Clinical trial NCT04103034
Conditions: Cerebrovascular Stroke Large-Artery Atherosclerosis (Embolus/Thrombosis) Intracranial Arteriosclerosis
Keywords: Secondary Stroke Prevention
Sponsor: Band Therapeutics
Start date: 2019-10-07; Completion date: 2020-09-14
Enrollment: 112 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Study BT200-01 is a first in human (FIH) study in male and female normal human volunteers (NHVs) that uses an Integrated Protocol Design. This Phase 1 study will comprise 4 sub-parts: Part A, a single ascending dose (SAD) study; Part B, a multiple ascending dose (MAD) study; Part C, a desmopressin challenge study to explore (i) whether desmopressin could be used as an antidote, and/or (ii) whether desmopressin stimulated vonWillebrand Factor (VWF) release is overcome with increasing BT200 doses; and Part D, a relative bioavailability (BA) study.

The primary objective of this study is to assess the safety and tolerability profile of BT200 in NHVs.

Detailed description:

Arms: arm 1: Subjects will receive a single subcutaneous dose of BT200 0.18mg arm 2: Subjects will receive a single subcutaneous dose of BT200 0.6mg arm 3: Subjects will receive a single subcutaneous dose of BT200 1.8mg arm 4: Subjects will receive a single subcutaneous dose of BT200 6.0mg arm 5: Subjects will receive a single subcutaneous dose of BT200 12.0mg arm 6: Subjects will receive a single subcutaneous dose of BT200 24.0mg arm 7: Subjects will receive a single subcutaneous (SC) dose of BT200 24.0mg by gradual SC infusion arm 8: Subjects will receive a single subcutaneous dose of placebo arm 9: Subjects will receive an initial subcutaneous loading doses of BT200 12.0mg followed by 4 weekly (every 7 days) maintenance doses of BT200 12.0mg arm 10: Subjects will receive an initial subcutaneous loading dose of BT200 24mg followed by 4 weekly (every 7 days) maintenance doses of BT200 24mg arm 11: Subjects will receive an initial subcutaneous loading dose of Placebo followed by 4 weekly (every 7 days) maintenance doses of placebo arm 12: Subjects will receive a single subcutaneous dose of BT200 48.0mg followed by IV infusion (over 30 min) of 0.3µg/kg desmopressin administered 24 hours after single dose of BT200 arm 13: Subjects will receive a single subcutaneous dose of placebo followed by IV infusion (over 30 min of 0.3µg/kg desmopressin administered 24 hours after single dose of placebo arm 14: Subjects will receive a single IV dose of placebo administered over 24 hours arm 15: Subjects will receive a single subcutaneous (SC) dose of BT200 36.0mg by gradual SC infusion arm 16: Subjects will receive a single subcutaneous dose (SC) of BT200 48.0mg by gradual SC infusion arm 17: Subjects will receive a single subcutaneous (SC) dose of BT200 18.0mg by gradual SC infusion arm 18: Subjects will receive a single IV dose of BT200 24mg administered over 24 hours
Interventions: intervention 1: BT200 intervention 2: Desmopressin intervention 3: Placebo
Intervention descriptions: intervention 1: BT200 is a PEGylated synthetic RNA oligonucleotide intervention 2: Sterile solution for injection intervention 3: Sterile saline for injection

Protocol documents:
Prot_000.pdf: 
Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 1 
 
 
BT200-01 
A SINGLE/MULTIPLE ASCENDING DOSE PHASE 1 STUDY OF THE SAFETY, TOLERABILITY, 
AND PHARMACOLOGIC ACTIVITY OF BT200 IN NORMAL HUMAN VOLUNTEERS 
Protocol identification number:   
BT200-01 
EudraCT No.:   
2019-001818-42 
Protocol version:   
FINAL VERSION 1.5.1, DATE 22-APR-2020 
Test product:   
BT200 
 
Principal Investigator: 
Ao. Univ.-Prof. Dr. Ulla Derhaschnig 
 
Sponsor: 
Band Therapeutics, LLC 
 
 
 
 
 
Confidentiality 
The contents of the protocol are confidential and may not be communicated verbally or in writing without 
permission from the study sponsor. 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 2 
CONTACT ADDRESSES 
 
Sponsor 
Band Therapeutics, LLC 
101 Hartwell Avenue, Suite 2 
Lexington, MA 02421 USA 
Phone: + 1.781.918.6580 
Email: jim.gilbert@bandtherapeutics.com 
Sponsor’s Medical 
Monitor 
James C. Gilbert, MD 
Chief Executive Officer 
Band Therapeutics, LLC 
Phone (mobile): +1.617.281.3550 
Email: jim.gilbert@bandtherapeutics.com 
Principal Investigator: 
Ao. Univ.-Prof. Dr. Ulla Derhaschnig 
Medical University of Vienna 
Department of Clinical Pharmacology 
Waehringer Guertel 18-20 
1090 Vienna, Austria 
Phone: +43 1 40400 29810 
Fax: +43 140400 29980 
Email: ulla.derhaschnig@meduniwien.ac.at 
Data Monitoring 
Committee 
Univ.-Prof. Dr.med. univ. Dr. Heinz Burgmann, Chairman 
Department of Internal Medicine I, Div. of Infectious Diseases 
Währinger Gürtel 18-20 
1090 Vienna, Austria 
Phone: +43 1 40400 44400 
Project Management 
Data Monitoring 
Celerion 
Hainburger Strasse 33 
1030 Vienna| Austria 
Phone: +43 1 403 38 05 – 54 
Fax: +43 1 403 38 05 -66  
www.celerion.com 
Data Management 
Statistics 
Assign Data Management and Biostatistics GmbH 
Stadlweg 23 
6020 Innsbruck 
Austria 
Ph: +43 512 890 064 121 
Fax: +43 512 281 514 
BT200 Bioanalysis 
QPS 
3 Innovation Way #240 
Newark, DE 19711 USA  
Phone:  +1. 302 369-5601 
Pharmacokinetic and 
Pharmacodynamic 
Analysis 
Certara 
2000 Peel Street, Suite 570 
Montréal, Québec 
H3A 2W5 Canada 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 3 
Tel: +1 514 789 2180 
Immunogenicity (Anti-
Drug Antibody) 
Analysis 
STC Biologics 
330 Nevada Street, Newton, MA 02460, USA 
Phone: +1 617 916-9659 
Drug Supply 
ABF Pharmaceutical Services GmbH 
Brunner Strasse 63/18-19 
1230 Vienna Austria 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 4 
Summary of Changes in Version 1.1 Relative to Version 1.0 
• 
Reference to contraceptives in the description of permitted concomitant medications was 
deleted as Not Applicable given that the inclusion of women volunteers has been restricted to 
those who are post-menopausal or status post hysterectomy. 
• 
Cohorts 8-10 of Part A will not be initiated before a Substantial Amendment summarizing the 
results of Part A Cohorts 1-7 has been submitted to EC and AGES and authorized. 
• 
Information supporting the IV route of administration was added to Section 3.1.1, Justification 
for Dose Regimen. 
 
Summary of Changes in Version 1.2 Relative to Version 1.1 
• 
Contact Information was updated with the correct new phone number for Band Therapeutics’ 
company offices. 
• 
The address for ABF Pharmaceutical Services GmbH was updated to correspond to the 
location of the company’s new facility where BT200 packaging and labeling is now being 
performed. 
• 
ABO blood group typing was added to the Screening Visit tests as an extra precaution so that 
in case a serious bleeding event should occur requiring urgent blood transfusion this 
information would already be available. 
• 
ISTH Bleeding Score was added as a specific and standardized safety assessment in case of 
the occurrence of "clinically evident bleeding". 
• 
A discrepancy between the Schedule of Events and the Lab Sampling table in Appendix 4 with 
respect to the timing of samples for anti-drug antibody testing in Part D was corrected. 
• 
An error in the Study Diagram for Part A was corrected, now placing the DSMB review after 
Cohort 7 and before Cohort 8, as per agreement with AGES. 
 
Summary of Changes in Version 1.3 Relative to Version 1.2 
Emerging PK and PD data from Part A suggest that the SC bioavailability of BT200 in humans may be 
lower than predicted.  To address this concern the following modifications of the Phase 1 plan have 
been introduced; 
• 
In Part A (the Single Ascending Dose part of the study) the mode of study drug administration 
was changed from rapid SC injection to gradual SC infusion. 
• 
In Part A two additional dose cohorts were added in order that: 
o 
the 24 mg dose could be repeated (in a new cohort of subjects) using the technique 
of gradual SC infusion; 
o 
the highest dose to be increased to 48 mg dose cohort (i.e., exceeding the previous 
top dose of 36 mg, which will be retained in the new version of the protocol). 
• 
Part D (the IV crossover part of the study) was moved ahead of Part B (the Multiple 
Ascending Dose part of the study) in the order of clinical operations so that a definitive read-
out of relative bioavailability of BT200 (SC versus IV) will be obtained prior to conduct of Part 
B in case modification of the dosing scheme for Part B should be required. 
• 
Part C (the desmopressin challenge part of the study) was reduced from two to one cohort of 
subjects. 
• 
A second DSMB review and Substantial Amendment based upon the results of the expanded 
Part A together with those of Part C and Part D will be performed prior to initiation of Part B. 
In addition, clarification of the timing of post-dose immunogenicity samples in Parts A, B, C, and D 
was added to the corresponding tables of Study Procedures. 
 
 Summary of Changes in Version 1.4 Relative to Version 1.3 
 
Emerging PK and PD data from the additional Part A cohorts introduced in the preceding amendment 
show a favorable trend toward increased SC bioavailability of BT200 after SC infusion relative to SC 
small volume bolus injection, but suggest that the dose needs to be increased further to achieve the 
therapeutic target concentration of BT200.  In order to accomplish this two new Part A cohorts have 
been added, both with BT200 administration by the SC infusion technique. 
• 
BT200 72 mg SC injection or infusion; N=8; 6:2 active:placebo randomization 
• 
BT200 96 mg SC injection or infusion; N=8; 6:2 active:placebo randomization 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 5 
The visit schedule and planned study assessments will remain the same as for all previous Part A 
cohorts DSMB review of safety after Part A cohorts 8-10 and Part D (the IV crossover cohort) will be 
completed prior to initiation of these two new Part A cohorts. 
 
In order to optimize the route, dose, and timing of BT200 administration for Part C according to the 
emerging PK data from Part A, study drug administration in Part C, is being changed as follows: 
• 
BT200 administration will now be done only by SC infusion; 
• 
The dose of BT200 will now be 48 mg, not 24 mg; 
• 
BT200 will now be administered 96 hours prior to desmopressin, not 24 hours.  
 
Summary of Changes in Version 1.5.1 Relative to Version 1.4 
Substantial Changes: 
After reviewing the safety and pharmacodynamic results of Part A Cohorts 8-10 and Part D Cohort 11 
the DSMB recommended not to escalate the dose of BT200 any further in healthy volunteers than the 
48 mg dose that had been administered in Part A Cohort 10.  Therefore, the following modifications to 
the study will be made via this amendment. 
 
• 
Part A Cohorts 16 (72 mg) and 17 (96 mg) will not be implemented as planned in Version 1.4 
of this study protocol.  Part A will now be closed. 
• 
With no further dose escalation there is no longer the need for another interim DSMB safety 
review before the initiation of Part B, the Multiple Ascending Dose component of this study. 
• 
The dose regimens for Part B can now be finalized based upon the safety, pharmacokinetics, 
and pharmacodynamics observed in the completed Part A. 
• 
Part B Cohort 13:  BT200 12 mg IV plus 12 mg SC on Day 0, then 12 mg SC on Days 7, 14, 
21, and 28 
• 
Part B Cohort 14:  BT200 24 mg IV plus 24 mg SC on Day 0, then 24 mg SC on Days 7, 14, 
21, and 28 
• 
Part B Cohort 15, the high dose cohort previously planned, will be eliminated. 
 
Part C, the desmopressin challenge will still be performed as planned in Version 1.4 of this study 
protocol (with a single dose of 48 mg of BT200). 
 
Miscellaneous Changes: 
• 
One additional VWF-related biomarker, VWF propeptide, will be added to the laboratory 
analysis program for Part A, in order to clarify the mechanism underlying the observed, 
unexpected rise in VWF antigen after BT200 treatment.  No additional blood sampling will be 
required as this assay can be performed with the unused PK back-up samples. 
• 
A typographical error in the heading of Table 3 Study Procedures Part B was corrected. 
• 
Screening for coronavirus by nasal swab testing was added to the Screening Visit procedures 
for Part B and Part C. 
 


Band Therapeutics, LLC 
1.5.1 
Approval of the Protocol 
Clinical Study Protocol BT200-01 FINAL VERSION 
':4 SINGLE/MULTIPLE ASCENDING DOSE PHASE 1 STUDY OF THE SAFETY, TOLERABILITY, AND 
PHARMACOLOGIC ACTIVITY OF BT2OO IN NORMAL HUMAN VOLUNTEERS* 
FINAL VERSION 1.5.1, DATE 22-APR-2O2O 
Representative of the Sponsor: Dr. James Gilbert, Chief Executive Officer, Band Therapeutics, LLC 
Date (DD Month YYYY) 
Principal Investigator: Ao. Univ.-Prof. Dr. Ulla Derhaschnig 
Signature 
Date (DD Month YYYY) 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 8 
PROTOCOL SYNOPSIS 
Title 
A SINGLE/MULTIPLE ASCENDING DOSE PHASE 1 STUDY OF THE 
SAFETY, TOLERABILITY, AND PHARMACOLOGIC ACTIVITY OF 
BT200 IN NORMAL HUMAN VOLUNTEERS  
Protocol Number 
BT200-01 
Version 
DRAFT VERSION 1.5.1, Date 22-APR-2020 
EUDRACT Number 
2019-001818-42 
Test Product 
BT200 
Phase 
Phase 1 
Indication 
Stroke prevention in high-risk patients 
Sponsor 
Band Therapeutics, LLC 
101 Hartwell Avenue, Suite 2 
Lexington, MA 02421 USA 
Phone: + 1.781.918.6580 
Email: jim.gilbert@bandtherapeutics.com 
Sponsor’s Medical 
Monitor 
James C. Gilbert, MD 
Chief Executive Officer 
Band Therapeutics, LLC 
Phone: + 1.781.918.6580 
Email: jim.gilbert@bandtherapeutics.com 
Principal Investigator 
Ao. Univ.-Prof. Dr. Ulla Derhaschnig 
Medical University of Vienna 
Department of Clinical Pharmacology 
Waehringer Guertel 18-20 
1090 Vienna, Austria 
Phone: +43 1 40400 29810 
Fax: +43 140400 29980 
Email: ulla.derhaschnig@meduniwien.ac.at 
Data Monitoring 
Committee 
Univ.-Prof. Dr. Heinz Burgmann, Chairman 
Department of Internal Medicine I, Div. of Infectious Diseases 
Währinger Gürtel 18-20 
1090 Vienna, Austria 
Phone: +43 1 40400 44400 
Project Management 
Data Monitoring 
Celerion 
Hainburger Strasse 33 
1030 Vienna| Austria 
Phone: +43 1 403 38 05 – 54 
Fax: +43 1 403 38 05 -66  
www.celerion.com 
Data Management 
Statistics 
Assign Data Management and Biostatistics GmbH 
Stadlweg 23 
6020 Innsbruck 
Austria 
Ph: +43 512 890 064 121 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 9 
Fax: +43 512 281 514 
BT200 Bioanalysis 
QPS 
3 Innovation Way #240 
Newark, DE 19711 USA  
Phone:  +1. 302 369-5601 
Pharmacokinetic and 
Pharmacodynamic 
Analysis 
Certara 
2000 Peel Street, Suite 570 
Montréal, Québec 
H3A 2W5 Canada 
Phone: +1 514 789 2180 
Immunogenicity (Anti-
Drug Antibody) 
Analysis 
STC Biologics 
330 Nevada Street, Newton, MA 02460, USA 
Phone: +1 617 916-9659 
Drug Supply 
ABF Pharmaceutical Services GmbH 
Brunner Strasse 63/18-19 
1230 Vienna Austria 
Phone: +43 1 8901200 
Study Design 
Prospective, double-blind, randomized, placebo-controlled First-In-
Human (FIH) study in male and female normal human volunteers (NHVs) 
with 4 sub-parts: 
• 
Part A, a single ascending dose (SAD) study; 
• 
Part B, a multiple ascending dose (MAD) study; 
• 
Part C, a desmopressin challenge study; 
• 
Part D, a relative bioavailability study. 
Rationale 
BT200 is a PEGylated aptamer that binds to the A1 domain of human von 
Willebrand Factor (VWF) and thereby inhibits VWF binding to platelet 
glycoprotein Ib (GP1b), the first step in the cascade of platelet-mediated 
thrombogenesis. Study BT200-01 is a Phase 1 FIH study designed to 
assess 
the 
human 
safety, 
tolerability, 
pharmacokinetics, 
and 
pharmacologic activity of BT200 in NHVs. In order to ensure the well-being 
of study subjects, some key safety measures have been incorporated into 
the design of this study, including use of sentinel pairs of subjects and an 
independent Data and Safety Monitoring Board (DSMB). In order to 
assess the effect of elevated VWF levels (as might be encountered in 
patients in the future) on the BT200 concentration-effect relationship,1 
single-dose cohort of BT200 administered together with a secretagogue 
for VWF (desmopressin) will be included as Part C. Finally, in order to 
assess the relative bioavailability of BT200 via subcutaneous (SC) vs. 
intravenous (IV) administration, a single dose IV cohort will be included as 
Part D. Based upon the PK and PD data observed in Parts A, C, and D 
the nominal dose levels specified in Part B may be adjusted by means of 
a Substantial Amendment to this protocol prior to initiation of dosing 
therein.   
Anticipated Start Date 
Q3/2019 
Duration of Study 
1.5 years 
Proposed Country 
Austria 
Study Site 
Medical University of Vienna 
Department of Clinical Pharmacology 
Waehringer Guertel 18-20 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 10 
1090 Vienna, Austria 
Phone: +43 1 40400 29810 
Fax: +43 140400 29980 
Email: klin-pharmakologie@meduniwien.ac.at 
Planned Sample Size 
Part A:80 NHVs 
Part B: 16 NHVs 
Part C: 8 NHVs 
Part D: 8 NHVs (including NHVs who may have previously participated 
in Part A) 
Primary Objective 
The primary objective of this study is to assess the clinical safety and 
tolerability of BT200 in NHVs. 
Secondary Objectives 
The secondary objective of this study is to assess the human PK of 
BT200. 
Exploratory Objectives 
The exploratory objectives of this study are to evaluate the human 
immunogenicity and PD of BT200, as follows: 
• 
To evaluate the presence of anti-drug antibodies (ADAs) against 
BT200 
• 
To evaluate the human pharmacodynamics (PD) of BT200 with 
respect to VWF-mediated platelet function  
• 
To evaluate the human PK/PD relationship of BT200 
• 
To evaluate potentially useful biomarkers for future clinical trials 
• 
To investigate the mechanism of action of BT200 on the human 
coagulation system 
Target Population 
NHVs 
Inclusion Criteria 
To be eligible for this study, subjects must meet all of the following 
inclusion criteria: 
1. Healthy male or female volunteers, age ≥ 18 years old at screening 
2. If female, must be post-menopausal or status post hysterectomy 
3. Able to comprehend and to give informed consent 
4. Able to cooperate with the Investigator, to comply with the 
requirements of the study, and to complete the full sequence of 
protocol-related procedures 
Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the 
study: 
1. Clinically significant medical history (including von Willebrand 
Disease, thrombocytopathy, or any type of bleeding diathesis) or 
ongoing chronic illness that would jeopardize the safety of the subject 
or compromise the quality of the data derived from his/her 
participation in this study 
2. Clinically relevant abnormal findings on physical examination or 
clinically relevant laboratory abnormalities 
3. History of infusion hypersensitivity reactions, significant drug allergy, 
or anaphylactic reactions 
4. Substance abuse, mental illness, or any reason that makes it unlikely 
in the judgment of the Investigator for the subject to be able to comply 
fully with study procedures 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 11 
5. Use of medication during 2 weeks before the start of the study, which 
in the judgment of the Investigator may adversely affect the subject’s 
welfare or the integrity of the study’s results  
6. Concurrent treatment with other experimental drugs or participation in 
another clinical trial with any investigational drug within 30 days or 
5 elimination half-lives (whichever is longer) prior to treatment start 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 12 
Treatments 
Administered 
Part A: 
• 
Randomization ratio for BT200 to placebo = 6:2 (except for the 
sentinel pair, which will be at a ratio of 1:1) 
• 
Single SC doses of placebo or BT200 at the following BT200 dose 
levels per cohort: 
o 
Cohort 1: 0.18 mg (N=8) 
o 
Cohort 2: 0.6 mg (N=8) 
o 
Cohort 3: 1.8 mg (N=8) 
o 
Cohort 4: 6.0 mg (N=8) 
o 
Cohort 5: 12.0 mg (N=8) 
o 
Cohort 6: 18.0 mg (N=8) 
o 
Cohort 7: 24.0 mg (N=8) 
o 
Cohort 8: 24.0 mg by SC infusion (N=8) 
o 
Cohort 9: 36.0 mg by SC infusion (N=8) 
o 
Cohort 10: 48.0 mg by SC infusion (N=8) 
 
Cohorts 8-10 will be initiated only after submission and authorization of a 
Substantial Amendment to EC and AGES summarizing the results of 
Cohorts 1-7. 
. 
 
Part B: 
• 
Randomization ratio for BT200 to placebo = 6:2 
• 
Loading and maintenance doses of placebo or BT200 via a 2-hour 
IV infusion and a SC injection at the following BT200 dose levels 
per cohort: 
o 
Cohort 13: Loading dose of 12.0 mg IV + 12.0 mg SC, 
followed by 4 weekly maintenance doses of 12.0 mg SC 
(N=8) 
o 
Cohort 14: Loading dose of 24.0 mg IV + 24.0 mg SC, 
followed by4 weekly  maintenance doses of 24.0 mg SC 
(N=8) 
. 
 
Part C: 
• 
Randomization ratio for BT200 to placebo = 6:2, plus 
desmopressin challenge 
• 
Single doses of placebo or BT200 via SC injection at the following 
BT200 dose levels per cohort: 
o 
Cohort 12:  BT200 + desmopressin challenge cohort: 
48.0 mg (N=8) Single IV dose of desmopressin at the 
following dose level for all NHVs: 
o 
0.3 µg/kg 
Part D: 
• 
Randomization ratio for BT200 to placebo = 6:2 
• 
Single IV dose of placebo or BT200 at the following BT200 dose 
level for all NHVs: 
o 
Cohort 11: 24.0 mg (N=8) 
. 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 13 
Treatment Schedule & 
Route of Administration 
Part A: 
• 
All dose cohorts will receive a single SC dose of BT200 or placebo 
on Day 0 at Time 0 
Cohorts 8-10 will be initiated only after submission and authorization of a 
Substantial Amendment to EC and AGES summarizing the results of 
Cohorts 1-7. 
Cohorts 16-17 will be initiated only after submission and authorization of 
a Substantial Amendment to EC and AGES summarizing the results of 
Cohorts 8-10 of Part A and Cohort 11 of Part D. 
 
Part B: 
• 
All dose cohorts will receive a total of 6 SC or IV doses of BT200 
or placebo: 
o 
Loading dose regimen consisting of equal IV and SC doses 
on Day 0 at Time 0 
o 
IV dose will be infused over 2 hours 
o 
Maintenance doses: 4 SC doses thereafter every 7 days 
 
Part C: 
• 
All subjects will receive only a single SC dose of BT200 or placebo 
on Day -4 
• 
All subjects will receive desmopressin by IV infusion over 
30 minutes on Day 0 at approximately 96 hours after the single 
SC dose of BT200 or placebo 
 
Part D: 
• 
One cohort will receive BT200 or placebo administered as an 
IV infusion over 24 hours 
Investigational 
Medicinal Product 
Test Product:  
• 
BT200 as a sterile solution for injection 
Comparator (Placebo): 
• 
Sterile saline for injection 
Non-investigational Medicinal Product (NIMP; Challenge Agent): 
• 
Desmopressin (MINIRIN® Injection) as a sterile solution for 
injection 
Primary Endpoint 
Overall safety and tolerability of BT200, assessed in terms of: 
• 
Serious, drug-related adverse events (AEs) 
• 
Premature terminations due to drug-related AEs 
• 
Patterns of serious or non-serious, drug-related AEs and/or 
clinically relevant laboratory abnormalities, vital signs, ECGs, or 
physical findings suggestive of one or more specific target organs 
for toxicity of BT200 
• 
Clinically evident bleeding assessed using the ISTH Bleeding 
Score (see Appendix 6) 
Secondary Endpoints 
Pharmacokinetic Endpoints: 
• 
Measured concentration of BT200 (and derived PK parameters) 
Exploratory Endpoints 
Immunogenicity Endpoint: 
• 
ADAs against BT200 
Pharmacodynamic Endpoints: 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 
1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 14 
• 
Platelet Function Analyzer (PFA-100®) 
• 
VWF:ristocetin co-factor assay (VWF:RiCo) 
• 
Multiplate electrode platelet aggregometer (ristocetin) 
• 
Enzyme-linked immunosorbent assay (ELISA) for unbound 
VWF-A1 domain (REAADS®) 
Biomarker Endpoints: 
• 
VWF antigen and propeptide 
• 
Factor VIIIc activity 
• 
aPTT FS (elagic acid) 
• 
Thrombin generation Calibrated Automated Thrombogram (CAT) 
assay (Thrombinoscope®) 
Statistical 
Considerations 
Sample Size Calculation: 
As this study is exploratory and descriptive in nature, no inferential 
statistical testing is planned and therefore an exact sample size 
requirement cannot be specified. The number of NHVs planned to be 
included is expected to be sufficient to fulfill the study’s objectives, but 
not excessive. 
Analysis Plan: 
For the analysis of AEs, summary tables will be generated for the 
incidence of AEs overall and by severity. The same will be calculated for 
serious adverse events (SAEs), related AEs, and related SAEs. The AE 
and SAE summary tables will provide the number and percentage of 
subjects with AEs and the 95% confidence intervals for the event rates. 
All safety analyses will be performed within the Safety Population. 
Pharmacokinetic sampling results (serum concentration of BT200) will be 
tabulated descriptively by sampling time point. The area under the curve 
from 0 to 24 hours (AUC[0-24h]) and area under the curve from time 0 to 
time t (AUC[0-t]) will be calculated via trapezoidal rule and will be tabulated 
together with the maximum plasma concentration (Cmax) and time to 
maximum plasma concentration (Tmax), descriptively. 
Details regarding further safety endpoints and the analysis of secondary 
or exploratory endpoints will be described in the Statistical Analysis Plan. 
Interim Analysis 
A complete interim analysis is not planned; however, the DSMB will 
review relevant safety data after Cohorts 1-7 of Part A prior to initiation 
of Cohorts 8-10 of Part A, and Part D; after Cohorts 8-10 of Part A and 
Cohort 11 of Part D and prior to initiation of Cohorts 16-17 of Part A and 
Cohort C;. The data prepared for DSMB review together with the 
resulting DSMB opinion will be provided to EC and AGES as part of a 
Substantial Amendment after Cohorts 1-7 of Part A prior to initiation of 
Cohorts 8-10 of Part A and Part D;; after Cohorts 8-10 of Part A and Part 
D prior to initiation of Part B. 
Study Plan 
First Subject In (FSI) to Part A: 
Q3/2019 
Last Subject In (LSI) to Part B: 
Q3/2020 
Last Subject Out (LSO): 
Q4/2020 
Database Lock: 
Q1/2021 
Clinical Study Report (CSR):  
Q2/2021 
 


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 15 
 
STUDY DIAGRAM 
Figure 1 
Study Diagram 
The following is an idealized diagram of the study intended to show the sequence and relative timing of dosing in Parts A, B, C, and D. Note that for the sake of 
visual simplicity, this idealized diagram gives the appearance of simultaneous dosing within each cohort; it does NOT reflect the sentinel pair dosing scheme for 
Part A, nor the possibility that the remainder of each cohort will be broken into small groups, each of which might be dosed on consecutive days.  The first DSMB 
and Regulatory interim review will occur after Cohorts 1-7 of Part A have been treated (shown in the diagram for Part A).  A second DSMB and Regulatory interim 
review will occur after Cohorts 8-10 of Part A and Cohort 11 of Part D and a third DSMB and Regulatory interim review will occur prior to initiation of Part B (not 
shown).  
 
 
 
STUDY PART A
W1
W2
W3
W4
W5
W6
W7
W8
W9
W10
W11
W12
End of 
Part A
1
↓
2
↓
3
↓
4
↓
5
 ↓
6
↓
7
↓
8
↓
9
↓
10
↓
DSMB #2 and Regulatory review
Part A Study Duration (Relative Weeks)
48.0 mg SC infusion
24.0 mg SC infusion
36.0 mg SC infusion
0.6 mg SC injection
24.0 mg SC injection
18.0 mg SC injection
12.0 mg SC injection
6.0 mg SC injection
1.8 mg SC injection
DSMB #1 and Regulatory review
Cohort 1
Single Placebo or BT200 Dose SC 2
N=8 per Cohort
0.18 mg SC injection
STUDY PART B
W1
W2
W3
W 4
W5
W 6
W7
W 8
W9
W10
W11
W12
W13
W14
End of 
Part B
Loading Placebo or BT200 Dose2
Maintenance 
Placebo or 
BT200 Dose 
SC injection 
or IV 2
13
12.0 mg IV + 12.0 mg SC
12.0 mg
↓
↓
↓
↓
↓
14
24.0 mg IV + 24.0 mg SC
24.0 mg
↓
↓
↓
↓
↓
Cohort 3
Part B Study Duration (Relative Weeks)
N=8 per Cohort


Band Therapeutics, LLC                                                 Clinical Study Protocol BT200-01 FINAL VERSION 1.5.1 
22-APR--2020 
Proprietary & Confidential Information 
pg. 16 
 
  
  
 
 
 
  
 
Abbreviations: ↓=dosing; DSMB=Data and Safety Monitoring Board; IV=intravenous(ly); N/A=not applicable; NHV=normal human volunteer; SC=subcutaneous(ly); W=week 
1. 
Part A Cohorts will also include NHVs treated with placebo (N=2 for all Cohorts). Each cohort will include a sentinel pair, with a randomization ratio of 1:1 for BT200 to placebo. All 
dose cohorts will receive a single SC dose of BT200 or placebo on Day 0 of Week 1 (Cohort 1), Week 2 (Cohort 2), Week 3 (Cohort 3), Week 4 (Cohort 4), Week 5 (Cohort 5), 
Week 6 (Cohort 6), Week 7 (Cohort 7),  Week 9 (Cohort 8), Week 10 (Cohort 9), Week 11 (Cohort 10),). 
2. 
In this figure, BT200 doses are shown for each cohort. 
3. 
Part B Cohorts will also include NHVs treated with placebo (N=2 for Cohorts 13 and 14). Both dose cohorts will receive total of 6 doses of BT200 or placebo, comprising the split IV 
+ SC loading dose  Day 0 and maintenance SC doses as follows: 4 doses every 7 days of Weeks 1 to 5 (Cohort 13)and Weeks 3 to 7 (Cohort 14). 
4. 
Part C Cohorts will also include NHVs treated with placebo (N=2 for Cohort 12 [BT200 + desmopressin challenge] All subjects will receive only a single SC injection  of BT200 or 
placebo on Day -4 of Week 1. All subjects will receive desmopressin by IV infusion over 30 minutes on Day 0 of Week 1 (Cohort 12) at approximately 96 hours after the single 
dose of BT200 or placebo. 
5. 
Part D Cohort 11 will also include NHVs treated with placebo (N=2). This cohort will receive BT200 or placebo administered as an IV infusion over 24 hours on Day 0 of Week 1. 
STUDY PART D
W1
W2
W3
W 4
W5
W 6
W7
W 8
End of 
Part D
11
↓
Part D Study Duration (Relative Weeks)
Cohort 5
Single Placebo or BT200 Dose IV 2
N=8
24.0 mg
STUDY PART C
W1
W2
W3
W 4
W5
W 6
W7
W 8
End of 
Part C
Cohort 4
Single Dose SC injection2
N=8 per Cohort
Part C Study Duration (Relative Weeks)
12
Placebo or BT200: 48.0 mg SC injection
↓
Desmopressin:
0.3 µg/kg IV

SAP_001.pdf: 
SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
Page 1 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
Statistical Analysis Plan 
Part A, Part B, Part C and Part D Analysis 
A SINGLE/MULTIPLE ASCENDING DOSE PHASE 1 STUDY OF THE 
SAFETY, TOLERABILITY, AND PHARMACOLOGIC ACTIVITY OF BT200 IN 
NORMAL HUMAN VOLUNTEERS 
Protocol: BT200-01 
Confidential 
Sponsor: 
Band Therapeutics, LLC 
NCT #04103034 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 2 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
Table of Contents 
 
1. 
OVERVIEW 
6 
1.1 
Study Objectives 
6 
1.1.1 
Primary Objective 
6 
1.1.2 
Secondary Objective 
6 
1.1.3 
Exploratory Objectives 
6 
1.2 
Study Design 
6 
1.3 
Endpoints 
7 
1.3.1 
Primary Endpoint 
7 
1.3.2 
Secondary Endpoints 
8 
1.3.3 
Exploratory Endpoints 
8 
1.4 
Sample Size Calculation 
8 
1.5 
Flowchart and Schedules of Assessments 
8 
2. 
GENERAL CONSIDERATIONS 
18 
2.1 
Rationale 
18 
2.2 
Conduct of Analysis 
18 
2.3 
Statistical Software and Quality Control 
18 
2.4 
Applicable Standard Operating Procedures 
18 
2.5 
Blinding and Randomization 
19 
2.6 
Descriptive Analyses 
19 
2.7 
Inferential Analyses 
19 
2.8 
Center and Country Effect 
19 
2.9 
Handling Missing Data 
19 
2.10 
Protocol Deviations 
20 
2.11 
Medical Coding 
20 
2.12 
Analysis Populations 
20 
2.12.1 
Safety Population 
20 
2.12.2 
Per-Protocol Population 
20 
2.13 
Subject Data Listings 
21 
2.14 
Columns in Tables 
21 
2.15 
Changes in the Conduct of the Study or Planned Analysis 
21 
2.16 
Effect of Covid-19 
21 
3. 
OVERALL STUDY INFORMATION 
21 
4. 
BASELINE EVALUATION 
22 
4.1 
Data Points 
22 
4.2 
Derivations and Definitions 
22 
5. 
PHARMACOKINETICS / PHARMACODYNAMICS / BIOMARKER / IMMUNOGENICITY 
23 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 3 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
5.1 
Pharmacokinetics 
23 
5.2 
Pharmacodynamics 
23 
5.3 
Biomarker 
23 
5.4 
Immunogenicity 
24 
6. 
SAFETY ANALYSIS 
24 
6.1 
Extent of Exposure 
24 
6.2 
Adverse Events and Bleeding Events 
24 
6.2.1 
Data Points 
24 
6.2.2 
Definitions and Derivations 
25 
6.3 
Laboratory Parameters 
26 
6.4 
Other Safety Parameters 
27 
7. 
LIST OF TABLES, DATA LISTINGS AND FIGURES 
28 
7.1 
List of Tables 
29 
7.2 
List of Data Listings 
34 
7.3 
List of Figures 
37 
8. 
SHELLS OF TABLES, DATA LISTINGS AND FIGURES 
38 
 
 




SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 5 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
List of Abbreviations 
 
ADA 
Anti-drug antibody 
AE 
Adverse Event 
AGES 
Austrian Agency for Health and Food Safety GmbH 
aPTT 
Activated partial thromboplastin time 
BA 
Bioavailability 
BDRM 
Blind Data Review Meeting 
BMI 
Body Mass Index 
CAT 
Calibrated Automated Thrombogram 
CI 
Confidence Interval 
CSP 
Clinical Study Protocol 
CSR 
Clinical Study Report 
DSMB 
Data and Safety Monitoring Board 
EC 
Ethics Committee 
ELISA 
Enzyme-linked immunosorbent assay 
FIH 
First-In-Human 
GP1b 
Glycoprotein Ib 
IV 
Intravenous 
MAD 
Multiple ascending dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
NHV 
Normal healthy volunteer 
PD 
Pharmacodynamic(s)  
PFA 
Platelet Function Analyzer 
PK 
Pharmacokinetic(s)  
PP 
Per-Protocol 
SAD 
Single ascending dose 
SC 
Subcutaneous 
SD 
Standard deviation 
SMQ 
Standardized MedDRA Query 
TLF 
Tables, Listings and Figures 
Tmax 
Time to Maximum Plasma Concentration 
VWF 
Von Willebrand Factor 
VWF:RiCo  
Von Willebrand Factor:ristocetin co-factor assay 
WHO 
World Health Organization 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 6 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
1. 
OVERVIEW 
1.1 
Study Objectives 
1.1.1 
Primary Objective 
The primary objective of this study is to assess the clinical safety and tolerability of BT200 in normal human 
volunteers (NHVs). 
1.1.2 
Secondary Objective 
The secondary objectives of this study are to assess the human pharmacokinetics (PK) of BT200. 
1.1.3 
Exploratory Objectives 
The exploratory objectives of this study are to evaluate the human immunogenicity and Pharmacodynamics (PD) of 
BT200, as follows:  
• 
To evaluate the presence of anti-drug antibodies (ADAs) against BT200  
• 
To evaluate the human PD of BT200 with respect to von Willebrand Factor (VWF)-mediated platelet 
function  
• 
To evaluate the human PK/PD relationship of BT200  
• 
To evaluate potentially useful biomarkers for future clinical trials  
• 
To investigate the mechanism of action of BT200 on the human coagulation system  
1.2 
Study Design 
Study BT200-01 is a prospective, double-blind, randomized, placebo-controlled First-In-Human (FIH) study of BT200 
in male and female NHVs with 4 sub-parts: Part A, a single ascending dose (SAD) study; Part B, a multiple ascending 
dose (MAD) study; Part C, a desmopressin challenge study; and Part D, a relative Bioavailability (BA) study. 
Part A, the SAD study in NHVs, will be conducted according to an ascending dose cohort paradigm in which a unique 
cohort of NHVs will be treated at each single dose level. There will be 10 cohorts of NHVs (6:2 ratio of 
BT200:placebo; except for the sentinel pair [1:1 ratio]). Cohorts 1 through 10 will consist of 8 NHVs each, comprising 
6 NHVs administered BT200 subcutaneous (SC) (0.18, 0.6, 1.8, 6.0, 12.0, 18.0, 24.0 by rapid SC injection, and 
24.0, 36.0 mg, 48.0 mg by gradual SC infusion, respectively, for each cohort) and 2 NHVs administered placebo SC. 
Not all NHVs in a given cohort in Part A will be dosed on the same day: a sentinel pair (1 BT200, 1 placebo) will be 
dosed on the first day, then with a lag of at least 48 hours staggered groups roughly of 2 to 3 NHVs per day will be 
dosed thereafter. Cohorts 8-10 of Part A will be initiated only after submission and authorization of a Substantial 
Amendment to Ethics Committee (EC) and Austrian Agency for Health and Food Safety (AGES) summarizing the 
results of Cohorts 1-7. 
Part B, the MAD study in NHVs, will also be conducted according to an ascending dose cohort paradigm. Part B will 
be initiated only after Substantial Amendment to EC and AGES has been submitted and authorized following 
completion of cohorts 8-10 of Part A and Part D. There will be 2 cohorts of NHVs, each consisting of 8 NHVs (6:2 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 7 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
ratio of BT200:placebo) in this part of the study. These cohorts will be administered an initial loading dose regimen 
of BT200 or placebo consisting of both a 2-hour IV infusion and an SC injection on Day 0, followed by 4 weekly (every 
7 days) doses of BT200 or placebo by SC injection The dose levels in Part B are: a loading dose of 12.0 mg IV infused 
over 2 hours plus 12.0 mg SC injection followed by 4 maintenance doses of 12.0 mg SC injection in Cohort 13; a 
loading dose of 24.0 mg IV infused over 2 hours plus 24.0 mg SC injection followed by 4 maintenance doses of 
24.0 mg SC injection in Cohort 14. Not all subjects in each of the cohorts of Part B will be dosed on the same day; 
rather, they will be dosed in staggered groups roughly of 2 to 3 subjects per day. 
Part C, the desmopressin challenge will be initiated only after a Substantial Amendment to EC and AGES has been 
submitted and authorized following cohorts 8-10 of Part A and Part D. Part C will consist of a single cohort, Cohort 
12, of 8 NHVs (6:2 ratio of BT200:placebo, plus desmopressin challenge) in this part of the study. Six subjects in 
Cohort 12 will be administered a single dose of 48.0 mg BT200 SC injection and 2 subjects administered a single 
dose of placebo on Day -4 as an SC injection All subjects will then be administered an intravenous (IV) infusion of 
0.3 μg/kg desmopressin over 30 minutes on Day 0 approximately 96 hours after the single dose of BT200 or 
placebo SC (i.e., at the predicted time to maximum plasma concentration [Tmax] for BT200). 
Part D, the relative BA crossover, will be initiated only after a Substantial Amendment to EC and AGES has been 
submitted and authorized following cohorts 1-7 of Part A. Part D will consist of 1 cohort of NHVs, consisting of 8 
NHVs (6:2 ratio of BT200:placebo) administered a single IV dose of BT200 of 24.0 and 2 NHVs administered a 
single dose of placebo IV over 24 hours on Day 0.. Part D could include NHVs who have previously participated in 
Part A. 
Firstly Part A (cohorts 1-7), secondly Part A (cohorts 8-10) and Part D, and finally Part C and Part B will be conducted 
sequentially. There will be a DSMB safety review after dosing of NHVs in Cohorts 1-7 of Part A is completed before 
Cohorts 8-10 of Part A are initiated; again after Cohorts 8-10 of Part A and Part D before Part C and Part B is initiated. 
The safety data provided to the DSMB and the resulting DSMB opinion will be submitted as a Substantial 
Amendment to EC and AGES prior to initiating Cohorts 8-10 of Part A and Part D; again prior to initiating Part C and 
Part B. 
1.3 
Endpoints 
1.3.1 
Primary Endpoint 
Overall safety and tolerability of BT200, assessed in terms of:  
 
Serious, drug-related adverse events (AEs)  
• 
Premature terminations due to drug-related AEs  
• 
Patterns of serious or non-serious, drug-related AEs, and/or clinically relevant laboratory abnormalities, 
vital signs, ECGs, or physical findings suggestive of one or more specific target organs for toxicity of BT200  
• 
Clinically evident bleeding  
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 8 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
1.3.2 
Secondary Endpoints 
Pharmacokinetic Endpoints:  
• 
Measured concentration of BT200  
• 
Derived PK parameters  
1.3.3 
Exploratory Endpoints 
 
Immunogenicity Endpoint: 
o 
ADAs against BT200 
• 
Pharmacodynamic Endpoints: 
o 
Platelet Function Analyzer (PFA-100®) 
o 
VWF:ristocetin co-factor assay (VWF:RiCo)  
o 
Multiplate electrode platelet aggregometer (ristocetin)  
o 
Enzyme-linked immunosorbent assay (ELISA) for unbound VWF-A1 domain (REAADS®) 
• 
Biomarker Endpoints: 
o 
VWF antigen and propeptide 
o 
Factor VIIIc activity (elagic acid activator)  
o 
Activated partial thromboplastin time (aPTT) FS (elagic acid activator)  
o 
Calibrated Automated Thrombogram (CAT) assay (Thrombinoscope®)  
1.4 
Sample Size Calculation 
As this study is exploratory and descriptive in nature, no inferential statistical testing was planned and therefore an 
exact sample size requirement cannot be specified. The number of NHVs planned to be included is expected to be 
sufficient to fulfill the study’s objectives, but not excessive. 
Part A: 80 NHVs; Part B: 16 NHVs; Part C: 8 NHVs; Part D: 8 NHVs (including NHVs who may have previously 
participated in Part A). 
1.5 
Flowchart and Schedules of Assessments 
Flowcharts for all study parts are provided in the Clinical Study Protocol (CSP), Section ‘Study Diagram’.  
 
 
 
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
 
 
 
Page 9 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or otherwise disclosed in any form or by any means 
without prior written consent of Assign DMB. 
Table 1: Study Procedures Part A (Weeks 1-14) (SAD) 
Visit 
Screening 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
PK and 
Immuno 
Sampling 
Visits 
Day 
 
Treatment 
Post-treatment 
D0 
D1 
D2 
D3 
D4 
D7 
D14 
D21 
D28 
D42, D56 
Time 
 
-1h 
0h 
0.5h 
1h 
4h 
8h 
14h 
24h 
48h 
72h 
96h 
168h 
 
 
 
 
Time Window 
D-28 to D-1 
±59’ 
 
±15’ 
±15’ 
±30’ 
±30’ 
±120’ 
±30’ 
±2h 
±2h 
±2h 
±2h 
±1d 
±1d 
±1d 
±2d 
Written Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic Data 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admit to Inpatient Unit 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion / Exclusion Criteria 
X 
X 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body Weight and Height 2 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Physical Examination, Full 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
 
Physical Examination, Brief 
 
X 
 
 
 
 
 
 
X 
X 
 
 
 
X 
X 
 
 
Vital Signs (BP, HR, body 
temperature) 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Cardiac Evaluation (12-lead 
ECG) 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
Serology for HIV, hepatitis B, 
and hepatitis C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
X 
X 
 
 
 
X 
 
 
X 
X 
 
 
X 
X 
X 
X 
 
Coagulation 
X 
X 
 
 
 
X 
 
 
X 
X 
 
 
X 
X 
X 
X 
 
Clinical Chemistry 
X 
X 
 
 
 
X 
 
 
X 
X 
 
 
X 
X 
X 
X 
 
Urinalysis 3 
X 
X 
 
 
 
 
 
 
X 
X 
 
 
X 
X 
X 
X 
 
PK Assessments 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 4 
Immuno Assessments 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 4 
PD Assessments 5 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
 
 
 
Page 10 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or otherwise disclosed in any form or by any means 
without prior written consent of Assign DMB. 
Visit 
Screening 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
PK and 
Immuno 
Sampling 
Visits 
Day 
 
Treatment 
Post-treatment 
D0 
D1 
D2 
D3 
D4 
D7 
D14 
D21 
D28 
D42, D56 
Time 
 
-1h 
0h 
0.5h 
1h 
4h 
8h 
14h 
24h 
48h 
72h 
96h 
168h 
 
 
 
 
Discharge from Inpatient 
Unit 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Concomitant Medications / 
Procedures 
X 
Ongoing 
Adverse Events 
X 
Ongoing 
 
Abbreviations: ’=minute(s); ADA=anti-drug antibody; BP=blood pressure; D=day; ECG=electrocardiogram; h=hour(s); HIV=human immunodeficiency virus; HR=heart rate; 
Immuno=immunogenicity; PD=pharmacodynamic(s); PK=pharmacokinetic(s); SAD=single ascending dose; V=visit 
1. At -1h (ie, before BT200 injection) on Day 0, site personnel will perform a brief recheck of inclusion/exclusion criteria (excluding reassessments of laboratory parameters) 
to ensure that the subject remains eligible to participate in the study. 
2. Body height will only be measured at Screening. 
3. Dipstick urinalysis will be performed. 
4. Late PK samples will be obtained at 6 and 8 weeks after the dose of study drug, whereas late immunogenicity samples will be obtained only at 8 weeks after the dose of 
study drug 
5. PD assessments also include biomarker assays and an exploratory coagulation assay. 
Note: Additional details regarding Part A laboratory blood sampling (hematology, coagulation, clinical chemistry, PK assessments, immunogenicity assessments, and PD 
assessments [including biomarker assays and an exploratory coagulation assay]) are provided in CSP Appendix 1: Laboratory Blood Sampling Supplement to Schedule of 
Assessments (Part A) and the laboratory manual. 
 
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
 
 
 
Page 11 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or otherwise disclosed in any form or by any means 
without prior written consent of Assign DMB. 
 
Table 2: Study Procedures Part B Week 1 (MAD) 
Visit 
Screening 
V1 
V2 
V3 
V4 
Day 
 
Treatment 
D0 
D1 
D2 
D3 
D4 
Time 
 
-1h 
0h 
0.5h 
1h  
4h 
8h 
14h 
24h 
48h 
72h 
96h 
Time Window 
D-28 to D-1 
±59’ 
 
±15’ 
±15’ 
±30’ 
±30’ 
±120’ 
±30’ 
±2h 
±2h 
±2h 
Written Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographic Data 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
Admit to Inpatient Unit 
 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion / Exclusion Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration 1 
 
 
X 
 
 
 
 
 
 
 
 
 
Body Weight and Height 2 
X 
X 
 
 
 
 
 
 
 
 
 
 
Physical Examination, Full 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination, Brief 
 
X 
 
 
 
 
 
 
X 
 
 
X 
Vital Signs (BP, HR, body temperature) 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cardiac Evaluation (12-lead ECG) 
X 
X 
 
 
 
 
 
 
X 
 
 
 
Serology for HIV, hepatitis B, and  
hepatitis C 
X 
 
 
 
 
 
 
 
 
 
 
 
Nasal swab screen for coronavirus 
X 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
Coagulation 
X 
X 
 
 
 
 
 
 
X 
 
 
X 
Clinical Chemistry 
X 
X 
 
 
 
 
 
 
X 
 
 
 
Urinalysis 3 
X 
X 
 
 
 
 
 
 
X 
 
 
 
PK Assessments 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity Assessments 
 
X 
 
 
 
 
 
 
 
 
 
 
PD Assessments 4 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Discharge from Inpatient Unit 5 
 
 
 
 
 
 
 
 
X 
 
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
 
 
 
Page 12 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or otherwise disclosed in any form or by any means 
without prior written consent of Assign DMB. 
Visit 
Screening 
V1 
V2 
V3 
V4 
Day 
 
Treatment 
D0 
D1 
D2 
D3 
D4 
Time 
 
-1h 
0h 
0.5h 
1h  
4h 
8h 
14h 
24h 
48h 
72h 
96h 
Concomitant Medications / Procedures 
X 
Ongoing 
Adverse Events 
X 
Ongoing 
 
Abbreviations: ’=minute(s); ADA=anti-drug antibodies; BP=blood pressure; D=day; ECG=electrocardiogram; h=hour(s); HIV=human immunodeficiency virus; HR=heart rate; 
MAD=multiple ascending dose; PD=pharmacodynamic(s); PK=pharmacokinetic(s); V=visit 
1. Study drug will be administered after all other study procedures for this visit have been completed. 
2. Body height will only be measured at Screening. 
3. Dipstick urinalysis will be performed. 
4. PD assessments also include biomarker assays and an exploratory coagulation assay. 
5. Based on the results from Part A, it may become apparent that the overnight stay and Hour 14 blood sample time point in Part B are superfluous. In this case, at the 
discretion of the Principal Investigator, the Hour 14 time point procedures may be omitted and the subjects discharged after the Hour 8 time point procedures have been 
completed. 
Note: Additional details regarding Part B laboratory blood sampling (hematology, coagulation, clinical chemistry, PK assessments, immunogenicity assessments, and PD 
assessments [including biomarker assays and an exploratory coagulation assay]) are provided in CSP Appendix 2: Laboratory Blood Sampling Supplement to Schedule of 
Assessments (Part B) and the laboratory manual. 
 
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
 
 
 
Page 13 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or otherwise disclosed in any form or by any means 
without prior written consent of Assign DMB. 
 
Table 3: Study Procedures Part B Weeks 2-12 (MAD) 
Visit 
V5-8 
V9-11 
V12 
PK and Immuno 
Sampling Visits 
Day 
Treatment 
Post-treatment 
D 7, D14, D21, D28 
D35, D42, D49 
D56 
D70, D84 
Time 
-1h 
0h 
1h 
0h 
0h 
±2d 
Time Window 
±59’ 
 
±30’ 
 
 
 
Study Drug Administration 
 
X 
 
 
 
 
Body weight 
X 
 
 
 
X 
 
Physical Examination, Full 
 
 
X 1 
 
X 1 
 
Physical Examination, Brief 
X 
 
X 
X 
 
 
Vital Signs (BP, HR, body temperature) 
X 
 
X 
X 
X 
 
Cardiac Evaluation (12-lead ECG) 
X 
 
 
 
X 
 
Hematology 
X 
 
 
X 
X 
 
Coagulation 
X  
 
 
X  
X 
 
Clinical Chemistry 
X  
 
 
X  
X 
 
Urinalysis 2 
X  
 
 
X  
X 
 
PK Assessments 
X 
 
 
X 
X 
X 3 
Immuno Assessments 
X 
 
 
 
 
X 3 
PD Assessments 4 
X 
 
 
X 
X 
 
Concomitant Medications / Procedures 
Ongoing 
Adverse Events 
Ongoing 
Abbreviations: ’=minute; BP=blood pressure; D=day; ECG=electrocardiogram; h=hour; HR=heart rate; Immuno=immunogenicity; MAD=multiple ascending dose; 
PD=pharmacodynamic(s); PK=pharmacokinetic(s); V=visit 
1. Full physical examination only on Days 28 and 56. 
2. Dipstick urinalysis will be performed. 
3. Late PK samples will be obtained at 6 and 8 weeks after the last dose of study drug, whereas late immunogenicity samples will be obtained only at 8 weeks after the 
dose of study drug. 
4. PD assessments also include biomarker assays and an exploratory coagulation assay. 
Note: Additional details regarding Part B laboratory blood sampling (hematology, coagulation, clinical chemistry, PK assessments, immunogenicity assessments, and PD 
assessments [including biomarker assays and an exploratory coagulation assay]) are provided in CSP Appendix 2: Laboratory Blood Sampling Supplement to Schedule of 
Assessments (Part B) and the laboratory manual. 
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
 
 
 
Page 14 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or otherwise disclosed in any form or by any means 
without prior written consent of Assign DMB. 
 
Table 4: Study Procedures Part C Weeks 1-9 (Desmopressin Challenge) 
Visit 
Scr 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
PK and 
Immuno 
SaV 
Day 
 
Treatment  
Post-treatment 
D -4 
D0 
D1 
D2 
D3 
D4 
D7 
D14 
D21 
D28 
D42, D56 
Time 
 
-96h 
-1h 
0h 
0.5h 
1h 
2h 
3h 
4h 
8h 
14h 
24h 
48h 
72h 
96h 
168h 
 
 
 
 
Time Window 
D-28 
to  
D-5 
±1h 
±59’ 
 
±15’ 
±15’ 
±15’ 
±15’ 
±30’ 
±30’ 
±120’ 
±30’ 
±2h 
±2h 
±2h 
±2h 
±1d 
±1d 
±1d 
±2d 
Written Informed 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic Data 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admit to Inpatient Unit 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion / Exclusion 
Criteria 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug 
Administration 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Desmopressin 
Administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body Weight and 
Height 1 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Physical Examination, 
Full 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
 
Physical Examination, 
Brief 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
 
 
Vital Signs (BP, HR, 
body temperature) 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Cardiac Evaluation 
(12-lead ECG) 
X 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
Serology for HIV, 
hepatitis B, and 
hepatitis C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nasal swab screen 
for coronavirus 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
 
 
 
Page 15 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or otherwise disclosed in any form or by any means 
without prior written consent of Assign DMB. 
Visit 
Scr 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
PK and 
Immuno 
SaV 
Day 
 
Treatment  
Post-treatment 
D -4 
D0 
D1 
D2 
D3 
D4 
D7 
D14 
D21 
D28 
D42, D56 
Time 
 
-96h 
-1h 
0h 
0.5h 
1h 
2h 
3h 
4h 
8h 
14h 
24h 
48h 
72h 
96h 
168h 
 
 
 
 
Hematology 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
X 
 
 
X 
 
Coagulation 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
X 
 
 
X 
 
Clinical Chemistry 
X 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
Urinalysis 2 
X 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
PK Assessments 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 3 
Immuno Assessments 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 3 
PD Assessments 4 
 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Discharge from 
Inpatient Unit 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Concomitant 
Medications / 
Procedures 
X 
Ongoing 
Adverse Events 
X 
Ongoing 
 
Abbreviations: ’=minute(s); BP=blood pressure; D=day; ECG=electrocardiogram; h=hour(s); HIV=human immunodeficiency virus; HR=heart rate; Immuno=immunogenicity; 
PD=pharmacodynamic(s); PK=pharmacokinetic(s); SaV=Sampling Visits; Scr=Screening; V=visit 
1. Body height will only be measured at Screening. 
2. Dipstick urinalysis will be performed. 
3. Late PK samples will be obtained at 6 and 8 weeks after the dose of study drug, whereas late immunogenicity samples will be obtained only at 8 weeks after the dose of 
study drug. 
4. PD assessments also include biomarker assays. 
Note: Additional details regarding Part C laboratory blood sampling (hematology, coagulation, clinical chemistry, PK assessments, immunogenicity assessments, and PD 
assessments [including biomarker assays]) are provided in CSP Appendix 3: Laboratory Blood Sampling Supplement to Schedule of Assessments (Part C) and the laboratory 
manual. 
 
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
 
 
 
Page 16 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or otherwise disclosed in any form or by any means 
without prior written consent of Assign DMB. 
 
Table 5: Study Procedures Part D Weeks 1-8 (Relative Bioavailability) 
Visit 
Screening 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
PK and 
Immuno 
Sampling 
Visits 
Day 
 
Treatment 
Post-treatment 
D0 
D1 
D2 
D3 
D4 
D7 
D14 
D21 
D28 
D42, 
D56 
Time 
 
-1h 
0h 
0.5h 
1h 
4h 
8h 
14h 
24h 
48h 
72h 
96h 
168h 
 
 
 
 
Time Window 
D-28 to 
D-1 
±59’ 
 
±15’ 
±15’ 
±30’ 
±30’ 
±120’ 
±30’ 
±2h 
±2h 
±2h 
±2h 
±1d 
±1d 
±1d 
±2d 
Written Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic Data 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admit to Inpatient Unit 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion / Exclusion Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration 
 
 
X4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body Weight and Height 1 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Physical Examination, Full 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
 
Physical Examination, Brief 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
 
 
Vital Signs (BP, HR, body 
temperature) 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Cardiac Evaluation (12-lead 
ECG) 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
Serology for HIV, hepatitis B, and 
hepatitis C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
Coagulation 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
Clinical Chemistry 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
Urinalysis 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
PK Assessments 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 2 
Immuno Assessments 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 2 
PD Assessments 3 
 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Discharge from Inpatient Unit 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
 
 
 
Page 17 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or otherwise disclosed in any form or by any means 
without prior written consent of Assign DMB. 
Visit 
Screening 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
PK and 
Immuno 
Sampling 
Visits 
Day 
 
Treatment 
Post-treatment 
D0 
D1 
D2 
D3 
D4 
D7 
D14 
D21 
D28 
D42, 
D56 
Time 
 
-1h 
0h 
0.5h 
1h 
4h 
8h 
14h 
24h 
48h 
72h 
96h 
168h 
 
 
 
 
Concomitant Medications / 
Procedures 
X 
 
Ongoing 
Adverse Events 
X 
 
Ongoing 
 
Abbreviations: ’=minute(s); ADAs=anti-drug antibodies; BP=blood pressure; D=day; ECG=electrocardiogram; h=hour(s); HIV=human immunodeficiency virus; HR=heart 
rate; Immuno=immunogenicity; PD=pharmacodynamic(s); PK=pharmacokinetic(s); V=visit 
1. Body height will only be measured at Screening. 
2. Late PK samples will be obtained at 6 and 8 weeks after the dose of study drug, whereas late immunogenicity samples will be obtained only at 8 weeks after the dose 
of study drug. 
3. PD assessments also include biomarker assays. 
Note: Additional details regarding Part D laboratory blood sampling (hematology, coagulation, clinical chemistry, PK assessments, immunogenicity assessments, and PD 
assessments [including biomarker assays]) are provided in Appendix 4: Laboratory Blood Sampling Supplement to Schedule of Assessments (Part D) and the laboratory 
manual. 
4. Continuous IV infusion over 24 hours beginning at Time 0. 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 18 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
2. 
GENERAL CONSIDERATIONS 
2.1 
Rationale 
BT200 is a PEGylated aptamer that binds to the A1 domain of human VWF and thereby inhibits VWF binding to 
platelet glycoprotein Ib (GP1b), the first step in the cascade of platelet-mediated thrombogenesis. Study BT200-01 
is a Phase 1 FIH study designed to assess the human safety, tolerability, pharmacokinetics, and pharmacologic 
activity of BT200 in NHVs. In order to ensure the well-being of study subjects, some key safety measures have been 
incorporated into the design of this study, including use of sentinel pairs of subjects and an independent Data and 
Safety Monitoring Board (DSMB). In order to assess the effect of elevated VWF levels (as might be encountered in 
patients in the future) on the BT200 concentration-effect relationship,1 single-dose cohort of BT200 administered 
together with a secretagogue for VWF (desmopressin) will be included as Part C. Finally, in order to assess the 
relative bioavailability of BT200 via SC vs. IV administration, a single dose IV cohort will be included as Part D. Based 
upon the PK and PD data observed in Parts A, C, and D the nominal dose levels specified in Part B may be adjusted 
by means of a Substantial Amendment to this protocol prior to initiation of dosing therein. 
2.2 
Conduct of Analysis 
For Part A, B, C and D, a formal interim analysis is not planned. After all subjects have all visits of the respective 
study part performed, a topline analysis will be performed for Part A and D separately. Tables, Listings and Figures 
(TLFs) for the topline analysis can be found in Section 7.Topline analyses might be based on cleaned data for which 
no SDV was performed yet (due to Covid-19 pandemic, see Section 2.16). The final analysis of all study parts will 
be performed, when all study parts were fully SDVd, cleaned and once all external data are available and reconciled 
and the database is closed. 
2.3 
Statistical Software and Quality Control 
All statistical analyses will be performed using SAS® version 9.3 or higher. Tables, figures and data listings will be 
generated in Microsoft® Word® as well as PDF® format. 
Quality control of SAS® programs will include a review of the whole process of result generation: 
 
Review of all analysis SAS® programs 
 
Review of SAS® log for errors, warnings and other notes that could indicate mistakes in the programs 
 
Review of all tables, listings and figures for completeness and correctness 
2.4 
Applicable Standard Operating Procedures 
The applicable Standard Operating Procedures (SOPs) of Assign DMB for this study are: 
STAT03 
Statistical Analysis Plan 
STAT04 
Interim Analysis 
STAT05 
Randomization and Unblinding 
STAT06 
Data Review Meeting 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 19 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
STAT07 
Report Writing 
SAS01 
SAS General Principles 
SAS04 
Handling of Statistical Analyses 
SAS06 
CDISC_ADaM 
SAS07 
CDSC_Quality_Control 
2.5 
Blinding and Randomization 
Subjects and study staff will be blinded to treatment assignment. Injections and infusions of BT200 or placebo will 
have a similar appearance. Unblinding for Part A and D will be performed after data entry for the respective study 
part is complete and database snapshot was performed for topline analysis. Unblinding for Part B and C will be 
performed after data entry for the respective study part is complete and database closure was performed. 
In Part A, NHVs will be randomized to treatment with BT200 or placebo in a ratio of 3:1 in Cohorts 1 and 2, and in 
a ratio of 6:2 in Cohorts 3 to 10, except for the sentinel pair of subjects (1:1 ratio). For each of the remaining study 
parts (Parts B, C, and D), NHVs will be randomized to treatment with BT200 or placebo in a ratio of 6:2. If the site is 
able to recruit Asians in addition to Caucasians, a stratified randomization procedure will be performed according 
to Ethnicity. This stratification is not performed formally within the randomization list, but the sites instructed to not 
consider Asians for the sentinel pairs (to increase probability for Asians to not receive placebo). 
2.6 
Descriptive Analyses 
Descriptive analyses of continuous variables (summary statistics) will be described with the number of non-missing 
observations, arithmetic mean, standard deviation (±SD), median, quartiles (Q1 and Q3) and range (minimum and 
maximum). 
Categorical variables (frequency statistics) will be described with the number of non-missing observations and 
percentages (%). Percentages will be calculated on the total number of non-missing observations, if not stated 
otherwise. 
2.7 
Inferential Analyses 
Two-sided 95% confidence intervals (CIs)will be calculated according to Altman will be calculated for certain safety 
tables (see Section 7).  
2.8 
Center and Country Effect 
Not applicable. This is a single-center study that will be conducted at the Department of Clinical Pharmacology, 
Medical University of Vienna at the Vienna General Hospital (AKH/MUW) in Vienna, Austria. 
2.9 
Handling Missing Data 
Generally, missing values will not be imputed and the analysis will be limited to observed values.  
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 20 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
2.10 Protocol Deviations 
For Part A and D, a Blind Data Review Meeting (BDRM) will be conducted prior to database snapshot for topline 
analysis. For Part B and C the BDRM will be conducted prior the database closure. BDRMs will be conducted on all 
data to review protocol deviations, to discuss specific unforeseeable data issues, and to allocate the subjects to the 
analysis sets. During the BDRM, two classifications will be performed:  
1. Protocol deviations will be classified as not relevant or relevant deviations, based on the potential influence 
on the PK and PD analysis. Relevant protocol violations will include the following but are not limited to:  
• 
Violations of major inclusion or exclusion criteria 
• 
Wrong treatment administration 
• 
Other protocol deviations with expected substantial influence on PK analysis 
2. Protocol deviations will be classified as important or not important with respect to the GCP (E3) definition 
(i.e. important protocol deviations are a subset of protocol deviations that may significantly impact the 
completeness, accuracy, and/or reliability of the study data or that may significantly affect a subject's rights, 
safety, or well-being). 
Protocol deviation classifications will be made on a case by case decision in the BDRM. The associated decisions 
will be documented and approved in the BDRM Report.  
Protocol violations classified as important and/or relevant will be described in the CSR (Clinical Study Report). 
2.11 Medical Coding 
Adverse events, medical history and concomitant procedures will be coded using MedDRA. Concomitant 
medications will be coded using WHO Drug Dictionary. Details are defined in the Coding Guideline. The used 
dictionary versions will be indicated in the respective tables and listings. 
2.12 Analysis Populations 
2.12.1 Safety Population 
The Safety Population will include all randomized NHVs who received at least 1 dose of BT200/placebo. Subjects 
will be analyzed according to the treatment that they actually received. The Safety Population will be used for all 
safety endpoints. 
2.12.2 Per-Protocol Population 
The Per-Protocol (PP) Population will comprise all NHVs of the Safety Population, if the following criteria are 
additionally met:  
 
All of the major inclusion criteria, none of the major exclusion criteria are fulfilled.  
 
Absence of other relevant protocol violations such as wrong treatment received.  
For each study part, a PP Population will be defined in the BDRM. The PP Population will represent the primary PK 
and PD analysis population. 
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 21 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
2.13 Subject Data Listings 
All subjects in the database will be included in listings if not stated otherwise. Data listings will include the subject 
number as identifier (and parameter and/or visit if available) and will be sorted by Dose cohort, subject ID (and 
parameter and/or visit if available). Every listing contains the column treatment group. 
2.14 Columns in Tables 
The following columns will be used for tables, if not stated otherwise: 
 
Part A: Pooled Placebo column (over all dose levels), Cohort 1 BT200, Cohort 2 BT200, Cohort 3 BT200, 
Cohort 4 BT200, Cohort 5 BT200, Cohort 6 BT200, Cohort 7 BT200, Cohort 8 BT200, Cohort 9 BT200 and 
Cohort 10 BT200. 
 
 Part B:Pooled Placebo (over all dose levels), Cohort 13 BT200, Cohort 14 BT200 and Pooled BT200 (all 
subjects treated with BT200 over all dose levels). 
 
Part C: Cohort 12 BT200 and Placebo column. 
 
Part D: Cohort 11 BT200 and Placebo column. 
In each analysis part, a column showing all subjects together will additionally used in the table summarizing the 
demographic information.  
2.15 Changes in the Conduct of the Study or Planned Analysis 
No changes to the statistical analysis as compared to CSP are planned. 
2.16 Effect of Covid-19 
Due to the Covid-19 pandemic no monitoring visits can be performed before database snapshot for topline analyses. 
Possible impact of Covid-19 pandemic and respective measures were discussed. Subject visits and time points will 
be partly affected by the pandemic. If visits can not be performed due to Covid-19 the visit will be documented as 
not performed in the eCFR with reason “COVID19”. Drop-outs due to Covid-19 will be documented in the eCRF on 
the end of study page with reason “other“ and specification “COVID19” as reason for early termination. No further 
effects are expected due to Covid-19. Statistical analysis will include a summary of drop-outs and early terminations 
due to Covid-19. In Part B and C, a screening for coronavirus by nasal swab testing will be performed at the screening 
visit. Subjects with positive coronavirus test will be excluded from the study. The results of the coronavirus screening 
will be tabulated and listed.  
Unexpected Covid-19 effects (e.g. overviews on missing data, Covid-19 related protocol deviations, missed visits, 
visits out of time-window and changes in study processes) will be described in the Clinical Study Report. 
 
3. 
OVERALL STUDY INFORMATION 
Tables will be provided for the Safety Population, if not stated otherwise and selected tables will be repeated for the 
PP Population. The following information will be analyzed descriptively and corresponding details on the subject 
level will be provided in data listings: 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 22 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
• 
Patient overview  
• 
Screening failures 
• 
Violated inclusion/exclusion criteria (will only be listed) 
• 
Subjects by dose level and overall 
• 
Study visit information (incl. Admission/Discharge Inpatient Unit information) 
• 
Missed visits due to Covid-19 (will be listed only) 
• 
End of study information (incl. drop-outs due to Covid-19) 
• 
Protocol deviations 
• 
Coronavirus screening (only applicable for Part B and C) 
Specifications of Tables, Listings and Figures (TLFs) are provided in Section 7. 
 
4. 
BASELINE EVALUATION 
Baseline data will be presented for Safety Population . 
4.1 
Data Points 
Data will be analyzed from the screening visit and the randomization visit (if applicable) The following information 
will be analyzed descriptively and corresponding details on the subject level will be provided in data listings: 
 
Demographics (including body height [cm] and body weight [kg], Body Mass Index (BMI) [kg/m2])  
 
Serology (will only be listed) 
 
Medical history overall and by SOC and PT 
 
Prior/Concomitant medications overall and by ATC level 
 
Prior/Concomitant procedures overall and by SOC and PT 
 
Childbearing-potential (will only be listed) 
Vital signs, ECG and physical examination results will be analyzed in the safety section (see Section 6.4). 
Specifications of TLFs are provided in Section 7. 
4.2 
Derivations and Definitions 
 
Medications stopped clearly prior to first study drug administration will be considered as prior medications, 
all other medications are considered to be concomitant. Medications with a missing or incomplete stop 
date where it cannot clearly be decided if the stop date was before or after Day 0 (Visit 1) will be considered 
as concomitant. 
 
Procedures stopped clearly prior to first study drug administration will be considered as prior procedures, 
all other procedures are considered to be concomitant. Procedures with a missing or incomplete stop date 
where it cannot clearly be decided if the stop date was before or after Day 0 (Visit 1) will be considered as 
concomitant. 
 
BMI [kg/m²] is defined as the weight [kg] divided by the  square of the body height [m] 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 23 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
5. 
PHARMACOKINETICS / PHARMACODYNAMICS / BIOMARKER / IMMUNOGENICITY 
Pharmacodynamics, biomarker and immunogenicity analysis will be performed for the PP Population and the Safety 
Population. 
5.1 
Pharmacokinetics 
Pharmacokinetics analysis will be performed by CERTARA and are not described in this Statistical Analysis Plan. 
5.2 
Pharmacodynamics 
The following tables will be performed for PFA-100, VWF:RiCo [%], multiplate aggregometer and REAADS and 
corresponding details on the subject level will be provided in data listings: 
 
Absolute values by time point 
 
Absolute change from randomization by time point 
 
Relative change [%] from randomization by time point 
The following figures will be provided for PFA-100, VWF:RiCo [%], multiplate aggregometer and REAADS separately: 
 
Absolute values by subject: For every subject separately, the time course over of the parameters mentioned 
above will be drawn, where the actual measurement time point since first dose will be shown on x-axis 
(hours) and the parameters values will be drawn on the y-axis. 
 
Absolute values by cohort: One graph will be drawn that includes the data of all cohorts. One line will be 
drawn per cohort, where the x-axis will show the planned time point of measurement (in hours) and the y-
axis will show the mean value of the respective cohort incl. standard error. Measurements of all scheduled 
visits will be included, where the EOS visit will be treated as the last visit. 
PD sampling results will be entered eCRF using a result specifier (i.e. <, ≤, >, ≥). For statistical analysis, values 
reported as <x, ≤x, >x or ≥x will be analyzed as x. E.g. <300, ≤300, >300 or ≥300 will be analyzed as value 300. 
Details are specified in Section 7. 
5.3 
Biomarker 
The following tables will be performed for VWF antigen [%], VWF propeptide [mIU/mL], Factor VIIIc activity [%], aPTT 
FS [sec], Thrombin generation CAT assay (Thrombinoscope) [nM], Fibrin D-dimer [mIU/mL] and Prothrombin 
fragment F1.2 [mIU/mL]. Corresponding details on the subject level will be provided in data listings: 
 
Absolute values by time point 
 
Absolute change from randomization by time point 
 
Relative change [%] from randomization by time point 
The following figures will be provided for VWF antigen [%], VWF propeptide [mIU/mL], Factor VIIIc activity [%], aPTT 
FS [sec],Thrombin generation CAT assay (Thrombinoscope) [nM] and Fibrin D-dimer [mIU/mL] and Prothrombin 
fragment F1.2 [mIU/mL] separately: 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 24 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
 
Absolute values by subject: For every subject separately, the time course over of the parameters mentioned 
above will be drawn, where the actual measurement time point will be shown on x-axis (hours) and the 
parameters values will be drawn on the y-axis. 
 
Absolute values by cohort: One graph will be drawn that includes the data of all cohorts. One line will be 
drawn per cohort, where the x-axis will show the planned time point of measurement (in hours) and the y-
axis will show the mean value of the respective cohort incl. standard error. Measurements of all scheduled 
visits will be included, where the EOS visit will be treated as the last visit. 
Details are specified in Section 7. 
5.4 
Immunogenicity 
The following tables will be produced for immunogenicity and corresponding details on the subject level will be 
provided in data listings: 
 
ADA results (positive/negative/not reportable/NA) by time point 
Details are specified in Section 7. 
 
6. 
SAFETY ANALYSIS 
All analyses will be performed for the Safety Population. Data from unscheduled visits will only be listed. Data from 
scheduled visits and early termination visits will be tabulated.  
6.1 
Extent of Exposure 
Study drug administration will be listed.  
For Part B, a cumulative dose level will be determined as the total amount of received study drug up to the current 
time point (loading dose and maintenance dose).  
For Part C, Desmopressin administration will be listed additionally. 
6.2 
Adverse Events and Bleeding Events 
Adverse Events (AEs) are documented in the eCRF section “Adverse Events” and Bleeding Events in the eCRF section 
“Bleedings”. AEs and bleeding events will be analyzed together.  
6.2.1 
Data Points 
The following tables will be generated: 
AE and bleeding event overview (e.g. any AE or bleeding event, any severe AE or bleeding event, any related AE or 
bleeding event, any hemorrhage (MedDRA SMQ), all embolic and thrombotic events (SMQ), Embolic and thrombotic 
events, arterial (SMQ), Embolic and thrombotic events, vessel type unspecified and mixed arterial and venous 
(SMQ), Embolic and thrombotic events, venous (SMQ)) 
 
) 
 
AEs and bleeding events overall and by SOC and PT 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 25 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
 
Related AEs and bleeding events overall and by SOC and PT 
 
Serious AEs and bleeding events overall and by SOC and PT 
 
Related serious AEs and bleeding events overall and by SOC and PT 
 
AEs and bleeding events by maximum severity 
 
Related AEs and bleeding events by maximum severity 
 
Serious AEs and bleeding events by maximum severity 
 
Related serious AEs and bleeding events by maximum severity 
 
AEs and bleeding events leading to permanently study drug discontinuation or leading to withdrawn from 
study 
 
Related AEs and bleeding events leading to permanently study drug discontinuation or leading to withdrawn 
from study 
 
Major bleeding events overall and by SOC and PT 
 
Total ISTH bleeding score (frequency table)  
 
Bleeding Assessment Score by symptom 
 
Maximum Bleeding Assessment Score 
 
AEs and bleeding events with missing assessments (will only be listed) 
6.2.2 
Definitions and Derivations 
 
AEs and bleeding events are considered as “related” if the causality to study drug is reported as “related” 
or “possible”.  
 
Tables showing AEs or bleeding events by causality, subjects will be counted only in the strongest 
relationship category but events will be counted in each category.  
 
In tables showing AEs or bleedings events by maximum severity, subjects will be counted only in the highest 
grading category but events will be counted in each category.  
 
An AE or bleeding event is considered as “leading to permanently study drug discontinuation” if “study drug 
permanently discontinued” is ticked for “action taken on study treatment”.  
 
An AE or bleeding event is considered as “leading to withdrawal from study” if for “Other action taken”, 
“withdrawn from study” is answered with “yes”. 
 
Missing assessments contains missing seriousness, severity and/or causality 
 
The Total ISTH Bleeding Score will be calculated as the sum of bleeding assessment scores (documented 
in the eCRF) overall symptoms of a subject. If a subject experienced a symptom more than once, the event 
with the higher bleeding score will be used. 
 
The SMQ code for Hemorrhage is 20000038 Haemorrhages (SMQ) which consists of SMQ codes 
20000039 “Haemorrhage terms (excl laboratory terms)” and 20000040 “Haemorrhage laboratory terms”. 
 
The SMQ code for arterial embolic and thrombotic events is 20000082 “Embolic and thrombotic events, 
arterial (SMQ)”. 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 26 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
 
The SMQ code for vessel type unspecified and mixed arterial and venous embolic and thrombotic events is 
20000083 “Embolic and thrombotic events, vessel type unspecified and mixed arterial and venous (SMQ)”. 
 
The SMQ code for venous embolic and thrombotic events is 20000084 “Embolic and thrombotic events, 
venous (SMQ)”. 
6.3 
Laboratory Parameters 
Laboratory data from scheduled visits and early termination visits will be tabulated. Listings will additionally include 
results from unscheduled visits. 
The following parameters will be assessed in the study and will be included in the statistical analysis: 
 
Hematology 
o 
Hemoglobin 
o 
Hematocrit 
o 
Red blood cells 
o 
White blood cells 
o 
Lymphocytes 
o 
Monocytes 
o 
Neutrophils 
o 
Eosinophils 
o 
Basophils 
o 
Platelets 
o 
Reticulocytes 
 
Coagulation 
o 
Prothrombin time 
 
Clinical Chemistry 
o 
Sodium 
o 
Potassium 
o 
Calcium 
o 
Chloride 
o 
Aspartate aminotransferase 
o 
Alanine aminotransferase 
o 
Alkaline phosphatase 
o 
Lactate dehydrogenase 
o 
Gamma-glutamyltransferase 
o 
Bilirubin 
o 
C-reactive protein 
o 
Blood Urea Nitrogen 
o 
Creatinine 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 27 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
o 
Glucose 
 
Urinalysis 
o 
Specific gravity 
o 
pH 
o 
Leukocytes 
o 
Nitrite 
o 
Protein 
o 
Glucose 
o 
Ketones 
o 
Urobilinogen 
o 
Bilirubin 
o 
Erythrocytes 
Quantitative laboratory parameters (i.e., hematology, clinical chemistry, coagulation, pH, Specific Gravity) will be 
analyzed descriptively: 
 
Absolute values by parameter and time point (summary statistics) 
 
Absolute change from randomization by parameter and time point (summary statistics) 
 
Relative change from randomization by parameter and time point (summary statistics) 
 
Number of subjects with values above/below normal range by parameter and time point (frequency 
statistics) 
Qualitative urinalysis parameters will be analyzed by tabulation of urinalysis result by parameter and time point 
(frequency statistics) 
One set of data listings will show parameters outside normal range (hematology, coagulation, clinical chemistry, 
quantitative urinalysis parameters) and abnormal qualitative urinalysis values, respectively.  
For every parameter, boxplots showing the absolute values by study day will be provided.  
All parameters will be analyzed using the unit registered by study site in the eCRF. No unit conversion will be done.  
6.4 
Other Safety Parameters 
Other safety data from scheduled visits will be tabulated as described below. Listings will additionally include results 
from unscheduled visits or early termination visit. 
Results from vital signs (systolic blood pressure [mmHg], diastolic blood pressure [mmHg], heart rate [beats/min], 
body temperature [C] and body weight [kg]) and ECG will be tabulated descriptively by: 
 
Absolute values by parameter and time points (summary statistics) 
 
Absolute changes from randomization by parameter and time points (summary statistics) 
 
Number of subjects with clinically relevant vital signs results by parameter and time point (frequency 
statistics) 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 28 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
 
ECG Interpretation (normal/abnormal/abnormal, clinically relevant/abnormal, not clinically relevant) by 
time point (frequency statistics) 
 
Physical examination results (normal/abnormal) by body system and time point (frequency statistics) 
Absolute values of vital signs parameters and continuous ECG parameters will be provided by time point. The x-axis 
will show the study day. A separate figure will be provided for every parameter. 
Details are specified in Section 7. 
 
7. 
LIST OF TABLES, DATA LISTINGS AND FIGURES 
The x in the numbering of the TLFs below has to be replaced by 1 for Part A, 2 for Part B, 3 for Part C and 4 for Part 
D.  
 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 29 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
7.1 
List of Tables 
No  
Topline 
Analysis 
Title 
Content/Comment 
Overall Study Information and Baseline Evaluation 
14.x.1.1.1 
Yes 
Patient Overview 
 
Number of subjects in 
Safety Population 
 
Number of subjects in PP 
Population 
 
Number of sentinel 
subjects (only applicable 
for Part A) 
 
Number of randomized 
subjects 
 
Screening of coronavirus 
(only applicable for Part 
B and C) 
Columns: Not randomized, 
column for each BT200 dose 
level and Placebo 
14.x.1.1.2 
No 
Number of Screening Failures and Reasons 
One column for all subjects 
14.x.1.1.3 
No 
Subjects by Visit (Safety Population) 
 
14.x.1.1.4 
No 
End of Study Information (Safety Population) 
• 
Visit attendance status 
• 
Primary reason for early 
termination 
• 
Early terminations due to 
Covid-19 
14.x.1.1.5 
No 
Protocol Deviations (Safety Population) 
• 
Any major protocol 
deviation 
• 
Major protocol 
deviations by category 
• 
Any minor protocol 
deviation 
• 
Minor protocol 
deviations by category 
14.x.1.1.6 
Yes 
Demographic Information (Safety Population) 
 
Gender 
 
Age [years] 
 
Race 
 
Ethnicity 
 
Body height [cm] 
 
Body weight [kg] 
 
BMI [kg/m2] at screening 
14.x.1.1.7 
No 
Medical History Overall and by SOC and PT (Safety 
Population) 
 
Any medical history 
 
By SOC and PT 
14.x.1.1.8 
No 
Prior Medications Overall and by ATC Level (Safety 
Population) 
 
Any prior medication 
 
By ATC level 
14.x.1.1.9 
No 
Concomitant Medications Overall and by ATC Level 
(Safety Population) 
 
Any concomitant 
medication 
 
By ATC level 
14.x.1.1.10 No 
Prior Procedures Overall and by SOC and PT (Safety 
Population) 
 
Any prior procedures 
 
By SOC and PT 
14.x.1.1.11 No 
Concomitant Procedures Overall and by SOC and PT 
(Safety Population) 
 
Any concomitant 
procedures 
 
By SOC and PT 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 30 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
14.x.1.2.3-
14.x.1.2.5 
No 
Repeat tables 14.x.1.1.3-5 for PP Population 
 
Pharmacodynamics/Biomarker/Immunogenicity 
14.x.2.1.1 
Yes 
Multiplate Aggregometer [U]: Absolute values by time 
point (PP Population) 
 
14.x.2.1.2 
No 
Multiplate Aggregometer [U]: Absolute change from 
randomization by time point (PP Population) 
 
14.x.2.1.3 
No 
Multiplate Aggregometer [U]:Relative change [%] from 
randomization by time point (PP Population) 
 
14.x.2.1.4 
Yes 
PFA-100 [sec]: Absolute values by time point (PP 
Population) 
 
14.x.2.1.5 
No 
PFA-100 [sec]: Absolute change from randomization 
by time point (PP Population) 
 
14.x.2.1.6 
No 
PFA-100 [sec]: Relative change [%] from 
randomization by time point (PP Population) 
 
14.x.2.1.7 
Yes 
REAADS: Absolute values by time point (PP 
Population) 
 
14.x.2.1.8 
No 
REAADS: Absolute change from randomization by 
time point (PP Population) 
 
14.x.2.1.9 
No 
REAADS: Relative change [%] from randomization by 
time point (PP Population) 
 
14.x.2.1.10 Yes 
VWF:RiCo [%]: Absolute values by time point (PP 
Population) 
 
14.x.2.1.11 No 
VWF:RiCo [%]: Absolute change from randomization 
by time point (PP Population) 
 
14.x.2.1.12 No 
VWF:RiCo [%]: Relative change [%] from 
randomization by time point (PP Population) 
 
14.x.2.1.13 Yes 
VWF antigen [%]: Absolute values by time point (PP 
Population) 
 
14.x.2.1.14 No 
VWF antigen [%]: Absolute change from 
randomization by time point (PP Population) 
 
14.x.2.1.15 No 
VWF antigen [%]: Relative change [%] from 
randomization by time point (PP Population) 
 
14.x.2.1.16 Yes 
VWF propeptide [mIU/mL]: Absolute values by time 
point (PP Population) 
 
14.x.2.1.17 No 
VWF propeptide [mIU/mL]: Absolute change from 
randomization by time point (PP Population) 
 
14.x.2.1.18 No 
VWF propeptide [mIU/mL]: Relative change [%] from 
randomization by time point (PP Population) 
 
14.x.2.1.19 Yes 
Factor VIIIc activity [%]: Absolute values by time point 
(PP Population) 
 
14.x.2.1.20 No 
Factor VIIIc activity [%]: Absolute change from 
randomization by time point (PP Population) 
 
14.x.2.1.21 No 
Factor VIIIc activity [%]: Relative change [%] from 
randomization by time point (PP Population) 
 
14.x.2.1.22 Yes 
aPTT FS [sec]: Absolute values by time point (PP 
Population) 
 
14.x.2.1.23 No 
aPTT FS [sec]: Absolute change from randomization 
by time point (PP Population) 
 
14.x.2.1.24 No 
aPTT FS [sec]: Relative change from randomization 
by time point (PP Population) 
 
14.x.2.1.25 Yes 
Thrombin generation CAT assay [nM]: Absolute 
values by time point (PP Population) 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 31 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
14.x.2.1.26 No 
Thrombin generation CAT assay [nM]: Absolute 
change from randomization by time point (PP 
Population) 
 
14.x.2.1.27 No 
Thrombin generation CAT assay [nM]: Relative 
change [%] from randomization by time point (PP 
Population) 
 
14.x.2.1.28 Yes 
Fibrin D-dimer [mIU/mL]: Absolute values by time 
point (PP Population) 
 
14.x.2.1.29 No 
Fibrin D-dimer [mIU/mL]: Absolute change from 
randomization by time point (PP Population) 
 
14.x.2.1.30 No 
Fibrin D-dimer [mIU/mL]: Relative change [%] from 
randomization by time point (PP Population) 
 
14.x.2.1.31 Yes 
Prothrombin fragment F1.2 [mIU/mL]: Absolute 
values by time point (PP Population) 
 
14.x.2.1.32 No 
Prothrombin fragment F1.2 [mIU/mL]: Absolute 
change from randomization by time point (PP 
Population) 
 
14.x.2.1.33 No 
Prothrombin fragment F1.2 [mIU/mL]: Relative 
change [%] from randomization by time point (PP 
Population) 
 
14.x.2.1.34 No 
ADA results by time point (PP Population) 
 
14.x.2.2.1-
14.x.2.2.34 
No 
Repeat tables 14.x.2.1.1-14.x.2.1.34 for Safety 
Population 
 
Safety Analysis 
AEs and Bleeding Events 
14.x.3.1.1 
Yes 
AE and bleeding event overview (Safety Population) 
 
Any AE or bleeding event 
 
Any related AE or 
bleeding event 
 
Any severe AE or 
bleeding event 
 
Any related severe AE or 
bleeding event 
 
Any serious AE or 
bleeding event 
 
Any related serious AE or 
bleeding event 
 
Any Hemorrhage 
(MedDRA SMQ) 
 
Any AEs or bleeding 
events leading to 
permanently study drug 
discontinuation or 
leading to withdrawn 
from study 
 
Any related AEs or 
bleeding events leading 
to permanently study 
drug discontinuation or 
leading to withdrawn 
from study 
(repeat contents for bleeding 
events) 
 
Any Hemorrhage Event 
(MedDRA SMQ) 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 32 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
 
All embolic and 
thrombotic events (SMQ) 
 
Embolic and thrombotic 
events, arterial (SMQ) 
 
Embolic and thrombotic 
events, vessel type 
unspecified and mixed 
arterial and venous 
(SMQ) 
 
Embolic and thrombotic 
events, venous (SMQ) 
Incl. 2-sided 95% CIs 
14.x.3.1.2 
Yes 
AEs and bleeding events overall and by SOC and PT 
(Safety Population) 
 
14.x.3.1.3 
Yes 
Related AEs and bleeding events overall and by SOC 
and PT (Safety Population) 
 
14.x.3.1.4 
Yes 
Severe AEs and bleeding events overall and by SOC 
and PT (Safety Population) 
 
14.x.3.1.5 
Yes 
Related severe AEs and bleeding events overall and 
by SOC and PT (Safety Population) 
 
14.x.3.1.6 
Yes 
Serious AEs and bleeding events overall and by SOC 
and PT (Safety Population) 
 
14.x.3.1.7 
Yes 
Related serious AEs and bleeding events overall and 
by SOC and PT (Safety Population) 
 
14.x.3.1.8 
Yes 
AEs and bleeding events by maximum severity (Safety 
Population) 
Incl. 2-sided 95% CIs 
14.x.3.1.9 
Yes 
Related AEs and bleeding events by maximum severity 
(Safety Population) 
Incl. 2-sided 95% CIs 
14.x.3.1.10 Yes 
Serious AEs and bleeding events by maximum 
severity (Safety Population) 
Incl. 2-sided 95% CIs 
14.x.3.1.11 Yes 
Related serious AEs and bleeding events by 
maximum severity (Safety Population) 
Incl. 2-sided 95% CIs 
14.x.3.1.12 Yes 
AEs and bleeding events leading to permanently 
study drug discontinuation or leading to withdrawn 
from study by SOC and PT (Safety Population) 
 
14.x.3.1.13 Yes 
Related AEs and bleeding events leading to 
permanently study drug discontinuation or leading to 
withdrawn from study by SOC an PT (Safety 
Population) 
 
14.x.3.1.14 Yes 
Bleeding Events by SOC and PT (Safety population) 
Incl. 2-sided 95% CI 
14.x.3.1.15 Yes 
Major bleeding events overall and by SOC and PT 
(Safety Population) 
 
 
14.x.3.1.16 Yes 
Total ISTH Bleeding Score (Safety Population) 
 
14.x.3.1.17 Yes 
Bleeding Assessment Score by Symptom (Safety 
Population) 
 
14.x.3.1.18 Yes 
Maximum Bleeding Assessment Score (Safety 
Population) 
 
Laboratory parameter 
14.x.3.1.19 Yes 
Hematology and Coagulation: Absolute values by time 
point (Safety Population) 
 
14.x.3.1.20 Yes 
Hematology and Coagulation: Absolute change from 
randomization by time point (Safety Population) 
 
14.x.3.1.21 Yes 
Hematology and Coagulation: Relative change from 
randomization by time point (Safety Population) 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 33 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
14.x.3.1.22 Yes 
Hematology and Coagulation: Subjects outside 
normal range by time point (Safety Population) 
 
14.x.3.1.23 Yes 
Clinical Chemistry: Absolute values by time point 
(Safety Population) 
 
14.x.3.1.24 Yes 
Clinical Chemistry: Absolute change from 
randomization by time point (Safety Population) 
 
14.x.3.1.25 Yes 
Clinical Chemistry: Relative change from 
randomization by time point (Safety Population) 
 
14.x.3.1.26 Yes 
Clinical Chemistry: Subjects outside normal range by 
time point (Safety Population) 
 
14.x.3.1.27 Yes 
Quantitative Urinalysis: Absolute values by time point 
(Safety Population) 
 
14.x.3.1.28 Yes 
Quantitative Urinalysis: Absolute change from 
randomization by time point (Safety Population) 
 
14.x.3.1.29 Yes 
Quantitative Urinalysis: Relative change from 
randomization by time point (Safety Population) 
 
14.x.3.1.30 Yes 
Quantitative Urinalysis: Subjects outside normal 
range by time point (Safety Population) 
 
14.x.3.1.31 Yes 
Qualitative Urinalysis by time point (Safety 
Population) 
 
14.x.3.1.32 Yes 
Vital Signs: Absolute values by time point (Safety 
Population) 
 
systolic blood pressure 
[mmHg] 
 
diastolic blood pressure 
[mmHg] 
 
heart rate [beats/min] 
 
body temperature [C] 
 
body weight [kg] 
14.x.3.1.33 Yes 
Vital Signs: Absolute change from randomization by 
time point (Safety Population) 
 
 
Content see Table 14.x.3.1.32 
14.x.3.1.34 Yes 
Subjects with clinically relevant vital signs by time 
point (Safety Population) 
 
Content see Table 14.x.3.1.32 
14.x.3.1.35 Yes 
ECG: Absolute values by time point (Safety 
Population) 
 
PQ [ms]  
 
QRS [ms] 
 
QT [ms] 
 
QTcF [ms] 
 
P [ms] 
 
RR [ms] 
 
PP [ms] 
 
P [degree] 
 
QRS [degree] 
 
T [degree] 
14.x.3.1.36 Yes 
ECG: Absolute change from randomization by time 
point (Safety Population) 
 
Content see Table 14.x.3.1.35 
14.x.3.1.37 Yes 
Subjects with clinically relevant ECG values by time 
point (Safety Population) 
 
Content see Table 14.x.3.1.35 
14.x.3.1.38 Yes 
ECG Interpretation by time point (Safety Population) 
 
normal 
 
abnormal 
 
abnormal, clinically 
relevant 
 
abnormal, not clinically 
relevant 
14.x.3.1.39 Yes 
Physical Examination results by body system and 
time point (Safety Population) 
 
normal 
 
abnormal 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 34 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
 
7.2 
List of Data Listings 
No 
Topline 
Analysis 
Title 
Content/Comment 
Overall Study Information and Baseline Evaluation 
16.2.x.1.1 
No 
Analysis Population Details 
Actual dose cohort, Randomized dose 
cohort, Subject number, Sentinel (only 
applicable for Part A), Randomization 
performed, Date of randomization, Time 
of randomization, Reason not 
randomized, Safety Population, Reason 
not in Safety Population, PP Population, 
Reason not in PP Population 
16.2.x.1.2 
No 
Screening Failures with Reasons 
Subject number, Informed consent date, 
Subject’s withdrawal of consent, In/Ex 
criterion fulfilled, Adverse event, Other, 
Specification other reason 
16.2.x.1.3 
No 
Violated Entry Criteria 
Subject number, Visit, Criterion ID not 
met, Criterion description 
16.2.x.1.4 
No 
Visit Information and Admission/Discharge 
Inpatient Unit 
Dose cohort, Subject number, Visit, 
Reason for unscheduled visit, 
Visit/Admission/Discharge date, 
Visit/Admission/Discharge time, Reason 
visit not performed, Reason outside time 
window, Specification other reason, Age 
16.2.x.1.5 
No 
Missed Visits due to Covid-19 
Dose cohort, Subject number, Visit, 
Reason for unscheduled visit, Visit date, 
Visit time, Reason visit not performed, 
Reason outside time window, Age 
16.2.x.1.6 
No 
Protocol Deviations 
Dose cohort, Subject number, PD 
category, Classification, Reason for 
classification, PD description 
16.2.x.1.7 
Yes 
Study End Information 
Dose cohort, Subject number, Visit 
attendance status, Date of 
discontinuation, Primary reason for early 
termination, Specification other reason, 
Reason for recommended withdrawal, 
Death date, Primary cause of death 
16.2.x.1.8 
Yes 
Drop-outs due to Covid-19 
Dose cohort, Subject number, Visit 
attendance status, Date of 
discontinuation, Primary reason for early 
termination, Specification other reason, 
Reason for recommended withdrawal, 
Death date, Primary cause of death 
16.2.x.1.9 
Yes 
Demographic Data 
Dose cohort, Subject number, Subject re-
screened (only applicable for Part D), 
Subject number in Part A (only applicable 
for Part D), Date of informed consent, 
Year of birth, Age [years], Gender, 
Childbearing potential, Reason no 
childbearing potential, Specification other 
reason childbearing potential, Race, 
Specification other race, Ethnicity, Blood 
type, Rhesus factor, Body weight [kg] at 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 35 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
screening, Body Height [cm], BMI [kg/m2] 
at screening 
16.2.x.1.10 
No 
Medical History 
Dose cohort, Subject number, Condition, 
SOC, PT, Start date, End date, Ongoing at 
study end 
16.2.x.1.11 
No 
Concomitant Medications 
Dose cohort, Subject number, 
Medication/Therapy, ATC Level 2, ATC 
Level 3, Start date, End date, Ongoing at 
study end, Dose, Dose Unit, Dose Form, 
Frequency, Route, Indication category, 
prior/concomitant 
16.2.x.1.12 
No 
Concomitant Procedures 
Dose cohort, Subject number, Procedure, 
SOC, PT, Start date, End date, Ongoing at 
study end, Indication category, Indication, 
prior/concomitant 
16.2.x.1.13 
No 
Serology 
Dose cohort, Subject number, Visit, 
Serology sample collected, Reason not 
collected, Collection date, Collection 
time, Test name, Result, Not done 
16.2.x.1.14 
No 
Screening for coronavirus by nasal swab 
testing (only applicable for Part B and C) 
Dose cohort, Subject number, Sample 
collected, Reason not collected, 
Collection date, Collection time, Result 
Pharmacodynamics/Biomarker/Immunogenicity 
16.2.x.2.1 
Yes 
Pharmacodynamics Results 
Dose cohort, Subject number, Visit, 
Sampling Date/Time, Sample taken, 
Reason not done, Test, Result 
specification, Result, Unit, Absolute 
Change, Relative Change [%] 
16.2.x.2.2 
Yes 
Biomarker Results 
Dose cohort, Subject number, Visit, 
Sampling Date/Time, Sample taken, 
Reason not done, Test, Result 
specification, Result, Unit, Absolute 
Change, Relative Change [%] 
16.2.x.2.2 
Yes 
Additional Biomarker Results   
Dose cohort, Subject number, Visit, 
Parameter, Result, Unit, Absolute 
Change, Relative Change [%] 
16.2.x.2.3 
No 
ADA Results 
Dose cohort, Subject number, Nominal 
Day, Collection date, Collection time, Ave, 
Stdev, CV%, Reported Result 
Safety Analysis 
16.2.x.3.1.1 
Yes 
Study Drug Administration 
Dose cohort, Subject number, Visit, Study 
drug administered, Study drug 
administered as, Reason not 
administered, Administration Start Date, 
Administration Start Time, Administration 
End Date, Administration End Time, 
Location, Other Location, Dose level, 
Study drug administration performed 
according to protocol, Cumulative dose 
level (only applicable for Part B) 
16.2.x.3.1.2 
Yes 
Desmopressin Administration (only 
applicable for Part C) 
Dose cohort, Subject number, 
Desmopressin administered, Reason not 
administered, Administration Start Date, 
Administration Start Time, Administration 
End Date, Administration End Time, 
Administration dose (ug) 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 36 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
16.2.x.3.2 
Yes 
Adverse Events (Part I) 
Dose cohort, Subject number, Source, 
Term, SOC, PT, Start date, Start time, 
Serious, Serious Criteria, Severity, 
Causality to study treatment, Causality to 
desmopressin (only applicable for Part C) 
16.2.x.3.3 
Yes 
Adverse Events (Part II) 
Dose cohort, Subject number, AE Term, 
Action taken on study treatment, Action 
taken on desmopressin (only applicable 
for Part C), Other action taken, 
Specification other action taken, 
Outcome, Recovering date, recovering 
time, Ongoing at final examination 
16.2.x.3.4 
Yes 
Serious Adverse Events (Part I) 
See Listing 16.x.3.1 
16.2.x.3.5 
Yes 
Serious Adverse Events (Part II) 
See Listing 16.x.3.2 
16.2.x.3.6 
Yes 
Haemorrhage terms (SMQ) (Part I) 
See Listing 16.x.3.1 
16.2.x.3.7 
Yes 
Haemorrhage terms (SMQ) (Part II) 
See Listing 16.x.3.2 
16.2.x.3.8 
Yes 
Embolic and thrombotic events, arterial 
(SMQ) (Part I) 
See Listing 16.x.3.1 
16.2.x.3.9 
Yes 
Embolic and thrombotic events, arterial 
(SMQ) (Part II) 
See Listing 16.x.3.2 
16.2.x.3.10 
Yes 
Embolic and thrombotic events, vessel type 
unspecified and mixed arterial and venous 
(SMQ) (Part I) 
See Listing 16.x.3.1 
16.2.x.3.11 
Yes 
Embolic and thrombotic events, vessel type 
unspecified and mixed arterial and venous 
(SMQ) (Part II) 
See Listing 16.x.3.2 
16.2.x.3.12 
Yes 
Embolic and thrombotic events, venous 
(SMQ) (Part I) 
See Listing 16.x.3.1 
16.2.x.3.13 
Yes 
Embolic and thrombotic events, venous 
(SMQ) (Part II) 
See Listing 16.x.3.2 
16.2.x.3.14 
No 
Adverse Events with missing assessments 
(Part I) 
See Listing 16.x.3.1 
16.2.x.3.15 
No 
Adverse Events with missing assessments 
(Part II) 
See Listing 16.x.3.2 
16.2.x.3.16 
Yes 
Additional Assessments for Bleeding Events Dose cohort, Subject number, Bleeding 
event, Bleeding event verbatim, Start 
date, Start time, Bleeding Assessment 
Score, ISTH clinical relevant major 
bleeding, Major bleeding criteria, ISTH 
clinical relevant non-major bleeding, Non-
major bleeding criteria, End date, End 
time 
16.2.x.3.17 
Yes 
Hematology and Coagulation Values 
Outside Normal Range 
Dose Level, Subject number, Parameter, 
Visit, Lab performed, Reason not 
performed, Collection date, Collection 
time, same as visit/admission/discharge 
date, Test, Result, Unit, not done, Reason 
not done, Outside laboratory limits, Lower 
limit, Upper limit, Clinically relevant 
16.2.x.3.18 
Yes 
Clinical Chemistry Values Outside Normal 
Range  
See Listing 16.x.3.9 
16.2.x.3.19 
No 
Quantitative Urinalysis Values Outside 
Normal Range  
See Listing 16.x.3.9 
16.2.x.3.20 
No 
Abnormal Qualitative Urinalysis Results 
Dose level, Subject number, Parameter, 
Visit, Lab performed, Reason not 
performed, Collection date, Collection 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 37 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
time, same as visit/admission/discharge 
date, Result, not done, Reason not done, 
Clinically relevant 
16.2.x.3.21 
No 
Vital Signs 
Dose level, Subject number, Visit, Vital 
signs collection, Reason not collected, 
Collection date, Collection time, same as 
visit/admission/discharge date, Test, 
Result, Clinically relevant, not done 
16.2.x.3.22 
No 
ECG 
Dose level, Subject number, Visit, ECG 
performed, Reason not performed, Date, 
Time, Same as visit/admission/discharge 
date, Test, Result, Abnormal, Clinically 
relevant, not analyzed/not available 
16.2.x.3.23 
No 
Physical Examination 
Dose level, Subject number, Visit, Extent 
of physical examination, Examination 
performed, Reason not performed, 
Examination Date, Examination Time, 
same as visit/admission/discharge date, 
Body system, Result, Specification other 
body system 
7.3 
List of Figures 
No 
Topline 
Analysis 
Title 
Content/Comment 
PD / Biomarker  
14.x.2.1.29 Yes 
Multiplate Aggregometer [U]: Absolute values 
by subject (PP Population) 
 
14.x.2.1.30 Yes 
Multiplate Aggregometer [U]: Absolute values 
by cohort (PP Population) 
 
14.x.2.1.31 Yes 
PFA-100 [sec]: Absolute values by subject (PP 
Population) 
 
14.x.2.1.32 Yes 
PFA-100 [sec]: Absolute values by cohort (PP 
Population) 
 
14.x.2.1.33 Yes 
REAADS: Absolute values by subject (PP 
Population) 
 
14.x.2.1.34 Yes 
REAADS: Absolute values by cohort (PP 
Population) 
 
14.x.2.1.35 Yes 
VWF:RiCo [%]: Absolute values by subject (PP 
Population) 
 
14.x.2.1.36 Yes 
VWF:RiCo [%]: Absolute values by cohort (PP 
Population) 
 
14.x.2.1.37 Yes 
VWF antigen [%]:Absolute values by subject 
(PP Population) 
 
14.x.2.1.38 Yes 
VWF antigen [%]: Absolute values by cohort 
(PP Population) 
 
14.x.2.1.39 Yes 
VWF propeptide [mIU/mL]: Absolute values by 
subject (PP Population) 
 
14.x.2.1.40 Yes 
VWF propeptide [mIU/mL]: Absolute values by 
cohort (PP Population) 
 
14.x.2.1.41 Yes 
Factor VIIIc activity [%]:Absolute values by 
subject (PP Population) 
 
14.x.2.1.42 Yes 
Factor VIIIc activity [%]:Absolute values by 
cohort (PP Population) 
 
14.x.2.1.43 Yes 
aPTT FS [sec]: Absolute values by subject (PP 
Population) 
 


SAP (BT200-01, Final 3.0, 17-Sep-2020) 
Adapted from: 
 
Page 38 of 38 
STAT03_A Statistical Analysis Plan 
Version 6.0, Effective Date 16-Feb-2018 
Confidential and intellectual property of Assign DMB. No part of this document or its contents may be duplicated, referenced, published or 
otherwise disclosed in any form or by any means without prior written consent of Assign DMB. 
14.x.2.1.44 Yes 
aPTT FS [sec]: Absolute values by cohort (PP 
Population) 
 
14.x.2.1.45 Yes 
Thrombinoscope [nM]: Absolute values by 
subject (PP Population) 
 
14.x.2.1.46 Yes 
Thrombinoscope [nM]: Absolute values by 
cohort (PP Population) 
 
14.x.2.1.47 Yes 
Fibrin D-dimer [mIU/mL]: Absolute values by 
subject (PP Population) 
 
14.x.2.1.48 Yes 
Fibrin D-dimer [mIU/mL]: Absolute values by 
cohort (PP Population) 
 
14.x.2.1.49 Yes 
Prothrombin fragment F1.2 [mIU/mL]: 
Absolute values by subject (PP Population) 
 
14.x.2.1.50 Yes 
Prothrombin fragment F1.2 [mIU/mL]: 
Absolute values by cohort (PP Population) 
 
Safety Analysis 
14.x.3.1.40 Yes 
Boxplots of hematology values by group and 
visit (Safety Population) 
Separate figures for every group and 
every parameter 
14.x.3.1.41 Yes 
Boxplots of coagulation values by group and 
visit (Safety Population) 
Separate figures for every group and 
every parameter 
14.x.3.1.42 Yes 
Boxplots of clinical chemistry values by group 
and visit (Safety Population) 
Separate figures for every group and 
every parameter 
14.x.3.1.43 Yes 
Boxplots of urinalysis values by group and 
visit (Safety Population) 
Separate figures for every group and 
every parameter 
14.x.3.1.44 Yes 
Vital signs values by group and visit (Safety 
Population) 
Separate figures for every group and 
every parameter 
14.x.3.1.45 Yes 
ECG values by group and Visit (Safety 
Population) 
Separate figures for every group and 
every parameter 
 
8. 
SHELLS OF TABLES, DATA LISTINGS AND FIGURES 
 
For this analysis, no table shells or mock tables are produced, but analysis drafts of TLFs will be generated based 
on dummy group allocation (dummy randomization list) and dummy immunogenicity data. These drafts will reviewed 
by the sponsor.