 
17.2 Study Documentation and Case Report Forms
The investigator will maintain complete and accurate paper format study documentation in a 
separate file. Study documentation may include information defined as “source data” (see 
Section 9.8), records detailing the progress of the study for each subject, signed ICFs, 
correspondence with the EC and the study monitor/sponsor, screening information, CRFs, 
Serious Adverse Event Reports, laboratory reports (if applicable), and data clarifications 
requested by the sponsor.
The investigator will comply with the procedures for data recording and reporting. Any 
corrections to paper study documentation must be performed as follows: 1) the first entry will be 
crossed out entirely, remaining legible; and 2) each correction must be dated and initialed by the 
person correcting the entry; the use of correction fluid and erasing are prohibited.
The investigator is responsible for the procurement of data and for the quality of data recorded 
on the CRFs. Case report forms will be provided in electronic form.
If paper format CRFs are provided by the sponsor, all required study data, including corrections, 
will be clearly and accurately recorded by authorized study site personnel on the CRFs. The 
CRFs will remain at the site until they are reviewed by the study monitor or sponsor’s 
representative. All original CRFs will be collected by the study monitor, and an identical copy of 
the complete set of CRFs for each subject will remain in the investigator file at the study site in 
accordance with the document and data retention policy (see Section 17.2).
The handling of data by the sponsor, including data quality assurance, will comply with 
regulatory guidelines ( eg, ICH GCP) and the standard operating procedures of the sponsor. 
Alternative approaches may be used to ensure data quality and integrity as well as maintaining 
subject safety ( eg, remote source data verification (SDV) or telephone contact). See the 
monitoring plan for the detailed approach.
17.3 Document and Data Retention 
The investigator will retain study documentation and data (paper and electronic forms) in 
accordance with applicable regulatory requirements and the document and data retention policy, 
as described in the CTA.
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18. FINANCING AND INSURANCE
The investigator will comply with investigator financing, investigator/sponsor insurance, and 
subject compensation policies, if applicable, as described in the CTA.
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19. PUBLICATION POLICY
The investigator will comply with the publication policy as described in the CTA.
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20. SUPPLEMENTS
20.1 Study Flow Chart
Figure 1. Study Design for Subjects Entering Study with BAX 930 ORT
1.
Acute TTP events in the prophylaxis arm will be treated with the treatment agent the subject is receiving in 
the current period.
2.
Initial prophylactic dose and dosing regimen may be adjusted based on current SoC treatment (i.e., Q1Week) 
for subjects currently receiving FFP or S/D plasma Q1Week.
3.
Interval visits will be every 3 months.
4.
A single dose modification may be mandated based on clinical outcomes.
5.
PK-III will be conducted on a smaller subset of subjects who receive BAX 930 SIN in Period 3 (adults 
≥18 years, N=4, pediatric and adolescent subjects 0-17 years, N=2). It will be required for pediatric subjects 
(<12 years old) and subjects who receive a weekly (Q1Week) dosing regimen.
6.
A total of at least 12 subjects in the prophylactic cohort will be pediatric or adolescent subjects (0-17 years).
7.
A total of at least 3 pediatric or adolescent subjects are to be enrolled in the on-demand cohort. 
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Figure 2. Study Design for Subjects Entering Study with BAX 930 SIN
1.
Acute TTP events in the prophylaxis arm will be treated with the treatment agent the subject is receiving in the 
current period.
2.
Initial prophylactic dose and dosing regimen may be adjusted based on current SoC treatment (i.e., Q1Week) 
for subjects currently receiving FFP or S/D plasma Q1Week.
3.
Interval visits will be every 3 months.
4.
A single dose modification may be mandated based on clinical outcomes.
5.
PK-III will be conducted on all subjects in the prophylactic cohort who initiate the study with BAX 930 SIN.
6.
A total of at least 12 subjects in the prophylactic cohort will be pediatric or adolescent subjects (0-17 years).
7.
A total of at least 3 pediatric subjects are to be enrolled in the on-demand cohort. 
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20.2 Pediatric Subjects
20.2.1 Prophylactic Cohort
This Phase 3 study will include 12 pediatric or adolescent subjects with all age groups in the 
prophylactic cohort which are represented and enrolled in the following distribution:
Table 5. Pediatric Enrollment (Prophylactic Cohort)
Age
Number of Pediatric 
Subjects
Criteria
DMC Review Required
>12-≤17
4
5 adult subjects each have at least 
10 exposures with BAX 930
Yes
>6-<12
4
NA
No
0-<6
4
NA
No
Enrollment for subjects 12-17 years of age started after 5 adult subjects each had at least 
10 exposures of BAX 930 in the prophylaxis cohort, collected data was reviewed by the DMC 
and endorsement was obtained. Pediatric and adolescent subjects age 0-17 who enter the study 
prior to the availability of BAX 930 SIN in Period 1, will initiate treatment with BAX 930 ORT 
during Period 1 or Period 2 and switch to BAX 930 SIN during Period 3. Once BAX 930 SIN is 
available, pediatric subjects will initiate Period 1 or Period 2 with BAX 930 SIN and continue 
treatment with BAX 930 SIN until completion of Period 3. Pediatric subjects, age 0-17 will be 
permitted to receive BAX 930 SIN when 5 adult subjects have had 10 exposures with BAX 930 
SIN. In France, no subjects younger than 18 years of age will be enrolled into the study before 
the first adult subject has been treated with BAX 930 for a minimum of 6 months. 
In line with the Pediatric Information Plan (P/0048/2012), the prophylactic cohort of the study is 
planned to enroll a total of 12 children from birth to less than 18 years of age, at least 6 of whom 
will be less than 12 years old. Pediatric and adolescent subjects will be replaced for drop out if 
they have less than 6 months’ exposure of BAX 930, up to 2 subjects per age cohort unless 
3 pediatric or adolescent subjects have each had 6 months’ exposure of BAX 930 at the time of 
drop out. The replaced subject will be assigned into the same slot (i.e., BAX 930 – SoC or 
SoC - BAX 930) as the discontinued subject. Pediatric subjects who replace dropout subjects 
will receive BAX 930 ORT, per randomization schedule until 01 Oct 2021. 
Each subject in the prophylactic cohort of the study is planned to have a full or limited PK 
evaluation, based on age, which can be used to further guide the initial treatment regimen. 
Based on available registry data, the proposed dosing strategy for the pediatric initial dose at all 
age groups will be the same as the initial adult dose.
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20.2.2 On-demand Cohort
The availability of potential subjects for the on-demand cohort is extremely limited. Although 
symptoms develop soon after birth in approximately 50% of subjects, in others, symptoms do not 
occur until the second or third decade of life. It should also be noted that the occurrence of an 
acute TTP event is potentially life-threatening, and subjects who have previously experienced an 
event will most likely be placed on prophylactic treatment with the current SoC. This Phase 3 
study will include at least 3 pediatric subjects in the on-demand cohort which will be represented 
and enrolled in the following distribution:
Table 6. Pediatric Enrollment (On-demand Cohort)
Age
Number of Pediatric Subjects
>12-≤17
1-3
>6-<12
0-1
0-<6
0-1
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20.3 Schedule of Study Procedures and Assessments
Table 7. Schedule of Study Procedures and Assessments for Subjects on Prophylaxis Cohort
Procedures/
Assessments*
Screening
Visit
Day -28
to 0
PK-I
Period 1
Prophylaxis 
(6 months)a
Period 2
Prophylaxis 
(6-months)a
PK-II
Period 3
Prophylaxis 
(6 months)a
PK-IIIo,r
Period 
1, 2, or 
3 Acute 
TTP 
Event
Study
Completion/
Termination
Visite
28 ±3 days 
after the last
IP infusion
PK 1 
Infusion
PK 1 
blood 
drawsc,i
PK 2 
Infusionb
±2 days
PK 2 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 3 
Infusionb
±2 days
PK 3 
blood 
drawsc,i
PK 4 
Infusionb
±2 days
PK 4 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 5 
Infusionb
±2 days
PK 5 
blood 
drawsc,i
As 
Needed
Informed 
Consentf
X
Eligibility 
Criteria
X
Randomizationn
Xn
X
Medical History
X
ECG
X
X
Physical Exam
X
X
Concomitant 
Medications and 
non-Drug 
Therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP Infusiong (see
Section 9.2.1)
X
Xh
X
X
X
Xh
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratoriesi
X
Xj
Xj
Xj
Xj
X
X
Xj
Xj
Xj
Xj
X
X
X
X
X
Vital Signs
X
Xj
Xj
Xj
Xj
Xm
Xm
Xj
Xj
Xj
Xj
Xm
X
X
X
X
Height/ Weightk
X
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
X
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Table 7. Schedule of Study Procedures and Assessments for Subjects on Prophylaxis Cohort
Procedures/
Assessments*
Screening
Visit
Day -28
to 0
PK-I
Period 1
Prophylaxis 
(6 months)a
Period 2
Prophylaxis 
(6-months)a
PK-II
Period 3
Prophylaxis 
(6 months)a
PK-IIIo,r
Period 
1, 2, or 
3 Acute 
TTP 
Event
Study
Completion/
Termination
Visite
28 ±3 days 
after the last
IP infusion
PK 1 
Infusion
PK 1 
blood 
drawsc,i
PK 2 
Infusionb
±2 days
PK 2 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 3 
Infusionb
±2 days
PK 3 
blood 
drawsc,i
PK 4 
Infusionb
±2 days
PK 4 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 5 
Infusionb
±2 days
PK 5 
blood 
drawsc,i
As 
Needed
Pediatric 
Development 
Markersq
X
X
X
X
X
HRQoLl
Xp
X
p
X
p
Xp
Xp
Schedule Next 
Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ALT=alanine aminotransferase; AST=aspartate aminotransferase; C=Testing at central laboratory; CBC=complete blood count; CD4=cluster of differentiation 4; CHO=Chinese
hamster ovary; ECG=electrocardiogram; EQ-5D-3L=EuroQol 5 Dimensions Questionnaire 3-Level; EQ-5D-Y=EQ-5D-youth; HAV=hepatitis A virus; HBc=hepatitis B core 
antigen; HBs=hepatitis B surface antibody; HBsAg=hepatitis B surface antigen; HCV=hepatitis C virus; HIV=human immunodeficiency virus; HRQoL=health related quality of 
life; cTTP=congenital thrombotic thrombocytopenic purpura; IP=investigational product; L=Testing at local laboratory; LDH=lactate dehydrogenase; MCH=mean corpuscular 
hemoglobin; MCHC=mean corpuscular hemoglobin concentration; MCV=mean corpuscular volume; Ped QL=Pediatric Quality of Life Inventory; PK=pharmacokinetic; 
PRO=patient reported outcome; RBC=red blood cell; SF-36=36-Item Short Form Health Survey; SoC=Standard of Care; TSQM-9=Treatment Satisfaction Questionnaire for 
Medication; TTP=thrombotic thrombocytopenic purpura; VWF=von Willebrand factor; VWF:Ag=von Willebrand factor: antigen; VWF:RCo=von Willebrand factor: ristocetin
cofactor activity
Note: Subjects of less than 18 years of age will be enrolled according to the criteria defined in Table 5.
* Sites in Germany should refer to Table A1 for assessments.
a.
The length of Period 1 and Period 2 is 6 months each. If a subject cannot switch to the next period at the end of month 6, due to either logistic or medical reasons, the length of 
Period 1 and Period 2 can be extended to up to 7 months. For subjects enrolled before November 2017, Period 1 can be extended to up to 24 months. The length of Period 3 is 
6 months or until the continuation study is open at the subject’s study site.
b.
If the subject received SoC agent to treat an acute episode of TTP, at least 15 days (360 hr) must have elapsed and the subject must not show any TTP-related symptoms.
c.
See Table 11 for adult visit schedule. See Table 12 for pediatric visit schedule. See Table 13 for PK-III adult and pediatric visit schedule. 
d.
Assumes Q2W dosing. Visit schedule and accompanying tests should be modified based on dosing frequency (see Section 9.2.1.3 for SoC dosing and Section 9.2.1.4 for 
BAX 930 dosing). For subjects on Q1W treatment, labs will be drawn on Q2W schedule. Subjects on Q3W SoC treatment should have labs, vital signs and all assessment at 
the time of their visits according to the Q3W schedule.
e.
Also applies to subjects who prematurely withdraw from the study.
f.
Occurs at enrollment (prior to any study-specific procedure).
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Table 7. Schedule of Study Procedures and Assessments for Subjects on Prophylaxis Cohort
Procedures/
Assessments*
Screening
Visit
Day -28
to 0
PK-I
Period 1
Prophylaxis 
(6 months)a
Period 2
Prophylaxis 
(6-months)a
PK-II
Period 3
Prophylaxis 
(6 months)a
PK-IIIo,r
Period 
1, 2, or 
3 Acute 
TTP 
Event
Study
Completion/
Termination
Visite
28 ±3 days 
after the last
IP infusion
PK 1 
Infusion
PK 1 
blood 
drawsc,i
PK 2 
Infusionb
±2 days
PK 2 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 3 
Infusionb
±2 days
PK 3 
blood 
drawsc,i
PK 4 
Infusionb
±2 days
PK 4 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 5 
Infusionb
±2 days
PK 5 
blood 
drawsc,i
As 
Needed
g.
Subjects requiring a vaccination during the course of treatment should schedule the vaccination administration within 72 hours after a prophylactic treatment dose. Subjects 
receiving a COVID-19 vaccination during the study period should be monitored frequently by telephonic health checks and for thrombocytopenia for 14 consecutive days 
following vaccination, as deemed appropriate by the investigator. Elective surgeries should be scheduled 24 hours after the last prophylactic dose and ADAMTS13 levels 
should be monitored after surgery.
h.
The infusion (SoC, BAX 930 ORT, or BAX 930 SIN depending on randomization) on Day 13 is to be administered after the 288-hr PK sample has been collected.
i.
For laboratory assessments, see Table 9.
j.
PK assessments will be done at the following timepoints post-PK infusion for subjects undergoing Q2W and Q3W: 15 ±5 min, 60±5 min, 3±0.5 hr, 9±2 hr, 24±2 hr, 72±4 hr, 
120±12 hr, 168±12 hr, 216±24 hr, and 288±24 hr. Vital signs for adult and adolescent subjects (≥12 years of age), should be recorded within 1 hr before PK infusion and at the 
following timepoints post infusion: 15±5 min, 60±5 min, 3±0.5 hr, 9±2 hr, 24±2 hr, 72±4 hr, 120±12 hr, 168±12 hr, 216±24 hr, and 288±24 hr. For pediatric subjects 
(<12 years of age), vital signs should be recorded within 1 hr before PK infusion and at the following timepoints post infusion: 30±5 min, 12±2 hr, 24±2 hr, 48±2 hr, 96±2 hr 
and 168±4 hr. Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for pediatric subjects <6 years of age may be adjusted and/or 
omitted and the timing of assessments associated with blood collections will be adjusted accordingly; refer also to Section 11.3.1 and Section 12.2.1. PK Post-Infusion 
Laboratory Assessments for subjects undergoing Q1W dosing should not be performed at 168±12 hrs, 216±12 hrs and 288±12 hrs timepoints, after PK Infusion #1. However, 
PK assessments up to 168±12 hrs timepoint should be performed after PK Infusion #2, and PK #3. Please refer to the tables below to see the assessment schedule for subjects 
undergoing Q1W dosing. PK timepoints for subjects in Q3W dosing will be the same as subjects on Q2W dosing.
k.
Height will be measured at screening only for subjects >=12 years of age. Height will be measured at screening, Visit1/Day 1, dosing visits and at study 
completion/termination for subjects <12 years of age. Weight will be measured for all subjects at screening, Day 1, PK 2 infusion (if BAX 930 is being administered for this 
infusion), PK 3 infusion, PK 4 infusion, PK 5 infusion, prophy dosing visits and at study completion/termination.
l.
SF-36v2, TSQM-9, EQ-5D-3L or EQ-5D-Y, PedsQL, and a cTTP-specific PRO and health-resource use items. 
m. Vital signs will be collected at each dosing visit within 1 hour before and after PI infusion.
n.
Randomization can be done on day 1 or the day before day 1. IP dispensation will be allowed on the day before the visit.
o.
PK-III assessments may be conducted in a minimum of 4 adult (≥18 years), and 2 pediatric (0-17 years) subjects who receive BAX 930 SIN in Period 3 on a voluntary basis. It 
will be required for pediatric subjects (<12 years old), subjects who receive a weekly (Q1Week) dosing regimen, and all subjects who receive BAX 930 SIN in PK-I, Period 1, 
or Period 2.
p.
HRQoL assessments will be conducted only at the screening visits and at the end of the period (i.e., the last visit in the period, or at the early termination visit, if applicable).
q.
For subjects 0-<6 years old, pediatric growth, development, and cognitive performance will be assessed if/when applicable, per the Investigator’s discretion.
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Table 7. Schedule of Study Procedures and Assessments for Subjects on Prophylaxis Cohort
Procedures/
Assessments*
Screening
Visit
Day -28
to 0
PK-I
Period 1
Prophylaxis 
(6 months)a
Period 2
Prophylaxis 
(6-months)a
PK-II
Period 3
Prophylaxis 
(6 months)a
PK-IIIo,r
Period 
1, 2, or 
3 Acute 
TTP 
Event
Study
Completion/
Termination
Visite
28 ±3 days 
after the last
IP infusion
PK 1 
Infusion
PK 1 
blood 
drawsc,i
PK 2 
Infusionb
±2 days
PK 2 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 3 
Infusionb
±2 days
PK 3 
blood 
drawsc,i
PK 4 
Infusionb
±2 days
PK 4 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 5 
Infusionb
±2 days
PK 5 
blood 
drawsc,i
As 
Needed
r.
Subjects enrolling into the continuation study will be allowed to remain in the 281102 study until the continuation study is open for enrolment. After the last IP Infusion, 
subjects will be enrolled and followed in the continuation study. Subjects who experience an acute TTP event will be treated with the assigned treatment at the time of said 
acute TTP event, before rolling over into the continuation study.
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Table 8. Schedule of Study Procedures and Assessments for Subjects on On-Demand Cohort
Procedures/
Assessments
Screening Visit 
and 
Dosing Visit 1
Day 1
Period 1
Study Completion/
Termination Visita
28 ±3 days after the last IP 
infusion or termination of 
treatment phase
On-Demand
(SoC or BAX 930)
V 2 Stabilizationb
Day 2, 3, 4, 5, 6, 7c
Informed Consentd
X
Eligibility Criteria
X
Medical History
X
X
ECG
X
X
Physical Exam
X
X
Concomitant Medications and non-Drug 
Therapy
X
X
X
IP Infusion (see Section 9.2.2)
X
Current dosing as required
Adverse Events
X
X
X
Laboratoriese
X
X
X
Vital Signs
X
X
X
Height/Weightf
X
X
HRQoLg
Xi
Xh
Xj
Schedule Next Visit
X
X
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Table 8. Schedule of Study Procedures and Assessments for Subjects on On-Demand Cohort
Procedures/
Assessments
Screening Visit 
and 
Dosing Visit 1
Day 1
Period 1
Study Completion/
Termination Visita
28 ±3 days after the last IP 
infusion or termination of 
treatment phase
On-Demand
(SoC or BAX 930)
V 2 Stabilizationb
Day 2, 3, 4, 5, 6, 7c
ECG=electrocardiogram; EQ-5D-3L=EuroQol 5 Dimensions Questionnaire 3-Level; EQ-5D-Y=EQ-5D-youth; HRQoL=health related quality of life; cTTP=congenital 
thrombotic thrombocytopenic purpura; IP=investigational product; LDH=lactate dehydrogenase; Ped QL=Pediatric Quality of Life Inventory; PK=pharmacokinetic; 
PRO=patient reported outcome; SF-36=36-Item Short Form Health Survey; TSQM-9=Treatment Satisfaction Questionnaire for Medication
Note: Subjects of less than 18 years of age will be enrolled according to the criteria defined in Table 5.
a.
Also applies to subjects who prematurely withdraw from the study. Subjects who are unable to move into prophylactic cohort due to data lock timelines may rollover 
directly into the continuation study. 
b.
Actual number of visits will vary. Subjects will receive treatment until 2 days after the acute TTP event is resolved. 
c.
Based on number of visits.
d.
Occurs at enrollment (prior to any study-specific procedure). 
e.
For laboratory assessments, see Table 10.
f.
Height will be measured at screening only. Weight will be measured at Screening/Visit1/Day 1, and at study completion/termination.
g.
SF-36v2, TSQM-9, EQ-5D-3L or EQ-5D-Y, Ped QL, health-resource use items and a cTTP-specific PRO.
h.
This assessment will be done only at the end of Period 1 (i.e., the last visit in the period). 
i.
Only at screening.
j.
Only required if a subject terminates the study early.
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20.4 Clinical Laboratory Assessments
Table 9. Clinical Laboratory Assessments: Prophylaxis Treatment (Prophylaxis Cohort)*
Assessments
Screening 
Visit
SoC PK Infusion 
and BAX 930 
PK Infusion 
#1, 2, 3, 4& 5a,b
Prophy Dosing 
Visits 
(Every 2 
weeks ±2 dayc)
Interval Study Visits
(Every 3 months ±2 weeks 
during SoC and BAX 930 
treatment phases of Periods 1, 
2, & 3 to align with dosing 
visits)s
Acute TTP event 
Dosing Visits
(Daily until 2 days 
following the 
resolution of the 
acute TTP event)
Study Completion/
Termination Visitd
28 ±3 days after 
the last IP infusion
Complete Blood Counte
C
C, Lf, p
C, Lp
C, Lp
C, Lp
C
Clinical Chemistryg
C
C, Lf, q
C, Lq
C, Lq
C, Lq
C
Urinalysish
C
C
PK Testsi
C
Ci
Pre-Infusion ADAMTS13
Cf
Cf
Post-Infusion 
ADAMTS13
Cn
Cn
Immunogenicityj
C
Cf
Cr
Cf
C
cTnT, cTnI, CK-MBu
Cf
Lt,v
Lv
S100B, NSEu
Cf
Cf
C
C
Viral Serologyk
Ck
Ck
Genetic Testingl
C
Blood Groupm
L
Pregnancy Test
L°/C
L°/C
C
C
Coombs test
Lf
Evaluation of Schistocytes
Lf
ALT=alanine aminotransferase; AST=aspartate aminotransferase; C=Testing at central laboratory; CBC=complete blood count; CD4=cluster of differentiation 4; 
CHO=Chinese hamster ovary; CK-MB=creatine kinase myocardial band; cTnI=cardiac troponin I, cTnT=cardiac troponin T; HAV=hepatitis A virus; HBc=hepatitis B core 
antigen; HBs=hepatitis B surface antibody; HBsAg=hepatitis B surface antigen; HCV=hepatitis C virus; HEV=hepatitis E virus; HIV=human immunodeficiency virus; 
L=Testing at local laboratory; LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin concentration; 
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Table 9. Clinical Laboratory Assessments: Prophylaxis Treatment (Prophylaxis Cohort)*
Assessments
Screening 
Visit
SoC PK Infusion 
and BAX 930 
PK Infusion 
#1, 2, 3, 4& 5a,b
Prophy Dosing 
Visits 
(Every 2 
weeks ±2 dayc)
Interval Study Visits
(Every 3 months ±2 weeks 
during SoC and BAX 930 
treatment phases of Periods 1, 
2, & 3 to align with dosing 
visits)s
Acute TTP event 
Dosing Visits
(Daily until 2 days 
following the 
resolution of the 
acute TTP event)
Study Completion/
Termination Visitd
28 ±3 days after 
the last IP infusion
MCV=mean corpuscular volume; NSE=neuron-specific enolase; PK=pharmacokinetic; RBC=red blood cell; S100B=calcium binding protein B; SoC=Standard of Care; 
TTP=thrombotic thrombocytopenic purpura; VWF=von Willebrand factor; VWF:Ag=von Willebrand factor: antigen; VWF:RCo=von Willebrand factor: ristocetin cofactor 
activity
a.
If the subject received SoC agent to treat an acute episode of TTP at least 15 days (360 hr) must have elapsed and the subject must not show any TTP-related symptoms.
b.
PK Infusions to occur 14 days ±2 days.
c.
Assumes Q2W dosing. Visit schedule and accompanying tests should be modified based on dosing frequency (see Section 9.2.1.3 for SoC dosing and Section 9.2.1.4 for 
BAX 930 dosing). For subjects on Q1W treatment, labs will be drawn on Q2W schedule. Subjects on Q3W SoC treatment should have labs, vital signs and all 
assessments at the time of their visits according to the Q3W schedule.
d.
Also applies to subjects who prematurely withdraw from the study.
e.
CBC: RBC count, hemoglobin, hematocrit, haptoglobin, reticulocyte count, MCV, MCH, MCHC, leukocytes (i.e., white blood cell count) with differential (i.e., 
basophils, eosinophils, lymphocytes, monocytes, and neutrophils) and platelet counts.
f.
Sampling within 60 min prior to start of infusion
g.
Clinical chemistry assessments: sodium, potassium, chloride, ALT, AST, LDH, bilirubin, albumin (screening only), alkaline phosphatase, blood urea nitrogen, creatinine, 
and glucose.
h.
Urinalysis dipstick assessments: erythrocytes, specific gravity, urobilinogen, ketones, glucose, protein, bilirubin, nitrite, and pH.
i.
Samples for ADAMTS13 activity, ADAMTS13 antigen, VWF:RCo, VWF:Ag, VWF multimer analysis in adult and adolescent subjects (≥12 years of age) will done 
according to Table 11. Sampling for pediatric subjects (<12 years of age) will be done according to Table 12. Samples specific to PK-III are found in Table 13
j.
Immunogenicity assessments and antibodies to other proteins: BAX 930 binding antibody, plasma-derived ADAMTS13 and BAX 930 neutralizing antibody and 
anti-CHO protein antibodies. ADAMTS13 specific IgE antibodies will be assessed in case of allergic reactions as an additional safety measure.
k.
Viral serology: anti-HIV 1, HIV 2, anti-HAV, HBsAg, anti-HBc, anti-HBs, anti-HCV, anti-HEV, and anti-parvovirus B19 will be tested at screening and at completion 
of standard of care treatment. CD4 levels will be determined at screening in HIV-positive subjects. 
l.
Genetic testing: cell pellet (buffy coat and erythrocytes) will be retained for ADAMTS13 gene mutational analysis unless the information is already available.
m.
Only if not available in subject’s medical history.
n.
Sampling within 60 ±5 min following infusion
o.
Serum or urine pregnancy test should be done locally; if not available, serum pregnancy test will be done centrally. Negative pregnancy test is required no more than 
7 days before first dosing for subjects receiving first administration of BAX 930 at PK infusion #1, or receiving first administration of BAX 930 at PK infusion #2.
p.
Only platelet count is required to be run locally; local lab results should be entered in CRF 
q.
Only LDH is required to be run locally; local lab results should be entered in CRF.
r.
Immunogenicity assessments should be run every 4 weeks and at the last IP infusion visit of in Period 3. All antibody samples should be collected prior dosing.
s.
If an Interval Study Visit and Prophy Dosing Visit are combined, all laboratory samples applicable to both visits will be collected but CBC and Clinical Chemistry 
assessments will not be performed twice.
t.
If subject is symptomatic and cardiac markers are abnormal, testing will be repeated at dosing until it becomes normal. If cardiac markers are normal, it will not be re-
tested.
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Table 9. Clinical Laboratory Assessments: Prophylaxis Treatment (Prophylaxis Cohort)*
Assessments
Screening 
Visit
SoC PK Infusion 
and BAX 930 
PK Infusion 
#1, 2, 3, 4& 5a,b
Prophy Dosing 
Visits 
(Every 2 
weeks ±2 dayc)
Interval Study Visits
(Every 3 months ±2 weeks 
during SoC and BAX 930 
treatment phases of Periods 1, 
2, & 3 to align with dosing 
visits)s
Acute TTP event 
Dosing Visits
(Daily until 2 days 
following the 
resolution of the 
acute TTP event)
Study Completion/
Termination Visitd
28 ±3 days after 
the last IP infusion
u.
Blood samples collected from subjects <18 years of age, for exploratory outcome measures, can be collected at the discretion of the investigator and are not to exceed the 
local EC and applicable regulatory guidelines for daily and monthly maximum blood volume limits.
v.
Testing is only applicable if available at local laboratory.
* Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for pediatric subjects <6 years of age may be adjusted and/or omitted and the 
timing of assessments associated with blood collections will be adjusted accordingly; refer also to Section 11.3.1 and Section 12.2.1.
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Table 10. Clinical Laboratory Assessments: Acute Treatment (On-Demand Cohort)*
Assessments
Screening
Visita
Dosing Visits
(Daily until 2 days following the 
resolution of the acute TTP 
event)
Study Completion/
Termination Visitb
28 ±3 days after the last IP 
infusion
Complete Blood Countc
C
C, Ll
C
Clinical Chemistryd
C
C, Lm
C
Urinalysise
C
C
Pre-Infusion ADAMTS13
Cf
Post-Infusion ADAMTS13
Cg
Immunogenicityh
C
C
cTnT, cTnI, CK-MBp
Lq
Lo,q
Lq
S100B, NSEp
C
C
C
Viral Serologyi
Ci
Ci
Genetic Testingj
C
Blood Groupk
L
Pregnancy Test
Ln/C
C
Coombs test
Lf
Evaluation of Schistocytes
Lf
ALT=alanine aminotransferase; AST=aspartate aminotransferase; C=Testing at central laboratory; CBC=complete blood 
count; CD4=cluster of differentiation 4; CHO=Chinese hamster ovary; CK-MB=creatine kinase myocardial band; 
cTnI=cardiac troponin I; cTnT=cardiac troponin T; HAV=hepatitis A virus; HBc=hepatitis B core antigen; HBs=hepatitis B 
surface antibody; HBsAg=hepatitis B surface antigen; HCV=hepatitis C virus; HEV=hepatitis E virus; HIV=human 
immunodeficiency virus; L=Testing at local laboratory; LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; 
MCHC=mean corpuscular hemoglobin concentration; MCV=mean corpuscular volume; NSE=neuron-specific enolase; 
PK=pharmacokinetic; RBC=red blood cell; SoC=Standard of Care; S100B= calcium binding protein B; TTP=thrombotic 
thrombocytopenic purpura; VWF=von Willebrand factor; VWF:Ag=von Willebrand factor: antigen; VWF:RCo=von 
Willebrand factor: ristocetin cofactor activity
a.
Subjects in the on-demand cohort will have their screening and first dosing visit on Day 1
b.
Also applies to subjects who prematurely withdraw from the study.
c.
CBC: RBC count, hemoglobin, hematocrit, haptoglobin, reticulocyte count, MCV, MCH, MCHC, leukocytes (i.e., 
white blood cell count) with differential (i.e., basophils, eosinophils, lymphocytes, monocytes, and neutrophils) and 
platelet counts.
d.
Clinical chemistry assessments: sodium, potassium, chloride, ALT, AST, LDH, bilirubin, albumin (screening only), 
alkaline phosphatase, blood urea nitrogen, creatinine, and glucose.
e.
Urinalysis dipstick assessments: erythrocytes, specific gravity, urobilinogen, ketones, glucose, protein, bilirubin, 
nitrite, and pH.
f.
Sampling within 60 min prior to start of infusion
g.
Sampling within 60 ±5 min following infusion
h.
Immunogenicity assessments and antibodies to other proteins: anti-ADAMTS13 antibody (binding and neutralizing) 
and anti-CHO protein antibodies. Anti-ADAMTS13 Ab and anti-CHO Ab samples should be collected prior dosing. 
ADAMTS13 specific IgE antibodies will be assessed in case of allergic reactions as an additional safety measure. 
i.
Viral serology: anti-HIV 1, HIV 2, anti-HAV, HBsAg, anti-HBc, anti-HBs, anti-HCV, anti-HEV, and anti-parvovirus 
B19 will be tested at screening and at completion of standard of care treatment. CD4 levels will be determined at 
screening in HIV-positive subjects.
j.
Genetic testing: cell pellet (buffy coat and erythrocytes) will be retained for ADAMTS13 gene mutational analysis 
unless the information is already available.
k.
Only if not available in subject’s medical history.
l.
Only platelet count is required to be run locally; local lab results should be entered in eCRF
m.
Only LDH is required to be run locally; local lab results should be entered in eCRF
n.
Serum or urine pregnancy test should be done locally; if not available, serum pregnancy test will be done centrally. 
Negative pregnancy test required no more than 7 days before first dosing
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Table 10. Clinical Laboratory Assessments: Acute Treatment (On-Demand Cohort)*
Assessments
Screening
Visita
Dosing Visits
(Daily until 2 days following the 
resolution of the acute TTP 
event)
Study Completion/
Termination Visitb
28 ±3 days after the last IP 
infusion
o.
If subject is symptomatic and cardiac markers are abnormal, testing will be repeated at dosing until it becomes normal. 
If cardiac markers are normal, it will not be re-tested.
p.
Blood samples collected from subjects <18 years of age, for exploratory outcome measures, can be collected at the 
discretion of the investigator and are not to exceed the local EC and applicable regulatory guidelines for daily and 
monthly maximum blood volume limits.
q.
Testing is only applicable if available at local laboratory.
* Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for 
pediatric subjects <6 years of age may be adjusted and/or omitted and the timing of assessments associated 
with blood collections will be adjusted accordingly; refer also to Section 11.3.1 and Section 12.2.1.
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Table 11. Adult and Adolescent Subjects (≥12 Years of Age) PK Laboratory Assessments
Procedure/ Assessment
Within 
1 hr 
pre-infe
15 
±5 min
60
±5 min
3
±0.5 hr
9 
±2 hr
24 
±2 hr
72 
±4 hr
120 
±12 hr
168 
±12 hr
216 
±24 hr
288 
±24 hr
CBC with differentiala
X
X
X
X
X
X
X
Serum chemistry panelb
X
X
X
X
X
X
cTnT, cTnI, CK-MB, 
NSE, S100Bc
X
X
X
X
X
X
X
PKd/f 
X
X
X
X
X
X
X
X
X
X
X
Immunogenicityg
X
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CBC=complete blood count; CK-MB=creatine kinase 
myocardial band; LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; NSE=neuron-specific enolase; PK=pharmacokinetic; RBC=red blood cell; 
cTnT=cardiac troponin T; cTnI=cardiac troponin I; WF=von Willebrand factor; VWF:Ag=von Willebrand factor: antigen; 
VWF:RCo=von Willebrand factor: ristocetin cofactor activity
a. CBC: RBC count, hemoglobin, hematocrit, haptoglobin, reticulocyte count, MCV, MCH, MCHC, leukocytes (i.e., white 
blood cell count) with differential (i.e., basophils, eosinophils, lymphocytes, monocytes, neutrophils) and platelet counts
b. Clinical chemistry assessments: sodium, potassium, chloride, ALT, AST, LDH, bilirubin, albumin (screening only), 
alkaline phosphatase, blood urea nitrogen, creatinine, and glucose
c. Blood samples collected from subjects <18 years of age, for exploratory outcome measures, can be collected at the 
discretion of the investigator and are not to exceed the local EC and applicable regulatory guidelines for daily and monthly 
maximum blood volume limits.xxi
d. ADAMTS13 activity, ADAMTS13 antigen, VWF:RCo, VWF:Ag, and VWF multimer pattern.
e. 1mL of fresh frozen plasma from each bag infused will be drawn and analyzed for ADAMTS13:Ag and ADAMTS13 
activity.
f. PK sampling for subjects undergoing Q1W should not be performed at 168±12hrs, 216±12hrs and 288±12hrs timepoints, 
after PK Infusion #1, PK assessments up to 168±12hrs timepoint should be performed after PK Infusion #2
g. Sampling will be conducted within 60 min prior to start of infusion. Immunogenicity assessments and antibodies to other 
proteins: BAX 930 binding antibody, plasma-derived ADAMTS13 and BAX 930 neutralizing antibody and anti-CHO 
protein antibodies. ADAMTS13 specific IgE antibodies will be assessed in case of allergic reactions as an additional safety 
measure
                                                
xxi
Maximum allowable blood draw volumes. Seattle Children’s Hospital website. 
www.seattlechildrens.org/pdf/blood-volume-chart.pdf. 
Updated August 21, 2001. Accessed January 27, 2017.
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Table 12. Pediatric (<12 Years of Age) PK Laboratory Assessment Adolescent Subjects*
Procedure/Assessment
Within 
1 hr 
pre-infe
30 ±5 min
12 ±2 hr
24 ±2hr
48 ±2 hr
96 ±2 hr
168 ±4 hr
CBC with differentiala
X
X
Serum chemistry panelb
X
X
TnT, TNI, CK-MB, NSE, 
S100Bc
X
X
X
PKd
X
X
X
X
X
X
X
Immunogenicityf
X
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CBC=complete blood count; CK-MB=creatine kinase 
myocardial band; LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin 
concentration; MCV=mean corpuscular volume; NSE=neuron-specific enolase; PK=pharmacokinetic; RBC=red blood cell; 
cTnT=cardiac troponin T; cTnI=cardiac troponin I; WF=von Willebrand factor; VWF:Ag=von Willebrand factor: antigen; 
VWF:RCo=von Willebrand factor: ristocetin cofactor activity
a.
CBC: RBC count, hemoglobin, hematocrit, haptoglobin, reticulocyte count, MCV, MCH, MCHC, leukocytes (i.e., white 
blood cell count) with differential (i.e., basophils, eosinophils, lymphocytes, monocytes, neutrophils) and platelet counts
b.
Clinical chemistry assessments: sodium, potassium, chloride, ALT, AST, LDH, albumin (screening only),bilirubin, 
alkaline phosphatase, blood urea nitrogen, creatinine, and glucose
c.
Blood samples collected from subjects <18 years of age, for exploratory outcome measures, can be collected at the 
discretion of the investigator and are not to exceed the local EC and applicable regulatory guidelines for daily and monthly 
maximum blood volume limits
d.
ADAMTS13 activity, ADAMTS13 antigen, VWF:RCo, VWF:Ag, VWF multimer pattern. Timepoints may be adjusted to 
optimize the sampling scheme as pediatric data become available.
e.
1 mL of fresh frozen plasma from each bag infused will be drawn and analyzed for ADAMTS13:Ag and ADAMTS13 
activity.
f.
Sampling will be conducted within 60 min prior to start of infusion. Immunogenicity assessments and antibodies to other 
proteins: BAX 930 binding antibody, plasma-derived ADAMTS13 and BAX 930 neutralizing antibody and anti-CHO 
protein antibodies. ADAMTS13 specific IgE antibodies will be assessed in case of allergic reactions as an additional 
safety measure
* Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for pediatric subjects 
<6 years of age may be adjusted and/or omitted and the timing of assessments associated with blood collections will be 
adjusted accordingly; refer also to Section 11.3.1 and Section 12.2.1.
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Table 13. End of Study, PK-III Assessment, PK Laboratory Assessments by Age 
Within 
1 hr 
pre-inf
15 ±5 
min
30 ±5
min
60 ±5 
min
9±2hr
72 ±8 hr
168 ±12 hr
288±24 hrb
Adult and adolescent 
subject ≥12 yearsa,c
X
X
X
X
X
X
Pediatric subjects 
<12 yearsa,c,d
X
X
X
X
X
X
a.
ADAMTS13 activity, ADAMTS13 antigen. Timepoints may be adjusted to optimize the sampling scheme as pediatric 
data become available.
b. PK sampling for subjects on Q1W treatment should not be performed at 288±24 hours.
c.
Vital signs should be collected at the same time points that blood samples are collected.
d. Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for pediatric subjects <6 
years of age may be adjusted and/or omitted and the timing of assessments associated with blood collections will be 
adjusted accordingly; refer also to Section 11.3.1 and Section 12.2.1.
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20.5 Contraceptive Methods for Female Subjects of Childbearing Potential
In this study, subjects who are women of childbearing potential must agree to utilize a highly 
effective contraceptive measure throughout the course of the study and for 30 days after the last 
administration of investigational product. In accordance with the Clinical Trial Facilitation 
Group (CTFG) recommendations related to contraception and pregnancy testing in clinical trials 
(version 2014-09-15)xxii, birth control methods which may be considered as highly effective 
include the following:

Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation:
Oral
Intravaginal
Transdermal

Progestogen-only hormonal contraception associated with inhibition of ovulation:
Oral
Injectable
Implantablexxiii

Intrauterine device (IUD)xxiii

Intrauterine hormone-releasing system (IUS)xxiii

Bilateral tubal occlusionxxiii

Vasectomised partner(s)xxiii

Sexual abstinence during the entire study period
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not 
acceptable methods of contraception. Female condom and male condom should not be used 
together.
                                                
xxii Clinical Trial Facilitation Group (CTFG) recommendations related to contraception and pregnancy testing in 
clinical trials: cTTP://www.hma.eu/fileadmin/dateien/
Human_Medicines/01About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf
xxiii Contraception methods that are considered to have low user dependency.
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20.6 Contraceptive Method for Male Subjects
In this study, sexually active males with women of childbearing potential must use an 
acceptable and effective method of contraception (such as condom with spermicide) during the 
treatment and until a minimum of 16 days after the last dose of IP administered.
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21. REFERENCES
Allford, S. L., Harrison, P., Lawrie, A. S., Liesner, R., Mackie, I. J. & Machin, S. J. 2000. Von 
Willebrand factor--cleaving protease activity in congenital thrombotic thrombocytopenic 
purpura. Br. J. Haematol, 111, 1215-1222.
Allford, S. L., Hunt, B. J., Rose, P. & Machin, S. J. 2003. Guidelines on the diagnosis and 
management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol,
120, 556-573.
Barbot, J., Costa, E., Guerra, M., Barreirinho, M. S., Isvarial, P., Robles, R., Gerritsen, H. E., 
Lämmle, B. & Furlan, M. 2001. Ten years of prophylactic treatment with fresh-frozen 
plasma in a child with chronic relapsing thrombotic thrombocytopenic purpura as a result 
of a congenital deficiency of von Willebrand factor-cleaving protease. Br J Haematol,
113, 649-657.
Bharmal, M., Payne, K., Atkinson, M. J., Desrosiers, M. P., Morisky, D. E. & Gemmen, E. 2009. 
Validation of an abbreviated treatment satisfaction questionnaire for medication (TSQM-
9) among patients on antihypertensive medications. Health Qual. Life Outcomes, 7, 36.
Fujimura, Y., Kokame, K., Yagi, H., Isonishi, A., Matsumoto, M. & Miyata, T. 2015. Hereditary 
Deficiency of ADAMTS13 Activity: Upshaw-Schulman Syndrome. In: George M. 
Rodgers (ed.) ADAMTS13 Biology and Disease. Springer.
Furlan, M. & Lämmle, B. 2001. Aetiology and pathogenesis of thrombotic thrombocytopenic 
purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving 
protease. Best Pract Res Clin Haematol, 14, 437-454.
Furlan, M., Robles, R., Morselli, B., Sandoz, P. & Lämmle, B. 1999. Recovery and half-life of 
von Willebrand factor-cleaving protease after plasma therapy in patients with thrombotic 
thrombocytopenic purpura. Thromb Haemost, 81, 8-13.
George, J. N. 2006. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med,
354, 1927-1935.
George, J. N. 2007. Evaluation and management of patients with thrombotic thrombocytopenic 
purpura. J. Intensive Care Med, 22, 82-91.
Heger, A., Kannicht, C., Romisch, J. & Svae, T. E. 2007. Normal levels of ADAMTS13 and 
factor H are present in the pharmaceutically licensed plasma for transfusion (Octaplas®) 
and in the universally applicable plasma (Uniplas) in development. Vox Sang, 92, 206-
212.
Heim, M. U., Meyer, B. & Hellstern, P. 2009. Recommendations for the use of therapeutic 
plasma. Curr Vasc Pharmacol, 7, 110-119.
Hellstern, P., Muntean, W., Schramm, W., Seifried, E. & Solheim, B. G. 2002. Practical 
guidelines for the clinical use of plasma. Thromb Res, 107 Suppl 1, S53-S57.
Howard, M. A., Williams, L. A., Terrell, D. R., Duvall, D., Vesely, S. K. & George, J. N. 2006. 
Complications of plasma exchange in patients treated for clinically suspected thrombotic 
thrombocytopenic purpura-hemolytic uremic syndrome. An additional study of 57 
consecutive patients, 2002-2005. Transfusion, 46, 154-156.
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18 Nov 2021
Huisman, E. L., de Silva, S. U. & de Peuter, M. A. 2014. Economic evaluation of pooled 
solvent/detergent treated plasma versus single donor fresh-frozen plasma in patients 
receiving plasma transfusions in the United States. Transfus. Apher. Sci, 51, 17-24.
Kentouche, K., Budde, U., Furlan, M., Scharfe, V., Schneppenheim, R. & Zintl, F. 2002. 
Remission of thrombotic thrombocytopenic purpura in a patient with compound 
heterozygous deficiency of von Willebrand factor-cleaving protease by infusion of 
solvent/detergent plasma. Acta Paediatr, 91, 1056-1059.
Kiss, J. E. 2010. Thrombotic thrombocytopenic purpura: recognition and management. Int J 
Hematol, 91, 36-45.
Kovarova, P., Hrdlickova, R., Blahutova, S. & Cermakova, Z. 2018. ADAMTS13 kinetics after 
therapeutic plasma exchange and plasma infusion in patients with Upshaw-Schulman 
syndrome. Journal of Clinical Apheresis, 1-8.
Loirat, C., Veyradier, A., Girma, J. P., Ribba, A. S. & Meyer, D. 2006. Thrombotic 
thrombocytopenic purpura associated with von Willebrand factor-cleaving protease 
(ADAMTS13) deficiency in children. Semin Thromb Hemost, 32, 90-97.
Lotta, L. A., Garagiola, I., Palla, R., Cairo, A. & Peyvandi, F. 2010. ADAMTS13 mutations and 
polymorphisms in congenital thrombotic thrombocytopenic purpura. Hum. Mutat, 31, 11-
19.
Lotta, L. A., Wu, H. M., Mackie, I. J., Noris, M., Veyradier, A., Scully, M. A., Remuzzi, G., 
Coppo, P., Liesner, R., Donadelli, R., Loirat, C., Gibbs, R. A., Horne, A., Yang, S., 
Garagiola, I., Musallam, K. M. & Peyvandi, F. 2012. Residual plasmatic activity of 
ADAMTS13 correlates with phenotype severity in congenital thrombotic 
thrombocytopenic purpura. Blood, 120, 440-448.
Mansouri Taleghani, M., von Krogh, A. S., Fujimura, Y., George, J. N., Hrachovinova, I., Knöbl, 
P. N., Quist-Paulsen, P., Schneppenheim, R., Lämmle, B. & Kremer Hovinga, J. A. 2013. 
Hereditary thrombotic thrombocytopenic purpura and the hereditary TTP registry. 
Hamostaseologie, 33, 138-143.
Moake, J. L. & McPherson, P. D. 1989. Abnormalities of von Willebrand factor multimers in 
thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. Am. J. Med,
87, 9N-15N.
Peyvandi, F., Mannucci, P. M., Valsecchi, C., Pontiggia, S., Farina, C. & Retzios, A. D. 2013. 
ADAMTS13 content in plasma-derived factor VIII/ von willebrand factor concentrates. 
Am. J. Hematol, 88, 895-898.
Plaimauer, B., Kremer Hovinga, J. A., Juno, C., Wolfsegger, M. J., Skalicky, S., Schmidt, M., 
Grillberger, L., Hasslacher, M., Knöbl, P., Ehrlich, H. & Scheiflinger, F. 2011. 
Recombinant ADAMTS13 normalizes von Willebrand factor-cleaving activity in plasma 
of acquired TTP patients by overriding inhibitory antibodies. J Thromb Haemost, 9, 936-
944.
Plaimauer, B. & Scheiflinger, F. 2004. Expression and characterization of recombinant human 
ADAMTS13. Semin. Hematol, 41, 24-33.
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TAK-755-281102 Protocol Amendment 15 (Global)
18 Nov 2021
Raval, J. S., Padmanabhan, A., Kremer Hovinga, J. A. & Kiss, J. E. 2015. Development of a 
clinically significant ADAMTS13 inhibitor in a patient with hereditary thrombotic 
thrombocytopenic purpura. Am J Hematol, 90, e22.
Rock, G., Yousef, H., Neurath, D. & Lu, M. 2006. ADAMTS13 levels in fresh, stored, and 
solvent detergent treated plasma. Transfus Apher Sci, 35, 235-238.
Schiviz, A., Wuersch, K., Piskernik, C., Dietrich, B., Hoellriegl, W., Rottensteiner, H., 
Scheiflinger, F., Schwarz, H. P. & Muchitsch, E. M. 2012. A new mouse model 
mimicking thrombotic thrombocytopenic purpura: correction of symptoms by 
recombinant human ADAMTS13. Blood, 119, 6128-6135.
Schneppenheim, R., Budde, U., Oyen, F., Angerhaus, D., Aumann, V., Drewke, E., Hassenpflug, 
W., Häberle, J., Kentouche, K., Kohne, E., Kurnik, K., Mueller-Wiefel, D., Obser, T., 
Santer, R. & Sykora, K. W. 2003. von Willebrand factor cleaving protease and 
ADAMTS13 mutations in childhood TTP. Blood, 101, 1845-1850.
Schneppenheim, R., Kremer Hovinga, J. A., Becker, T., Budde, U., Karpman, D., Brockhaus, 
W., Hrachovinova, I., Korczowski, B., Oyen, F., Rittich, S., von Rosen, J., Tjønnfjord, G. 
E., Pimanda, J. E., Wienker, T. F. & Lämmle, B. 2006. A common origin of the 
4143insA ADAMTS13 mutation. Thromb. Haemost, 96, 3-6.
Tsai, H. M. 2003. Advances in the pathogenesis, diagnosis, and treatment of thrombotic 
thrombocytopenic purpura. J. Am. Soc. Nephrol, 14, 1072-1081.
Willis, M. S. & Bandarenko, N. 2005. Relapse of thrombotic thrombocytopenic purpura: is it a 
continuum of disease? Semin Thromb Hemost, 31, 700-708.
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Appendix 1 Country-Specific Information
The following study procedure adaptations pertain to sites in Germany only.
Appendix 1.1 Physical Examinations
At study sites in Germany, subjects will have physical examinations at Screening and every 
3 months (±2 weeks), until study completion/termination. 
Appendix 1.2 12-lead Electrocardiogram
A 12-lead electrocardiogram (ECG) will be measured at screening, 3 and 6 months of first IP 
treatment period, before the start of Period 3 and at study completion/termination.
See Table A1 for the country-specific complete Schedule of Events.
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18 Nov 2021
Table A1 Germany Study Sites: Schedule of Study Procedures and Assessments for Subjects on Prophylaxis Cohort
Procedures/
Assessments
Screening
Visit
Day -28
to 0
PK-I
Period 1
Prophylaxis 
(6 months)a
Period 2
Prophylaxis 
(6-months)a
PK-II
Period 3
Prophylaxis 
(6 months)a
PK-IIIq,t
Period 
1, 2, or 
3 Acute 
TTP 
Event
Study
Completion/
Termination
Visite
28 ±3 days 
after the last
IP infusion
PK 1 
Infusion
PK 1 
blood 
drawsc,i
PK 2 
Infusionb
±2 days
PK 2 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 3 
Infusionb
±2 days
PK 3 
blood 
drawsc,i
PK 4 
Infusionb
±2 days
PK 4 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 5 
Infusionb
±2 days
PK 5 
blood 
drawsc,i
As 
Needed
Informed 
Consentf
X
Eligibility 
Criteria
X
Randomizationn
Xn
X
Medical History
X
ECG
X
Xo
Xo
Xo
X
Physical Exam
X
Xp
Xp
Xp
X
Concomitant 
Medications and 
non-Drug 
Therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP Infusiong (see
Section 9.2.1)
X
Xh
X
X
X
Xh
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratoriesi
X
Xj
Xj
Xj
Xj
X
X
Xj
Xj
Xj
Xj
X
X
X
X
X
Vital Signs
X
Xj
Xj
Xj
Xj
Xm
Xm
Xj
Xj
Xj
Xj
Xm
X
X
X
X
Height/ Weightk
X
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
Xk
X
Pediatric 
Development 
Markerss
X
X
X
X
X
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Table A1 Germany Study Sites: Schedule of Study Procedures and Assessments for Subjects on Prophylaxis Cohort
Procedures/
Assessments
Screening
Visit
Day -28
to 0
PK-I
Period 1
Prophylaxis 
(6 months)a
Period 2
Prophylaxis 
(6-months)a
PK-II
Period 3
Prophylaxis 
(6 months)a
PK-IIIq,t
Period 
1, 2, or 
3 Acute 
TTP 
Event
Study
Completion/
Termination
Visite
28 ±3 days 
after the last
IP infusion
PK 1 
Infusion
PK 1 
blood 
drawsc,i
PK 2 
Infusionb
±2 days
PK 2 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 3 
Infusionb
±2 days
PK 3 
blood 
drawsc,i
PK 4 
Infusionb
±2 days
PK 4 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 5 
Infusionb
±2 days
PK 5 
blood 
drawsc,i
As 
Needed
HRQoLl
Xr
X
r
X
r
Xr
Xr
Schedule Next 
Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ALT=alanine aminotransferase; AST=aspartate aminotransferase; C=Testing at central laboratory; CBC=complete blood count; CD4=cluster of differentiation 4; CHO=Chinese
hamster ovary; ECG=electrocardiogram; EQ-5D-3L=EuroQol 5 Dimensions Questionnaire 3-Level; EQ-5D-Y=EQ-5D-youth; HAV=hepatitis A virus; HBc=hepatitis B core 
antigen; HBs=hepatitis B surface antibody; HBsAg=hepatitis B surface antigen; HCV=hepatitis C virus; HIV=human immunodeficiency virus; HRQoL=health related quality of 
life; cTTP=congenital thrombotic thrombocytopenic purpura; IP=investigational product; L=Testing at local laboratory; LDH=lactate dehydrogenase; MCH=mean corpuscular 
hemoglobin; MCHC=mean corpuscular hemoglobin concentration; MCV=mean corpuscular volume; Ped QL=Pediatric Quality of Life Inventory; PK=pharmacokinetic; 
PRO=patient reported outcome; RBC=red blood cell; SF-36=36-Item Short Form Health Survey; SoC=Standard of Care; TSQM-9=Treatment Satisfaction Questionnaire for 
Medication; TTP=thrombotic thrombocytopenic purpura; VWF=von Willebrand factor; VWF:Ag=von Willebrand factor: antigen; VWF:RCo=von Willebrand factor: ristocetin
cofactor activity
Note: Subjects of less than 18 years of age will be enrolled according to the criteria defined in Table 5.
a.
The length of Period 1 and Period 2 is 6 months each. If a subject cannot switch to the next period at the end of month 6, due to either logistic or medical reasons, the length of 
Period 1 and Period 2 can be extended to up to 7 months. For subjects enrolled before November 2017, Period 1 can be extended to up to 24 months. The length of Period 3 is 
6 months or until the continuation study is open at the subject’s study site.
b.
If the subject received SoC agent to treat an acute episode of TTP, at least 15 days (360 hr) must have elapsed and the subject must not show any TTP-related symptoms.
c.
See Table 11 for adult visit schedule. See Table 12 for pediatric visit schedule. See Table 14 for PK-III adult and pediatric visit schedule.
d.
Assumes Q2W dosing. Visit schedule and accompanying tests should be modified based on dosing frequency (see Section 9.2.1.3 for SoC dosing and Section 9.2.1.4 for 
BAX 930 dosing). For subjects on Q1W treatment will draw labs on Q2W schedule. Subjects on Q3W SoC treatment should have labs, vital signs and all assessment at the 
time of their visits according to the Q3W schedule.
e.
Also applies to subjects who prematurely withdraw from the study.
f.
Occurs at enrollment (prior to any study-specific procedure).
g.
Subjects requiring a vaccination during the course of treatment should schedule the vaccination administration within 72 hours after a prophylactic treatment dose. Subjects 
receiving a COVID-19 vaccination during the study period should be monitored frequently by telephonic health checks and for thrombocytopenia for 14 consecutive days 
following vaccination, as deemed appropriate by the investigator. Elective surgeries should be scheduled 24 hours after the last prophylactic dose and ADAMTS13 levels 
should be monitored after surgery.
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18 Nov 2021
Table A1 Germany Study Sites: Schedule of Study Procedures and Assessments for Subjects on Prophylaxis Cohort
Procedures/
Assessments
Screening
Visit
Day -28
to 0
PK-I
Period 1
Prophylaxis 
(6 months)a
Period 2
Prophylaxis 
(6-months)a
PK-II
Period 3
Prophylaxis 
(6 months)a
PK-IIIq,t
Period 
1, 2, or 
3 Acute 
TTP 
Event
Study
Completion/
Termination
Visite
28 ±3 days 
after the last
IP infusion
PK 1 
Infusion
PK 1 
blood 
drawsc,i
PK 2 
Infusionb
±2 days
PK 2 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 3 
Infusionb
±2 days
PK 3 
blood 
drawsc,i
PK 4 
Infusionb
±2 days
PK 4 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 5 
Infusionb
±2 days
PK 5 
blood 
drawsc,i
As 
Needed
h.
The infusion (SoC, BAX 930 ORT, or BAX 930 SIN depending on randomization) on Day 13 is to be administered after the 288-hr PK sample has been collected.
i.
For laboratory assessments, see Table 9.
j.
PK assessments will be done at the following timepoints post-PK infusion for subjects undergoing Q2W and Q3W: 15 ±5 min, 60±5 min, 3±0.5 hr, 9±2 hr, 24±2 hr, 72±4 hr, 
120±12 hr, 168±12 hr, 216±24 hr, and 288±24 hr. Vital signs for adult and adolescent subjects (≥12 years of age), should be recorded within 1 hr before PK infusion and at the 
following timepoints post infusion: 15±5 min, 60±5 min, 3±0.5 hr, 9±2 hr, 24±2 hr, 72±4 hr, 120±12 hr, 168±12 hr, 216±24 hr, and 288±24 hr. For pediatric subjects 
(<12 years of age), vital signs should be recorded within 1 hr before PK infusion and at the following timepoints post infusion: 30±5 min, 12±2 hr, 24±2 hr, 48±2 hr, 96±2 hr 
and 168±4 hr. Note that, subject to discussion and agreement with the Sponsor, blood collection timepoints for pediatric subjects <6 years of age may be adjusted and/or 
omitted and the timing of assessments associated with blood collections will be adjusted accordingly; refer also to Section 11.3.1 and Section 12.2.1. PK Post-Infusion 
Laboratory Assessments for subjects undergoing Q1W dosing should not be performed at 168±12 hrs, 216±12 hrs and 288±12 hrs timepoints, after PK Infusion #1. However, 
PK assessments up to 168±12 hrs timepoint should be performed after PK Infusion #2, and PK #3. Please refer to the tables below to see the assessment schedule for subjects 
undergoing Q1W dosing. PK timepoints for subjects in Q3W dosing will be the same as subjects on Q2W dosing.
k.
Height will be measured at screening only for subjects >=12 years of age. Height will be measured at screening, Visit1/Day 1, dosing visits and at study 
completion/termination for subjects <12 years of age. Weight will be measured for all subjects at screening, Day 1, PK 2 infusion (if BAX 930 is being administered for this 
infusion), PK 3 infusion, PK 4 infusion, PK 5 infusion, prophy dosing visits and at study completion/termination.
l.
SF-36v2, TSQM-9, EQ-5D-3L or EQ-5D-Y, PedsQL, and a cTTP-specific PRO and health-resource use items. 
m. Vital signs will be collected at each dosing visit within 1 hour before and after PI infusion.
n.
Randomization can be done on day 1 or the day before day 1. IP dispensation will be allowed on the day before the visit.
o.
ECG will be measured at screening, 3 and 6 months of the first IP treatment period (Period 1 or Period 2, depending on randomization), before the start of Period 3 and at study 
completion. 
p.
Physical examination will be performed at screening and every 3 months (±2 weeks), until study completion/termination.
q.
PK-III assessments may be subjects in the prophylactic cohort who initiate the study with BAX 930 SIN, including a minimum of 4 adult (≥18 years), and 2 pediatric 
(0-17 years) subjects who receive BAX 930 SIN in Period 3 on a voluntary basis. It will be required for pediatric subjects (<12 years old) and subjects who receive a weekly 
(Q1Week) dosing regimen.
r.
HRQoL assessments will be conducted only at the screening visits and at the end of the period (i.e., the last visit in the period, or at the early termination visit, if applicable).
s.
For subjects <6 years old, pediatric growth, development, and cognitive performance will be assessed if/when applicable, per the Investigator’s discretion.
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Table A1 Germany Study Sites: Schedule of Study Procedures and Assessments for Subjects on Prophylaxis Cohort
Procedures/
Assessments
Screening
Visit
Day -28
to 0
PK-I
Period 1
Prophylaxis 
(6 months)a
Period 2
Prophylaxis 
(6-months)a
PK-II
Period 3
Prophylaxis 
(6 months)a
PK-IIIq,t
Period 
1, 2, or 
3 Acute 
TTP 
Event
Study
Completion/
Termination
Visite
28 ±3 days 
after the last
IP infusion
PK 1 
Infusion
PK 1 
blood 
drawsc,i
PK 2 
Infusionb
±2 days
PK 2 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 3 
Infusionb
±2 days
PK 3 
blood 
drawsc,i
PK 4 
Infusionb
±2 days
PK 4 
blood 
drawsc,i
Bi-Weekly 
Follow up 
Study 
Visits (Q2 
week+/
-2 days for 
6 monthsa,d
PK 5 
Infusionb
±2 days
PK 5 
blood 
drawsc,i
As 
Needed
t.
Subjects enrolling into the continuation study will be allowed to remain in the 281102 study until the continuation study is open for enrolment. After the last IP Infusion, 
subjects will be enrolled and followed in the continuation study. Subjects who experience an acute TTP event will be treated with the assigned treatment at the time of said 
acute TTP event, before rolling over into the continuation study.
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TAK-755-281102 Protocol Amendment 13 (Global)
28 Apr 2021
3. SUMMARY OF CHANGES FROM PREVIOUS VERSION
An overview of the updates incorporated into Amendment 11 and 13 is provided in the 
Table below
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
, MD was added as the signatory 
Investigator on the protocol signature page.
To reflect current study monitoring.
Protocol Signature Page
Section 1, Study 
Personnel
The estimated study completion date was 
changed from June 2023 to January 2024.
Based on current enrollment patterns 
and delays related to the COVID-19 
public health emergency, the 
estimated completion date is 
expected to be extended. 
Section 4, Synopsis
An interim assessment may be conducted in 30 
evaluable adult (≥18 years old) or adolescent 
(>12-≤17 years old) subjects from the 
prophylactic treatment group upon completion 
of PK-II by all subjects (ORT and SIN 
material crossover PK)
For a regulatory filing in the US, 
pending evidence of 
biocomparability between BAX 930 
ORT and BAX 930 SIN, and FDA
agreement for such filing
Section 4, Synopsis
Section 9.2
Section 14.4
Section 14.4.4.1
Subjects who are excluded from PK-II; 
Pediatric subjects (<12 years old), subjects 
who receive a weekly (Q1Week) dosing 
regimen, and on demand subjects that were 
treated with BAX 930 SIN and continue into 
the prophylactic cohort, will undergo a PK-III 
assessment. 
In these subjects, an initial PK 
assessment (PK-I) with BAX 930 
ORT and an end-of-study PK 
assessment (PK-III) with BAX 930 
SIN, is sufficient to investigate the 
effect of BAX 930 ORT versus BAX 
930 SIN on PK parameters. 
Section 4, Synopsis
Section 9.2.1.1.3
Section 20.3 (Table 7)
The total duration of the study is increased 
from 60 months to 70 months.
Enrollment delays related to 
COVID-19 has extended the 
estimated study duration.
Section 4, Synopsis 
Section 9.3
Exploratory outcome measures 1-3 were 
updated, by replacing the text, “subacute 
manifestations”, with “cTTP manifestations”. 
Footnote “a” was added for context.
These exploratory outcome 
measures were updated to reflect 
accuracy of the measurement and 
alignment with the information 
provided in Table 3. A footnote was 
added to explain the definition of 
composite. 
Section 4, Synopsis 
Section 9.4.3
Section 14.4.3
Assessment of von Willebrand factor (VWF) 
multimer patterns will be evaluated as an 
exploratory endpoint. The new exploratory 
outcome measure aims to assess PD 
biomarkers including but not limited to VWF 
multimer patterns, ADAMTS13 mediated 
VWF cleavage products, and coagulation 
readouts, at baseline and following infusion of 
the SoC agent and BAX 930 treatment during 
the initial PK assessment.
Alignment with intended use of data, 
i.e., for exploratory biomarker 
analyses.
Section 4, Synopsis 
Section 8.3.3
Section 8.4
Section 9.4.2.3
Section 9.4.3
Section 14.4.2.3.2
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BAX 930 (rADAMTS13)
TAK-755-281102 Protocol Amendment 13 (Global)
28 Apr 2021
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
Text was updated to reflect removal of the 
staggered pediatric enrollment. Pediatric 
subjects 0 to <12 years and 12 to ≤17 years 
may initiate Period 1 without a staggered 
enrollment approach. 
No safety or immunogenicity 
concerns with BAX 930 have been 
identified in adult or pediatric 
subjects based on preliminary safety 
data and information from named-
patient treatment of a neonate with 
BAX 930. The goal of the staggered 
approach, to introduce the youngest 
subjects after adequate safety and 
immunogenicity data were available 
from adults and the older pediatric 
population, is no longer required to 
support the safety of BAX 930 in 
pediatric subjects. Safety data from 
the adult and adolescent subjects 
currently enrolled in this study, 
coupled with the lack of adverse 
reactions and positive tolerability 
observed in the named-patient 
neonate, support the removal of the 
staggered enrollment approach. the 
Data Monitoring Committee 
endorsed removing the staggered 
enrollment approach. 
Section 4, Synopsis
Section 9.1
Section 9.2
Section 20.2.1
The total number of subjects was redefined as 
follows;
Prophylactic cohort: Approximately 36 adult 
(≥18 years old) subjects and 12 adolescent 
(>12-≤17 years old) or pediatric (0-<12 years 
old) subjects.
On-demand cohort: Approximately 6 adult 
(≥18 years old) subjects and 3 adolescent 
(>12-≤17 years old) or pediatric (0-<12 years 
old) subjects.
Due to the low global prevalence of 
congenital thrombotic 
thrombocytopenic purpura (cTTP; 
resulting in a low number of eligible 
study subjects), coupled with the 
current enrollment status of this 
study, it was determined that a wide 
range of total subjects (36-68 
subjects) is no longer appropriate. 
The updated approximate number of 
subjects reflects the current, 
observed enrollment patterns and 
accounts for a 10% dropout rate.
Section 4, Synopsis 
Section 7.3
Section 14.1
Section 20.1
(Figure 1 and Figure 2)
After 30 September 2021, screened subjects in 
the prophylactic cohort may initiate the study 
with BAX 930 SIN. 
A clear cut-off date of 30 September 
2021 was established to provide 
guidance on switching subjects from 
BAX 930 ORT material to BAX 930 
SIN material. 
Section 4, Synopsis 
Section 9.2.1.2
Section 9.2.2.1
Section 20.2.1
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BAX 930 (rADAMTS13)
TAK-755-281102 Protocol Amendment 13 (Global)
28 Apr 2021
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
Figure 2 was generated to depict study flow in 
subjects who begin the study on BAX 930 SIN 
material. Figure 1 and Figure 2 were edited to 
reflect the updated study sample size and the 
addition of the PK-III assessment. 
Figure 1 was updated to reflect 
additional study components. 
Figure 2 was added to improve study 
design clarity.
Section 20.1, Study 
Flow Chart 
(Figure 1 and Figure 2)
Secondary efficacy outcome measures text was 
changed from “number and incidence of acute 
TTP episodes…” to “proportion of acute TTP 
episodes…”
The proportion of subjects with TTP 
episodes more clearly reflects the 
goals of the secondary objective of 
the study, which is to determine the 
number of subjects who experience 
acute TTP episodes with BAX 930 
vs standard of care (SoC). 
Section 4, Synopsis 
Section 9.4.2.1
Section 14.4.2.1
Text was added to reflect the option of 
at-home BAX 930 infusions for subjects 
receiving prophylactic treatment.
At-home infusions reduce subject 
burden and COVID-19-related risks.
Section 4, Synopsis 
Section 9.1
Section 9.2
Section 11.7
An interim analysis will be performed after 30 
adult (≥18 years old) or adolescent (>12-≤17 
years) subjects in the prophylactic cohort 
complete the study. All data collected by that 
time point in Study 281102, as well as the 
continuation Study TAK-755-3002 will be 
included in the statistical analysis. Data 
generated from this interim analysis will be 
used in the first data filing for an FDA 
submission.
The interim analysis will include final data 
from at least 30 subjects in the prophylactic 
cohort who completed the study.
The population of subjects included 
in the interim analysis was further 
defined for clarity.
Section 4, Synopsis 
Section 9.2
Section 14.4.4.1
Text was updated to describe that subjects 
receiving factor VIII:VWF concentrates 
prophylactic treatments qualify for a reduced 
SoC pharmacokinetic (PK) washout period of 
5 days.
Factor VIII contains very small 
amounts of ADAMTS13 (circulation 
levels of 0.1 IU/mL or below 
expected to be achieved within 
5 days) (Peyvandi et al., 2013).
Section 9.2.1
Text was clarified to describe that adult and 
adolescent subjects (≥12 years old) who enroll 
in the study with BAX 930 ORT material will 
undergo two randomized crossover PK 
assessments. This will include PK-I (BAX 930 
ORT and SoC) and PK-II (BAX 930 ORT and 
BAX 930 SIN).
Protocol text was revised to clarify 
that adult and pediatric subjects will 
initiate the study with PK-I 
(BAX 930 ORT and SoC) and 
subsequently receive BAX 930 
ORT. Subjects who are screened 
after 30 September 2021 will not 
receive BAX 930 ORT. In this case, 
the subjects will initiate the study 
with BAX 930 SIN, PK-I will 
consist of a crossover between 
BAX 930 SIN and SoC and no PK-II 
will be conducted.
Section 9.2
Section 9.2.1.1.2
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BAX 930 (rADAMTS13)
TAK-755-281102 Protocol Amendment 13 (Global)
28 Apr 2021
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
A brief summary and rationale for this 
protocol amendment was updated to include 
the removal of staggered pediatric enrollment, 
named-patient favorable outcome to treatment, 
availability of at-home infusions, and 
switching of BAX 930 material production 
from Orth, Austria, to Singapore. Crossover 
comparability PK assessments will be 
conducted to ensure safety.
The summary and rationale were 
updated to promote safe and 
logistically appropriate conduct of 
this trial.
Section 9.1
Clarifying text was added to explain that once 
subjects begin on-demand treatment with 
newly available BAX 930 SIN, subjects will 
continue prophylactic treatment with BAX 930 
SIN.
Text was added for clarity.
Section 9.2.2.1
Clarifying text was added to explain that 
subjects in the prophylactic cohort who enroll 
with BAX 930 SIN will have a randomized 
crossover PK comparison with SoC in PK-I. 
PK-II is not applicable in these subjects. 
Following PK-I these subjects will go through 
Periods 1, 2, and 3 with BAX 930 SIN.
Protocol text was revised to clarify 
that adult and adolescent subjects 
will initiate the study with PK-I 
(BAX 930 ORT and SoC) and 
subsequently receive BAX 930 
ORT. Subjects who are screened 
after 30 September 2021 will initiate 
the study with BAX 930 SIN. In this 
case, PK-I will consist of a crossover 
between BAX 930 SIN and SoC and 
no PK-II will be conducted.
Section 4, Synopsis 
Section 9.2.1
Standard of care treatment administered as the 
Investigator’s best judgment should include 
ADAMTS13 in a quantifiable dose. The 
administered dose will be recorded. Subjects 
who experience an allergic reaction to 
ADAMTS13-containing forms of SoC may be 
discontinued from the study.
For proper PK evaluation, 
ADAMTS13 must be detectable in 
blood samples as a result of a 
specific given dose.
Section 9.2.2
Section 9.7.3
Section 10.3
Recording of subject (patient) reported 
outcomes will be captured with electronic 
diaries, and a web-backup option will be 
available for temporary use.
Paper diaries are no longer 
appropriate for the purpose of this 
clinical trial.
Section 11.5
Text was added to clarify that subject-reported 
outcomes will also be measured at the 
termination visit.
Text was added for clarity.
Section 11.5
Section 13.9
Table 4
Section 20.3 (Table 7)
Compliance will be monitored at at-home 
visits by a licensed healthcare professional. 
Compliance will be captured 
at-home to accommodate for 
subjects receiving IV infusions at 
home
Section 11.7
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BAX 930 (rADAMTS13)
TAK-755-281102 Protocol Amendment 13 (Global)
28 Apr 2021
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
Subjects with reported ongoing AEs at the 
end-of-study visit, who move on to the 
continuation study prior to the end of the 
30-day AE follow up period will have all 
AE-related information captured and 
locked in the eCRF of Study 281102. 
At the time of enrollment into the 
continuation study, details surrounding 
an ongoing AE will be imported from 
Study 281102 into the subject’s eCRF for 
Study TAK-755-3002. Resolution of an 
AE that occurs in 281102, but is resolved in 
TAK-755-3002, will be captured in the 
subject’s eCRF for TAK-755-3002 only. 
If the severity rating for an ongoing AE 
changes before the event resolves, the 
original AE report will be revised 
(i.e., the event will not be reported as 
separate AE).
Clarifying text was added to capture 
AE reporting for subjects who enter 
the continuation study prior to AE 
resolution in the pivotal, 281102 
study. 
Section 13.1.2
The biochemical marker, creatine kinase 
myocardial band fraction (CK-MB) will be 
measured at a local laboratory rather than at 
the central laboratory.
CK-MB is a key cardiovascular 
biomarker. A local laboratory will 
have the ability to return test results 
more quickly than a central 
laboratory.
Section 13.7.3
Section 20.4
(Table 9 and Table 10)
Alternative approaches to data monitoring may 
be employed to maintain data quality and 
integrity, and subject safety.
In-clinic visits may be limited due to 
global COVID-19 pandemic. 
Alternative monitoring approaches 
may be employed to decrease risk to 
study subjects.
Section 17
The list of clinical laboratory assessments was 
updated to include the following biomarkers; 
cTnT, cTnI, CK-MB, S100B, and NSE.
These are biomarkers of organ 
damage (heart, brain) that will be 
analyzed as part of the exploratory 
endpoints
Section 20.4
(Table 9 and Table 10)
An end-of-study, PK-III assessment may be 
implemented for a subset of subjects 
including; 1) Any subject in the prophylactic 
cohort, including any subject who switches 
from on-demand treatment to prophylactic 
treatment, who initiates the study with 
BAX 930 SIN, and 2) A minimum of 4 adults 
(≥18 years old), and a minimum of 2 pediatric 
or adolescent subjects (age 0-17 years) who 
received BAX 930 SIN in Period 3. Subjects 
who do not initiate the clinical trial with 
BAX 930 SIN may voluntarily opt for a PK-III 
assessment, regardless of the treatment 
administered at study initiation.
PK-III is added to assess the impact 
of time on long-term exposure to 
BAX 930 SIN.
Section 4, Synopsis 
Section 8.3.3
Section 9.2
Section 9.2.1.1.3
Section 9.2.2
Section 12.2
Section 20.1
(Figure 1 and Figure 2)
Section 20.3
(Table 7 and Table 13)
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BAX 930 (rADAMTS13)
TAK-755-281102 Protocol Amendment 13 (Global)
28 Apr 2021
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
Pediatric subjects (<12 years old), subjects 
who receive a weekly (Q1Week) dosing 
regimen, and on demand subjects that were 
treated with BAX 930 SIN and continue into 
the prophylactic cohort, will undergo a PK-III 
assessment.
PK 5 infusion was added below the PK-III 
subheading in Table 7 to indicate sequential 
PK infusions and blood draws.
Table 13 was added to indicate PK-III 
assessments and timepoints. 
The incidence of subacute manifestations in 
subjects receiving prophylactic treatment is 
added as an exploratory outcome measure.
The exploratory outcome measures 
were updated for accuracy and to 
reflect the exploratory objectives of 
this study
Section 4, Synopsis 
Section 8.4
Section 9.4.3
The impact of immunogenicity on 
ADAMTS13 PK parameters and 
pharmacodynamic (PD) variables is included 
as a PK/PD study objective and will be 
assessed as a secondary PK/PD outcome 
measure, accordingly. 
The impact of immunogenicity on 
PK/PD is included to present a more 
comprehensive understanding of 
potential SoC or BAX 930-derived 
immunogenicity, beyond the 
previous, limited scope of safety and 
efficacy.
Section 4, Synopsis 
Section 8.3.3
Section 9.4.2.3
Section 20.4
(Table 11 and Table 12)
The following exploratory objective measure 
was added, “to characterize the PK profile of 
ADAMTS13 activity at the end of the study”.
This exploratory objective was 
added to highlight the importance of 
characterizing the PK profile of 
ADAMTS13 activity throughout the 
duration of the study. 
Section 4, Synopsis 
Section 8.4
Subjects who experience an acute event will be 
treated with the assigned treatment at the time 
of said acute event, before rolling over into the 
continuation study.
Text was added for clarity in the 
case of an acute event. 
Section 20.3 (Table 7)
Subjects who were unable to move into the 
prophylactic cohort due to data lock timelines 
may move into the continuation study.
Subjects in the on-demand cohort 
are likely to qualify for enrollment in 
the Phase 3b continuation study. 
This allowance gives subjects an 
opportunity to receive prophylactic 
treatment following lock timelines.
Section 20.3 (Table 8)
A footnote was added to Table 11 to indicate 
the immunogenicity assessments and antibody 
proteins to be measured as an additional safety 
measure. 
Text was added as a footnote to 
clarify sampling and corresponds to 
safety immunogenicity objectives in 
the body of the protocol. 
Section 20.4
(Table 11 and Table 12)
One month was defined as 28 days.
Study participants are referred to as “subjects,” 
instead of “subjects” and “patients” used 
interchangeably.
Text was added to improve clarity 
and accuracy.
Throughout document
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Page 11
BAX 930 (rADAMTS13)
TAK-755-281102 Protocol Amendment 13 (Global)
28 Apr 2021
Summary of Change(s) Since Last Version of Approved Protocol
Description of Change
Purpose for Change
Section(s) Affected 
by Change
The table numbering was updated throughout 
to reflect the removal of the previously 
numbered, Table 1 from the synopsis. 
Continuous table numbering is initiated in the 
body of the protocol only. The contents of the 
table in the synopsis is retained and is
provided in Table 3 of the body of the 
protocol.
The Synopsis is a stand-alone 
document and should include 
external links to Sections or Tables 
in the body of the protocol.
Throughout the 
document
Summary of Change(s) Since Protocol Amendment 11 (Global)
Description of Change
Purpose for Change
Section(s) Affected 
by Change
Subjects receiving a COVID-19 vaccination 
during the study period should be monitored 
frequently by telephonic health checks and for 
thrombocytopenia for 14 consecutive days 
following vaccination, as deemed appropriate 
by the investigator. 
Based on safety concerns following 
the recent pause of the Johnson & 
Johnson and AstraZeneca COVID-
19 vaccines, subjects receiving 
COVID-19 vaccinations during the 
study should be monitored closely as 
a safety precaution. 
This change was introduced 
following the submission of Protocol 
Amendment 11 (Global) in the US. 
Section 9.2.1.3
Section 9.2.1.4
Section 20.3 (Table 7)
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Page 5 
BAX 930 (rADAMTS13) 
TAK-755-281102 Protocol Amendment 11 (Global) 
 
24 Feb 2021 
 
 
3. SUMMARY OF CHANGES FROM PREVIOUS VERSION 
An overview of the updates incorporated into Amendment 11 is provided in the Table below 
Summary of Change(s) Since Last Version of Approved Protocol 
Description of Change 
Purpose for Change 
Section(s) Affected 
by Change 
, MD was added as the signatory 
Investigator on the protocol signature page. 
To reflect current study monitoring. 
Protocol Signature Page 
Section 1, Study 
Personnel 
The estimated study completion date was 
changed from June 2023 to January 2024. 
Based on current enrollment patterns 
and delays related to the COVID-19 
public health emergency, the 
estimated completion date is 
expected to be extended.  
Section 4, Synopsis 
An interim assessment may be conducted in 30 
evaluable adult (≥18 years old) or adolescent 
(>12-≤17 years old) subjects from the 
prophylactic treatment group upon completion 
of PK-II by all subjects (ORT and SIN 
material crossover PK) 
For a regulatory filing in the US, 
pending evidence of 
biocomparability between BAX 930 
ORT and BAX 930 SIN, and FDA  
agreement for such filing 
Section 4, Synopsis 
Section 9.2 
Section 14.4 
Section 14.4.4.1 
Subjects who are excluded from PK-II; 
Pediatric subjects (<12 years old), subjects 
who receive a weekly (Q1Week) dosing 
regimen, and on demand subjects that were 
treated with BAX 930 SIN and continue into 
the prophylactic cohort, will undergo a PK-III 
assessment.  
 
In these subjects, an initial PK 
assessment (PK-I) with BAX 930 
ORT and an end-of-study PK 
assessment (PK-III) with BAX 930 
SIN, is sufficient to investigate the 
effect of BAX 930 ORT versus BAX 
930 SIN on PK parameters.  
Section 4, Synopsis 
Section 9.2.1.1.3 
Section 20.3 (Table 7) 
The total duration of the study is increased 
from 60 months to 70 months. 
Enrollment delays related to 
COVID-19 has extended the 
estimated study duration. 
Section 4, Synopsis 
Section 9.3 
Exploratory outcome measures 1-3 were 
updated, by replacing the text, “subacute 
manifestations”, with “cTTP manifestations”. 
Footnote “a” was added for context. 
These exploratory outcome 
measures were updated to reflect 
accuracy of the measurement and 
alignment with the information 
provided in Table 3. A footnote was 
added to explain the definition of 
composite.  
Section 4, Synopsis 
Section 9.4.3 
Section 14.4.3 
Assessment of von Willebrand factor (VWF) 
multimer patterns will be evaluated as an 
exploratory endpoint. The new exploratory 
outcome measure aims to assess PD 
biomarkers including but not limited to VWF 
multimer patterns, ADAMTS13 mediated 
VWF cleavage products, and coagulation 
readouts, at baseline and following infusion of 
the SoC agent and BAX 930 treatment during 
the initial PK assessment. 
Alignment with intended use of data, 
i.e., for exploratory biomarker 
analyses. 
Section 4, Synopsis 
Section 8.3.3 
Section 8.4 
Section 9.4.2.3 
Section 9.4.3 
Section 14.4.2.3.2 
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BAX 930 (rADAMTS13) 
TAK-755-281102 Protocol Amendment 11 (Global) 
 
24 Feb 2021 
 
 
Summary of Change(s) Since Last Version of Approved Protocol 
Description of Change 
Purpose for Change 
Section(s) Affected 
by Change 
Text was updated to reflect removal of the 
staggered pediatric enrollment. Pediatric 
subjects 0 to <12 years and 12 to ≤17 years 
may initiate Period 1 without a staggered 
enrollment approach.  
No safety or immunogenicity 
concerns with BAX 930 have been 
identified in adult or pediatric 
subjects based on preliminary safety 
data and information from named-
patient treatment of a neonate with 
BAX 930. The goal of the staggered 
approach, to introduce the youngest 
subjects after adequate safety and 
immunogenicity data were available 
from adults and the older pediatric 
population, is no longer required to 
support the safety of BAX 930 in 
pediatric subjects. Safety data from 
the adult and adolescent subjects 
currently enrolled in this study, 
coupled with the lack of adverse 
reactions and positive tolerability 
observed in the named-patient 
neonate, support the removal of the 
staggered enrollment approach. the 
Data Monitoring Committee 
endorsed removing the staggered 
enrollment approach.  
Section 4, Synopsis 
Section 9.1 
Section 9.2 
Section 20.2.1 
The total number of subjects was redefined as 
follows; 
 
Prophylactic cohort: Approximately 36 adult 
(≥18 years old) subjects and 12 adolescent 
(>12-≤17 years old) or pediatric (0-<12 years 
old) subjects. 
 
On-demand cohort: Approximately 6 adult 
(≥18 years old) subjects and 3 adolescent 
(>12-≤17 years old) or pediatric (0-<12 years 
old) subjects. 
 
 
Due to the low global prevalence of 
congenital thrombotic 
thrombocytopenic purpura (cTTP; 
resulting in a low number of eligible 
study subjects), coupled with the 
current enrollment status of this 
study, it was determined that a wide 
range of total subjects (36-68 
subjects) is no longer appropriate. 
The updated approximate number of 
subjects reflects the current, 
observed enrollment patterns and 
accounts for a 10% dropout rate.   
Section 4, Synopsis 
Section 7.3 
Section 14.1 
Section 20.1  
(Figure 1 and Figure 2) 
 
After 30 September 2021, screened subjects in 
the prophylactic cohort may initiate the study 
with BAX 930 SIN.  
A clear cut-off date of 30 September 
2021 was established to provide 
guidance on switching subjects from 
BAX 930 ORT material to BAX 930 
SIN material.  
Section 4, Synopsis 
Section 9.2.1.2 
Section 9.2.2.1 
Section 20.2.1 
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BAX 930 (rADAMTS13) 
TAK-755-281102 Protocol Amendment 11 (Global) 
 
24 Feb 2021 
 
 
Summary of Change(s) Since Last Version of Approved Protocol 
Description of Change 
Purpose for Change 
Section(s) Affected 
by Change 
Figure 2 was generated to depict study flow in 
subjects who begin the study on BAX 930 SIN 
material. Figure 1 and Figure 2 were edited to 
reflect the updated study sample size and the 
addition of the PK-III assessment.  
Figure 1 was updated to reflect 
additional study components. 
Figure 2 was added to improve study 
design clarity. 
Section 20.1, Study 
Flow Chart  
(Figure 1 and Figure 2) 
 
Secondary efficacy outcome measures text was 
changed from “number and incidence of acute 
TTP episodes…” to “proportion of acute TTP 
episodes…” 
The proportion of subjects with TTP 
episodes more clearly reflects the 
goals of the secondary objective of 
the study, which is to determine the 
number of subjects who experience 
acute TTP episodes with BAX 930 
vs standard of care (SoC).  
Section 4, Synopsis 
Section 9.4.2.1 
Section 14.4.2.1 
Text was added to reflect the option of 
at-home BAX 930 infusions for subjects 
receiving prophylactic treatment. 
At-home infusions reduce subject 
burden and COVID-19-related risks. 
Section 4, Synopsis 
Section 9.1 
Section 9.2 
Section 11.7 
An interim analysis will be performed after 30 
adult (≥18 years old) or adolescent (>12-≤17 
years) subjects in the prophylactic cohort 
complete the study. All data collected by that 
time point in Study 281102, as well as the 
continuation Study TAK-755-3002 will be 
included in the statistical analysis. Data 
generated from this interim analysis will be 
used in the first data filing for an FDA 
submission. 
The interim analysis will include final data 
from at least 30 subjects in the prophylactic 
cohort who completed the study. 
The population of subjects included 
in the interim analysis was further 
defined for clarity. 
Section 4, Synopsis 
Section 9.2 
Section 14.4.4.1 
 
Text was updated to describe that subjects 
receiving factor VIII:VWF concentrates 
prophylactic treatments qualify for a reduced 
SoC pharmacokinetic (PK) washout period of 
5 days. 
Factor VIII contains very small 
amounts of ADAMTS13 (circulation 
levels of 0.1 IU/mL or below 
expected to be achieved within 
5 days) (Peyvandi et al., 2013). 
Section 9.2.1 
 
Text was clarified to describe that adult and 
adolescent subjects (≥12 years old) who enroll 
in the study with BAX 930 ORT material will 
undergo two randomized crossover PK 
assessments. This will include PK-I (BAX 930 
ORT and SoC) and PK-II (BAX 930 ORT and 
BAX 930 SIN).   
Protocol text was revised to clarify 
that adult and pediatric subjects will 
initiate the study with PK-I 
(BAX 930 ORT and SoC) and 
subsequently receive BAX 930 
ORT. Subjects who are screened 
after 30 September 2021 will not 
receive BAX 930 ORT. In this case, 
the subjects will initiate the study 
with BAX 930 SIN, PK-I will 
consist of a crossover between 
BAX 930 SIN and SoC and no PK-II 
will be conducted. 
Section 9.2 
Section 9.2.1.1.2 
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BAX 930 (rADAMTS13) 
TAK-755-281102 Protocol Amendment 11 (Global) 
 
24 Feb 2021 
 
 
Summary of Change(s) Since Last Version of Approved Protocol 
Description of Change 
Purpose for Change 
Section(s) Affected 
by Change 
A brief summary and rationale for this 
protocol amendment was updated to include 
the removal of staggered pediatric enrollment, 
named-patient favorable outcome to treatment, 
availability of at-home infusions, and 
switching of BAX 930 material production 
from Orth, Austria, to Singapore. Crossover 
comparability PK assessments will be 
conducted to ensure safety. 
The summary and rationale were 
updated to promote safe and 
logistically appropriate conduct of 
this trial. 
Section 9.1 
Clarifying text was added to explain that once 
subjects begin on-demand treatment with 
newly available BAX 930 SIN, subjects will 
continue prophylactic treatment with BAX 930 
SIN. 
Text was added for clarity. 
Section 9.2.2.1 
Clarifying text was added to explain that 
subjects in the prophylactic cohort who enroll 
with BAX 930 SIN will have a randomized 
crossover PK comparison with SoC in PK-I. 
PK-II is not applicable in these subjects. 
Following PK-I these subjects will go through 
Periods 1, 2, and 3 with BAX 930 SIN. 
Protocol text was revised to clarify 
that adult and adolescent subjects 
will initiate the study with PK-I 
(BAX 930 ORT and SoC) and 
subsequently receive BAX 930 
ORT. Subjects who are screened 
after 30 September 2021 will initiate 
the study with BAX 930 SIN. In this 
case, PK-I will consist of a crossover 
between BAX 930 SIN and SoC and 
no PK-II will be conducted. 
Section 4, Synopsis 
Section 9.2.1 
 
Standard of care treatment administered as the 
Investigator’s best judgment should include 
ADAMTS13 in a quantifiable dose. The 
administered dose will be recorded. Subjects 
who experience an allergic reaction to 
ADAMTS13-containing forms of SoC may be 
discontinued from the study. 
For proper PK evaluation, 
ADAMTS13 must be detectable in 
blood samples as a result of a 
specific given dose. 
Section 9.2.2 
Section 9.7.3 
Section 10.3 
Recording of subject (patient) reported 
outcomes will be captured with electronic 
diaries, and a web-backup option will be 
available for temporary use. 
Paper diaries are no longer 
appropriate for the purpose of this 
clinical trial. 
Section 11.5 
Text was added to clarify that subject-reported 
outcomes will also be measured at the 
termination visit. 
Text was added for clarity. 
Section 11.5 
Section 13.9 
Table 4 
Section 20.3 (Table 7) 
Compliance will be monitored at at-home 
visits by a licensed healthcare professional.  
Compliance will be captured 
at-home to accommodate for 
subjects receiving IV infusions at 
home 
Section 11.7 
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Page 9 
BAX 930 (rADAMTS13) 
TAK-755-281102 Protocol Amendment 11 (Global) 
 
24 Feb 2021 
 
 
Summary of Change(s) Since Last Version of Approved Protocol 
Description of Change 
Purpose for Change 
Section(s) Affected 
by Change 
Subjects with reported ongoing AEs at the 
end-of-study visit, who move on to the 
continuation study prior to the end of the 
30-day AE follow up period will have all 
AE-related information captured and 
locked in the eCRF of Study 281102. 
At the time of enrollment into the 
continuation study, details surrounding 
an ongoing AE will be imported from 
Study 281102 into the subject’s eCRF for 
Study TAK-755-3002. Resolution of an 
AE that occurs in 281102, but is resolved in 
TAK-755-3002, will be captured in the 
subject’s eCRF for TAK-755-3002 only. 
If the severity rating for an ongoing AE 
changes before the event resolves, the 
original AE report will be revised 
(i.e., the event will not be reported as 
separate AE). 
Clarifying text was added to capture 
AE reporting for subjects who enter 
the continuation study prior to AE 
resolution in the pivotal, 281102 
study.  
Section 13.1.2 
The biochemical marker, creatine kinase 
myocardial band fraction (CK-MB) will be 
measured at a local laboratory rather than at 
the central laboratory. 
CK-MB is a key cardiovascular 
biomarker. A local laboratory will 
have the ability to return test results 
more quickly than a central 
laboratory. 
Section 13.7.3 
Section 20.4  
(Table 9 and Table 10) 
Alternative approaches to data monitoring may 
be employed to maintain data quality and 
integrity, and subject safety. 
In-clinic visits may be limited due to 
global COVID-19 pandemic. 
Alternative monitoring approaches 
may be employed to decrease risk to 
study subjects. 
Section 17 
The list of clinical laboratory assessments was 
updated to include the following biomarkers; 
cTnT, cTnI, CK-MB, S100B, and NSE. 
These are biomarkers of organ 
damage (heart, brain) that will be 
analyzed as part of the exploratory 
endpoints 
Section 20.4  
(Table 9 and Table 10) 
An end-of-study, PK-III assessment may be 
implemented for a subset of subjects 
including; 1) Any subject in the prophylactic 
cohort, including any subject who switches 
from on-demand treatment to prophylactic 
treatment, who initiates the study with 
BAX 930 SIN, and 2) A minimum of 4 adults 
(≥18 years old), and a minimum of 2 pediatric 
or adolescent subjects (age 0-17 years) who 
received BAX 930 SIN in Period 3. Subjects 
who do not initiate the clinical trial with 
BAX 930 SIN may voluntarily opt for a PK-III 
assessment, regardless of the treatment 
administered at study initiation. 
 
PK-III is added to assess the impact 
of time on long-term exposure to 
BAX 930 SIN. 
Section 4, Synopsis 
Section 8.3.3 
Section 9.2 
Section 9.2.1.1.3 
Section 9.2.2 
Section 12.2 
Section 20.1  
(Figure 1 and Figure 2) 
Section 20.3  
(Table 7 and Table 13) 
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TAK-755-281102 Protocol Amendment 11 (Global) 
 
24 Feb 2021 
 
 
Summary of Change(s) Since Last Version of Approved Protocol 
Description of Change 
Purpose for Change 
Section(s) Affected 
by Change 
Pediatric subjects (<12 years old), subjects 
who receive a weekly (Q1Week) dosing 
regimen, and on demand subjects that were 
treated with BAX 930 SIN and continue into 
the prophylactic cohort, will undergo a PK-III 
assessment. 
 
PK 5 infusion was added below the PK-III 
subheading in Table 7 to indicate  sequential 
PK infusions and blood draws. 
 
Table 13 was added to indicate PK-III 
assessments and timepoints.  
The incidence of subacute manifestations in 
subjects receiving prophylactic treatment is 
added as an exploratory outcome measure. 
The exploratory outcome measures 
were updated for accuracy and to 
reflect the exploratory objectives of 
this study 
Section 4, Synopsis 
Section 8.4 
Section 9.4.3 
The impact of immunogenicity on 
ADAMTS13 PK parameters and 
pharmacodynamic (PD) variables is included 
as a PK/PD study objective and will be 
assessed as a secondary PK/PD outcome 
measure, accordingly.  
The impact of immunogenicity on 
PK/PD is included to present a more 
comprehensive understanding of 
potential SoC or BAX 930-derived 
immunogenicity, beyond the 
previous, limited scope of safety and 
efficacy.   
Section 4, Synopsis 
Section 8.3.3 
Section 9.4.2.3 
Section 20.4  
(Table 11 and Table 12) 
The following exploratory objective measure 
was added, “to characterize the PK profile of 
ADAMTS13 activity at the end of the study”. 
This exploratory objective was 
added to highlight the importance of 
characterizing the PK profile of 
ADAMTS13 activity throughout the 
duration of the study.  
Section 4, Synopsis 
Section 8.4 
Subjects who experience an acute event will be 
treated with the assigned treatment at the time 
of said acute event, before rolling over into the 
continuation study. 
Text was added for clarity in the 
case of an acute event.  
Section 20.3 (Table 7) 
Subjects who were unable to move into the 
prophylactic cohort due to data lock timelines 
may move into the continuation study. 
Subjects in the on-demand cohort 
are likely to qualify for enrollment in 
the Phase 3b continuation study. 
This allowance gives subjects an 
opportunity to receive prophylactic 
treatment following lock timelines. 
Section 20.3 (Table 8) 
A footnote was added to Table 11 to indicate 
the immunogenicity assessments and antibody 
proteins to be measured as an additional safety 
measure.  
Text was added as a footnote to 
clarify sampling and corresponds to 
safety immunogenicity objectives in 
the body of the protocol.  
Section 20.4  
(Table 11 and Table 12) 
One month was defined as 28 days. 
Study participants are referred to as “subjects,” 
instead of “subjects” and “patients” used 
interchangeably. 
Text was added to improve clarity 
and accuracy. 
Throughout document 
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Page 11 
BAX 930 (rADAMTS13) 
TAK-755-281102 Protocol Amendment 11 (Global) 
 
24 Feb 2021 
 
 
Summary of Change(s) Since Last Version of Approved Protocol 
Description of Change 
Purpose for Change 
Section(s) Affected 
by Change 
The table numbering was updated throughout 
to reflect the removal of the previously 
numbered, Table 1 from the synopsis. 
Continuous table numbering is initiated in the 
body of the protocol only. The contents of the 
table in the synopsis is retained and is 
provided in Table 3 of the body of the 
protocol. 
The Synopsis is a stand-alone 
document and should include 
external links to Sections or Tables 
in the body of the protocol. 
Throughout the 
document 
 
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22. SUMMARY OF CHANGES
Protocol 281102: Global Amendment 9 2020 MAR 06
Replaces: Global Amendment 5 2018 DEC 06xxiv
In this section, changes from Global Protocol Amendment 5, dated 2018 DEC 06, are 
described and their rationale is given.
1.
Title page, throughout document
Description of Change:
Addition of TAK-755, as the newer name given to SHP655 by its current sponsor, 
Baxalta, now part of Shire, at first mention.
2.
Throughout document
Description of Change:
Syntax or grammar have been improved, or minor clarifications have been added.
3.
Section 1, Throughout document
Description of Change:
Some study personnel were updated due to organizational changes.
4.
Section 3 Study Synopsis, Section 6.3, Section 8.2
Description of Change: 
-
6 more subjects have been added to the study, in the prophylaxis cohort. Subject 
Selection section updated accordingly.
-
Planned study period was changed, to reflect current situation.
-
It was clarified that prophy subjects will receive a cross-over PK evaluation 
after period 2 and once BAX 930 SIN is available with the exception of subjects 
enrolled prior the temporary study halt.
-
Study design was changed to remove information on a previous protocol
amendment.  Some clarifications were made to the text for example to clarify 
that Period 3 would last until the continuation study had opened at the subject’s 
study site.
                                                
xxiv
This also replaces all local amendments that followed Global Amendment 5. However, only changes 
made to Global Amendment 5 are detailed in this section.
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-
The statistical section was amended accordingly, and some clarifying statements 
were added.
-
It was clarified that for subjects receiving factor VIII (FVIII):VWF concentrates, 
the minimum required SoC PK dose washout period may be reduced to 5 days.
5.
Section 7.3.4 Health Related Quality of Life and Resource Utilization
Description of Change: 
Health Related Quality of Life and Resource Utilization moved to be included 
under secondary objectives.
6.
Section 8.2 Overall Study Design
Description of Change: 
Clarification regarding switching to BAX 930 SIN material added.
7.
Section 8.2.1.1.1 PK-II
Description of Change:  Clarification regarding exclusion from PK-II assessments.
8.
Section 8.7.2 Administration
Description of Change: 
Clarification regarding blood draw sampling and vital signs recording.
9.
Section 10.2 Subject Identification Code
Description of Change: Subject digit numbering system was updated.
10. Section 10.5 Patient Reported Outcomes
Description of Change: Information on subject diaries was clarified.
11. Section 10.8 Acute events during PK Assessment
Description of Change:
Information on acute events during PK assessment was clarified.
12. Section 11.2 Assessment of Pharmacokinetics and Pharmacodynamics
Description of Change: 
PK timepoints added for subjects undergoing Q1W dosing. PK assessments for 
subjects on Q3W clarified.
13. Section 12.1.1.2 Suspected Unexpected Serious Adverse Reaction (SUSAR)
Description of Change: Update to SUSAR reporting section.
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14. Section 12.7.5.5 VWF Multimer Analysis and ADAMTS13 mediated VWF 
cleavage products
Description of Change: VWF multimer analysis was updated.
15. Section 12.7.6.2 Anti-CHO Protein
Description of Change: 
The following text was added:
A positive result without known hypersensitivity to hamster proteins, such as a 
history of anaphylactic or anaphylactoid reactions or other severe allergic 
manifestations upon exposure to hamster-derived substances, will not constitute an 
exclusion criteria for randomization..
16. Section 12.7.7 Viral Serology
Description of Change: Information on viral serology testing was clarified.
17. Section 12.7.8 Genetic Testing
Description of Change: HLA genotype determination was removed.
18. Section 12.7.9 Pregnancy Test
Description of Change: Information on pregnancy test requirements was added.
19. Section 12.8 Vital Signs and 12-lead Electrocardiogram
Description of Change: Timing of vital signs testing was clarified.
20. Section 12.9 Health-related Quality of Life / Table 5
Description of Change: 
PRO section- Ped QL was updated, clarifications were added.
21. Section 13 STATISTICS, 
Section 20 SUPPLEMENTS
Description of Change: 
Changes to number of subjects in the study were reflected in the text; clarifications 
were made including the age groups in Tables 6a and 6b.
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22. Section 20.3 Schedule of Study Procedures and Assessments / Table 7
Description of Change: Table 7 updated to reflect changes in protocol procedures.
23. Section 20.4 Clinical Laboratory Assessments / Table 9, Table 11, Table 12
Description of Change: 
Tables 9 and 11 were updated and Table 12 was added to reflect changes in 
protocol procedures.
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22. SUMMARY OF CHANGES
Protocol 281102: Global Amendment 5 2018 DEC 06
Replaces: Global Amendment 2 2017 MAY 09
In this section, changes from Global Protocol Amendment 2, dated 2017 MAY 09, are 
described and their rationale is given.
1.
Throughout the document
Description of Change:
Particularly on the title page and all pages preceding the document text, changes 
have been made to make the document align better with the current Shire protocol 
template.   The address of Baxalta US, Inc., has also been updated.
Change of hereditary TTP to its current name: congenital TTP.
Addition of SHP655, as the newer name given to BAX 930 by its current sponsor, 
Shire at first mention.
2.
Section 3 Study Synopsis
Description of Change: 
Nomenclature of BAX 930 adjusted to include its newer name: SHP655 at first 
instance.
Study period updated to reflect current status
PK comparability aspect of study added to reflect current planned study conduct
Numbers of subjects for planned enrollment (ie sample size), enrollment of 
pediatric subjects, duration of time for subjects in the prophylaxis cohort, and 
planned study period dates and study duration were amended.
Windows (+/-) were added to planned dose levels.
Inclusion criteria were slightly amended/clarified.
Small changes to the exclusion criteria were made.
Specific information on the planned interim analysis was added.
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3.
Section 6.3
Description of Change: 
Sample size amended from 60 to 62.
4.
Section 6.4
Description of Change: 
Description of Q97R sequence variant added.
5.
Section 6.4.2.3
Mention of the Technozym ADAMTS13 activity ELISA removed.
6.
Section 6.5 
Description of Change: 
Information on Q97R variant added.
7.
Section 7.3.3 
Description of Change: 
PK/PD points added to reflect the PK comparability study.
8.
Section 8.1
Description of Change: 
Information on this amendment and its purpose was added, to specify study conduct 
after the temporary study halt.
9.
Section 8.2
Description of Change: 
Information on the PK comparability study and interim analysis were added to 
study design.
10. Section 8.3
Description of Change: 
Length of subject participation in the study updated.
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11. Section 8.5
Description of Change: 
Additional randomization sequence added, as part of the PK comparability study.
12. Section 8.6
Description of Change: 
The following statement was added:
If this study is halted for reasons listed in this section, restarting the trial will 
require a substantial amendment.
13. Section 8.7
Description of Change: 
Changes were made to the timing of testing for vital signs, timing of pulse rate 
monitoring, measurement of body weight, and Section 8.7.4 (dosing justification) 
was added to the document.
14. Section 9.1
Description of Change: 
Inclusion criterium 2 was amendment as follows:
Subject is 0 to 70 years of age, inclusive, at the time of screening. (Subjects 
<18 years of age will be enrolled only after at least 5 adults (≥18 years of age) 
each have at least 10 exposures with BAX 930 and reviewed by the DMC. In 
France, no patients younger than 18 years of age will be enrolled into the study 
before the first adult patient has been treated with BAX 930 for a minimum of 
6 months.
Inclusion criteria 8 and 9 were amended as follows:
If female of childbearing potential, subject presents with a negative blood or urine 
pregnancy test, confirmed no more than 7 days before the first administration, 
and agrees to employ adequate birth control measures for the duration of the study 
and to undergo quarterly pregnancy testing
Sexually active males must use an accepted and effective method of 
contraception during the treatment and until a minimum of 16 days after the 
last dose administered.
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15. Section 9.2
Description of Change: 
Point 8 on patients with diagnosed hepatic dysfunction removed the exclusion 
criterion that international normalized ratio would be >1.5.  The following 
exclusion criterion was also added:  
16. Section 10.3.1
Description of Change: 
Section added to describe screening process for pediatric subjects.
17. Section 10.4
Description of Change: 
The third point under Medications (not permitted within 30 days before study entry 
and during the course of the study) was changed to read:
Another IP or interventional drug within 30 days prior to enrollment
The first point under Medications (permitted within 30 days before study entry and 
during the course of the study) was changed to read:

FFP or any other ADAMTS13-containing products interfering with ADAMTS13 
PK will have to be paused at least 14 days [+/- 2 days] prior to the IP infusion for 
PK assessment. However, for PK-I, if subjects are receiving weekly treatment 
as part of their SoC prophylaxis regimen, washout periods can be reduced to 
1 week at the discretion of the investigator.
18. Section 10.8
Description of Change: 
Section added to describe treatment of acute events during PK assessment.
19. Section 11.2, Section 12.7.1, 12.7.2, 12.7.3, and Tables 9, 10 and 11
Description of Change: 
Timing of blood sample draws was changed.  Albumin was added to clinical 
chemistry panel to be taken at screening. Creatine kinase parameter specified to be 
measured at the central laboratory.
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20. Section 12.7.5.1
Description of Change: 
Section rewritten to reflect that the FRETS assay will measure ADAMTS13 activity.
21. Section 12.7.6 and in Table 9
Description of Change: 
Tiered approach to antibody testing added.  Addition of IgE antibody testing in 
case of allergic reactions.
22. Section 12.7.7
Description of Change: 
Viral seromarkers 4 was changed, and 5 was added as follows:
HCV: Chemiluminescence 
HEV: anti-HEV
23. Section 12.7.9
Description of Change: 
Period 3 treatment phase added.
24. Section 12.7.10
Description of Change: 
Excluded from lab values recorded on CRF to include platelet count and LDH.
25. Section 12.8
Description of Change: 
Timing of vital signs measurements and height and weight measurements changed.
26. Section 12.9
Description of Change: 
Table 5 changed to include HRU questions in the eDiary/daily evening report.
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27. Section 13
Description of Change: 
Sample revised to 62 subjects; cohort sizes changed; MFAS analysis set added and 
described; interim analysis added; Section 13.4 (Methods of Analysis) expanded 
and updated; analyses of pediatric subjects and of the various cohorts described 
and expanded upon; references to Technozym ADAMTS13 activity assay removed.
28. Section 15
Description of Change: 
The following statement was added:
This trial will also include a safety evaluation after first 6 subjects each have at 
least 3 BAX 930 SIN infusions (including PK infusions) to evaluate the 
ADAMTS13 activity.
29. Section 20
Description of Change: 
Section was updated to include and describe study conduct of PK comparability 
study, interim analyses, prophylactic and on-demand cohorts, pediatric patients 
(except in France, where pediatric patients under 18 years of age will not be 
enrolled in the study until the first adult patient in the study has been treated for at 
least 6 months), updated timing of study procedures and assessments, and 
contraceptive requirements for male subjects during the study.
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22. SUMMARY OF CHANGES
Protocol 281102: Amendment 2 2017 MAY 09
Replaces: Amendment 1 2017 MAR 15
In this section, changes from Protocol Amendment 1, dated 2017 MAR 15, are described 
and their rationale is given.
1.
Section 3 Study Synopsis
Description of Change: 
Clarified PK treatment order following randomization
ADAMTS13 trough levels re-defined as pre-infusion ADAMTS13
Clarified that subjects in the SoC prophylaxis cohort can have dose adjustments 
based on clinical symptoms and laboratory signs at the investigator’s discretion
Defined severe TTP signs
Clarified secondary outcome measures
Specified that subjects enrolling in the on-demand cohort and moving to the 
prophylaxis cohort will be analyzed separately and will not count towards the 40 
patient cap on the prophylaxis cohort
Clarified how subjects can move from the on-demand cohort to the prophylaxis 
cohort
Update the planned population PK analysis
2.
Section 6.3 Population To Be Studied
Description of Change: 
Specified that subjects enrolling in the on-demand cohort and moving to the 
prophylaxis cohort will not count towards the 40 patient cap on the prophylaxis 
cohort
3.
Section 7.3 Secondary Outcome measures
Description of Change: 
ADAMTS13 trough levels re-defined as pre-infusion ADAMTS13
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4.
Section 8.2 Overall Study Design
Description of Change: 
Clarified PK treatment order following randomization
5.
Section 8.2.1 Prophylaxis Treatment Cohort
Description of Change: 
Clarified that subjects in the SoC prophylaxis cohort can have dose adjustments 
based on clinical symptoms and laboratory signs at the investigator’s discretion
6.
Section 8.2.2 On-Demand Treatment Cohort
Description of Change: 
Clarified how subjects can move from the on-demand cohort to the prophylaxis 
cohort
7.
Section 8.4.2 Secondary Outcome Measures
Description of Change: 
Clarified secondary outcome measures
8.
Section 8.4.3 Exploratory Outcome Measures
Description of Change: 
Clarified exploratory outcome measures
9.
Section 9.1 Inclusion Criteria
Description of Change: 
Defined severe TTP signs
Specified that subjects in the prophylactic cohort must have the ability to tolerate 
SoC prophylactic dosing
Updated criteria for enrolling adolescent subjects
10. Section 12.1.1.2 Suspected Unexpected Serious Adverse Reaction (SUSAR)
Description of Change: 
Clarified how the FDA will be notified of AEs
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11. Section 12.7.10.1 Assessment of Abnormal Laboratory Values
Description of Change: 
Noted that normal values from the Coombs test and the evaluation of schistocytes 
should reported in the CRF
12. Section 13.1 Sample Size
Description of Change: 
Specified that subjects enrolling in the on-demand cohort and moving to the 
prophylaxis cohort will not count towards the 40 patient cap on the prophylaxis 
cohort
13. Section 13.4 Methods of Analysis
Description of Change: 
Clarified how efficacy analysis will be conducted for subjects who switch from the 
on-demand to the prophylaxis cohorts
14. Section 13.4.2.1 Secondary Outcome Measures
Description of Change: 
Clarified secondary outcome measures
15. Section 17.2 Study Documentation and Case Report
Description of Change: 
Case report forms will be provided in electronic format
16. Section 20.4 Schedule of Study Procedures and Assessments for Subjects on 
Prophylaxis Cohort: Table 7
Description of Change: 
Removed all information for the on-demand cohort (and created Table 8)
Specified a 14-21 day period between PK infusions and study periods
Specified that all assumptions are based on Q2Week dosing
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17. Section 20.4 Schedule of Study Procedures and Assessments for Subjects on 
On-Demand Cohort: Table 8
Description of Change: 
Created table to specify procedures and assessments for subjects in the on-demand 
cohort
18. Section 20.4 Clinical Laboratory Assessments: Prophylaxis Treatment 
(Prophylaxis Cohort), Table 9
Description of Change: 
Removed all information for the on-demand cohort (and created Table 10)
Added an ADAMTS13 post-infusion assessment for acute event and interval study 
visits
Clarified assessments to occur as part of acute event dosing visits
Added a Coombs test during acute event dosing visits
Added the evaluation of schistocytes as part of acute event visits
Changed blood group assessments to the local lab
Added a comblete blood count and pre-infusion ADAMTS13 activity assessments to 
prophylactic dosing visits
Added complete blood count, clinical chemistry, immunogenicity, and pregnancy 
tests assessments to the study completion visit
Specified a ± 2 day window for PK infusions
Specified that all assumptions are based on Q2Week dosing
19. Section 20.4 Clinical Laboratory Assessments: Acute Treatment 
(On-Demand Cohort): Table 10
Description of Change: 
Created table to specify assessments for subjects in the on-demand cohort
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22. SUMMARY OF CHANGES
Protocol 281102: Amendment 1 2017 MAR 15
Replaces: Original: 2017 FEB 13
In this section, changes from the previous version of the Protocol, dated 2017 FEB 13, 
are described and their rationale is given.
1.
Throughout Document
Description of Change:
hTTP replaced with cTTP
Purpose for Changes: Consistency with published guidance on standardization of 
terminology. (Scully M, Cataland  S, Coppo P, de la Rubia J, Friedman KD, 
Kremer Hovinga J, Lämmle B, Matsumoto M, Pavenshi K, Sadler E, Sarode R, 
Wu H, on behalf of the international working group for Thrombotic 
thrombocytopenic purpura (TTP). Consensus on the standardization of terminology 
in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. 
J Thromb Haemost 2017;15:312-322)
2.
Section 20.1 Study Flow Chart, Figure 1
Description of Change: 
Adapted PK infusion numbers.
Adapted language in footnote 3.
Purpose for Changes: Clarification of PK infusion dates.
3.
Section 20.3 Schedule of Study Procedures and Assessments, Table 7
Description of Change: 
PK Infusion #1: 
“Day 2, 4, 6, 7, 8, 9, 10, 11, 12” changed to “Day 2, 3, 5, 8, 9, 10, 11, 12, 13”.
PK Infusion #2:
“Day 26” changed to “Day 15”.
“Day 27, 29, 30, 32, 33, 34, 35, 36” changed to “Day 16, 17, 19, 22, 23, 24, 25, 26, 
27”.
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Period 1:
“V 21-45” changed to “V 21-32” to reflect 2x a month visit schedules for 6 months.
“Day 37, 51, 65, 79, 93, 107, 121, 135, 149, 163, 177, 191” changed to “Day 29, 43, 
57, 71, 85, 99, 113, 127, 141, 155, 169, 183”
Period 2
“V 46-70” changed to “V 33-44” 
“Day 205, 219, 233, 247, 261, 275, 289, 303, 317, 331, 345, 359” change to 
“Day 197, 211, 225, 239, 253, 267, 281, 295, 309, 323, 337, 351”.
Period 3
“V 71-85” changed to “V 45-56” for the same reasons as in Periods 1&2.
“Day 373, 387, 401, 415, 429, 443, 457, 485, 499, 513, 527” changed to “Day 365, 
379, 393, 407, 421, 435, 449, 463, 477, 491, 505, 519”.
PK Infusion #3:
“V 86” changed to “V 57”.
“Day 336” changed to “Day 533”.
“V 87-95” changed to “V 58-66”.
“Day 337, 338, 340, 341, 343, 344, 345, 346, 347, 348” changed to “Day 534, 535, 
537, 540, 541, 542, 543, 544, 545”
Footnotes:
The following was added to ensure clarity in the timing between periods: 
“*There is a 14-21 day period between PK Infusion # 1, PK Infusion # 2, Period 1, 
Period 2, Period 3, and PK Infusion # 3.”
Purpose for Changes: Clarification of study visit dates post-adjustment.
4.
Section 20.4 Clinical Laboratory Assessments, Table 9
Description of Change: 
Removed PK test from dosing visits. ADAMTS13 trough measures will be 
measured.
Added footnotes “n”, “o” and “p”.
Deleted footnote f under the SoC PK Infusion column and PK tests row.
Purpose for Changes: Clarification of PK test dates post-adjustment.
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