Phase 2b Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of a Subcutaneous Prophylaxis Treatment Regimen of CB2679d, in Adult Subjects With Hemophilia B
Phase: PHASE2
Conditions: Hemophilia B
Sponsor: Catalyst Biosciences

16 APPENDICES 
16.1 
Study Information 
16.1.1 
Protocol and Protocol Amendments 
The documents listed below are provided in this section. 
 
Protocol DLZ-201 Version 1 dated 23-March-2018 
Protocol DLZ-201 Amendment 1 Version 2 dated 17-October-2018 
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Catalyst Biosciences, Inc. 
 
CLINICAL RESEARCH PROTOCOL 
 
Phase 2b Study of Next-Generation Recombinant Factor IX Variant, CB2679d, in Adult 
Subjects with Hemophilia B 
 
Protocol Identifying Number: 
DLZ-201 
Official Title: 
Phase 2b study to evaluate the pharmacokinetics, 
pharmacodynamics, efficacy and safety of a subcutaneous 
prophylaxis treatment regimen of CB2679d, in adult subjects 
with hemophilia B. 
IND/IDE Sponsor:  
 
Catalyst Biosciences, Inc. 
611 Gateway Blvd., Suite 710, South San Francisco, California, 
USA  94080 
Investigational Product: 
Recombinant Factor IX, CB2679d 
Development Phase: 
2b 
Draft or Version Number: 
v.1.0 
Effective Date: 
23 March 2018 
Sponsor Contact: 
Name: 
 
Howard Levy, MD, PhD, MMM 
                                    CMO, Catalyst Biosciences, Inc. 
Telephone: 
 
+1.650.266.8671 
Fax: 
 
 
+1.650.871.2475 
E-mail:  
 
hlevy@catbio.com 
 
Prepared by: 
Catalyst Biosciences, Inc. 
 
Confidentiality Statement 
The information in this document contains trade secrets and commercial information that 
are privileged or confidential and may not be disclosed unless such disclosure is required 
by applicable law or regulations. In any event, persons to whom the information is disclosed 
must be informed that the information is privileged or confidential and may not be further 
disclosed by them. These restrictions on disclosure will apply equally to all future information 
supplied to you that is indicated as privileged or confidential. 
Compliance Statement: 
This study will be conducted in accordance with the clinical 
research guidelines established by the U.S. Code of Federal Regulations (Title 21, Parts 50 
[including Subpart D], 54, 56 and 312), the regulations and guidelines of the Therapeutic 
Goods Administration, and the International Conference on Harmonization (ICH) Guidelines 
for Good Clinical Practice. Study documents will be maintained in accordance with 
applicable regulations. 
 
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INVESTIGATOR SIGNATURE PAGE 
 
PROTOCOL TITLE: 
Phase 2b study to evaluate the pharmacokinetics, 
pharmacodynamics, efficacy and safety of a subcutaneous 
prophylaxis treatment regimen of CB2679d, in adult subjects with 
hemophilia B. 
PROTOCOL No.: 
DLZ-201 
VERSION NUMBER: 
1.0 
 
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study subjects enrolled under my supervision and 
providing the Sponsor with complete and timely information, as outlined in the protocol. 
Furthermore, on behalf of the study staff and myself, I agree to conduct the study as 
outlined in the protocol in accordance with the guidelines outlined in the study protocol 
and all applicable government regulations. In addition, I agree to provide all the 
information requested in the case report forms (CRFs) presented to me by the Sponsor in a 
manner that assures legibility and accuracy. I also agree that all information provided to 
me by the Sponsor, including pre-clinical data, protocols, CRFs, verbal and written 
information, will be kept strictly confidential and confined to the clinical personnel involved 
in conducting the study. It is recognized that this information may be relayed in confidence 
to the Institutional Review Board (IRB)/ Independent Ethics Committee (IEC). In addition, no 
reports or information about the study or its progress will be provided to anyone who is not 
involved in the study, other than Sponsor or designee, the IRB/IEC, or the appropriate 
regulatory agencies. 
The trial will be conducted in accordance with International Conference on Harmonisation 
Good Clinical Practice (ICH GCP), applicable United States (US) Code of Federal 
Regulations (CFR) (Title 21, Parts 50 [including Subpart D], 54, 56 and 312), the regulations 
and guidelines of the Therapeutic Goods Administration (TGA). The Principal Investigator 
(PI) will assure that no deviation from, or changes to the protocol will take place without 
prior agreement from the sponsor, funding agency and documented approval from the 
IRB, except where necessary to eliminate an immediate hazard(s) to the trial participants. 
All personnel involved in the conduct of this study have completed Human Subjects 
Protection and ICH GCP Training. Study documents will be maintained in accordance with 
applicable regulations. 
I agree to ensure that all staff members involved in the conduct of this study are informed 
about their obligations in meeting the above commitments.  
 
 
 
 
Investigator Signature  
 
Date 
 
Print Name and Title 
 
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SPONSOR SIGNATURE PAGE 
 
Protocol Title: 
Phase 2b study to evaluate the pharmacokinetics, 
pharmacodynamics, efficacy and safety of a subcutaneous 
prophylaxis treatment regimen of CB2679d, in adult subjects 
with hemophilia B. 
Protocol Number: 
 
DLZ-201 
Version Number: 
1.0, dated 23 March 2018 
 
 
 
 
 
_________________________________________________________  
 23rd March 2018                               
Howard Levy, MD, PhD, MMM 
 
 
 
 
 
Date 
Chief Medical Officer, Catalyst Biosciences, Inc. 
 
 
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ABBREVIATIONS 
 
% 
Percent 
ADL 
Activities of daily living 
AE 
Adverse event 
AESI 
Adverse Events of Special Interest 
ALT 
Alanine aminotransferase 
aPTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
ATIII 
Anti-thrombin III 
AUC 
Area under the curve 
AUC0-inf 
Area under the curve from time 0 to the last measurable concentration 
AUC0-t 
Area under the curve-time curve 
CAD 
Coronary artery disease 
CB2679d 
Recombinant Factor IX variant 
CBC 
Complete blood count 
CD4 
Cluster of differentiation 4 
CFR 
Code of Federal Regulations 
Cmax 
Concentration maximum 
CMO 
Chief Medical Officer 
Cr 
Creatinine 
CRF 
Case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
dL 
Deciliter 
DVT 
Deep venous thrombosis 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
eCRF  
Electronic Case Report Forms  
F1+2 
Prothrombin fragment 1+2 
FDA 
Food and Drug Administration 
FVIII 
Factor VIII 
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FVIIIa 
Factor VIII activated 
FIX 
Factor IX 
FIXa 
Factor IX activated 
FX 
Factor X 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transpeptidase 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GS 
Gilbert’s syndrome 
Hr 
Hour 
HTC 
Hemophilia Treatment Centre  
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IDE 
Investigational Device Exemption 
IEC 
Independent Ethics Committee 
IMT 
Immunomodulatory therapy 
IND 
Investigational New Drug Application 
IP 
Investigational product 
IRB 
Institutional Review Board 
IU 
International unit 
IV 
Intravenous 
Kg 
Kilogram 
L 
Liter 
LLN 
Lower limit of normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Myocardial Infarction 
Min 
Minute 
NCT 
National Clinical Trial 
OTC 
Over-the-counter 
PD 
Pharmacodynamics 
pdFIX 
Plasma-derived factor IX 
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PE 
Pulmonary embolism 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PT 
Prothrombin time 
QA 
Quality Assurance 
QC 
Quality Control 
QoL 
Quality of life 
r 
Recombinant 
rFIX 
Recombinant factor IX  
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SQ 
Subcutaneous 
SOA 
Schedule of Activities 
SOC 
Standard of Care 
SOP 
Standard Operating Procedure 
T1/2 
Half-life 
TAT 
Thrombin-antithrombin complexes 
TBIL 
Total bilirubin level 
TE 
Thromboembolic event 
TEAE 
Treatment-emergent adverse event 
TGA 
Therapeutic Goods Administration 
Tmax 
Time that studied drug is present at the maximum concentration in serum 
µmol 
Micromole 
ULN 
Upper limit of normal 
US 
United States 
VTE 
Venous thromboembolic event 
WFH 
World Federation of Hemophilia 
 
 
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TABLE OF CONTENTS 
Contents 
INVESTIGATOR SIGNATURE PAGE ................................................................................................ 2 
SPONSOR SIGNATURE PAGE ........................................................................................................ 3 
ABBREVIATIONS ............................................................................................................................. 4 
TABLE OF CONTENTS ..................................................................................................................... 7 
1.  
PROTOCOL SUMMARY ....................................................................................................... 11 
1.1  
SYNOPSIS ........................................................................................................................................................ 11 
1.2  
SCHEMA .......................................................................................................................................................... 16 
1.3  
SCHEDULE OF ACTIVITIES (SOA) ........................................................................................................................... 17 
2. INTRODUCTION ........................................................................................................................ 20 
2.1 
STUDY RATIONALE ................................................................................................................................................. 20 
2.2 
BACKGROUND ....................................................................................................................................................... 20 
2.2.1 
Rationale for Prophylaxis with SQ Administration of FIX .......................................................................... 21 
2.2.2 
Experience with CB2679d in the Clinic ...................................................................................................... 22 
3.  
OBJECTIVES .......................................................................................................................... 24 
3.1  
PRIMARY ......................................................................................................................................................... 24 
3.2  
SECONDARY ..................................................................................................................................................... 24 
4.  
STUDY DESIGN ...................................................................................................................... 25 
4.1 
OVERALL DESIGN ................................................................................................................................................... 25 
4.2  
END OF STUDY DEFINITION .................................................................................................................................. 27 
5.  
STUDY POPULATION ............................................................................................................ 28 
5.1 
INCLUSION CRITERIA ............................................................................................................................................... 28 
5.2 
EXCLUSION CRITERIA .............................................................................................................................................. 28 
5.3  
LIFESTYLE CONSIDERATIONS ................................................................................................................................. 29 
5.4  
SCREEN FAILURES .............................................................................................................................................. 29 
6.  
STUDY INTERVENTION .......................................................................................................... 30 
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6.1  
STUDY INTERVENTION(S) ADMINISTRATION ............................................................................................................. 30 
6.1.1  
Study Intervention Description ................................................................................................................. 30 
6.1.2  
Dosing and Administration ...................................................................................................................... 30 
6.2  
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY .............................................................................. 31 
6.2.1  
Acquisition and Accountability ................................................................................................................. 31 
6.2.2  
Product Storage and Stability ................................................................................................................... 31 
6.2.3  
Preparation .............................................................................................................................................. 32 
6.3  
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING ................................................................................. 33 
6.4  
STUDY INTERVENTION COMPLIANCE ...................................................................................................................... 33 
6.5  
CONCOMITANT THERAPY .................................................................................................................................... 33 
7.  
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................................ 34 
7.1  
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY .............................................................................. 34 
7.2  
LOST TO FOLLOW‐UP ......................................................................................................................................... 34 
8.  
STUDY ASSESSMENTAND PROCEDURES ............................................................................ 36 
8.1  
STUDY PROCEDURES .......................................................................................................................................... 36 
8.1.1  
Screening ................................................................................................................................................. 36 
8.1.2  
Part 1, Weeks 1 and 2 (Duration 7 days) .................................................................................................. 37 
8.1.3  
Part 2, Week 3 (Duration: 7 days) ............................................................................................................ 39 
8.1.4  
Part 3, Weeks 4 and 5 (Duration: 14 days) ............................................................................................... 41 
8.1.5  
Washout Period, Unscheduled Visits and End of Study evaluations .......................................................... 43 
8.2  
STUDY ASSESSMENTS ......................................................................................................................................... 45 
8.2.1  
Efficacy Assessments................................................................................................................................ 45 
8.2.2  
Physical Examination ............................................................................................................................... 46 
8.2.3  
Vital signs ................................................................................................................................................ 46 
8.2.4  
Hematology ............................................................................................................................................. 46 
8.2.5  
Chemistry ................................................................................................................................................. 47 
8.2.6  
Coagulation assays .................................................................................................................................. 47 
8.2.7  
Thrombogenicity markers ........................................................................................................................ 47 
8.2.8  
Antibody response and neutralizing antibodies to CB2679d ..................................................................... 47 
8.2.9  
Clinical signs of thrombosis (Appendix A) ................................................................................................. 47 
8.2.10  
Concomitant medications .................................................................................................................... 47 
8.2.11  
ECG ..................................................................................................................................................... 47 
8.3  
SAFETY AND OTHER ASSESSMENTS ........................................................................................................................ 48 
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8.3.1  
AEs and SAEs ............................................................................................................................................ 48 
8.3.2  
Injection site reactions ............................................................................................................................. 48 
8.4  
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS .................................................................................................... 48 
8.4.1  
Definition of Adverse Events (AE) ............................................................................................................. 48 
8.4.2  
Definition of Serious Adverse Events (SAE) ............................................................................................... 49 
8.4.3  
Classification of an Adverse Event ............................................................................................................ 50 
8.4.4  
Time Period and Frequency for Event Assessment and Follow‐Up ............................................................ 51 
8.4.5  
Adverse Event Reporting .......................................................................................................................... 52 
8.4.6  
Serious Adverse Event Reporting .............................................................................................................. 53 
8.4.7  
Adverse Events of Special Interest (AESIs) ................................................................................................ 54 
8.4.8  
Reporting of Pregnancy ........................................................................................................................... 55 
9.  
STATISTICAL CONSIDERATIONS .......................................................................................... 56 
9.1 
STUDY HYPOTHESIS ................................................................................................................................................ 56 
9.2 
SAMPLE SIZE DETERMINATION .................................................................................................................................. 57 
9.3 
POPULATIONS FOR ANALYSES ................................................................................................................................... 57 
9.4 
STATISTICAL ANALYSIS ............................................................................................................................................. 57 
9.4.1 
General Approach .................................................................................................................................... 57 
9.4.2  
Analysis of the Primary Efficacy Endpoint(s) ............................................................................................. 58 
9.4.3  
Analysis of the Secondary Endpoint(s) ...................................................................................................... 58 
9.4.4  
Safety Analysis ......................................................................................................................................... 58 
9.4.5  
Baseline Descriptive Statistics .................................................................................................................. 59 
9.4.6  
Planned Interim Analyses ......................................................................................................................... 59 
9.4.7  
Sub‐Group Analyses ................................................................................................................................. 59 
9.4.8  
Tabulation of Individual Participant Data ................................................................................................ 59 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ...................... 60 
10.1 REGULATORY, ETHICAL AND STUDY OVERSIGHT CONSIDERATIONS ...................................................................................... 60 
10.1.1 
 Informed Consent Process .................................................................................................................. 60 
10.1.2  
Institutional Review Board/Independent Ethics Committee ................................................................. 60 
10.1.3  
Study Discontinuation and Closure ...................................................................................................... 61 
10.1.4  
Confidentiality and Privacy .................................................................................................................. 61 
10.1.5  
Future Use of Stored Specimens and Data ........................................................................................... 62 
10.1.6  
Clinical Monitoring .............................................................................................................................. 62 
10.1.7  
Quality Assurance (QA) and Quality Control (QC) ................................................................................ 63 
10.1.8  
Data Handling and Record Keeping ..................................................................................................... 63 
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10.1.9  
Protocol Amendments ......................................................................................................................... 64 
10.1.10  
Publication and Data Sharing Policy .................................................................................................... 64 
10.2  
PROTOCOL AMENDMENT HISTORY ........................................................................................................................ 65 
11.  
REFERENCES ..................................................................................................................... 66 
APPENDICES ................................................................................................................................ 70 
APPENDIX A – CLINICAL SIGNS OF THROMBOSIS ..................................................................................................................... 70 
APPENDIX B – DETAILED STUDY SCHEMA ............................................................................................................................. 79 
 
 
 
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1.  
PROTOCOL SUMMARY 
 
1.1  
SYNOPSIS 
Title of Study: Phase 2b study to evaluate the pharmacokinetics, pharmacodynamics, 
efficacy and safety of a subcutaneous prophylaxis treatment regimen of CB2679d in 
adult subjects with hemophilia B. 
Primary Objective: To evaluate the dose required to achieve a steady-state of >12% 
factor IX (FIX) levels.  
Secondary Objectives:  
 To determine the pharmacokinetics (PK) of subcutaneous (SQ) regimens of CB 2679d. 
 To determine the pharmacodynamics (PD) of SQ regimens of CB 2679d. 
 To evaluate the levels of thrombogenicity markers of SQ regimens of CB 2679d. 
 To evaluate for evidence of the development of antibodies to CB2679d and to 
determine if these are neutralizing antibodies. 
 To monitor and evaluate safety parameters of SQ regimens of CB2679d. 
Study Population: Five male subjects, aged 18 or older, with confirmed diagnosis of 
severe congenital hemophilia B (<2% FIX level). 
Phase of Development:  Phase 2b 
Description of Sites: Single center study. 
Study Duration: Approximately 6 months. 
Participant Duration: The duration of treatment for each subject is approximately 6 weeks.  
Screening: Up to 4 weeks. 
Study Drug Administration: SQ prophylaxis treatment regimens over a 6-week period with 
the goal to achieve steady-state levels above 12% FIX activity when dosed daily, every 
second day or every third day. 
Note: Where interruptions to study drug dosing days occur, study duration may be 
extended to incorporate full dosing schedule. 
Follow-up: 30 days (± 2 days) after last dose for PK/PD/safety follow-up. 
Study Methodology 
This single-center, open-label Phase 2b study will evaluate the PK, PD, efficacy and safety 
parameters of SQ prophylaxis treatment regimens with CB2679d in adult subjects with 
hemophilia B. The study will enroll and dose subcutaneously, a total of 5 adult male 
subjects with severe congenital hemophilia B.  
At the screening visit and prior to any study procedures, subjects will sign an informed 
consent form (ICF).  Eligibility to participate in the study will be determined by inclusion 
and exclusion criteria elicited from medical history, hemophilia history, physical 
examination, laboratory assessments and an electrocardiogram (ECG). The screening 
period duration may be up to 4 weeks. 
I 
I 
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At enrollment, subjects will be provided with a diary in which they will be instructed to 
record any adverse events (AEs) and concomitant medication.   
 
After the initial intravenous (IV) dose of CB2679d, and subsequent SQ doses, the following 
will be monitored daily: injection site reaction, any AEs the subject may experience, and 
any bleeding episodes (location, inciting event if not spontaneous, and treatment 
administered). 
IV/SQ Study Drug Administration and Assessments: 
Initial IV Load Dose Followed by Daily SQ study drug administration  
Part 1; Weeks 1 and 2: The subject will receive an IV loading dose of 70 IU/kg followed 30 
minutes later by a SQ dose of 140 IU/kg. Daily SQ doses of 140 IU/kg will be administered 
until Day 14 (14 total SQ doses). On day 1, PK, PD, and safety assessments will be done at 
pre-IV dose and repeated 30 minutes later prior to the SQ dose. Subsequent PK, PD and 
safety assessments will be performed 7 hours post-SQ dose on Day 1, Day 2 at hour 24 
post-SQ dose and pre-dose on days 5, 8, 11 and 14.  
Every Second Day SQ study drug administration  
Part 2; Week 3: The subject will receive a SQ dose every second day of 280 IU/kg, starting 
on Day 15 until Day 21 (total of 4 SQ doses). On Day 15 only, PK, PD, and safety 
assessments will be done at pre-dose and repeated at hour 7.  Subsequent PK, PD and 
safety assessments will be performed on Day 16 at hour 24 and pre-dose on days 17, 19 
and 21.  
Every Third Day SQ study drug administration  
Part 3; Weeks 4 and 5: The subject will receive a SQ dose every third day of 420 IU/kg, 
starting on Day 23 until Day 32 (total of 4 SQ doses). On days 23 and 32 only, PK, PD, and 
safety assessments will be done at pre-dose and repeated at hour 7.  Subsequent PK, PD, 
and safety assessments will be performed at Day 24 at hour 24 and pre-dose on days 26, 
and 29. 
Washout Period 
PK, PD, and safety assessments will be done on Days 33, 34, 35, 37 and 38. Daily FIX 
activity levels will be measured, except on Day 36, unless FIX activity level is known to be 
< 5%, as measured by local laboratory. 
An End of Study visit will occur 30 days (± 2 days) after the last dose of study drug. 
Treatment of a bleeding episode: Subjects will self-administer their currently prescribed FIX 
replacement product for treatment of any spontaneous or traumatic bleed that occurs 
while on study drug.  If treatment for a breakthrough spontaneous bleeding episode is 
needed, then subjects will contact the clinical investigative team immediately to report 
the event; treatment dose administered; and arrange for an urgent follow-up visit to the 
study site for additional evaluation and laboratory testing, if needed.   
Dose interruption: SQ study drug injections will be interrupted if any of the following 
occurs: a thrombotic event; clinical evidence of inhibitor formation; or laboratory results 
suggesting a high titer antibody may be developing; trough activity levels >80% or peak 
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levels >175%, where subsequent dosing will be determined in consultation with the 
sponsor. 
Surgery: If there is an urgent need for a surgical procedure or an event requiring 
extended (>48 hours) hospitalization, a FIX activity level will be urgently obtained and 
measured prior to the event, and the PI will confer with the Sponsor Medical 
representative regarding the need for any additional treatment and whether study drug 
requires interruption.   
Measurements:   
PK, PD, and safety assessments: CB2679d activity levels, as well as fibrinogen, D-dimer, 
prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complexes (TAT). PT and 
aPTT will be measured at screening and end of study visit only. 
Immunogenicity assays: Specimens for immunogenicity testing (antibody to CB 2679d, 
wild-type FIX cross reactivity, and neutralizing activity) will be drawn at screening, on days 
1, 8, 15, 23, 32, and end of study. 
If the FIX activity level decreases unexpectedly by more than 25%, ie, IU/dL, as measured 
by the central or local lab, CB2679d activity levels will be drawn for analysis within 24 
hours and immediately sent to the central laboratory.  Specimens for fibrinogen, D-dimer, 
F1+2, and TAT and immunogenicity testing will also be drawn. 
Number of planned subjects: 5 
Trial population: 
Inclusion criteria: 
1. Confirmed diagnosis of severe (<2%) congenital hemophilia B. 
2. Male, age 18 or older. 
3. Agreement to use highly effective birth control throughout the study.  
4. Affirmation of informed consent with signature confirmation before any trial-
related activities. (Trial related activities are any procedure that would not have 
been performed during normal clinical management of the subject). 
5. Stated willingness to comply with all study procedures and availability for the 
duration of the study.  
Exclusion criteria: 
1. Patients with a history or a family history of FIX inhibitors. 
2. Positive antibody to FIX detected by central laboratory at screening. 
3. Previous participation in and subsequent treatment in a clinical trial within the 
previous 30 days or 3-half-lives, whichever is longer, or absence of clinical effect.  
4. History of clinically relevant coagulation disorders other than congenital 
hemophilia B including Factor V Leiden or other identified activated Protein C 
resistance. 
5. Platelet count <100,000 based on screening laboratory assessments. 
6. Advanced atherosclerotic disease (ie, known history of coronary artery disease 
(CAD), ischemic stroke, etc.), or known deep venous thrombosis (DVT) or 
considered to be at a high risk of venous thromboembolic event (VTE) as judged 
by the Investigator. 
7. Known or suspected allergy to trial product or related products. 
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8. Known absolute cluster of differentiation 4 (CD4) count <200 cells/μL. 
9. Receiving immunomodulatory therapy (IMT). 
10. Compromised hepatic or renal function: 
o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels 
≥5 times the upper limit of normal (ULN) 
o Total bilirubin level (TBIL) ≥2 mg/dL (>35 µmol /L) unless there is a known 
history of Gilbert’s syndrome (GS) 
o Serum albumin ≤ the lower limit of normal (LLN) 
o Serum creatinine (Cr) level >1.25 x ULN   
11. Inability or medical, psychosocial, or familial issues that might prevent full 
participation and cooperation with the procedures and requirements of the 
clinical trial as determined by the potential subject and physician investigator. 
Investigational product, dose, and mode of administration:  
Investigational Product: Recombinant FIX variant; CB2679d  
Dosage and mode of administration:  
Part 1: Weeks 1 and 2 (Days 1-14): IV loading dose of 70 IU/kg followed 30 minutes later 
with 140 IU/kg SQ administration daily x 14 (14 total doses). 
Part 2: Week 3 (Days 15, 17, 19 and 21): 280 IU/kg, SQ administration every second day (4 
total doses). 
Part 3: Weeks 4 and 5 (Days 23, 26, 29, 32): 420 IU/kg SQ administration every third day (4 
total doses) 
Reference therapy: None 
Concomitant Medications: In the event of spontaneous or traumatic bleeding, treatment 
for a bleeding episode will be permitted using the subject’s current treatment regimen. 
Efficacy and Safety Evaluations 
Primary endpoints: 
 
Number of subjects who achieve a steady-state FIX activity level above 12%, 30% and 
50% with daily, every second day or every third day dosing. 
Secondary endpoints: 
 
Safety assessments: Occurrence of antibody formation resulting in a decreased 
endogenous level of FIX; occurrence of a clinical thrombotic event not attributable to 
another cause. 
 
Occurrence of a conformed antibody response with high titer to CB2679d and 
whether it is inhibitory and cross-reactive to wild-type FIX.   
 
Change in CB2679d activity levels, and from pre-dose. 
 
Clinically significant levels of thrombogenicity markers resulting from SQ administration 
of CB 2679d.  
 
Feasibility of using an adjusted-dose SQ prophylaxis treatment regimen clinically. 
 
 
 
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Statistics 
Primary Analysis Plan:  
Appropriate descriptive statistics of all measured parameters will be reported, including 
95% confidence intervals. 
The dose required to achieve steady-state levels >12%, >30% and >50% will be reported 
for daily, every second day or every third day dosing, including 95% confidence intervals. 
Rationale for Number of Subjects: 
5 subjects will provide guidance on dose required to achieve steady-state activity >12%, 
30% or 50% and starting SQ dose for subsequent studies. 
Name of sponsor: Catalyst Biosciences 
 
 
 
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1.2  
SCHEMA 
Figure 1. Schematic of Study Design  
 
 
• 
Concomitant Medications 
• 
Vital Signs 
• 
Weight 
• 
Physical examination 
• 
Clinical Signs ofThrombosis 
• 
Hematology and Chemistry 
(Days 1 Pre-IV Dose, 8 and 14 
only) 
• Thrombogenicity Markers 
• 
PK Sampling 
• 
lmmunogenicity Assays (Day 
8 only) 
• 
Diary Entry Training 
• 
Diary Entry 
• 
Adverse Events 
• 
CB2679d Administration (IV 
Load Dose + SQ Daily Dose) 
• Joint Evaluation (Day 32) 
• 
Concomitant Medications 
• 
Vital Signs 
• 
Weight 
• 
Physical examination 
• 
Clinical Signs ofThrombosis 
• 
Hematology and Chemistry 
• Thrombogenicity Markers 
• 
PK Sampling 
• 
lmmunogenicity Assays 
• 
Diary Entry 
• 
Adverse Events 
• 
CB2679d SQ Administration 
(Every 3rd Day) 
• 
Concomitant Medications 
• 
Clinical Signs ofThrombosis 
• Thrombogenicity Markers 
• 
PK Sampling 
• 
Diary Entry 
• 
Adverse Events 
• 
Informed Consent 
• 
Demographic Parameters 
• Joint evaluation 
• 
Inclusion and Exclusion Criteria 
• 
Medical and Hemophilia 
History 
• 
Concomitant Medications 
• Vital Signs 
• 
Height & Weight 
• 
Physical examination 
• 
Clinical Signs ofThrombosis 
• 
Hematology and Chemistry 
• 
Coagulation Assays 
• Thrombogenicity Markers 
• 
lmmunogenicity Assays 
• 
ECG 
• 
Diary Entry Training 
• Adverse Events 
• 
Concomitant Medications 
• Vital Signs 
• Weight 
• 
Physical examination 
• 
Clinical Signs ofThrombosis 
• 
Hematology and Chemistry 
• Thrombogenicity Markers 
• 
PK Sampling 
• 
lmmunogenicity Assays 
• 
Diary Entry 
• Adverse Events 
• 
CB2679d SQ Administration 
(Every 2'1d Day) 
• 
Concomitant Medications 
• Vital Signs 
• 
Physical examination 
• 
Clinical Signs ofThrombosis 
• 
Hematology and Chemistry 
• Thrombogenicity Markers 
• 
PK Sampling 
• 
lmmunogenicity Assays 
• 
Diary Entry 
• Adverse Events 
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1.3  
SCHEDULE OF ACTIVITIES (SOA) 
Table 1. Part 1: Weeks 1 and 2 
Study Period 
Screening 
Weeks 1 and 2 (Days 1 – 14)  
Study Day 
Day -28 to -1 
Day 1,  
IV Pre-dose 
(- 5 min) 
Day 1,  
SQ dose 
30 min 
Post IV 
Day 1,  
Hour 7 (+ 
1 hour) 
Day 2, 
Hour 24 (+ 1 
hour) 
Days 5, 8, 11, 147 
Pre-dose (- 5 min) 
Informed Consent 
X 
 
 
 
 
 
Demographic Parameters 
X 
 
 
 
 
 
Joint Evaluation1 
X 
 
 
 
 
 
Inclusion and Exclusion Criteria 
X 
 
 
 
 
 
Medical and Hemophilia History2 
X 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
Height (screening only) & Weight 
X 
X 
 
 
 
 
Physical Examination2 
X 
X 
X 
X 
X 
X 
Clinical Signs of Thrombosis3 
X 
X 
X 
X 
X 
X 
Hematology and Chemistry4 
X 
X 
 
 
 
X (Days 8 and 14 only) 
Coagulation Assays5 
X 
 
 
 
 
 
Thrombogenicity markers5 
X 
X 
X 
X 
X 
X 
Pharmacokinetic (PK) sampling5 
 
X 
X 
X 
X 
X 
Immunogenicity assays5 
X 
 
 
 
 
X (Day 8 only) 
ECG 
X 
 
 
 
 
 
Diary entry training6 
 
X 
 
 
 
 
Diary entry of any bleeding 
episodes, AEs, injection site 
 
------------------------------------------------------------------------------------------------------- 
Adverse Events 
X 
X 
X 
X 
X 
X 
CB 2679d administration7 
 
 
-------------------------------------------------------- 
1. 
As per Standard of Care at hemophilia treatment center. 
2. 
Complete evaluation at Screening followed by interim targeted evaluation, per Investigator’s discretion, as indicated on presentation of subject at study visit. 
3. 
Clinical Signs of Thrombosis per protocol 
4. 
Local Laboratory: Hematology - CBC and platelet count.  Chemistry - Sodium, potassium, chloride, bicarbonate, hepatic enzymes (ALT, AST, GGT), bilirubin, albumin, 
creatinine. 
5. 
Central Laboratory:  Coagulation assays – PT and aPTT.  Thrombogenicity markers – Fibrinogen, D-dimer, F1.2, and TAT.  Pharmacokinetics – CB 2679d activity.  
Immunogenicity assays – to BeneFIX and CB 2679d. 
6. 
Diary entry training consists of investigational drug administration, injection site assessment, adverse events, any bleeding episodes & treatment. 
7. 
IV load dose (70 IU/kg) followed by SQ dose (140 IU/kg) 30 minutes (+ 30 mins) after.  Daily SQ (140 IU/kg) dosing until Day 14 (14 total SQ doses). 
8. 
Post dose assessments performed 7 hours (+ 1 hour) after SQ dose 
 
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Part 2.  Week 3 
Study Period 
Week 3 (Days 15 – 21)  
Study Day/Hour 
Day 15,  
Pre-dose 
(- 5 min) 
Day 15,  
Hour 7 
(± 1 hour) 
Day 16,  
Hour 24  
(± 1 hour) 
Day 17,  
Pre-dose 
(- 5 min) 
Day 19,  
Pre-dose 
(- 5 min) 
Day 21,  
Pre-dose 
(- 5 min) 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
Weight 
X 
 
 
 
 
X 
Physical Examination1 
X 
X 
X 
X 
X 
X 
Clinical Signs of Thrombosis2 
X 
X 
X 
X 
X 
X 
Hematology and Chemistry3 
 
 
 
 
 
X 
Thrombogenicity markers4 
X 
X 
X 
X 
X 
X 
Pharmacokinetic (PK) sampling4 
X 
X 
X 
X 
X 
X 
Immunogenicity assays4 
X 
 
 
 
 
 
Diary entry of any bleeding 
episodes, AEs, injection site 
assessment5 
------------------------------------------------------------------------------------------------------------ 
Adverse Events 
X 
X 
X 
X 
X 
X 
CB2679d administration6 
 
-------------------------------------------------------------------------------------------- 
 
1. 
Targeted evaluation, per Investigator’s discretion, as indicated on presentation of subject at study visit. 
2. 
Clinical Signs of Thrombosis: per protocol 
3. 
Local Laboratory: Hematology - CBC and platelet count.  Chemistry - Sodium, potassium, chloride, bicarbonate, hepatic enzymes (ALT, AST, GGT), bilirubin, albumin, 
creatinine.  
4. 
Central Laboratory:  Thrombogenicity markers – Fibrinogen, D-dimer, F1.2, and TAT.  Pharmacokinetics – CB 2679d activity.  Immunogenicity assays – to BeneFIX and CB 
2679d. 
5. 
Diary entry consists of investigational drug administration, injection site assessment, adverse events, any bleeding episodes & treatment. 
6. 
Dosing every second day SQ (280 IU/kg) starting Day 15 until Day 21 (4 total doses).   
 
 
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Part 3.  Weeks 4 and 5, Washout, Unscheduled and End of Study 
Study Period 
Weeks 4 and 5 (Days 23-32) 
WASH-
OUT 
Un-
scheduled 
End of 
Study9 
Study Day/Hour 
Day 23,  
Pre-dose 
(- 5 min) 
Day 23,  
Hour 7 
(± 1 hr) 
 Day 24,  
Hour 24  
(± 1 hr) 
 Day 26,  
Pre-dose 
(- 5 min) 
 Day 29, 
Pre-dose 
(- 5 min) 
Day 32, 
Pre-dose  
(- 5 min) 
Day 32, 
Hour 7 
(± 1 hr) 
Days 33, 
34, 35, 
37, 388 
 
 
Joint evaluation1 
 
 
 
 
 
 
X 
 
 
 
Medical and Hemophilia History2 
 
 
 
 
 
 
 
 
X 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Weight 
X 
 
 
 
 
 
 
 
X 
 
Physical Examination2 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
Clinical Signs of Thrombosis3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology and Chemistry4 
X 
 
 
 
 
 
X 
 
X 
X 
Coagulation Assays5 
 
 
 
 
 
 
 
 
 
X 
Thrombogenicity markers5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic (PK) sampling5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity assays5 
X 
 
 
 
 
X 
 
 
X 
X 
Diary entry of any bleeding 
episodes, AEs, injection site 
assessment6 
------------------------------------------------------------------------------------------------------------------------------------------------------------- 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CB2679d administration7 
 
------------------------------------------------------------------------------- 
 
 
 
1. 
As per Standard of Care at hemophilia treatment center. 
2. 
Targeted evaluation, per Investigator’s discretion, as indicated on presentation of subject at study visit. 
3. 
Clinical Signs of Thrombosis per protocol 
4. 
Local Laboratory: Hematology - CBC and platelet count.  Chemistry - Sodium, potassium, chloride, bicarbonate, hepatic enzymes (ALT, AST, GGT), bilirubin, albumin, 
creatinine. 
5. 
Central Laboratory:  Coagulation assays – PT and aPTT. Thrombogenicity markers – Fibrinogen, D-dimer, F1.2, and TAT.  Pharmacokinetics – CB 2679d activity.  
Immunogenicity assays – to BeneFIX and CB 2679d. 
6. 
Diary entry training consists of investigational drug administration, injection site assessment, adverse events, any bleeding episodes & treatment. 
7. 
Dosing every third day SQ (420 IU/kg) starting Day 23 until Day 32 (4 total doses).   
8. 
Daily FIX activity levels needed (except Day 36), unless FIX activity level known to be < 5%, as per local lab. 
9. 
End of Study Visit will occur 30 ± 2 days after the last dose. 
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2. INTRODUCTION 
 
2.1 STUDY RATIONALE 
 
The rapid clearance of FIX necessitates frequent intravenous (IV) administrations 
to achieve effective prophylaxis for patients with hemophilia B. Subcutaneous 
(SQ) administration, a preferred administration route, has historically been limited 
by low bioavailability and potency. CB2679d, formerly known as ISU304, was 
developed using a rational design approach to be the next-generation SQ 
coagulation prophylactic FIX therapy.  
2.2 BACKGROUND 
 
Hemophilia B, or sometimes referred to as Christmas disease, is a hereditary X 
chromosomal-linked recessive bleeding disorder caused by Factor IX (FIX) 
deficiency.1 Hemophilia B, especially in severe phenotypes, is characterized by 
frequent and spontaneous bleeding1,2 into joints, muscles and body cavities, and 
can lead to arthropathy with progressive cartilage damage, chronic pain, 
disability, diminished quality of life (QoL) and ultimately joint destruction.1 Disease 
classification of mild (factor activity >5 % and <40%), moderate (1 to 5%) or severe 
phenotype (<1%) is based on residual plasma FIX levels.3,4 The number of patients 
with mild, moderate and severe phenotypes of hemophilia B is not well 
established, however community studies have estimated that 60–70% of patients 
with hemophilia B have a moderate or severe form.5-7 Historically, treatment for 
hemophilia B has been on demand, that is, clotting FIX replacement therapy 
administered when a hemorrhage occurs or before a surgical procedure.8 
Currently, the standard of care treatment for hemophilia B is FIX replacement 
therapy administered prophylactically, at regular intervals to maintain FIX levels 
greater than 1%, to prevent the onset of bleeding episodes.8-11 Routine prophylaxis 
therapy has been demonstrated to substantially reduce the frequency of 
bleeding episodes11-13, prevent joint diseases11,14 and even reduce the risk of 
death. 15,15 Treatment with FIX products, initially purified from plasma-derived factor 
IX product (pdFIX) and subsequently as recombinant human FIX (rFIX), require 2 or 
3 IV infusions per week to achieve effective bleeding prevention due mostly to the 
half-life (t1/2)17-20, rFIX has a t1/2 of approximately 18 hours.21 High frequency of 
infusions can be a major barrier to adhering to the prescribed prophylactic 
regimen, especially in pediatric patients; in those with poor venous access22-24; and 
in those concerned about the associated complications of infection and 
thrombosis.25-27 A FIX product with a longer t1/2 to prolong the protective 
hemostatic effect, would potentially enable fewer injections, thereby reducing 
the need for repeated venous access. This could potentially improve the 
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acceptance of prophylactic regimens by patients with hemophilia. SQ 
administration is the preferred route of administration for convenience and less 
pain but has been limited historically by low bioavailability and potency of the 
marketed FIX products.28  
 
2.2.1 Rationale for Prophylaxis with SQ Administration of FIX 
 
There is currently no cure for hemophilia.29 The prevention of bleeding episodes in 
hemophilia patients requires life-long prophylaxis.29,30 Due to the short t1/2 of rFIX, 
prophylaxis and treatment for bleeding episodes requires frequent IV dosing (2-3 
IV infusions per week).17-21 IV dosing often requires a medical professional or family 
member to perform the venipuncture, making home prophylaxis cumbersome, 
particularly for pediatric patients.30,31 Other challenges include patient 
adherence, and reliable IV access.32,33 IV administration requires direct 
venipuncture or sterile entry into a central venous access device on a regular 
basis, which makes it time-consuming and negatively influences adherence.32 
SQ administration presents a major advantage over IV administration because it 
enables at-home injection, improves quality of life, and reduces health care 
costs.33 While home IV administration has been essential to the provision of 
comprehensive hemophilia care, it nonetheless remains a significant barrier.32 SQ 
dosing allows improved ease of self-administration and obviates the need for 
home nursing or a visit to a hemophilia center to provide an IV infusion when a 
patient or a family member has not been able to do so.33  
CB2679d, a novel rFIX variant, is being developed by Catalyst Biosciences (the 
Sponsor) to address the unmet need for medical management of hemophilia B 
patients.  CB2679d was developed using a rational design approach with three-
point mutations in two loops within the FIX protein: (1) arginine-318 is transformed 
into tyrosine (Arg318Tyr) located in ‘loop-150’(also known as the autolysis loop), 
can stabilize the activation structure of activated FIX (FIXa), as well as directly 
interact with factor X (FX), a substrate of FIX and anti-thrombin III (ATIII), a key 
inhibitor; (2) arginine-338 is transformed into glutamic acid (Arg338Glu); and (3) 
threonine-343 is transformed into arginine (Thr343Arg), both located in ‘loop-170’, 
can significantly enhance affinity to the cofactor VIII and stabilize FIXa. These 
mutations in the molecular structure enable CB2679d to increase catalytic activity 
(CB2679d has demonstrated 3 times the catalytic efficiency to factor X 
[substrate]); increase affinity for activated factor VIII (FVIIIa) (CB2679d has a 10 
times higher affinity to cofactor FVIIIa) and improve resistance to inhibition by ATIII 
(CB2679d has 15 times the resistivity to inhibitor ATIII compared to wild-type FIX), 
with a resultant 20-fold enhanced potency in vitro (clotting activity) and in vivo 
(tail clip model) and 8-fold increased duration of aPTT activity in vivo compared 
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with recombinant wild-type FIX dosed at the same mass.34-35 The SQ half-life in mini-
pig studies was found to be 33 hours and the bioavailability was 20-42%.36  
These qualities are expected to prolong the interval between doses, improve 
convenience of treatment, and facilitate use of the product for bleeding 
prophylaxis. 
 
2.2.2 Experience with CB2679d in the Clinic 
 
To date, the safety, PK, and PD of CB2679d, is being evaluated in an open-label 
IV to SQ cross-over clinical study (NCT03186677), which will recruit 12 adult subjects 
with hemophilia B (all male).37,38 The trial design is provided below. IV PK (antigen 
and activity) was sampled at pre-dose, 0, 0.25, 0.5, 1, 3, 6, 9, 24, 48 and 72 hours. 
SQ PK was sampled at pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours. Cohort 5 
has PK sampled before each injection, 6 hours after first and 6th injection and 24 
hours after 6th daily injection. Hematology, chemistry and coagulation was 
measured at Seoul Clinical Laboratories (Yongin-si, South Korea). FIX antigen and 
FIX activity, anti-drug antibody to BeneFIX® and CB2679d and neutralizing 
antibody were measured at Haematologic Technologies Inc (Essex Junction, VT). 
A safety follow-up was done 2 weeks after last visit. FIX antigen was measured 
using VisuLizeTM Factor IX Antigen KitAG (Affinity Biologicals, Inc, Ancaster, ON, 
Canada) and FIX activity was measured using a one-stage clotting assay using 
ACL TOP 700 and Instrumentation Laboratories (Bedford, MA) reagents. The 
calculation of area under the curve (AUC) was based on the trapezoidal rule. To 
calculate the additional AUC from time 0 to the last measurable concentration 
(AUC0-inf), the log-linear regression line for the last three-time points was fit and 
extrapolated to the x-intercept. The calculation of t1/2 was based on the use of 
Demitasse 2000 (version 1.1.3, M. Lee, 2000) which uses an iterative piecewise 
fitting algorithm based on a robust (M-regression) log-linear model. All activity 
data were adjusted for baseline before analysis, assuming exponential falloff after 
IV administration and a t1/2 of 20 hours. Bioavailability was calculated from the 
AUC-time curve (AUC0-t) for the IV and SQ data using FIX activity data. 
Subject safety was reviewed by an external Data Safety Monitoring Board and 
also an internal Data Monitoring Committee. 
Interim results showed PK and activity of CB2679d as 22-fold greater potency over 
BeneFIX® and longer mean residence time. Single-dose bioavailability was 18.2-
23.6%, SQ beta t1/2 was 66-103 hours and time that CD2679d is present at the 
maximum concentration in serum (Tmax) was 6-24 hours. One subject reported 
transient fever and a mild SQ injection site reaction. Cohort 4 was omitted as 
sufficient data had been gained from single dosing SQ in Cohorts 2 and 3. The SQ 
dose in Cohort 5 was reduced from 300 IU/kg to 150 IU/kg daily. PK and activity 
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levels after 6 daily doses in 5 subjects reached a median of 15.7% [interquartile 
range 14.9% to 16.6%] Four of 5 subjects had levels above 12%. Half-life was 63.2 
hours [interquartile range 60.2 to 64.0 hours]. The interim study results support the 
aim of achieving normal or high mild hemophilia FIX levels in individuals with 
hemophilia B with repeated SQ dosing. Mild pain, erythema and redness was 
reported at the injection site in initial injections and not a later injection. One 
subject reported these adverse events to be moderate for the first 2 injections and 
mild thereafter. An intravenous loading dose has been added in this study to see 
if it eliminates these local adverse events as they are believed to be due to low 
FIX levels because of washout of prior treatment. 
 
 
 
 
ISU304/CB 2679d IV 
vs BeneFIX IV 
Coho<! 1 (n~) 
-
ISU304/CB 2679d IV to SQ 
IV to SQ Crossover - Ascending Dose Cohorts 2 - 4 
Cohort 3 (n=3) 
Coho<l 4 (n=J) 
ISU304/CB 2679d 
Multi-Dose 
Cohort 5 (n=5) 
Six Oaily-Ooses 
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3.  
OBJECTIVES  
 
3.1  
PRIMARY  
 
The primary objective is: 
 
To evaluate the dose required to achieve steady-state FIX levels >12% of SQ 
prophylaxis treatment regimens of CB2679d, in adult subjects with hemophilia 
B. 
 
3.2  
SECONDARY 
 
The secondary objectives are: 
 To determine the PK of SQ regimens of CB2679d. 
 To determine the PD of SQ regimens of CB2679d. 
 To evaluate the levels of thrombogenicity markers of SQ regimens of CB2679d. 
 To evaluate for evidence of the development of antibodies to CB2679d and 
to determine if these are neutralizing antibodies. 
 To monitor and evaluate safety parameters of SQ regimens of CB2679d. 
 
 
 
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4.  
STUDY DESIGN 
  
4.1 
OVERALL DESIGN 
 
This is a single-center, open-label Phase 2b study designed to evaluate the PK, 
PD, efficacy and safety of SQ prophylaxis treatment regimens with CB2679d in 
adult subjects with hemophilia B. It is an open-label study, so subjects and 
members of the clinical study team will not be blinded to treatment. It is 
estimated that it will take approximately 6 months from when the study opens 
enrollment until completion of last patient last visit. The study will enroll a total of 5 
adult male subjects with severe congenital hemophilia B. Participants will be 
given SQ prophylaxis CB2679d regimens over a 6-week period, with the goal to 
achieve steady-state levels above 12% FIX activity when dosed daily, every 
second day or every third day. 
Each subject will participate for approximately 6-weeks of SQ CB2679d drug 
administrations:  
Part 1; Weeks 1 and 2: Each participant will receive an IV loading dose of 70 
IU/kg followed 30 minutes later by a SQ dose of 140 IU/kg. Daily SQ doses of 140 
IU/kg will be administered until Day 14 (14 total SQ doses). On day 1, PK, PD, and 
safety assessments will be done at pre-IV dose and repeated 30 minutes later 
prior to the SQ dose. Subsequent PK, PD and safety assessments will be 
performed 7 hours post-SQ dose on Day 1, Day 2 at hour 24 post-SQ dose and 
pre-dose on days 5, 8, 11 and 14.  
Part 2; Week 3: Each participant will receive a SQ dose every second day of 280 
IU/kg, starting on Day 15 until Day 21 (total of 4 SQ doses). On Day 15 only, PK, 
PD, and safety assessments will be done at pre-dose and repeated at hour 7.  
Subsequent PK, PD and safety assessments will be performed on Day 16 at hour 
24 and pre-dose on days 17, 19 and 21. 
Part 3; Weeks 4 and 5: Each participant will receive a SQ dose every third day of 
420 IU/kg, starting on Day 23 until Day 32 (total of 4 SQ doses). On days 23 and 32 
only, PK, PD, and safety assessments will be done at pre-dose and repeated at 
hour 7.  Subsequent PK, PD, and safety assessments will be performed at Day 24 
at hour 24 and pre-dose on days 26, and 29. 
Washout Period 
PK, PD, and safety assessments will be done on Days 33, 34, 35, 37 and 38. Daily 
FIX activity levels will be measured, except on Day 36, unless FIX activity level is 
known to be < 5%, as measured by local laboratory. 
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An End of Study visit will occur 30 days (± 2 days) after the last dose of study drug. 
Subjects will sign an ICF at the Screening Visit, prior to any study procedures. 
Eligibility to participate in the study will be determined by inclusion and exclusion 
criteria from medical history, hemophilia history, laboratory investigations and 
ECG. The screening period duration may be up to 4 weeks.  
At enrollment, subjects will receive training and diary entry of self-administered 
investigational drug administration & injection site assessment, bleeding episodes 
& treatment, evaluation & entry of AEs.   
Treatment of a spontaneous or traumatic bleeding episode: Subjects will use 
their current prescribed treatment regimen for any spontaneous or traumatic 
bleed that occurs while on study drug. If treatment for a spontaneous or 
traumatic bleeding episode is needed, then subjects will contact the clinical 
investigative team immediately to report the event, treatment dose 
administered, and determine follow-up plans for that event including whether to 
arrange for a blood specimen to be drawn (if feasible) before further 
administration of either study drug or the current prescribed treatment regimen 
used.  Decision whether to continue daily study drug administration will also be 
determined by the clinical study team after discussion with the Sponsor.  
Dose interruption: SQ study drug injections will be interrupted if any of the 
following occurs: a thrombotic event; clinical evidence of inhibitor formation; or 
laboratory results suggesting a high titer antibody may be developing; trough 
activity levels >80% or peak levels >175% where subsequent dosing will be 
determined in consultation with the sponsor. 
Surgery: If there is an urgent need for a surgical procedure or an event requiring 
extended (>48 hours) hospitalization, a FIX activity level will be urgently obtained 
and measured prior to the event, and the PI will confer with the Sponsor Medical 
representative regarding the need for any additional treatment and whether 
study drug requires interruption.   
 
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Measurements:   
PK, PD, and safety assessments: CB2679d activity levels, as well as fibrinogen, D-
dimer, F1+2, and TAT. PT and aPTT will be measured at screening and end of 
study visit only. 
Immunogenicity assays: Specimens for immunogenicity testing (antibody to CB 
2679d, wild-type FIX cross reactivity, and neutralizing activity) will be drawn at 
screening, pre-dose on days 1, 8, 15, 23, 32 and end of study. 
If the FIX activity level decreases unexpectedly by more than 25%, ie, IU/dL, as 
measured by the central or local lab, CB2679d activity levels will be drawn for 
analysis within 24 hours and immediately sent to the central laboratory.  
Specimens for fibrinogen, D-dimer, F1+2, and TAT and immunogenicity testing will 
also be drawn. 
 
4.2  
END OF STUDY DEFINITION 
 
The duration of treatment for each subject is approximately 6 weeks. 
Up to 4 weeks for screening period; SQ prophylaxis treatment regimens over a 6-
week period with the goal to achieve steady-state levels above 12% FIX activity 
when dosed daily, every second day or every third day. 
Where interruptions to study drug dosing days occur, study duration may be 
extended to incorporate full dosing schedule. 
The end of study visit will be 30 days ± 2 days after the last dose of study drug 
treatment. 
 
 
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Catalyst Biosciences, Inc. 
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5.  
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
 
An individual must meet all of the following criteria to be eligible to participate in 
this study: 
1. Confirmed diagnosis of severe (<2%) congenital hemophilia B. 
2. Male, age 18 or older. 
3. Agreement to use highly effective birth control throughout the study.  
4. Affirmation of informed consent with signature confirmation before any 
trial-related activities. (Trial related activities are any procedure that would 
not have been performed during normal clinical management of the 
subject). 
5. Stated willingness to comply with all study procedures and availability for 
the duration of the study.  
 
5.2 
EXCLUSION CRITERIA  
 
An individual who meets any of the following criteria will be excluded from 
participation in this study: 
1. Patients with a history or a family history of FIX inhibitors. 
2. Positive antibody to FIX detected by central laboratory at screening. 
3. Previous participation in and subsequent treatment in a clinical trial within 
the previous 30 days or 3-half-lives, whichever is longer, or absence of 
clinical effect.  
4. History of clinically relevant coagulation disorders other than congenital 
hemophilia B including Factor V Leiden or other identified activated 
Protein C resistance. 
5. Platelet count <100,000 based on screening laboratory assessments. 
6. Advanced atherosclerotic disease (ie, known history of CAD, ischemic 
stroke, etc.), or known DVT or considered to be at a high risk of VTE as 
judged by the Investigator. 
7. Known or suspected allergy to trial product or related products. 
8. Known absolute CD4 count <200 cells/μL. 
9. Receiving IMT. 
10. Compromised hepatic or renal function: 
o ALT and AST levels ≥5 x ULN 
o TBIL ≥2 mg/dL (>35 µmol /L) unless there is a known history of GS 
o Serum albumin ≤ LLN 
o Cr level >1.25 x ULN   
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11. Inability or medical, psychosocial, or familial issues that might prevent full 
participation and cooperation with the procedures and requirements of 
the clinical trial as determined by the potential subject and physician 
investigator. 
 
5.3  
LIFESTYLE CONSIDERATIONS 
 
There are no specific lifestyle considerations. 
 
5.4  
SCREEN FAILURES 
 
An individual who does not meet the criteria for participation in this trial (screen 
failure) because of an out of range laboratory parameter may be rescreened.  
 
 
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6.  
STUDY INTERVENTION 
 
6.1  
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1  Study Intervention Description 
 
Description and Composition of the Drug Product 
Recombinant Factor IX variant; CB2679d, formerly known as ISU304, will be 
provided as a powder for injection, at a 2.0 mg/vial dosage strength. The drug 
product is supplied in a 5-mL vial that is sealed with a 20mm lyophile stopper and 
20mm aluminum over-seal. CB2679d is supplied in vials which contain excipients 
(stabilizer, buffer, etc.) and packaged in a lyophilized form. Before lyophilization, 
each vial contains 1.42 mg/mL of CB2679d drug substance is filled with 1.4 mL of 
formulation buffer. The lyophilized drug product will be reconstituted for SQ 
injection. 
 
6.1.2  Dosing and Administration 
 
This is an open-label study. Each subject will receive the study drug: 
CB2679d loading dose of 70 IU/kg IV, followed 30 minutes later with a 140 IU/kg, 
SQ administration daily x 14 (total 1 IV dose and 14 SQ doses); then a 280 IU/kg, 
SQ administration every second day, starting on Day 15 until Day 21 (total 4 SQ 
doses); then a 420 IU/kg SQ every third day, starting on Day 23 until Day 32 (total 
of 4 SQ doses).  
 
6.1.2.1  
Guidelines for Treatment Interruption  
 
CB2679d SQ study injections will be interrupted, as needed, when: 
 
A surgical procedure is needed 
 
There is a medical event requiring extended (>48 hours) hospitalization 
 
If there is a thrombotic event 
 
If there is clinical evidence of inhibitor formation 
 
If there are laboratory results suggesting an antibody may be developing 
Cb2679d SQ study injections may be interrupted, as needed, when: 
 
A spontaneous bleeding event occurs 
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 
A traumatic bleeding event occurs 
Subjects will use their current treatment regimen for any spontaneous or 
traumatic bleed that occurs while on study. A spontaneous bleeding episode is 
defined as one that is precipitated by normal activities of daily living (ADL).  If 
treatment for a spontaneous or traumatic bleeding episode is needed, then 
subjects will contact the clinical investigative team immediately to report the 
event; treatment dose administered; and determine follow-up plans for that 
event, including to arrange for a blood specimen to be drawn (if feasible). This 
information will also be recorded in the subjects’ diary. 
 
6.2  
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
6.2.1  Acquisition and Accountability 
 
Upon receipt of the CB2679d shipment, the pharmacist, or a designee, will 
conduct an inventory and return an acknowledgement that all IP was received 
refrigerated and undamaged, thereby maintaining the Good Manufacturing 
Practice (GMP) status of the product during shipment. 
 
All used and unused investigational product (IP) must be returned by the subject 
to the study site. Subjects must return all IP packages and vials (including used, 
empty, and unused vials) for reconciliation of IP. 
The investigator, or approved representative (eg, pharmacist) must maintain 
adequate records documenting the receipt, use, loss, or other disposition of the 
IP. The sponsor will supply drug accountability forms to be used in this study. 
The sponsor or designee will arrange for the return of unused IP.  The IP 
destruction procedure for used vials is to be decided locally to comply with local 
regulations and procedures. 
Drug accountability will be reviewed by the monitor during routine monitoring 
visits.  No IP can be destroyed or returned until the study monitor has reconciled 
all vials of IP. 
 
6.2.2  Product Storage and Stability 
 
The investigator, or an approved representative, eg, pharmacist, will ensure that 
all IPs are stored in a secured area with controlled access under recommended 
storage conditions and in accordance with applicable regulatory requirements.  
The IP and its storage and preparation requirements will be provided by the 
Sponsor, or designee. 
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IP should be stored in its original container and in accordance with the drug 
label.  The Sponsor will provide the Investigator with packaged IP in accordance 
with specific country label requirements.  
Site systems must be capable of measuring and documenting (for example, via 
a log), at a minimum, daily minimum and maximum temperatures for all site 
storage locations (as applicable, including frozen, refrigerated and/or room 
temperature products). This should be captured from the time of IP receipt 
throughout study. Even for continuous monitoring systems, a log or site procedure 
which ensures active daily evaluation for excursions should be available. The 
operation of the temperature monitoring device and storage unit (for example, 
refrigerator), as applicable, should be regularly inspected to ensure it is 
maintained in working order.  
Any excursions from the product storage conditions should be reported upon 
discovery. The site should actively pursue options for returning the product to 
appropriate storage conditions, as soon as possible. Deviations from the storage 
requirements, including any actions taken, must be documented and reported 
to the Sponsor, or designee.  
Once an excursion is identified, the IP must be quarantined and not used until 
the Sponsor, or designee, provides documentation of permission to use the IP. 
Specific details regarding information the site should report for each excursion 
will be provided to the site.  
Receipt of materials, door opening and closing, and other routine handling 
operations where the product(s) are briefly out of labeled temperature range 
are not considered excursions. Site staff will instruct subjects on the storage 
requirements for take home medications including how to report temperature 
excursions.  
 
6.2.3  Preparation 
 
CB2679d will be provided as a powder for injection, at a 2.0 mg/vial dosage 
strength, and is supplied in a 5-mL vial.  The lyophilized drug product will be 
reconstituted with 1.4 mL sterile water for SQ injection. 
Details regarding the dosing administration, will be provided by the Sponsor, or 
designee. 
At the study site, the CB2679d SQ dose will be prepared and administered by an 
appropriately qualified and experienced member of the study staff (eg, 
physician, nurse, physician assistant, nurse practitioner, or pharmacist) as allowed 
by local, state, and institutional guidance.   
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6.3  
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
The study is an open-label study; subjects and members of the clinical study 
team will not be blinded to treatment.  
 
6.4  
STUDY INTERVENTION COMPLIANCE 
 
Reasonable efforts should be made to ensure that study drug administration is 
administered according to the schedule.  However, if an unavoidable disruption 
of the administration occurs, and a dose is not administered on the assigned day 
then the subject should take the dose as soon as possible. In the event that the 
subject remembers more than 2 days late, then the subject must contact the 
research site for instructions on how to proceed.  
 
6.5  
CONCOMITANT THERAPY 
 
Enrolled subjects will record all concomitant medications administered from the 
Screening Visit to Study termination (including the date and time of 
administration) in their diary. 
For this protocol, a prescription medication is defined as a medication that can 
be prescribed only by a properly authorized/licensed clinician. Medications to 
be reported in the electronic Case Report Form (eCRF) are concomitant 
prescription medications, over-the-counter (OTC) medications and 
supplements.] 
There are no concomitant medication restrictions.   
If an individual has previously been enrolled on a clinical trial evaluating a 
treatment (as specified in exclusion criteria #3) in clinical investigation he will be 
permitted to enroll onto this study, provided it is greater than 30 days since 
exposure to that study drug, or 3-half-lives, whichever is longer, or absence of 
clinical effect. 
The following medications will be permitted during the study: 
 
In the event of spontaneous or traumatic bleeding, treatment for a 
spontaneous or traumatic bleeding episode will be permitted using the 
subject’s current prescribed treatment regimen which could be BeneFIX® or 
Rixubis®. 
 
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7.  
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1  
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Subjects are free to withdraw from participation in the study at any time upon 
request.   
An investigator may discontinue or withdraw a participant from the study for the 
following reasons: 
 
Significant study intervention non-compliance  
 
If any clinical AE, laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be 
in the best interest of the participant 
 
If the participant meets a criterion (either newly developed or not previously 
recognized) that precludes further study participation 
 
Decision by Investigator or Sponsor 
The reason for participant discontinuation or withdrawal from the study and the 
date will be recorded on the eCRF.   
Replacement of a subject occurs for the following reason: 
 
If a subject does not complete at least 2 doses of every third day SQ dosing 
as defined in the protocol, another subject may be enrolled. 
If the subject withdraws from the study and also withdraws consent for disclosure 
of future information, no further evaluations should be performed, and no 
additional data should be collected. The sponsor may retain and continue to 
use any data collected before such withdrawal of consent. 
7.2  
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he fails to return for two 
consecutive scheduled visits and is unable to be contacted by the study site 
staff.  
The following actions must be taken if a participant fails to return to the clinic for 
a required study visit: 
The site will attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain if the participant wishes to and/or 
should continue in the study. 
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Before a participant is deemed lost to follow-up, the investigator or designee will 
make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record or study file.  
Should the participant continue to be unreachable, he will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up.] 
In any circumstance, every effort should be made to document subject 
outcome, if possible.  The investigator should inquire about the reason for 
withdrawal, request the subject to return all used and unused IP(s), request the 
subject to return for a final visit, if applicable, and follow up with the subject 
regarding any unresolved AEs. 
 
 
 
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8.  
STUDY ASSESSMENTAND PROCEDURES 
 
8.1  
STUDY PROCEDURES 
 
Study procedures and evaluations to be done as part of the study. Please refer 
to Section 1.3, Schedule of Activities (SOA) for the sequence of events.   
 
8.1.1  Screening 
 
Please refer to Section 1.3, Schedule of Activities (SOA) and specifically Table 1 
for the sequence of events that should occur during the screening process.  
Screening should occur within 4 weeks prior to enrollment.   
 
Informed consent 
 
Demographic parameters 
 
Joint evaluation (as per SOC at hemophilia treatment center) 
 
Inclusion and Exclusion Criteria review 
 
Medical and hemophilia history 
 
Concomitant medications 
 
Vital signs 
 
Height (screening only) and weight 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Hematology and chemistry: (see Footnote 4 for Table 1 in Section 1.3, 
Schedule of Activities)  
 
Coagulation assays: PT and aPTT (both at screening and end of study visit 
only) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT  
 
Immunogenicity assays: antibody to CB 2679d and BeneFIX 
 
ECG 
 
Adverse events  
 
 
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8.1.2  Part 1, Weeks 1 and 2 (Duration 7 days) 
 
Please refer to Section 1.3, Schedule of Activities (SOA) and specifically Table 1 
for the sequence of events that should occur during the Part 1 process.   
 
8.1.2.1  
Day 1 Pre-dose evaluations  
 
 
Concomitant medications 
 
Vital signs 
 
Weight 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Hematology and chemistry (see Footnote 4 for Table 1 in Section 1.3, 
Schedule of Activities) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: CB2679d activity 
 
Study Subject training on drug administration and injection site assessment 
 
Review of diary entry of injection site assessment, adverse events, 
bleeding episodes & treatment  
 
Adverse events 
 
8.1.2.2  
CB2679d administration (Every day from Day 1 to Day 14) 
 
 
Subjects will receive a loading IV dose of 70 IU/kg, followed 30 minutes 
later with a 140 IU/kg SQ dose of CB2679d  
 
Subjects will then administer a 140 IU/kg daily SQ dose of CB2679d 
 
SQ CB2679d should be self-administered by subjects at approximately the 
same time every day.  
 
 
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8.1.2.3  
Day 1 at SQ dose administration (30 minutes post-IV dose) 
 
Blood will be collected at 30-minutes post-IV dose for the following evaluations: 
 
Clinical signs of thrombosis (see Appendix A) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: CB2679d activity 
Other evaluations will include: 
 
Concomitant medications 
 
Vital signs 
 
Physical examination 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events 
 
8.1.2.4  
Day 1 Post-SQ dose (Hour 7) and Day 2 Post-SQ dose (Hour 24) 
evaluations 
 
Blood will be collected at hour 7 post-dose on Day 1 and hour 24 post-dose on 
Day 2 for the following evaluations: 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: CB2679d activity  
Other evaluations will include: 
 
Concomitant medications 
 
Vital sign 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events (from Hr 6 to 24 hours) 
 
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8.1.2.5  
Day 5, 8, 11 and 14 Pre-dose evaluations  
Blood will be collected at -5 minutes pre-dose for the following evaluations: 

Days 8 and 14 only: Hematology and chemistry (see Footnote 4 for Table 1
in Section 1.3, Schedule of Activities)

Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT

PK: CB2679d activity

On Day 8 only: Immunogenicity assays to BeneFIX and CB2679d
Other evaluations will include: 

Concomitant medications

Vital signs

Physical examination

Clinical signs of thrombosis (see Appendix A)

Review of diary entry of investigational drug administration, injection site
assessment, adverse events, bleeding episodes & treatment

Adverse events
8.1.3 Part 2, Week 3 (Duration: 7 days) 
Please refer to Section 1.3, Schedule of Activities (SOA) and specifically Table 2 
for the sequence of events that should occur during the Part 2 process.   
8.1.3.1 
CB2679d administration (Day 15, Day 17, Day 19 and Day 21)  

Subjects will receive a 280 IU/kg SQ dose of CB2679d every second day,
starting on Day 15 to Day 21 (total of 4 SQ doses).

SQ CB2679d should be self-administered by subjects at approximately the
same time every second day.
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8.1.3.2  
Day 15 Pre-dose evaluations 
 
 
Concomitant medications 
 
Vital signs 
 
Weight 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: CB2679d activity 
 
Immunogenicity assays to BeneFIX and CB2679d 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
8.1.3.3  
Day 15 Post-dose (Hour 7), Day 16 Post-dose (Hour 24), Day 17 and 
Day 19 Pre-dose evaluations  
 
 
Concomitant medications 
 
Vital signs 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: CB2679d activity 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
8.1.3.4  
Day 21 Pre-dose evaluations  
 
 
Concomitant medications 
 
Vital signs 
 
Weight 
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
Physical examination

Clinical signs of thrombosis (see Appendix A)

Hematology and chemistry (see Footnote 3 for Table 2 in Section 1.3,
Schedule of Activities)

Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT

PK: CB2679d activity

Review of diary entry of investigational drug administration, injection site
assessment, adverse events, bleeding episodes & treatment

Adverse events
8.1.4  Part 3, Weeks 4 and 5 (Duration: 14 days) 
Please refer to Section 1.3, Schedule of Activities (SOA) and specifically Table 3 
for the sequence of events that should occur during the Part 3 process.   
8.1.4.1 
CB2679d administration (Day 23, Day 26, Day 29, and Day 32)  

Subjects will receive a 420 IU/kg SQ dose of CB2679d every third day,
starting on Day 23 until Day 32 (total of 4 SQ doses)

SQ CB2679d should be self-administered by subjects at approximately the
same time of day every third day.
8.1.4.2  
Day 23 and Day 32 Pre-dose evaluations  

Concomitant medications

Vital signs

Day 23 only: Weight

Physical examination

Clinical signs of thrombosis (see Appendix A)

Day 23 only: Hematology and chemistry (see Footnote 4 for Table 3 in
Section 1.3, Schedule of Activities)

Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT

PK: CB2679d activity
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 
Immunogenicity assays to BeneFIX and CB2679d 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
8.1.4.3  
Day 23 Post-dose evaluations (Hour 7) 
 
 
Concomitant medications 
 
Vital signs 
 
Clinical signs of thrombosis (see Appendix A) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: CB2679d activity 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
8.1.4.4  
Day 24 Post-dose (Hour 24) and Day 26 and Day 29 Pre-dose 
evaluations 
 
 
Concomitant medications 
 
Vital signs 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: CB2679d activity 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
 
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8.1.4.5  
Day 32 Post-dose evaluations (Hour 7) 

Joint evaluation (as per SOC at hemophilia treatment center)

Concomitant medications

Vital signs

Physical examination

Clinical signs of thrombosis (see Appendix A)

Hematology and chemistry (see Footnote 4 for Table 3 in Section 1.3,
Schedule of Activities)

Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT

PK: CB2679d activity

Review of diary entry of investigational drug administration, injection site
assessment, adverse events, bleeding episodes & treatment

Adverse events
8.1.5  Washout Period, Unscheduled Visits and End of Study evaluations 
Please refer to Section 1.3, Schedule of Activities (SOA) and specifically Table 3 
for the sequence of events that should occur during the washout period and 
end of study process.   
8.1.5.1  
Washout period evaluations (Day 33, 34, 35, 37 and 38) 

Concomitant medications

Clinical signs of thrombosis (see Appendix A)

Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT

PK: CB2679d activity

Review of diary entry of investigational drug administration, injection site
assessment, adverse events, bleeding episodes & treatment

Adverse events
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8.1.5.2  
Unscheduled visit evaluations  
 
Should a subject need to be seen at any time while enrolled onto the trial, and 
not on a study scheduled visit, the following assessments may need to be 
conducted based on the judgement of the clinical study team. 
 
Medical and Hemophilia History  
 
Concomitant medications 
 
Vital signs 
 
Weight 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Hematology and chemistry (see Footnote 3 for Table 1 in Section 1.3, 
Schedule of Activities) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: CB2679d activity 
 
Immunogenicity assays to BeneFIX and CB2679d 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
8.1.5.2  
End of Study visit evaluations (30 days after last dose) 
 
The following procedures will be performed: 
 
Concomitant medications 
 
Vital signs 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Hematology and chemistry (see Footnote 4 for Table 3 in Section 1.3, 
Schedule of Activities) 
 
Coagulation assays: PT and aPTT (both at screening and end of study visit 
only) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
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 
PK: CB2679d activity 
 
Immunogenicity assays to BeneFIX and CB2679d 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
8.2  
STUDY ASSESSMENTS 
 
8.2.1  Efficacy Assessments 
 
Subjects will be asked to record daily SQ injections, any injection site reactions, 
any AEs experienced, and all spontaneous or traumatic bleeding episodes and 
concomitant medications administered into the Diary, including (but not limited 
to) the following: 
 
Bleeding episode (date/time of onset and date/time of resolution) 
 
Cause of bleeding (spontaneous or traumatic) 
 
Bleeding site: joint (ankle, knee, elbow, other [right or left]); muscle (iliopsoas, 
calf, forearm, other [right or left]); mucous membranes (mouth, gums, nose, 
genitourinary tract); gastrointestinal (gastric ulcer, fissure, other [requiring 
transfusion – yes, no]), neck/throat, intracranial. 
 
Hemostatic drugs used for treatment of bleeding episodes (time/date of 
administration, type, amount [international units or mg and/or number of 
infusions]) 
A spontaneous bleeding episode is defined as one that is precipitated by normal 
ADL. 
Investigators will document:  
 
Subject demographics (sex, age, race and ethnicity) will be recorded at the 
screening visit.  
 
All ongoing conditions and relevant medical and hemophilia history 
(including all major hospitalizations and surgeries), as well as the subject’s 
current medical status will be recorded at the screening visit.   
 
Diagnosis of severe congenital hemophilia B will be documented including 
the frequency of spontaneous or traumatic bleeding episodes in the past 6 
months and in the past 50 days.   
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 
Notation will be made regarding history of orthopedic procedures including 
joint aspiration, synovectomy, fusion, or joint replacements or other 
complications of hemophilia including pseudotumors. 
 
Concomitant medication use including treatment used for control of 
spontaneous or traumatic bleeding events (infusion therapies, anti-fibrinolytic 
agents, local agents) and for management of pain and other complications 
related to hemophilia. 
 
Vital signs, height, weight, general physical examination will be performed at 
screening. 
Evaluations related to PK and PD will include: 
 
CB2679d activity levels over time post-dose and calculation of standard PK 
parameters. Study evaluations will be performed at a central laboratory.  
However, FIX activity levels may be performed at a local laboratory for safety. 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT. These 
evaluations will be performed at a central laboratory. 
 
8.2.2  Physical Examination 
 
A full physical assessment of the major body systems will be recorded at 
Screening followed by interim targeted evaluation, per Investigator’s discretion, 
as indicated on presentation of subject at study visit. 
 
8.2.3  Vital signs  
 
One measurement of blood pressure, heart rate, respiratory rate, and body 
temperature will be taken after the subject has been sitting quietly for at least 5 
minutes. 
 
8.2.4  Hematology  
 
Complete blood cell count (CBC), and platelet counts will be will be measured 
using standard laboratory testing methods at a local laboratory. 
 
 
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8.2.5  Chemistry 
Sodium, potassium, chloride, bicarbonate, hepatic enzymes (ALT, AST and GGT), 
TBIL, albumin, and creatinine (Cr) will be measured using standard laboratory 
testing methods at a local laboratory. 
8.2.6  Coagulation assays  
PT and aPTT (at screening and end of study ONLY) will be performed at a central 
laboratory. 
8.2.7  Thrombogenicity markers  
Fibrinogen, D-dimer, F1+2, and TAT. These evaluations will be performed at a 
central laboratory. 
8.2.8 Antibody response and neutralizing antibodies to CB2679d 
These evaluations will be performed and tested at a central laboratory. 
8.2.9 Clinical signs of thrombosis (Appendix A) 
This assessment will be included as part of the study subject training, provided as 
a reference in the Diary and will be a scheduled evaluation at clinical study visits. 
8.2.10  Concomitant medications  
Subjects will record concomitant medications (including name of medication, 
dose taken, day and time) they may be taking in their daily diaries. Diaries will be 
reviewed by the clinical staff at each visit.  
8.2.11  ECG 
A12-lead ECG will be performed using local standard methods.  
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For participants that may discontinue or withdraw early, it is important to capture 
the rationale during the final visit. See Section 7, Study Intervention 
Discontinuation and Participant Discontinuation/Withdrawal, for details. 
 
8.3  
SAFETY AND OTHER ASSESSMENTS 
 
Evaluations related to safety will include: 
 
8.3.1  AEs and SAEs 
 
Subjects will record any AEs that occur during the study in their daily diaries. 
Diaries will be reviewed by the clinical staff at each visit.   
 
8.3.2  Injection site reactions 
 
Subjects will record site injection reactions in their daily diaries. Diaries will be 
reviewed by the clinical staff at each visit.   
 
8.4  
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.4.1  Definition of Adverse Events (AE) 
 
Definition of an AE: An AE is any untoward medical occurrence in a patient or 
clinical trial subject administered a medicinal product that may not necessarily 
have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (including a clinically significant laboratory 
abnormality, for example), symptom, or disease temporarily associated with the 
use of a medicinal (investigational) product, whether or not related to the 
medicinal (investigational) product.  
 
Pre-existing conditions, diseases or disorders are not considered AEs unless there 
is a change in the intensity, frequency or quality. 
  
 
 
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8.4.2  Definition of Serious Adverse Events (SAE) 
 
Definition of a SAE: Definition of a SAE:  An AE or suspected adverse reaction is 
considered "serious" if, in the view of either the investigator or sponsor, it results in 
any of the following outcomes: death, a life-threatening AE, inpatient 
hospitalization or prolongation of existing hospitalization, a persistent or 
significant incapacity or substantial disruption of the ability to conduct normal life 
functions, or a congenital anomaly/birth defect. Important medical events that 
may not result in death, be life-threatening, or require hospitalization may be 
considered serious when, based upon appropriate medical judgment, they may 
jeopardize the participant and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. Examples of such medical 
events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result 
in inpatient hospitalization, or the development of drug dependency or drug 
abuse. 
 
 
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8.4.3  Classification of an Adverse Event 
 
8.4.3.1  
Severity of Event 
 
All AEs will be assessed by the study clinician using the Common Terminology 
Criteria for Adverse Events (CTCAE) Version 5.0 where applicable.39   
For those AEs that are not included under the CTCAE v5.0, the following 
guidelines will be used to describe severity.  
Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities.  
Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
Severe – Events interrupt a participant’s usual ADL and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-
threatening or incapacitating.  Of note, the term “severe” does not necessarily 
equate to “serious”. 
 
8.4.3.2  
Relationship to Study Drug 
 
All AEs must have their relationship to study drug assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and 
his/her clinical judgment. The degree of certainty about causality will be graded 
using the categories below. In a clinical trial, the study product must always be 
suspect.  
Related – The AE is known to occur with the study intervention, there is a 
reasonable possibility that the study intervention caused the AE, or there is a 
temporal relationship between the study intervention and event. Reasonable 
possibility means that there is evidence to suggest a causal relationship between 
the study intervention and the AE. 
Not Related – There is not a reasonable possibility that the administration of the 
study intervention caused the event, there is no temporal relationship between 
the study intervention and event onset, or an alternate etiology has been 
established. 
 
 
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8.4.3.3  
Action Taken  
 
None: No changes were made to Study Drug administration and dose  
Permanently discontinued: Study drug was discontinued and not restarted 
Temporarily interrupted, restarted same dose: Dosing was temporarily 
interrupted or delayed due to the AE and restarted at the same dose without 
unblinding to treatment group 
 
8.4.3.4  
Expectedness 
 
The Principle Investigator (or Co-PI) will be responsible for determining whether 
an AE is expected or unexpected.  An AE will be considered unexpected if the 
nature, severity, or frequency of the event is not consistent with the risk 
information previously described for the study intervention. 
 
8.4.4  Time Period and Frequency for Event Assessment and Follow-Up 
 
Subjects will be instructed regarding direct reporting and diary entries of AEs; 
diaries will be reviewed at each visit and subjects queried if evidence of an AE 
recorded. 
The occurrence of an AE or SAE may come to the attention of study personnel 
during study visits and interviews of a study participant presenting for medical 
care, or upon review by a study monitor.   
All AEs including local and systemic reactions not meeting the criteria for SAEs will 
be captured on the appropriate CRF. Information to be collected includes event 
description, time of onset, clinician’s assessment of severity, relationship to study 
product (assessed only by those with the training and authority to make a 
diagnosis), and time of resolution/stabilization of the event. All AEs occurring 
while on study must be documented appropriately regardless of relationship. All 
AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened 
will be considered as baseline and not reported as an AE. However, if the study 
participant’s condition deteriorates at any time during the study, it will be 
recorded as an AE.  
Changes in the severity of an AE will be documented to allow an assessment of 
the duration of the event at each level of severity to be performed. AEs 
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characterized as intermittent require documentation of onset and duration of 
each episode. 
Subject Withdrawal from the Study Due to an Adverse Event:  
Every reasonable effort should be made to maintain subject compliance and 
participation in the study. All enrolled subjects who received the study drug must 
be followed through the Follow-Up visit, regardless of the reason for withdrawal. If 
a subject who has a clinically significant laboratory abnormality or AE withdraws 
from the study, every effort must be made to follow these events until satisfactory 
resolution. 
 
8.4.5  Adverse Event Reporting 
 
Members of the study team will record all reportable events with start dates 
occurring any time after informed consent is obtained until study completion, or 
discharge, for non-serious AEs.  At each study visit, the investigator will inquire 
about the occurrence of AE since the last visit.  Events will be followed for 
outcome information until resolution or stabilization. 
The Investigator will categorize the outcome of each AE according to the 
definitions below: 
Resolved: 
 
The subject recovered from the AE.   
Ongoing:  
At the time of the last assessment, the event is ongoing, with 
an undetermined outcome.  Note: Ongoing AEs are not 
considered resolved as a result of death. No AE stop date 
should be recorded with an AE that is ongoing. 
Chronic/Stable: 
At the time of the last assessment, the event is ongoing and 
stabilized, with no change to the event outcome 
anticipated.  
Unknown:  
There is an inability to access the subject or the subject’s 
records to determine the outcome (ie, subject withdraws 
consent or is lost to follow-up). 
All protocol-defined adverse events will be reported from the time a patient is 
enrolled in the study until the end of study visit. 
Spontaneous or traumatic bleeding events will not be reported as an AE unless 
considered serious and should then be reported per the standard process for 
reporting.   
All bleeds should be entered into the diary including spontaneous bleeds, 
traumatic bleeds or bleeds related to procedure/surgery (see Section 4.1). Only 
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bleeds (spontaneous bleeds, traumatic bleeds or bleeds related to 
procedure/surgery) that are considered serious as per definition (see Section 
8.4.6) should be reported as an SAE in the CRF. Non-serious bleeds are not 
considered adverse events for the purpose of this protocol and should not be 
reported as adverse event in the eCRF.  
The study drug has the potential risk of causing the following AEs based on 
information associated with other drugs in the same category, ie, FIX agents for 
treatment of hemophilia; these are: 
Thrombotic events (see Appendix A) 
The study drug has the potential risk of causing thrombotic events based on 
information associated with other drugs for treatment of hemophilia.  See 
Appendix A for signs and symptoms listed for the subjects and the study team 
personnel as those requiring urgent reporting and attention.  
Development of Drug Antibodies and Inhibitors 
There is a risk with the study drug of developing an immune response resulting in 
antibody formation and potentially an inhibitory antibody response.  This will also 
be monitored for throughout the study.    
Skin injection site may become reddened or painful.  
Risks associated with blood collection:  
A blood draw may cause faintness, inflammation of the vein, pain, bruising, or 
bleeding at the site of puncture.  There is also a slight chance of infection. 
 
8.4.6  Serious Adverse Event Reporting 
 
Members of the study team will record all reportable events within 24 hours of 
knowledge of the SAE with start dates occurring any time after informed consent 
is obtained until 30 days after the last day of study participation.  At each study 
visit, the investigator will inquire about the occurrence of SAEs since the last visit.  
Events will be followed for outcome information until resolution or stabilization. 
The Investigator will categorize the outcome of each SAE according to the 
definitions below: 
Resolved: 
 
The subject recovered from the AE.   
Ongoing:  
At the time of the last assessment, the event is ongoing, with 
an undetermined outcome.  Note: Ongoing AEs are not 
considered resolved as a result of death. No AE stop date 
should be recorded with an AE that is ongoing. 
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Chronic/Stable: 
At the time of the last assessment, the event is ongoing and 
stabilized, with no change to the event outcome 
anticipated.  
Death:  
 
The AE directly caused death. 
Unknown:  
There is an inability to access the subject or the subject’s 
records to determine the outcome (ie, subject withdraws 
consent or is lost to follow-up). 
Definitions: 
Death: Any event resulting in a subject’s death must be reported as an SAE.  
However, death, in and of itself, is not an AE; it is only an outcome.  The cause of 
death is the AE.  Therefore, the investigator should make every effort to obtain 
and document the cause of death for all subjects who die during the study.  If, 
despite all efforts, the cause of death remains unknown, the AE should be 
documented as an “unspecified fatal event”. 
Life threatening AE:  Any AE that places the patient or subject, in the view of the 
investigator, at immediate risk of death from the reaction as it occurred (ie, it 
does not include a reaction that, had it occurred in a more severe form, might 
have caused death). 
Hospitalization:  It should be noted that hospitalization, in and of itself, does not 
represent an SAE.  It is the AE leading to the subject’s hospitalization that 
becomes “serious” when it requires inpatient care.  Consequently, an SAE should 
not be reported in the case of pre-planned hospitalizations for pre-existing 
conditions that did not worsen during the study. 
Disability: A substantial disruption of a person’s ability to conduct normal life 
functions. 
 
8.4.7  Adverse Events of Special Interest (AESIs) 
 
The study drug has the potential risk of causing the following AESIs based on 
information associated with other drugs in the same category. These are: 
1. Thromboembolic events (TEs) based on information associated with other 
drugs for treatment of hemophilia. TEs include myocardial infarction (MI); 
venous thrombosis, and pulmonary embolism (PE); and stroke. See 
Appendix A for signs and symptoms listed for the subjects and the study 
team personnel as those requiring urgent reporting and attention.  
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2. Immune response resulting in antibody formation and potentially an 
inhibitory antibody response. This will also be monitored for throughout the 
study.  
 
8.4.8  Reporting of Pregnancy 
 
Although pregnancy itself is not considered an adverse event or a serious 
adverse event, the partner of a male participant should be followed until 
termination or to term to ensure absence of congenital anomaly or birth defect 
that may have resulted from maternal exposure or transmission of the study drug 
via semen following paternal exposure. 
Please advise all participants to use a highly effective method of birth control 
from the first dose of study drug through 28 days after dosing to protect the 
health and safety of the mother and/or child. Despite the warnings provided 
and precautions taken, pregnancy may occur during research participation. 
Investigators must be aware of the requirements related to reporting and follow-
up in the event a research participant’s partner becomes pregnant. 
If a participant’s partner becomes pregnant during this study, please provide an 
authorization form to present to the partner. If she is in agreement, that 
authorization will function as consent to approve the study doctor’s access to 
medical information to allow the regulatory required monitoring of the 
pregnancy, and the birth and the health of the child.  
Please report the pregnancy of a participant’s partner to Catalyst Biosciences, or 
it’s designee, and the IRB, and include the following information: expected date 
of delivery, last menstruation, estimated conception date and pregnancy result 
(if known).  
Pregnancy should be reported as “Information” (not as an “Adverse Event” or 
“Other Problem or Event”). 
 
Pregnancy does NOT have to be reported to the IRB if the subject is receiving 
follow-up only, and conception occurred outside of the time period that the 
study protocol requires contraception (ie, 28 days after the last dose of the 
study drug and the pregnancy occurred after that time). 
 
Subsequent reports containing follow-up information regarding a pregnancy 
is not required unless the pregnancy results in a congenital anomaly. The 
congenital anomaly should be promptly reported.  
 
NOTE: If you suspect that exposure to a medical product prior to conception 
or during pregnancy may have resulted in an adverse outcome in the child, it 
must be reported to the Food and Drug Administration (FDA). 
 
 
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9.  
STATISTICAL CONSIDERATIONS  
 
9.1 
STUDY HYPOTHESIS 
 
Please note that there is no study hypothesis, as this study is not intended to be 
inferential. 
Primary Analysis Plan:  
Appropriate descriptive statistics of all measured parameters will be reported, 
including 95% confidence intervals. 
The dose required to achieve steady-state levels >12%, >30% and >50% will be 
reported for daily, every second day and every third day dosing, including 95% 
confidence intervals. 
Primary Endpoint 
The primary endpoint will include: 
 
Number of subjects who achieve a steady-state FIX activity level above 12%, 
30% and 50% with daily, every second day or every third day dosing. 
 
Secondary Endpoints 
The secondary endpoints will include: 
 
Safety assessments: Occurrence of antibody formation resulting in a 
decreased endogenous level of FIX; occurrence of a clinical thrombotic 
event not attributable to another cause. 
 
Occurrence of a conformed antibody response with high titer to CB2679d 
and whether it is inhibitory and cross-reactive to BeneFIX.   
 
Change in CB2679d activity levels, and from pre-dose. 
 
Occurrence of clinically significant levels of thrombogenicity markers resulting 
from SQ administration of CB 2679d.  
 
Feasibility of using an adjusted-dose SQ prophylaxis treatment regimen 
clinically.  
 
 
 
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9.2 
SAMPLE SIZE DETERMINATION 
 
5 subjects are sufficient to provide guidance on range of dose required to 
achieve steady-state activity 12%, >30% or >50% and starting SQ dose for 
subsequent studies. As this study is not inferential, no formal sample size 
calculation is required. 
 
9.3 
POPULATIONS FOR ANALYSES 
 
Safety population: any patient who receives at least one dose 
Efficacy/PD population: any patient who receives at least one week of dosing 
and PK specimens obtained 
 
If a subject does not complete the study as defined in the protocol another 
subject will need to be enrolled in replacement. 
 
9.4 
STATISTICAL ANALYSIS 
 
9.4.1 General Approach 
 
Various pharmacokinetic parameters will be calculated, including area under 
the time curve (o-t and 0-infinity), clearance, volume of distribution at steady-
state, Tmax and Cmax, and terminal (beta phase) t1/2, will be calculated. A semi-
parametric model described by Lee et al40 will be used to calculate the terminal 
t1/2. Other parameters will be calculated using a standard noncompartmental 
approach. Descriptive statistics will be reported for each parameter and will 
include mean ± standard deviation and median ± interquartile range. The dosing 
profile and adjustments made will be reported. 
The evaluation of the primary endpoint is descriptive, but 95% confidence 
intervals will be calculated as appropriate. 
There will be a formal Statistical Analysis Plan (SAP) completed prior to database 
lock.  
 
 
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9.4.2  Analysis of the Primary Efficacy Endpoint(s) 
 
The analysis of the primary endpoint will include: 
 
Number of subjects who achieve a steady-state FIX activity level above 12%, 
30% and 50% with daily, every second day or every third day dosing. 
 
9.4.3  Analysis of the Secondary Endpoint(s) 
 
Study drug exposure and compliance will be provided for both phases, and by 
treatment group for the Treatment Phase.  
The following parameters will be documented: 
 
Occurrence of clinical thrombotic event not attributable to another cause, 
and occurrence of antibody formation resulting in a decreased endogenous 
level of FIX. 
 
Change in coagulation parameters (fibrinogen, and CB2679d activity levels) 
from pre-dose. 
 
Occurrence of an antibody response to CB2679d and whether it is inhibitory 
and cross-reactive to BeneFIX. 
 
Clinically significant levels of thrombogenicity markers resulting from SQ 
administration of CB2679d  
The frequencies of these events will be summarized as proportions and counts. 
Protocol deviations will be listed.  All major protocol deviations (in particular 
those regarding entry criteria) will be summarized in the study report.  
 
9.4.4  Safety Analysis  
 
Adverse Events 
All AEs will be listed, documenting the course, outcome, severity, and causality 
to study drug. Verbatim terms on CRFs will be mapped to preferred terms and 
related system organ class using the Medical Dictionary for Regulatory Activities 
(MedDRA).  
Incidence rates of AEs and the proportion of subjects prematurely withdrawn 
from the study due to AEs will be shown for. Incidence rates will also be displayed 
based on severity and relationship to study drug. AEs with a relationship of 
“possibly” or “probably” related will be considered by the Sponsor as “related” 
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to the study drug. Events assessed as “unrelated”, “unlikely” related, or where the 
relationship was not reported will be considered by the Sponsor as “not related” 
to the study drug. The incidence of SAEs will be provided for each phase. All 
incidence rates will be categorized and displayed by system organ class and 
preferred term. 
Vital Signs  
Safety analyses will include descriptive statistical summaries of shifts in vital signs 
(blood pressure, heart rate, respiratory rate) and in laboratory values for each 
phase. 
 
9.4.5  Baseline Descriptive Statistics  
 
Demographic and baseline measurement variables will be summarized using 
descriptive statistics.  
 
9.4.6  Planned Interim Analyses 
 
Not applicable to this study. 
 
9.4.7  Sub-Group Analyses 
 
Not applicable to this study. 
 
9.4.8  Tabulation of Individual Participant Data 
 
Individual participant data will be listed by measure and time point. 
 
 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1  
Informed Consent Process 
 
The written informed consent documents will be prepared in the language(s) of 
the potential subject population, based on an English version provided by the 
Sponsor and should be easy to understand.   
Before a subject’s participation in the trial, the investigator is responsible for 
obtaining written information consent from the subject after adequate 
explanation of the aims, methods, anticipated benefits, and potential hazards of 
the study and before any protocol specific screening procedures or any study 
drugs are administered. Sufficient time must be given to consider whether to 
participate in the study. 
The informed consent form should be signed and personally dated by the 
subject and by the study person who conducted the informed consent 
discussion. The original signed informed consent form should be retained in the 
Study Master File and in any other locations required by institutional policy, and a 
copy of the signed consent form should be provided to the subject. 
 
10.1.2  Institutional Review Board/Independent Ethics Committee 
 
Before initiation of the study, the investigator must submit for approval the 
protocol, ICF, Investigator’s Brochure, and any advertisements to an IRB/IEC for 
written approval. The Investigator must ensure IRB/IEC compliance with the 
applicable regulations. A copy of written IRB/IEC approval of the protocol, ICF, 
and all advertisements must be provided to Sponsor or designee prior to initiation 
of the study and shipment of study drug.  The Investigator is responsible for 
obtaining continued review of the clinical research at intervals not exceeding 
one year or at more frequent intervals if specified by the IRB/IEC. The Investigator 
must supply Sponsor or designee with written documentation of continued 
review of the clinical research. 
The Investigator is responsible for reporting the following to the IRB/IEC: 
 
All SAEs (including deaths) regardless of cause and whether anticipated or 
unanticipated (reported immediately) 
 
Significant findings that become known in the course of the study that might 
affect the willingness of subjects to continue to participate  
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 
Protocol, or consent amendments prior to the implementation of the change 
 
Study progress reports at least once a year, if applicable 
 
Notification of study completion or termination. 
Sponsor may amend the protocol as needed to ensure that the clinical 
investigation is being conducted as intended. Sponsor will initiate protocol 
amendments in writing if any change significantly affects the safety of subjects, 
the scope of the investigation, or the scientific quality of the study. Protocol 
changes must be submitted to the IRB/IEC as a protocol amendment. If 
necessary, the ICF will be revised to reflect the changes in the amendment and 
will be submitted to the IRB/IEC for review and approval. A copy of the 
amendment must be signed by the Investigator and returned to Sponsor or 
designee. Written documentation of IRB/IEC approval is required before the 
amendment is implemented. Investigators may not perform study-specific 
assessments that are not included in the protocol unless agreed to by Sponsor.  
 
10.1.3  Study Discontinuation and Closure  
 
This study may be temporarily suspended or prematurely terminated if there is 
sufficient reasonable cause.  Written notification, documenting the reason for 
study suspension or termination, will be provided by the suspending or 
terminating party to study subjects, investigator, and regulatory authorities.  If the 
study is prematurely terminated or suspended, the PI will promptly inform study 
participants, the IRB/IEC, and sponsor and will provide the reason(s) for the 
termination or suspension.  Study subjects will be contacted, as applicable, and 
be informed of changes to study visit schedule. 
When a study is prematurely terminated, refer to Section 7, Study Intervention 
Discontinuation and Participant Discontinuation/Withdrawal, for handling of 
enrolled study participants. 
 
10.1.4  Confidentiality and Privacy 
 
Participant confidentiality and privacy is strictly held in trust by the participating 
investigators, their staff, and the sponsor, or designee. The study protocol, 
documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study, or the data will be released to 
any unauthorized third party without prior written approval of the sponsor.  
All research activities will be conducted in as private a setting as possible. 
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The study monitor, other authorized representatives of the sponsor, 
representatives of the IRB/IEC, or regulatory agencies may inspect all documents 
and records required to be maintained by the investigator, including but not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for 
the participants in this study. The clinical study site will permit access to such 
records. 
The study participant’s contact information will be securely stored at each 
clinical site for internal use during the study. At the end of the study, all records 
will continue to be kept in a secure location for as long a period as dictated by 
the reviewing IRB/IEC, Institutional policies, or sponsor requirements. 
 
10.1.5  Future Use of Stored Specimens and Data 
 
There is no genetic testing performed in relation to this study. 
 
10.1.6  Clinical Monitoring 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of 
trial participants are protected, that the reported trial data are accurate, 
complete, and verifiable, and that the conduct of the trial is in compliance with 
the currently approved protocol/amendment(s), with ICH GCP, and with 
applicable regulatory requirement(s).  
The Sponsor, or its designee, and regulatory authority inspectors are responsible 
for contacting and visiting the Investigator for the purpose of inspecting the 
facilities and, upon request, inspecting the various records of the trial (e.g., CRFs 
and other pertinent data) provided that subject confidentiality is respected. The 
Sponsor monitor is responsible for inspecting the CRFs at regular intervals 
throughout the study to verify adherence to the protocol; completeness, 
accuracy, and consistency of the data; and adherence to local regulations on 
the conduct of clinical research. The monitor should have access to subject 
medical records and other study-related records needed to verify the entries on 
the CRFs. The Investigator agrees to cooperate with the monitor to ensure that 
any problems detected in the course of these monitoring visits, including delays 
in completing CRFs, are resolved. 
To ensure the quality of clinical data a clinical data management review will be 
performed on subject data received by the Sponsor. During this review, subject 
data will be checked for consistency, omissions, and any apparent 
discrepancies. In addition, the data will be reviewed for adherence to the 
protocol and GCP.  
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Independent audits may be conducted by the Sponsor, or designee, or 
regulatory authority inspectors to inspection the Study Center facilities (e.g., 
pharmacy, drug storage areas, laboratories) and review of study related records 
to evaluate the trial conduct and compliance with the protocol, ICH GCP, and 
applicable regulatory requirements. 
The Principal Investigator will sign and date the indicated places on the CRF. 
These signatures will indicate that the principal Investigator inspected or 
reviewed the data on the CRF, the data queries, and the Study Center 
notifications, and agrees with the content. 
 
10.1.7  Quality Assurance (QA) and Quality Control (QC) 
 
The Sponsor, or designee, will be responsible for data management of this study, 
including quality checking of the data. Sites will be responsible for data entry into 
the electronic data capture (EDC) system (eCRFs). In the event of data 
discrepancy, the Sponsor, or designee, will request data clarification from the 
sites, which the sites will resolve electronically in the EDC system.  
The eCRFs and correction documentation will be maintained in the EDC system 
audit trail.  
Diary data will be entered into the eCRF.  
Following written Standard Operating Procedures (SOPs), the monitors will verify 
that the clinical trial is conducted, and data are generated, and biological 
specimens are collected, documented (recorded), and reported in compliance 
with the protocol, ICH GCP, and applicable regulatory requirements (e.g., Good 
Laboratory Practices [GLP], GMP).  
The investigational site will provide direct access to all trial related sites, source 
data/documents, and reports for the purpose of monitoring and auditing by the 
sponsor, and inspection by local and regulatory authorities. 
 
10.1.8  Data Handling and Record Keeping 
 
10.1.8.1  
Data Collection and Management Responsibilities 
 
Data collection is the responsibility of the clinical trial staff at the site under the 
supervision of the site investigator. The investigator is responsible for ensuring the 
accuracy, completeness, legibility, and timeliness of the data reported. 
 
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All source documents should be completed in a neat, legible manner to ensure 
accurate interpretation of data.   
Clinical data (including AEs, concomitant medications, and expected adverse 
reactions data) and clinical laboratory data will be entered into Medidata Rave 
EDC, a 21 CFR Part 11-compliant data capture system. The data system includes 
password protection and internal quality checks, such as automatic range 
checks, to identify data that appear inconsistent, incomplete, or inaccurate. 
Clinical data will be entered directly from the source documents.] 
 
10.1.8.2  
Study Records Retention 
 
Study documents should be retained as required by local regulations. No records 
will be destroyed without the written consent of the sponsor, if applicable. It is the 
responsibility of the sponsor to inform the investigator when these documents no 
longer need to be retained 
 
10.1.9  Protocol Amendments 
 
Sponsor may amend the protocol as needed to ensure that the clinical 
investigation is being conducted as intended. Sponsor will initiate protocol 
amendments in writing if any change significantly affects the safety of subjects, 
the scope of the investigation, or the scientific quality of the study. Protocol 
changes must be submitted to the IRB/IEC as a protocol amendment. If 
necessary, the ICF and assent form will be revised to reflect the changes in the 
amendment and will be submitted to the IRB/IEC for review and approval. A 
copy of the amendment must be signed by the Investigator and returned to 
Sponsor or designee. Written documentation of IRB/IEC approval is required 
before the amendment is implemented. Investigators may not perform study-
specific assessments that are not included in the protocol unless agreed to by 
Sponsor. Additionally, a site-specific amendment and revised ICF and assent 
form must be generated and submitted for approval to the IRB/IEC. 
 
10.1.10  
Publication and Data Sharing Policy 
 
The final clinical study report is also intended to form the basis for a manuscript 
intended for publication in a peer-reviewed scientific journal. The authorship, 
timetable and any arrangements for review by the participating investigators will 
be coordinated by Catalyst Biosciences.  No partial subset of data from 
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individual investigational sites can be presented or published until after the 
primary manuscript for the entire study has been accepted for publication in a 
peer reviewed scientific journal. 
 
10.2  PROTOCOL AMENDMENT HISTORY 
 
Version 
Date 
Description of Change 
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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11.  
REFERENCES 
 
1. Mannucci PM, Tuddenham EG. The hemophilias--from royal genes to 
gene therapy. N Engl J Med. 2001;344(23):1773-1779. 
2. Berntorp E, Shapiro AD. Modern haemophilia care. Lancet. 
2012;379(9824):1447-1456.  
3. White GC 2nd, Rosendaal F, Aledort LM, Definitions in hemophilia. 
Recommendation of the scientific subcommittee on factor VIII and factor 
IX of the scientific and standardization committee of the International 
Society on Thrombosis and Haemostasis. Thromb Haemost. 2001;85(3):560. 
4. World Federation of Hemophilia. Guidelines for the Management of 
Hemophilia. 2nd Edition. https://www1.wfh.org/publication/files/pdf-
1472.pdf. Accessed December 18, 2017. 
5. Aznar JA, Lucía F, Abad-Franch L, Jiménez-Yuste V, Pérez R, Batlle J, Balda 
I, Parra R, Cortina VR. Haemophilia in Spain. Haemophilia. 2009;15(3):665-
675. 
6. Katz J. Prevalence of factor IX inhibitors among patients with haemophilia 
B: results of a large-scale North American survey. Haemophilia 
1996;2(1):28–31. 
7. Nerich V, Tissot E, Faradji A, Demesmay K, Bertrand MA, Lorenzini JL, Briquel 
ME, Pouzol P, Woronoff-Lemsi MC. Cost-of-illness study of severe 
haemophilia A and B in five French haemophilia treatment centres. Pharm 
World Sci. 2008;30(3):287-292. 
8. Giangrande P. Haemophilia B: Christmas disease. Expert Opin 
Pharmacother. 2005;6(9):1517-1524. 
9. Fischer K, Van Den Berg M. Prophylaxis for severe haemophilia: clinical 
and economical issues. Haemophilia. 2003;9(4):376-381. 
10. Ljung RC. Prophylactic infusion regimens in the management of 
hemophilia. Thromb Haemost. 1999;82(2):525-530.  
11. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne 
R, Ingram JD, Manco-Johnson ML, Funk S, Jacobson L, Valentino LA, Hoots 
WK, Buchanan GR, DiMichele D, Recht M, Brown D, Leissinger C, Bleak S, 
Cohen A, Mathew P, et al. Prophylaxis versus episodic treatment to 
prevent joint disease in boys with severe hemophilia. N Engl J Med. 
2007;357(6):535-544. 
12. Tagliaferri A, Franchini M, Coppola A, Rivolta GF, Santoro C, Rossetti G, 
Feola G, Zanon E, Dragani A, Iannaccaro P, Radossi P, Mannucci PM.  
Effects of secondary prophylaxis started in adolescent and adult 
haemophiliacs. Haemophilia 2008;14(5):945-951. 
13. Valentino LA, Mamonov V, Hellmann A, Quon DV, Chybicka A, Schroth P, 
Patrone L, Wong WY; Prophylaxis Study Group. A randomized comparison 
of two prophylaxis regimens and a paired comparison of on-demand and 
Dalcinonacog alfa (DalcA) 
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prophylaxis treatments in hemophilia A management. J Thromb Haemost. 
2012;10(3):359-367. 
14. Oldenburg J, Zimmermann R, Katsarou O, Theodossiades G, Zanon E, 
Niemann B, Kellermann E, Lundin B; Cross-sectional MRI study investigators. 
Controlled, cross-sectional MRI evaluation of joint status in severe 
haemophilia A patients treated with prophylaxis vs. on demand. 
Haemophilia. 2015;21(2):171-179. 
15. Andersson NG, Auerswald G, Barnes C, Carcao M, Dunn AL, Fijnvandraat 
K, Hoffmann M, Kavakli K, Kenet G, Kobelt R, Kurnik K, Liesner R, 
Mäkipernaa A, Manco-Johnson MJ, Mancuso ME, Molinari AC, Nolan B, 
Perez Garrido R, Petrini P, Platokouki HE, et al. Intracranial haemorrhage in 
children and adolescents with severe haemophilia A or B - the impact of 
prophylactic treatment. Br J Haematol. 2017;179(2):298. Epub 2017 Jul 12. 
16. Stieltjes N, Calvez T, Demiguel V, Torchet MF, Briquel ME, Fressinaud E, 
Claeyssens S, Coatmelec B, Chambost H; French ICH Study Group. French 
ICH Study Group. Intracranial haemorrhages in French haemophilia 
patients (1991–2001): clinical presentation, management and prognosis 
factors for death. Haemophilia. 2005;11:452–458. 
17. White GC 2nd, Courter S, Bray GL, Lee M, Gomperts ED. A multicenter 
study of recombinant factor VIII (Recombinate) in previously treated 
patients with hemophilia A. The Recombinate Previously Treated Patient 
Study Group. Thromb Haemost. 1997;77(4):660-667. 
18. Santagostino E. Prophylaxis in haemophilia B patients: unresolved issues 
and pharmacoeconomic implications. Haemophilia. 2010;16(Suppl 6):13-
17. 
19. Schulte S. Half-life extension through albumin fusion technologies. Thromb 
Res. 2009;124(Suppl 2):S6-S8. 
20. National Hemophilia Foundation. Fast Facts. Available at 
https://www.hemophilia.org/About-Us/Fast-Facts. Accessed on 
December 18, 2017. 
21. BeneFIX® Coagulation Factor IX (Recombinant) Prescribing Information, 
Wyeth Pharmaceuticals Inc. June 2017. 
22. De Moerloose P, Urbancik W, Van Den Berg HM, Richards M. A survey of 
adherence to haemophilia therapy in six European countries: results and 
recommendations. Haemophilia. 2008;14(5):931-938. 
23. Blanchette P, Rivard G, Israels S, Robinson S, Ali K, Walker I, Stain AM, 
Blanchette V; Association of Hemophilia Clinic Directors of Canada and 
Canadian Association of Nurses in Hemophilia Care. A survey of factor 
prophylaxis in the Canadian haemophilia A population. Haemophilia. 
2004;10(6):679-683. 
24. Hacker MR, Geraghty S, Manco-Johnson M. Barriers to compliance with 
prophylaxis therapy in haemophilia. Haemophilia. 2001;7(4):392-396. 
Dalcinonacog alfa (DalcA) 
Study DLZ-201, Clinical Study Report
Catalyst Biosciences, Inc. 
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25. Gater A, Thomson TA, Strandberg-Larsen M. Haemophilia B: impact on 
patients and economic burden of disease. Thromb Haemost. 
2011;106(3):398-404.  
26. Manco-Johnson MJ. Update on treatment regimens: prophylaxis versus 
on-demand therapy. Semin Hematol. 2003;40(3 Suppl 3):3-9. 
27. Peters RT, Low SC, Kamphaus GD, Dumont JA, Amari JV, Lu Q, Zarbis-
Papastoitsis G, Reidy TJ, Merricks EP, Nichols TC, Bitonti AJ. Prolonged 
activity of factor IX as a monomeric Fc fusion protein. Blood. 
2010;115(10):2057-2064.  
28. Russell KE, Olsen EH, Raymer RA, Merricks EP, Bellinger DA, Read MS, Rup 
BJ, Keith JC Jr, McCarthy KP, Schaub RG, Nichols TC. Reduced bleeding 
events with subcutaneous administration of recombinant human factor IX 
in immune-tolerant hemophilia B dogs. Blood. 2003;102(13):4393-4398.  
29. Nienhuis AW, Nathwani AC, Davidoff AM. Gene Therapy for Hemophilia. 
Mol Ther. 2017;25(5):1163-1167.  
30. Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: 
diagnosis, treatments, and its complications. Lancet. 2016;388(10040):187-
197.  
31. Hartmann J, Croteau SE. 2017 Clinical trials update: Innovations in 
hemophilia therapy. Am J Hematol. 2016;91(12):1252-1260.  
32. Hacker MR, Geraghty S, Manco-Johnson M. Barriers to compliance with 
prophylaxis therapy in haemophilia. Haemophilia. 2001l;7(4):392-396. 
33. Stoner KL, Harder H, Fallowfield LJ, Jenkins VA. Intravenous versus 
Subcutaneous Drug Administration. Which Do Patients Prefer? A 
Systematic Review. The Patient - Patient-Centered Outcomes Research. 
2015;8(2):145–153. 
34. Hong S-B, Levy H, Jung JY, Park M, Seo AR, Seo SH, Madison E. 
Pharmacokinetics of Subcutaneously Administered CB2679d/ISU304 in 
Wild-Type and Hemophilia B Mice. Blood  2016,128(22):1389. 
35. You CW, Shin H-J, Levy H, Lee M, Hong S-B, Siegel JE, Park JY. Phase 1/2 
Trial of Subcutaneously Administered Factor IX Variant CB2679d/ISU304: 
Pharmacokinetics and Activity. Blood 2017 130:87. 
36. Hong S-B, Levy H, Jung JY, Park M, Seo AR, Park JY. Pharmacokinetics of 
Subcutaneously Administered CB2679d/ISU304 in MiniPig Compared With 
BeneFIX. Presented at the European Association for Harmophilia and 
Allied Disorders (EAHAD) in Paris, France. 1-3 February, 2017. Poster 
Number P074.  
37. U.S. National Library of Medicine. ClinicalTrials.gov. Dose-escalation Study 
to Investigate the Safety, PK, and PD of ISU304/CB2679d in Hemophilia B 
Patients. NCT03186677. Available at 
https://clinicaltrials.gov/ct2/show/NCT03186677?term=CB2679d&cond=He
mophilia&rank=1. Accessed on December 30, 2017. 
Dalcinonacog alfa (DalcA) 
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38. You CW, Shin H-J, Levy H, Lee M, Hong S-B, Siegel JE, Park JY. Phase 1/2 
Trial of Subcutaneously Administered Factor IX Variant CB2679d/ISU304: 
Pharmacokinetics and Activity. Presented at the 59th Annual Meeting of 
the American Society of Hematology (ASH) in Atlanta, Georgia. 
December 9-12, 2017. Poster Number 87. 
39. Common Terminology Criteria for Adverse Events, Version 5.0. 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/c
tc.htm#ctc_50. November 27, 2017. Accessed December 31, 2017. 
40. Lee ML, Poon Wai-Yin, Kingdon HS. A two-phase linear regression model 
for biologic half-life data. Journal of Laboratory and Clinical Medicine. 
1990;115(6):745-748. 
41. Blanchette VS, Key NS, Ljung LR, et al. Definitions in hemophilia: 
communication from the SSC of the ISTH. J Thromb Haemost 
2014;12:1935−1939. 
 
 
 
 
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APPENDICES 
 
APPENDIX A – CLINICAL SIGNS OF THROMBOSIS 
 
  
http://www.heart.org/HEARTORG/Conditions/VascularHealth/VenousThromboembolism/
Symptoms-and-Diagnosis-of-Venous-Thromboembolism-VTE_UCM_479057_Article.jsp# 
• 
American 
Heart 
Assoc ton. 
life wtrr 
LOCALI FO 
U 
a ma Search 
HEALTHY LIVING CO DITIO S SUPPORT PROFESSIO 
RESEARCH EDUCATOR CPR & ECC 
Arm 
mla 
Cholesterol 
Congo Ital 
Defects Ch ldren 
&Adults 
Heart Attack 
Heart Fa ure 
High Blood 
P essure 
Symptoms and Diagnosis of Venous Thromboembolism (VTE) 
Sh•"' 
0 iti1itil f 11#51 
G+l 
2 
VTE ncludes deep vei thrombos (DVT), when a blood 
clot forms In a deep ve n. us ally In 
e leg. And I Includes 
pulmonary embol sm (PE), 
en the clo breaks off and 
travels from 
e leg p to the lungs. DVT and PE a e 
serious. life-threa enlng conditions that require Immediate 
medteal attention. 
What are the warning signs? 
DVT ma ly affects the large ve ns n the lower leg and 
lgh, almost always on one s e of e body at a time. The 
dot can book blood flow and ca se: 
• Leg pai or tende ess of the th h o calf 
• Leg swelling (edema) 
• Skin that feels warm to the touch 
• Redd sh discoloration or red strea 
48 
Updated:Mar 9.2017 
PE, or 
Imo 
ry e bollsm. can be fata and occurs whe the DVT b eaks f ee from a vein wall and blocks some or 
all of the blood s 
ply to the I ngs, cau ng: 
• Unexpla ned shoMess or breath 
• Rapid breathing 
• Chest pain a ywhere under 
e rib cage (may be worse with deep brea 
ng) 
• Fas heart rate 
• Light 
adedness or passing o t 
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http://www.heart.org/HEARTORG/Conditions/HeartAttack/WarningSignsofaHeart
Attack/Warning-Signs-of-a-Heart-
Attack_UCM_002039_Article.jsp#.WkkEAWeYpfw  
V
""-
American 
Heart 
Association~ 
life is whyr. 
Common Heart Attack 
Warning Signs 
Pain or discomfort 
in chest 
Ughtheadedness, 
nausea, or vomiting 
Jaw, neck or 
back pain 
Discomfort or pain in 
arm or shoulder 
Shortness of breath 
Learn more at Heart.org/HeartAttack. 
CQD18 ,.,_..., Hoowl,._...... Inc.All '9ill .........i. lklltAu\ood ,_ prclit,bd. 
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http://www.strokeassociation.org/STROKEORG/WarningSigns/Stroke-Warning-
Signs-and-Symptoms_UCM_308528_SubHomePage.jsp  
.. 
THREE NUMBERS: 
9-1-1 
Use the letters in 'fast 11 to spot stroke signs and 
know when to call 9-1-1. 
F A S T 
FACE 
DROOPING 
ARM 
WEAKNESS 
SPEECH 
mFFICULTY 
TIMETO 
CALL 911 
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!!!!!! 
~f'Ol<i!aHOC:iaJD'\.org 
Sometimes other symptoms appear, separately, 
In combination or with F.A.S.T. signs. 
m 
Sudden confusion, trouble speaking orundetstandlng 
spocch. 
11!1!1 Sudden numbnen or w~kn!!S< of f:ace. arm or leg 
liil Espo,cially on one side of the body. 
m 
Sudden trouble seeing In ono or Both O)ICS. 
1!'-1 Sudden trouble walking. d lnlness, loss of balance or 
lillil coordinatlon, 
m 
Sudden 5""Gro headache wtlh no known cau,e. 
If someone sho\vsanyot th?.58 symptoms. call g.1 .. 1 or 
emergency medical services lmmedlotely. 
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Symptoms and Signs of Venous Thromboembolism – Deep Vein Thrombosis (DVT) 
and Pulmonary Embolism (PE): 
 
Leg pain or tenderness of the thigh or calf 
Leg swelling (edema) 
Skin that feels warm to the touch 
Reddish discoloration or red streaks 
 
Unexplained shortness of breath 
Rapid breathing 
Chest pain anywhere under the rib cage (may be worse with deep breathing) 
Fast heart rate 
Light headedness or passing out 
 
 
Common Heart Attack Warning Signs 
 
Pain or discomfort in the chest 
Lightheadedness, nausea, or vomiting 
Jaw, neck, or back pain 
Discomfort or pain in arm or shoulder 
Shortness of breath 
 
Stroke Signs 
 
Face Drooping 
Arm Weakness 
Speech Difficulty 
 
Sudden confusion, trouble speaking or understanding speech 
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Sudden numbness or weakness of face, arm or leg.  Especially on one side of the 
body. 
Sudden trouble seeing in one or both eyes. 
Sudden trouble walking, dizziness, loss of balance or coordination. 
Sudden severe headache with no known cause. 
 
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Signs and Symptoms of Thrombosis 
The clinical spectrum of venous thromboembolism (VTE) ranges from deep vein thrombosis (DVT) to pulmonary 
embolism (PE). The symptoms of VTE depend on the location of the affected vessel and whether the vessel is totally or 
partially occluded by the clot.  
 
Table. Clinical Spectrum of VTE 
 
Type 
Signs and Symptoms 
Physical Examination 
Deep vein thrombosis (DVT) 
•Blood clots may form in the deep blood 
vessels, most commonly in the legs and groin, 
and can block normal blood flow returning from 
the legs to the heart. 
•Venous clots that form in regions of slow to 
moderate flow are composed of a mixture of 
red cells, platelets, and fibrin and are known as 
mixed platelet fibrin thrombi. 
•Partially occlusive venous thrombosis of the 
deep veins in the legs or abdomen may present 
with subtle symptoms and sometimes may not 
present until significant collateral circulation* 
has developed. 
 
 
Pain 
 
Swelling of the affected 
extremity/area with 
erythema and warmth over 
the vicinity of the clot 
 
Discoloration including a 
bluish or suffused color 
 
 
Positive Homan’s sign: pain with 
dorsiflexion of the foot 
 
Swelling 
 
Pain on palpation 
 
Presence of a palpable cord 
 
Evidence of collateral circulation, 
usually manifested by increased 
prominence of superficial veins 
 
Some people with a DVT may be 
asymptomatic 
 
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Pulmonary Embolism (PE) 
•PE results from a piece or all of a blood clot 
that breaks off and is carried by the blood 
stream to the lung where it obstructs the blood 
vessel. 
•The size of the clot and the site of the 
obstruction of blood flow in the vessel 
determine the extent and severity of the 
pulmonary embolus. 
•Proximal vein thrombosis is more likely to lead 
to fatal PE as compared to calf vein thrombosis. 
•The incidence of fatal PE can be markedly 
reduced if DVT is treated with anticoagulant 
therapy.  
 
Pulmonary emboli may present 
subtly with the following 
complaints listed in order of 
frequency: 
 
Dyspnea 
 
Rapid breathing, fast 
heartbeat and chest pain 
especially with inhalation 
 
Pleural pain: Some patients 
notice only a dull ache in 
their chest 
 
Apprehension, anxiety 
 
Cough 
 
Hemoptysis 
 
Sweats 
 
Syncope 
 
Fatigue 
 
Tachypnea 
 
Tachycardia 
 
Rales 
 
Fever 
 
Sweating 
 
Thrombophlebitis 
 
Accentuation of the pulmonary 
closure sound 
 
Gallop heart sound 
 
Cyanosis 
 
Some people with a PE may be 
asymptomatic 
 
Superficial Thrombophlebitis 
•Superficial thrombophlebitis is due to blood 
clots that form in veins that are closer to the 
surface of the skin and are associated with 
inflammation. 
 
These clots often partially block blood flow in affected veins and may 
cause pain and irritation. 
 
Redness and inflammation along the vein may occur; if hard and 
erythematous, the affected vein is often visible and most commonly 
occurs in the legs or arms.  
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•Superficial thrombophlebitis is often observed 
in individuals who are heterozygous or 
homozygous for the factor V Leiden mutation. 
 
 
Other associated symptoms include warmth and tenderness, 
surrounding purities and swelling. 
 
Pain along the vein: patients may report a throbbing or burning 
sensation beneath the skin’s surface; these symptoms may interfere 
with sleep as they progress. 
Fever: Patients with venous inflammation may develop an elevated 
temperature associated with an episode of thrombophlebitis. 
 
Adapted from IHTC. Signs and Symptoms of Thrombosis. Available at http://www.ihtc.org/payors/conditions-we-
treat/clotting-disorders/signs-and-symptoms-of-thrombosis.
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APPENDIX B – DETAILED STUDY SCHEMA 
 
 
 
 
SCREENING 
µp to 4 weeks prior 
Screening 
• Obtain informed consent 
• Review demographic parameters 
• Conduct a joint evaluation as per the SOC at hemophilia treatment center 
• Screen potential subjects by inclusion and exclusion criteria 
• Obtain medical and hemophilia history, document 
• 
Evaluate concomitant medications, check vital signs, height and weight 
• Conduct physical examination, check for clinical signs of thrombosis 
• Conduct testing for hematology and chemistry, coagulation assay, thrombogenicity markers, immunogenicity assays, and 
ECG 
• Adverse Events 
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Part 1- 14 days 
Day 1 Pre-IV Dose - S min 
Part 1 
• 
Evaluate concomitant medications, check vital signs, and weight 
• 
Conduct physical examination, check for clinical signs of thrombosis 
• 
Conduct testing for hematology and chemistry, coagulation assay, thrombogenicity markers, PK sampling, immunogenicity assays 
• 
Conduct study subject diary training 
• 
Diary entry of bleeding episodes, AEs, injection site assessment 
• 
Check for AEs 
Day 1 IV Dose Followed by SQ Dose; Day 2 to Day 14 SQ Dose 
Part 1 
• 
Day 1: Administer single IV 70 IU/kg loading dose of CB2679d 
• 
Day 1: 30 minutes later administer SQ 140 IU/kg dose of CB2679d 
• 
Day 2 to 14: Administer SQ 140 IU/kg dose of CB2679d 
Day 1 Post-Dose SQ Dose - (30 min and Hr 7); Day 2 Post-Dose SQ Dose - Hr 24 
Part 1 
• 
Evaluate concomitant medications and check vital signs 
• 
Conduct physical examination, check for clinical signs of thrombosis 
• 
Conduct testing for thrombogenicity markers, PK sampling 
• 
Diary entry of bleeding episodes, AEs, injection site assessment 
• 
Check for AEs 
Days 5, 8, 11 and 14 Pre Dose 
Part 1 
• 
Evaluate concomitant medications and check vital signs 
• 
Conduct physical examination, check for clinical signs of thrombosis 
• 
Day 8 and 14 only: Conduct testing for hematology and chemistry 
• 
Conduct testing for thrombogenicity markers, PK sampling 
• 
Day 8 only: Conduct testing for immunogenicity assays 
• 
Diary entry of bleeding episodes, AEs, injection site assessment 
• 
Check for AEs 
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Part 2 - 7 days 
Dose Hr O on Day 15, Day 17, Day 19, and Day 21 
Part 2 
• Administer280 IU/kg SQ dose of CB2679d (every second day) 
Day 15 Pre-Dose - 5 min 
Part 2 
• Evaluate concomitant medications, and check vital signs and weight 
• 
Conduct physical examination, check for clinical signs of thrombosis 
• Conduct testing for thrombogenicity markers, PK sampling, and immunogenicity assays 
• 
Diary entry of bleeding episodes, AEs, injection site assessment, check for AEs 
Day 15 Post-Dose at Hour 7 [± 1 hour]; Day 16 Post-Dose at Hour 24 [± 1 hour]; 
Day 17 and Day 19 Pre-Dose - 5 min 
• 
Evaluate concomitant medications and check vital signs 
• Conduct physical examination, check for clinical signs of thrombosis 
• 
Conduct testing for thrombogenicity markers, PK sampling 
• 
Diary entry of bleeding episodes, AEs, injection site assessment, check for AEs 
Day 21 Pre-Dose - 5 min 
• 
Evaluate concomitant medications, and check vital signs and weight 
• 
Conduct physical examination, check for clinical signs of thrombosis 
Part 2 
Part 2 
• 
Conduct testing for hematology and chemistry, thrombogenicity markers, PK sampling 
• 
Diary entry of bleeding episodes, AEs, injection site assessment, check for AEs 
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Part 3-14 Days 
Dose Hr O on Day 23, Day 26, Day 29, and Day 32 
Part 3 
• Administer420 IU/kg SQ dose of CB2679d (every third day) 
Day 23 and Day 32 Pre-Dose- 5 min 
Part 3 
• 
Evaluate concomitant medications and check vital signs 
• Conduct physical examination, check for clinical signs of thrombosis 
• 
Day 23 only: Check weight and conduct testing for hematology and chemistry 
• Conduct testing for thrombogenicity markers, PK sampling, immunogenicity assays 
• 
Diary entry of bleeding episodes, AEs, injection site assessment, check for AEs 
Day 24 Post-Dose at Hour 24 [± 1 hr]; Day 26 and 29 Pre-Dose- 5 min 
Part 3 
• 
Evaluate concomitant medications and check vital signs 
• Conduct physical examination, check for clinical signs of thrombosis 
• Conduct testing for thrombogenicity markers, PK sampling 
• 
Diary entry of bleeding episodes, AEs, injection site assessment, check for AEs 
Day 32 Post-Dose at Hour 7 [± 1 hour] 
Part 3 
• Conduct a joint evaluation as per the SOC at hemophilia treatment center 
• 
Evaluate concomitant medications and check vital signs 
• Conduct physical examination, check for clinical signs of thrombosis 
• Conduct testing for hematology and chemistry, thrombogenicity markers, PK sampling 
• 
Diary entry of bleeding episodes, AEs, injection site assessment, check for AEs 
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Washout Period - Days 33, 34, 35, 37, 38 
• Evaluate concomitant medications, check for clinical signs of thrombosis 
• Conduct testing for thrombogenicity markers, PK sampling 
• 
Diary entry of bleeding episodes, AEs, injection site assessment, check for AEs 
Unscheduled 
• 
Review medical and hemophilia history, document 
• 
Evaluate concomitant medications, check vital signs, and weight 
• Conduct physical examination, check for clinical signs of thrombosis 
• Conduct testing for hematology and chemistry, thrombogenicity markers, PK sampling, 
immunogenicity assays 
• 
Diary entry of bleeding episodes, AEs, injection site assessment, check for AEs 
Unscheduled 
• Review medical and hemophilia history, document 
• Evaluate concomitant medications, check vital signs, and weight 
• Conduct physical examination, check for clinical signs of thrombosis 
• Conduct testing for hematology and chemistry, thrombogenicity markers, PK sampling, 
immunogenicity assays 
• 
Diary entry of bleeding episodes, AEs, injection site assessment, check for AEs 
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Dalcinonacog alfa_DLZ‐201 VERSION 2.0, Amendment 1 
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        17 October 2018 
Catalyst Biosciences, Inc. 
 
CLINICAL RESEARCH PROTOCOL 
 
Phase 2b Study of Next-Generation Recombinant Factor IX Variant,  CB 2679d, in Adult 
Subjects with Hemophilia B 
 
Protocol Identifying Number: 
DLZ-201 
Official Title: 
Phase 2b study to evaluate the pharmacokinetics, 
pharmacodynamics, efficacy and safety of a subcutaneous 
prophylaxis treatment regimen of CB2679d, in adult subjects 
with hemophilia B  
IND/IDE Sponsor:  
 
Catalyst Biosciences, Inc. 
611 Gateway Blvd., Suite 710, South San Francisco, California, 
USA  94080 
Investigational Product: 
Recombinant Factor IX,  CB 2679d (formerly ISU304) 
Development Phase: 
2b 
Draft or Version Number: 
v.2.0, Amendment 1 
Effective Date: 
17 October 2018 
Sponsor Contact: 
Name: 
 
Howard Levy, MD, PhD, MMM 
                                    CMO, Catalyst Biosciences, Inc. 
Telephone: 
 
+1.650.266.8671 
Fax: 
 
 
+1.650.871.2475 
E-mail:  
 
hlevy@catbio.com 
 
Prepared by: 
Catalyst Biosciences, Inc. 
 
Confidentiality Statement 
The information in this document contains trade secrets and commercial information that 
are privileged or confidential and may not be disclosed unless such disclosure is required 
by applicable law or regulations. In any event, persons to whom the information is disclosed 
must be informed that the information is privileged or confidential and may not be further 
disclosed by them. These restrictions on disclosure will apply equally to all future information 
supplied to you that is indicated as privileged or confidential. 
Compliance Statement: 
This study will be conducted in accordance with the clinical 
research guidelines established by the U.S. Code of Federal Regulations (Title 21, Parts 50 
[including Subpart D], 54, 56 and 312), the regulations and guidelines of the Therapeutic 
Goods Administration, and the International Conference on Harmonization (ICH) Guidelines 
for Good Clinical Practice. Study documents will be maintained in accordance with 
applicable regulations. 
 
Dalcinonacog alfa (DalcA) 
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Catalyst Biosciences, Inc. 
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INVESTIGATOR SIGNATURE PAGE 
 
PROTOCOL TITLE: 
Phase 2b study to evaluate the pharmacokinetics, 
pharmacodynamics, efficacy and safety of a subcutaneous 
prophylaxis treatment regimen of CB2679d, in adult subjects with 
hemophilia B 
PROTOCOL No.: 
DLZ-201 
VERSION NUMBER: 
2.0, Amendment 1 
 
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study subjects enrolled under my supervision and 
providing the Sponsor with complete and timely information, as outlined in the protocol. 
Furthermore, on behalf of the study staff and myself, I agree to conduct the study as 
outlined in the protocol in accordance with the guidelines outlined in the study protocol 
and all applicable government regulations. In addition, I agree to provide all the 
information requested in the case report forms (CRFs) presented to me by the Sponsor in a 
manner that assures legibility and accuracy. I also agree that all information provided to 
me by the Sponsor, including pre-clinical data, protocols, CRFs, verbal and written 
information, will be kept strictly confidential and confined to the clinical personnel involved 
in conducting the study. It is recognized that this information may be relayed in confidence 
to the Institutional Review Board (IRB)/ Independent Ethics Committee (IEC). In addition, no 
reports or information about the study or its progress will be provided to anyone who is not 
involved in the study, other than Sponsor or designee, the IRB/IEC, or the appropriate 
regulatory agencies. 
The trial will be conducted in accordance with International Conference on Harmonisation 
Good Clinical Practice (ICH GCP), applicable United States (US) Code of Federal 
Regulations (CFR) (Title 21, Parts 50 [including Subpart D], 54, 56 and 312), the regulations 
and guidelines of the Therapeutic Goods Administration (TGA). The Principal Investigator 
(PI) will assure that no deviation from, or changes to the protocol will take place without 
prior agreement from the sponsor, funding agency and documented approval from the 
IRB, except where necessary to eliminate an immediate hazard(s) to the trial participants. 
All personnel involved in the conduct of this study have completed Human Subjects 
Protection and ICH GCP Training. Study documents will be maintained in accordance with 
applicable regulations. 
I agree to ensure that all staff members involved in the conduct of this study are informed 
about their obligations in meeting the above commitments.  
 
 
 
 
Investigator Signature  
 
Date 
 
Print Name and Title 
 
Dalcinonacog alfa (DalcA) 
Study DLZ-201, Clinical Study Report
Catalyst Biosciences, Inc. 
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SPONSOR SIGNATURE PAGE 
 
Protocol Title: 
Phase 2b study to evaluate the pharmacokinetics, 
pharmacodynamics, efficacy and safety of a subcutaneous 
prophylaxis treatment regimen of CB2679d, in adult subjects 
with hemophilia B 
Protocol Number: 
 
DLZ-201 
Version Number: 
2.0, Amendment 1 
 
 
 
 
 
_________________________________________________________  
 17 October 2018                              
Howard Levy, MD, PhD, MMM 
 
 
 
 
 
Date 
Chief Medical Officer, Catalyst Biosciences, Inc. 
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DETAILED SUMMARY OF PROTOCOL CHANGES 
 
Protocol Number: 
DLZ-201 
Protocol Title: 
Phase 2b study to evaluate the pharmacokinetics, pharmacodynamics, efficacy and safety of a 
subcutaneous prophylaxis treatment regimen of CB2679d, in adult subjects with hemophilia B 
 
 
Version Number 
Version Date 
Current Approved Protocol 
1.0 
23 March 2018 
Amended Protocol 
2.0, Amendment 1 
17 October 2018 
 
Description of Changes: 
Section 
Update 
Details 
Title Page 
Replacement 
 
VERSION NUMBER: 
1.0 
With: 
VERSION NUMBER: 
2.0, Amendment 1 
Title Page 
Replacement 
 
Effective Date: 
 
23 March 2018 
With: 
Effective Date: 
 
17 October 2018 
Investigator Signature Page 
Replacement 
 
VERSION NUMBER: 
1.0 
With: 
VERSION NUMBER: 
2.0, Amendment 1 
Sponsor Signature Page 
Replacement 
 
Version Number: 1.0, dated 23 March 2018 
With: 
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Version Number: 2.0, Amendment 1 
Abbreviations 
Updated 
SQ
With: 
SC 
1.1 Synopsis: Study Population: 
Updated 
Five male subjects, aged 18 or older, with confirmed diagnosis of 
severe congenital hemophilia B (<2% FIX level). 
With: 
Six male subjects, aged 18 or older, with confirmed diagnosis of 
severe congenital hemophilia B (<2% FIX level). 
1.1 Synopsis: Participant Duration: 
Updated 
The duration of treatment for each subject is approximately 6 
weeks.   
With: 
The duration of treatment for each subject is approximately 4 
weeks.   
1.1 Synopsis: IV/SQSC Study Drug 
Administration and Assessments 
Updated 
 
Part 1; Weeks 1 and 2: The subject will receive an IV loading dose of 
70 IU/kg followed 30 minutes later by a SQ dose of 140 IU/kg. Daily 
SQ doses of 140 IU/kg will be administered until Day 14 (14 total SQ 
doses). On day 1, PK, PD, and safety assessments will be done at 
pre-IV dose and repeated 30 minutes later prior to the SQ dose. 
Subsequent PK, PD and safety assessments will be performed 7 
hours post-SQ dose on Day 1, Day 2 at hour 24 post-SQ dose and 
pre-dose on days 5, 8, 11 and 14. 
With: 
Treatment: Day 1 to Day 28:  The subject will receive an IV loading 
dose of 50 IU/kg followed 35 ± 5 minutes later by a SC dose of 100 
IU/kg. Daily SC doses of 100 IU/kg will be administered until Day 28 
(28 total SC doses).  On Day 1, PK, PD, and safety assessments will 
Dalcinonacog alfa (DalcA) 
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Catalyst Biosciences, Inc. 
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be done at pre-IV dose and repeated 35 (± 5) minutes later prior to 
the SC dose. Subsequent PK, PD and safety assessments will be 
performed pre-dose on days 2, 3, 7, 14, 21 and 28. 
1.1 Synopsis: IV/SQSC Study Drug 
Administration and Assessments 
Deletions 
 
Every Second Day SQ study drug administration  
Part 2; Week 3: The subject will receive a SQ dose every second day 
of 280 IU/kg, starting on Day 15 until Day 21 (total of 4 SQ doses). On 
Day 15 only, PK, PD, and safety assessments will be done at pre-
dose and repeated at hour 7.  Subsequent PK, PD and safety 
assessments will be performed on Day 16 at hour 24 and pre-dose 
on days 17, 19 and 21.  
Every Third Day SQ study drug administration  
Part 3; Weeks 4 and 5: The subject will receive a SQ dose every third 
day of 420 IU/kg, starting on Day 23 until Day 32 (total of 4 SQ 
doses). On days 23 and 32 only, PK, PD, and safety assessments will 
be done at pre-dose and repeated at hour 7.  Subsequent PK, PD, 
and safety assessments will be performed at Day 24 at hour 24 and 
pre-dose on days 26, and 29. 
1.1 Synopsis: Washout Period 
Updated 
Days 33, 34, 35, 37, and 38
With: 
Days 29, 30, 31, 32, and 33 
1.1 Synopsis: Measurements: and 
Throughout  
Updated 
CB2679d activity levels 
With: 
FIX activity levels 
1.1 Synopsis: Measurements:  
Added 
Genotype testing will be performed at screening. 
1.1 Synopsis: Measurements: 
Immunogenicity assays 
Updated 
Specimens for immunogenicity testing (antibody to CB2679d, wild-
type FIX cross reactivity, and neutralizing activity) will be drawn at 
screening, on days 1, 8, 15, 23, 32, and end of study. 
Dalcinonacog alfa (DalcA) 
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Catalyst Biosciences, Inc. 
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With: 
Specimens for immunogenicity testing (antibody to CB2679d, 
BeneFIX®, and neutralizing activity) will be drawn at screening, on 
days 7, 14, 21, 28, and end of study. 
1.1 Synopsis: Measurements: 
Immunogenicity assays and 
Throughout 
Updated 
Wild-type FIX 
With: 
BeneFIX® 
1.1 Synopsis: Number of planned 
subjects 
Updated 
5 
With: 
6 
1.1 Synopsis: Exclusion Criteria: 
Added 
12.  Factor IX gene mutation 128G>A. 
1.1 Synopsis: Dosage and mode of 
administration: 
Updated 
Part 1: Weeks 1 and 2 (Days 1-14): IV loading dose of 70 IU/kg 
followed 30 minutes later with 140 IU/kg SQ administration daily x 14 
(14 total doses). 
Part 2: Week 3 (Days 15, 17, 19 and 21): 280 IU/kg, SQ administration 
every second day (4 total doses). 
Part 3: Weeks 4 and 5 (Days 23, 26, 29, 32): 420 IU/kg SQ 
administration every third day (4 total doses) 
With: 
IV loading dose of 50 IU/kg, followed 35 ± 5 minutes later with 100 
IU/kg SC administration, then daily SC administration until Day 28 
(28 total SC doses). 
1.1 Synopsis: Primary Endpoints 
Updated 
Number of subjects who achieve a steady-state FIX activity level 
above 12%, 30% and 50% with daily, every second day or every 
third day dosing. 
With: 
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Number of subjects who achieve a steady-state FIX activity level 
above 12% with daily dosing. 
1.1 Synopsis: Secondary Endpoints 
Deletion 
Feasibility of using an adjusted-dose SQ prophylaxis treatment 
regimen clinically. 
1.1 Synopsis: Primary Analysis Plan 
Updated 
The dose required to achieve steady-state levels >12%, >30% and 
>50% will be reported for daily, every second day or every third day 
dosing, including 95% confidence intervals. 
 
With: 
The dose required to achieve steady-state levels >12% will be 
reported for daily dosing, including 95% confidence intervals. 
1.1 Synopsis: Rationale for Number of 
Subjects 
Updated 
5 subjects will provide guidance on dose required to achieve 
steady-state activity >12%, 30% or 50% and starting SQ dose for 
subsequent studies. 
 
With: 
 
6 subjects will provide guidance on dose required to achieve 
steady-state activity >12% and starting SC dose for subsequent 
studies. 
1.2 Schema 
Updated 
Figure 1. Schematic of Study Design 
1.3 Schedule of Activities (SOA) 
Updated and 
Deletions 
Updated Table. 
Deleted Tables for Parts 2 and 3. 
2.2.2 Experience with CB2679d in the 
Clinic 
Updated and 
Addition 
An intravenous loading dose has been added in this study to see if it 
eliminates these local adverse events as they are believed to be due 
to low FIX levels because of washout of prior treatment. 
With: 
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Final
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An IV loading dose has been added to cohort 6 in this study to see if 
it eliminates injection site adverse events as they are believed to be 
due to low FIX levels because of washout of prior treatment (Figure 
2). 
ADDED: 
The nadir activity after IV plus SC dosing was 20% in both subjects in 
cohort 6 and thereafter levels increased to >30%. It is clear that the 
IV loading dose increased the bioavailability of SC CB2679d by 
increasing the saturation of the extravascular compartment and 
resulted in greater activity levels than simple addition of SC to IV 
activity. Neutralizing antibodies developed in both subjects, 
(transiently in one subject). A root cause analysis determined that the 
most likely cause was a 3-month gap between dosing in cohort 5 and 
cohort 6 in these 2 participants (Figure 3).  
FIGURE 2. CB2679D PHASE 1/2 OPEN LABEL STUDY DESIGN 
FIGURE 3. CB2679D PHASE 1/2 STUDY: COHORT 5 & 6 FIX ACTIVITY 
RESULTS 
4.1 Overall Design 
Updated 
Each subject will participate for approximately 6-weeks of SQ 
CB2679d drug administrations:  
Part 1; Weeks 1 and 2: Each participant will receive an IV loading 
dose of 70 IU/kg followed 35 ± 5 minutes later by a SQ dose of 140 
IU/kg. Daily SQ doses of 140 IU/kg will be administered until Day 14 
(14 total SQ doses). On day 1, PK, PD, and safety assessments will be 
done at pre-IV dose and repeated 30 minutes later prior to the SQ 
dose. Subsequent PK, PD and safety assessments will be performed 
7 hours post-SQ dose on Day 1, Day 2 at hour 24 post-SQ dose and 
pre-dose on days 5, 8, 11 and 14.  
With: 
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Study DLZ-201, Clinical Study Report
Catalyst Biosciences, Inc. 
Final
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Treatment: Day 1 to Day 28: Each participant will receive an IV 
loading dose of 50 IU/kg followed 35 ± 5 minutes later by a SC dose 
of 100 IU/kg. Daily SC doses of 100 IU/kg will be administered until 
Day 28 (28 total SC doses). On day 1, PK, PD, and safety 
assessments will be done at pre-IV dose and repeated 35 (± 5) 
minutes later prior to the SC dose. Subsequent PK, PD and safety 
assessments will be performed pre-dose on days 2, 3, 7, 14, 21 and 
28.  
4.1 Overall Design 
Deletions 
Every Second Day SQ study drug administration  
Part 2; Week 3: The subject will receive a SQ dose every second day 
of 280 IU/kg, starting on Day 15 until Day 21 (total of 4 SQ doses). On 
Day 15 only, PK, PD, and safety assessments will be done at pre-
dose and repeated at hour 7.  Subsequent PK, PD and safety 
assessments will be performed on Day 16 at hour 24 and pre-dose 
on days 17, 19 and 21.  
Every Third Day SQ study drug administration  
Part 3; Weeks 4 and 5: The subject will receive a SQ dose every third 
day of 420 IU/kg, starting on Day 23 until Day 32 (total of 4 SQ 
doses). On days 23 and 32 only, PK, PD, and safety assessments will 
be done at pre-dose and repeated at hour 7.  Subsequent PK, PD, 
and safety assessments will be performed at Day 24 at hour 24 and 
pre-dose on days 26, and 29. 
4.1 Overall Design: Washout Period 
Updated 
Days 33, 34, 35, 37, and 38
With: 
Days 29, 30, 31, 32, and 33 
4.1 Overall Design: Measurements 
Added 
Genotype testing will be performed at screening. 
4.1 Overall Design: Measurements 
Updated 
Immunogenicity assays: Specimens for immunogenicity testing 
(antibody to CB2679d, wild-type FIX cross reactivity, and 
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neutralizing activity) will be drawn at screening, pre-dose on days 
1, 8, 15, 23, 32 and end of study. 
With: 
Immunogenicity assays: Specimens for immunogenicity testing 
(antibody to CB2679d, BeneFIX®, and neutralizing activity) will be 
drawn at screening, pre-dose on days 7, 14, 21, 28 and end of 
study. 
4.6 End of Study Definition 
Updated 
The duration of treatment for each subject is approximately 6 
weeks. 
With: 
The duration of treatment for each subject is approximately 4 weeks 
(28 days). 
5.2 Exclusion Criteria 
Added 
12. FIX mutation 128G>A. 
6.1.2 Dosing and Administration 
Updated 
 
CB2679d loading dose of 70 IU/kg IV, followed 30 minutes later with 
a 140 IU/kg, SQ administration daily x 14 (total 1 IV dose and 14 SQ 
doses); then a 280 IU/kg, SQ administration every second day, 
starting on Day 15 until Day 21 (total 4 SQ doses); then a 420 IU/kg 
SQ every third day, starting on Day 23 until Day 32 (total of 4 SQ 
doses).  
With: 
CB2679d loading dose of 50 IU/kg IV, followed 35 ± 5 minutes later 
with a 100 IU/kg, with SC administration daily until Day 28 (total 1 IV 
dose and 28 SC doses). 
6.4 Study Intervention Compliance 
Updated 
Reasonable efforts should be made to ensure that study drug 
administration is administered according to the schedule.  However, 
if an unavoidable disruption of the administration occurs, and a 
dose is not administered on the assigned day then the subject 
should take the dose as soon as possible. In the event that the 
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subject remembers more than 2 days late, then the subject must 
contact the research site for instructions on how to proceed.  
With: 
Reasonable efforts should be made to ensure that study drug 
administration is administered daily according to the schedule.  
However, if an unavoidable disruption of the administration occurs, 
and a dose is not administered on the assigned day then the 
subject should take the dose as soon as possible. In the event that 
the subject does not take study drug for more than 2 days, then the 
subject must contact the research site for instructions on how to 
proceed prior to administering a dose.  
7.1 Participant 
Discontinuation/Withdrawal from 
Study 
Updated 
Replacement of a subject occurs for the following reason: 
 
If a subject does not complete at least 2 doses of every third day 
SQ dosing as defined in the protocol, another subject may be 
enrolled. 
With: 
Replacement of a subject occurs for the following reason: 
 
If a subject does not complete 21 days of daily SC dosing, as 
defined in the protocol, another subject may be enrolled. 
8.1.1 Study Procedures: Screening 
Additions 
PK: FIX activity 
FIX genotype test 
8.1.2 Study Procedures: Screening 
Updated 
Part 1; Weeks 1 and 2 (Duration 7 days)
With: 
Treatment (Duration 28 days) 
8.1.2.1 Study Procedures: Day 1 Pre-
dose evaluations 
Updated  
Study Subject training on drug administration and injection site 
assessment 
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With: 
Study Subject training on diary entry, drug administration, adverse 
events and injection site assessment 
8.1.2.1 Study Procedures: Day 1 Pre-
dose evaluations 
Deletion 
Review of diary entry of investigational drug administration, 
injection site assessment, adverse events, bleeding episodes & 
treatment  
8.1.2.1 Administration 
Update 
CB2679d administration (Every day from Day 1 to Day 14) 
 
 
Subjects will receive a loading IV dose of 70 IU/kg, followed 
35 ± 5 minutes later with a 140 IU/kg SQ dose of CB2679d  
 
Subjects will then administer a 140 IU/kg daily SQ dose of 
CB2679d 
 
SQ CB2679d should be self-administered by subjects at 
approximately the same time every day.  
With: 
CB2679d administration (Daily from Day 1 to Day 28) 
 
 
Subjects will receive a loading IV dose of 50 IU/kg, followed 
35 ± 5 minutes later with a 100 IU/kg SC dose of CB2679d  
 
Subjects will then administer a 100 IU/kg daily SC dose of 
CB2679d from Day 2 until Day 28 
 
Daily SC dosing of CB2679d should be self-administered by 
subjects at approximately the same time every day.  
 
8.1.2.4 Day 2 and 3 Pre-SC dose 
Addition 
Hematology and chemistry – platelet count only (see Footnote 4 
and 5 in Section 1.3, SOA) 
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8.1.2.4 Day 2 and 3 Pre-SC dose 
evaluations 
 
Updated  
Day 1 Post-SQ dose (Hour 7) and Day 2 Post-SQ dose (Hour 24) 
evaluations 
Blood will be collected at hour 7 post-dose on Day 1 and hour 24 
post-dose on Day 2 for the following evaluations: 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: CB2679d activity  
Other evaluations will include: 
 
Concomitant medications 
 
Vital sign 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Review of diary entry of investigational drug administration, 
injection site assessment, adverse events, bleeding episodes 
& treatment  
 
Adverse events (from Hr 6 to 24 hours) 
With: 
Day 2 and 3 Pre-SC dose evaluations 
Blood will be collected pre-dose on Day 2 for the following 
evaluations: 
 
Hematology and chemistry – platelet count only (see 
Footnote 4 and 5 in Section 1.3, SOA): Day 2 ONLY 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: FIX activity  
Other evaluations will include: 
 
Concomitant medications 
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 
Vital sign 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Review of diary entry of investigational drug administration, 
injection site assessment, adverse events, bleeding episodes 
& treatment  
 
Adverse events 
8.1.2.5 Day 7, 14, 21 and 28 Pre-dose 
evaluations 
Updated 
8.1.2.5 Day 5, 8, 11 and 14 Pre-dose evaluations 
With:  
8.1.2.5 Day 7, 14, 21, and 28 Pre-dose evaluations 
8 Study Assessments 
Deletion of 
Selections 
8.1.3 Part 2, Week 3 (Duration: 7 days) 
8.1.3.1 CB2679d administration (Day 15, Day 17, Day 19, and Day 
21) 
8.1.3.2 Day 15 Pre-dose evaluations 
8.1.3.3 Day 15 Post-dose (Hour 7), Day 16 Post-dose (Hour 24), Day 
17 and Day 19 Pre-dose evaluations 
8.1.3.4 Day 21 Pre-dose evaluations 
8.1.4 Part 3, Weeks 4 and 5 (Duration: 14 days) 
8.1.4.1 CB2679d administration (Day 23, Day 26, Day 29, and Day 
32) 
8.1.4.2 Day 23 and Day 32 Pre-dose evaluations 
8.1.4.3 Day 23 Post-dose evaluations (Hour 7) 
8.1.4.4 Day 24 Post-dose (Hour 24) and Day 26 and Day 29 Pre-dose 
evaluations 
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8.1.4.5 Day 32 Post-dose evaluations (Hour 7) 
8.1.5 Washout period evaluations 
Updated 
8.1.5.1 Washout period evaluations (Days 33, 34, 35, 37, and 38) 
With: 
8.1.3.1 Washout period evaluations (Days 29, 30, 31, 32, and 33) 
8.2.1 Efficacy Assessments 
Updated 
All ongoing conditions and relevant medical and hemophilia history 
(including all major hospitalizations and surgeries), as well as the 
subject’s current medical status will be recorded at the screening 
visit.   
With: 
All ongoing conditions and relevant medical and hemophilia history 
(including all major hospitalizations and surgeries), as well as the 
subject’s current medical status and genotype will be recorded at 
the screening visit.   
8.2.4 Hematology 
Added 
Genotype test will be performed at screening. 
9.1 Study Hypothesis 
Updated 
The dose required to achieve steady-state levels >12%, >30% and 
>50% will be reported for daily, every second day and every third 
day dosing, including 95% confidence intervals. 
With: 
The dose required to achieve steady-state levels >12% will be 
reported for daily dosing, including 95% confidence intervals. 
9.1 Study Hypothesis 
Updated 
Primary Endpoint 
The primary endpoint will include: 
 
Number of subjects who achieve a steady-state FIX activity level 
above 12%, 30% and 50% with daily, every second day or every 
third day dosing. 
With: 
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Primary Endpoint 
The primary endpoint will include: 
Number of subjects who achieve a steady-state FIX activity level 
above 12% with daily dosing. 
9.1 Study Hypothesis 
Deletion 
Feasibility of using an adjusted-dose SQ prophylaxis treatment 
regimen clinically. 
9.2 Sample Size Determination 
Updated 
5 subjects are sufficient to provide guidance on range of dose 
required to achieve steady-state activity 12%, >30% or >50% and 
starting SQ dose for subsequent studies.  
With: 
6 subjects are sufficient to provide guidance on range of dose 
required to achieve steady-state activity >12% and starting SC dose 
for subsequent studies.  
9.3 Populations for Analyses 
Updated  
Efficacy/PD population: any patient who receives at least one week 
of dosing and PK specimens obtained 
With: 
Efficacy/PD population: any patient who receives at least one week 
of daily SC dosing and PK specimens obtained. 
9.4.2 Analysis of Primary Efficacy 
Endpoint(s) 
Updated 
Number of subjects who achieve a steady-state FIX activity level 
above 12%, 30% and 50% with daily, every second day or every 
third day dosing. 
With: 
Number of subjects who achieve a steady-state FIX activity level 
above 12% with daily dosing. 
10.2 Protocol Amendment History 
Updated 
2.0, Amendment 1, 17 October 2018 
Appendix B: Detailed Study Schema 
Updated 
Updated Schema according to changes 
 
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        17 October 2018 
 
 
Administrative changes: Minor changes involving grammar, wordsmithing, punctuation, and other editorial changes have been 
made throughout the document. All are clearly identified in the track-changes version of the amendment. 
 
 
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ABBREVIATIONS 
 
% 
Percent 
ADL 
Activities of daily living 
AE 
Adverse event 
AESI 
Adverse Events of Special Interest 
ALT 
Alanine aminotransferase 
aPTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
ATIII 
Anti-thrombin III 
AUC 
Area under the curve 
AUC0-inf 
Area under the curve from time 0 to the last measurable concentration 
AUC0-t 
Area under the curve-time curve 
CAD 
Coronary artery disease 
CB2679d 
Recombinant Factor IX variant 
CBC 
Complete blood count 
CD4 
Cluster of differentiation 4 
CFR 
Code of Federal Regulations 
Cmax 
Concentration maximum 
CMO 
Chief Medical Officer 
Cr 
Creatinine 
CRF 
Case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
dL 
Deciliter 
DVT 
Deep venous thrombosis 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
eCRF  
Electronic Case Report Forms  
F1+2 
Prothrombin fragment 1+2 
FDA 
Food and Drug Administration 
FVIII 
Factor VIII 
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FVIIIa 
Factor VIII activated 
FIX 
Factor IX 
FIXa 
Factor IX activated 
FX 
Factor X 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transpeptidase 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GS 
Gilbert’s syndrome 
Hr 
Hour 
HTC 
Hemophilia Treatment Centre  
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IDE 
Investigational Device Exemption 
IEC 
Independent Ethics Committee 
IMT 
Immunomodulatory therapy 
IND 
Investigational New Drug Application 
IP 
Investigational product 
IRB 
Institutional Review Board 
IU 
International unit 
IV 
Intravenous 
Kg 
Kilogram 
L 
Liter 
LLN 
Lower limit of normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Myocardial Infarction 
Min 
Minute 
NCT 
National Clinical Trial 
OTC 
Over-the-counter 
PD 
Pharmacodynamics 
pdFIX 
Plasma-derived factor IX 
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PE 
Pulmonary embolism 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PT 
Prothrombin time 
QA 
Quality Assurance 
QC 
Quality Control 
QoL 
Quality of life 
r 
Recombinant 
rFIX 
Recombinant factor IX  
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SOA 
Schedule of Activities 
SOC 
Standard of Care 
SOP 
Standard Operating Procedure 
T1/2 
Half-life 
TAT 
Thrombin-antithrombin complexes 
TBIL 
Total bilirubin level 
TE 
Thromboembolic event 
TEAE 
Treatment-emergent adverse event 
TGA 
Therapeutic Goods Administration 
Tmax 
Time that studied drug is present at the maximum concentration in serum 
µmol 
Micromole 
ULN 
Upper limit of normal 
US 
United States 
VTE 
Venous thromboembolic event 
WFH 
World Federation of Hemophilia 
 
 
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TABLE OF CONTENTS 
Contents 
INVESTIGATOR SIGNATURE PAGE ................................................................................................ 2 
SPONSOR SIGNATURE PAGE ........................................................................................................ 3 
DETAILED SUMMARY OF PROTOCOL CHANGES ....................................................................... 4 
ABBREVIATIONS ........................................................................................................................... 19 
TABLE OF CONTENTS ................................................................................................................... 22 
1.  
PROTOCOL SUMMARY ....................................................................................................... 26 
1.1  
SYNOPSIS ........................................................................................................................................................ 26 
1.2  
SCHEMA .......................................................................................................................................................... 30 
1.3  
SCHEDULE OF ACTIVITIES (SOA) ........................................................................................................................... 31 
2. INTRODUCTION ........................................................................................................................ 32 
2.1 
STUDY RATIONALE ................................................................................................................................................. 32 
2.2 
BACKGROUND ....................................................................................................................................................... 32 
2.2.1 
Rationale for Prophylaxis with SC Administration of FIX ........................................................................... 33 
2.2.2 
Experience with CB2679d in the Clinic ...................................................................................................... 34 
3.  
OBJECTIVES .......................................................................................................................... 37 
3.1  
PRIMARY ......................................................................................................................................................... 37 
3.2  
SECONDARY ..................................................................................................................................................... 37 
4.  
STUDY DESIGN ...................................................................................................................... 38 
4.1 
OVERALL DESIGN ................................................................................................................................................... 38 
4.2  
END OF STUDY DEFINITION .................................................................................................................................. 39 
5.  
STUDY POPULATION ............................................................................................................ 41 
5.1 
INCLUSION CRITERIA ............................................................................................................................................... 41 
5.2 
EXCLUSION CRITERIA .............................................................................................................................................. 41 
5.3  
LIFESTYLE CONSIDERATIONS ................................................................................................................................. 42 
5.4  
SCREEN FAILURES .............................................................................................................................................. 42 
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6.  
STUDY INTERVENTION .......................................................................................................... 43 
6.1  
STUDY INTERVENTION(S) ADMINISTRATION ............................................................................................................. 43 
6.1.1  
Study Intervention Description ................................................................................................................. 43 
6.1.2  
Dosing and Administration ...................................................................................................................... 43 
6.2  
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY .............................................................................. 44 
6.2.1  
Acquisition and Accountability ................................................................................................................. 44 
6.2.2  
Product Storage and Stability ................................................................................................................... 44 
6.2.3  
Preparation .............................................................................................................................................. 45 
6.3  
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING ................................................................................. 46 
6.4  
STUDY INTERVENTION COMPLIANCE ...................................................................................................................... 46 
6.5  
CONCOMITANT THERAPY .................................................................................................................................... 46 
7.  
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................................ 47 
7.1  
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY .............................................................................. 47 
7.2  
LOST TO FOLLOW‐UP ......................................................................................................................................... 47 
8.  
STUDY ASSESSMENTAND PROCEDURES ............................................................................ 49 
8.1  
STUDY PROCEDURES .......................................................................................................................................... 49 
8.1.1  
Screening ................................................................................................................................................. 49 
8.1.2  
Treatment (Duration 28 days) .................................................................................................................. 50 
8.1.3  
Washout Period, Unscheduled Visits and End of Study evaluations .......................................................... 52 
8.2  
STUDY ASSESSMENTS ......................................................................................................................................... 54 
8.2.1  
Efficacy Assessments................................................................................................................................ 54 
8.2.2  
Physical Examination ............................................................................................................................... 55 
8.2.3  
Vital signs ................................................................................................................................................ 55 
8.2.4  
Hematology ............................................................................................................................................. 55 
8.2.5  
Chemistry ................................................................................................................................................. 55 
8.2.6  
Coagulation assays .................................................................................................................................. 55 
8.2.7  
Thrombogenicity markers ........................................................................................................................ 56 
8.2.8  
Immunogenicity Assays ............................................................................................................................ 56 
8.2.9  
Pharmacokinetic Sampling ....................................................................................................................... 56 
8.2.10  
Clinical signs of thrombosis (Appendix A) ............................................................................................ 56 
8.2.11  
Concomitant medications .................................................................................................................... 56 
8.2.12  
ECG ..................................................................................................................................................... 56 
8.3  
SAFETY AND OTHER ASSESSMENTS ........................................................................................................................ 57 
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8.3.1  
AEs and SAEs ............................................................................................................................................ 57 
8.3.2  
Injection site reactions ............................................................................................................................. 57 
8.4  
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS .................................................................................................... 57 
8.4.1  
Definition of Adverse Events (AE) ............................................................................................................. 57 
8.4.2  
Definition of Serious Adverse Events (SAE) ............................................................................................... 57 
8.4.3  
Classification of an Adverse Event ............................................................................................................ 58 
8.4.4  
Time Period and Frequency for Event Assessment and Follow‐Up ............................................................ 59 
8.4.5  
Adverse Event Reporting .......................................................................................................................... 60 
8.4.6  
Serious Adverse Event Reporting .............................................................................................................. 62 
8.4.7  
Adverse Events of Special Interest (AESIs) ................................................................................................ 63 
8.4.8  
Reporting of Pregnancy ........................................................................................................................... 63 
9.  
STATISTICAL CONSIDERATIONS .......................................................................................... 65 
9.1 
STUDY HYPOTHESIS ................................................................................................................................................ 65 
9.2 
SAMPLE SIZE DETERMINATION .................................................................................................................................. 66 
9.3 
POPULATIONS FOR ANALYSES ................................................................................................................................... 66 
9.4 
STATISTICAL ANALYSIS ............................................................................................................................................. 66 
9.4.1 
General Approach .................................................................................................................................... 66 
9.4.2  
Analysis of the Primary Efficacy Endpoint(s) ............................................................................................. 67 
9.4.3  
Analysis of the Secondary Endpoint(s) ...................................................................................................... 67 
9.4.4  
Safety Analysis ......................................................................................................................................... 67 
9.4.5  
Baseline Descriptive Statistics .................................................................................................................. 68 
9.4.6  
Planned Interim Analyses ......................................................................................................................... 68 
9.4.7  
Sub‐Group Analyses ................................................................................................................................. 68 
9.4.8  
Tabulation of Individual Participant Data ................................................................................................ 68 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ...................... 69 
10.1 REGULATORY, ETHICAL AND STUDY OVERSIGHT CONSIDERATIONS ...................................................................................... 69 
10.1.1 
 Informed Consent Process .................................................................................................................. 69 
10.1.2  
Institutional Review Board/Independent Ethics Committee ................................................................. 69 
10.1.3  
Study Discontinuation and Closure ...................................................................................................... 70 
10.1.4  
Confidentiality and Privacy .................................................................................................................. 70 
10.1.5  
Future Use of Stored Specimens and Data ........................................................................................... 71 
10.1.6  
Clinical Monitoring .............................................................................................................................. 71 
10.1.7  
Quality Assurance (QA) and Quality Control (QC) ................................................................................ 72 
10.1.8  
Data Handling and Record Keeping ..................................................................................................... 72 
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10.1.9  
Protocol Amendments ......................................................................................................................... 73 
10.1.10  
Publication and Data Sharing Policy .................................................................................................... 73 
10.2  
PROTOCOL AMENDMENT HISTORY ........................................................................................................................ 74 
11.  
REFERENCES ..................................................................................................................... 75 
APPENDICES ................................................................................................................................ 79 
APPENDIX A – CLINICAL SIGNS OF THROMBOSIS ..................................................................................................................... 79 
APPENDIX B – DETAILED STUDY SCHEMA ............................................................................................................................. 88 
 
 
 
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1.  
PROTOCOL SUMMARY 
 
1.1  
SYNOPSIS 
Title of Study: Phase 2b study to evaluate the pharmacokinetics, pharmacodynamics, 
efficacy and safety of a subcutaneous prophylaxis treatment regimen of CB2679d in 
adult subjects with hemophilia B 
Primary Objective: To evaluate the dose required to achieve a steady-state of >12% 
factor IX (FIX) levels.  
Secondary Objectives:  
 To determine the pharmacokinetics (PK) of a subcutaneous (SC) regimen of CB2679d. 
 To determine the pharmacodynamics (PD) of a SC regimen of CB2679d. 
 To evaluate the levels of thrombogenicity markers of a SC regimen of CB2679d. 
 To evaluate for evidence of the development of antibodies to CB2679d and to 
determine if these are neutralizing antibodies. 
 To monitor and evaluate safety parameters of SC regimens of CB2679d. 
Study Population: Six male subjects, aged 18 or older, with confirmed diagnosis of severe 
congenital hemophilia B (<2% FIX level). 
Phase of Development:  Phase 2b 
Description of Sites: Single center study. 
Study Duration: Approximately 6 months. 
Participant Duration: The duration of treatment for each subject is approximately 4 weeks 
(28 days).   
Screening: Up to 4 weeks. 
Study Drug Administration: SC prophylaxis treatment regimens over a 4-week period with 
the goal to achieve steady-state levels above 12% FIX activity when dosed daily. 
Note: Where interruptions to study drug dosing days occur, study duration may be 
extended to incorporate full dosing schedule. 
Follow-up: 30 days (± 2 days) after last dose for PK/PD/safety follow-up. 
Study Methodology 
This single-center, open-label Phase 2b study will evaluate the PK, PD, efficacy and safety 
parameters of SC prophylaxis treatment regimens with CB2679d in adult subjects with 
hemophilia B. The study will enroll and dose subcutaneously, a total of 6 adult male 
subjects with severe congenital hemophilia B.  
At the screening visit and prior to any study procedures, subjects will sign an informed 
consent form (ICF).  Eligibility to participate in the study will be determined by inclusion 
and exclusion criteria elicited from medical history, hemophilia history, physical 
examination, laboratory assessments and an electrocardiogram (ECG). The screening 
period duration may be up to 4 weeks. 
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At enrollment, subjects will be provided with a diary in which they will be instructed to 
record any adverse events (AEs) and concomitant medication.   
After the initial intravenous (IV) dose of CB2679d, and with subsequent SC doses, the 
following will be monitored daily: injection site reaction, any AEs the subject may 
experience, and any bleeding episodes (location, inciting event if not spontaneous, and 
treatment administered). 
IV/SC Study Drug Administration and Assessments: 
Initial IV Load Dose Followed by Daily SC Study Drug Administration  
Treatment: Day 1 to Day 28: The subject will receive an IV loading dose of 50 IU/kg 
followed 35 ± 5 minutes later by a SC dose of 100 IU/kg. Daily SC doses of 100 IU/kg will be 
administered until Day 28 (28 total SC doses). On Day 1, PK, PD, and safety assessments 
will be done at pre-IV dose and repeated 35 (± 5) minutes later prior to the SC dose. 
Subsequent PK, PD and safety assessments will be performed pre-dose on days 2, 3, 7, 14, 
21 and 28.  
Washout Period 
PK, PD, and safety assessments will be done on Days 29, 30, 31, 32 and 33. Daily FIX 
activity levels will be measured, unless FIX activity level is known to be < 5%, as measured 
by local laboratory. 
An End of Study visit will occur 30 days (± 2 days) after the last dose of study drug. 
Treatment of a bleeding episode: Subjects will self-administer their currently prescribed FIX 
replacement product for treatment of any spontaneous or traumatic bleed that occurs 
while on study drug.  If treatment for a breakthrough spontaneous bleeding episode is 
needed, then subjects will contact the clinical investigative team immediately to report 
the event; treatment dose administered; and arrange for an urgent follow-up visit to the 
study site for additional evaluation and laboratory testing, if needed.   
Dose interruption: SC study drug injections will be interrupted if any of the following 
occurs: a thrombotic event; clinical evidence of inhibitor formation; or laboratory results 
suggesting a high titer antibody may be developing; trough activity levels >80%, where 
subsequent dosing will be determined in consultation with the sponsor. 
Surgery: If there is an urgent need for a surgical procedure or an event requiring 
extended (>48 hours) hospitalization, a FIX activity level will be urgently obtained and 
measured prior to the event, and the PI will confer with the Sponsor Medical 
representative regarding the need for any additional treatment and whether study drug 
requires interruption.   
Measurements:   
PK, PD, and safety assessments: FIX activity levels, as well as fibrinogen, D-dimer, 
prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complexes (TAT). PT and 
aPTT will be measured at screening and end of study visit only. Genotype testing will be 
performed at screening.  
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Immunogenicity assays: Specimens for immunogenicity testing (antibody to CB2679d, 
BeneFIX®, and neutralizing activity) will be drawn at screening, on days 7, 14, 21, 28 and 
end of study. 
If the FIX activity level decreases unexpectedly by more than 25%, ie, IU/dL, as measured 
by the central or local lab, if applicable, FIX activity levels will be drawn for analysis within 
24 hours and immediately sent to the central laboratory.  Specimens for fibrinogen, D-
dimer, F1+2, and TAT and immunogenicity testing will also be drawn. 
Number of planned subjects: 6 
Trial population: 
Inclusion criteria: 
1. Confirmed diagnosis of severe (<2%) congenital hemophilia B. 
2. Male, age 18 or older. 
3. Agreement to use highly effective birth control throughout the study.  
4. Affirmation of informed consent with signature confirmation before any trial-
related activities. (Trial related activities are any procedure that would not have 
been performed during normal clinical management of the subject). 
5. Stated willingness to comply with all study procedures and availability for the 
duration of the study.  
Exclusion criteria: 
1. Patients with a history or a family history of FIX inhibitors. 
2. Positive antibody to FIX detected by central laboratory at screening. 
3. Previous participation in and subsequent treatment in a clinical trial within the 
previous 30 days or 3-half-lives, whichever is longer, or absence of clinical effect.  
4. History of clinically relevant coagulation disorders other than congenital 
hemophilia B including Factor V Leiden or other identified activated Protein C 
resistance. 
5. Platelet count <100,000 based on screening laboratory assessments. 
6. Advanced atherosclerotic disease (ie, known history of coronary artery disease 
(CAD), ischemic stroke, etc.), or known deep venous thrombosis (DVT) or 
considered to be at a high risk of venous thromboembolic event (VTE) as judged 
by the Investigator. 
7. Known or suspected allergy to trial product or related products. 
8. Known absolute cluster of differentiation 4 (CD4) count <200 cells/μL. 
9. Receiving immunomodulatory therapy (IMT). 
10. Compromised hepatic or renal function: 
o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels 
≥5 times the upper limit of normal (ULN) 
o Total bilirubin level (TBIL) ≥2 mg/dL (>35 µmol /L) unless there is a known 
history of Gilbert’s syndrome (GS) 
o Serum albumin ≤ the lower limit of normal (LLN) 
o Serum creatinine (Cr) level >1.25 x ULN   
11. Inability or medical, psychosocial, or familial issues that might prevent full 
participation and cooperation with the procedures and requirements of the 
clinical trial as determined by the potential subject and physician investigator. 
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12. Factor IX gene mutation 128G>A. 
Investigational product, dose, and mode of administration:  
Investigational Product: Recombinant FIX variant; CB2679d  
Dosage and mode of administration:  
IV loading dose of 50 IU/kg, followed 35 ± 5 minutes later with 100 IU/kg SC administration, 
then daily SC administration until Day 28 (28 total SC doses). 
Reference therapy: None 
Concomitant Medications: In the event of spontaneous or traumatic bleeding, treatment 
for a bleeding episode will be permitted using the subject’s current treatment regimen. 
Efficacy and Safety Evaluations 
Primary endpoints: 
 
Number of subjects who achieve a steady-state FIX activity level above 12% with daily 
dosing. 
Secondary endpoints: 
 
Safety assessments: Occurrence of antibody formation resulting in a decreased 
endogenous level of FIX; occurrence of a clinical thrombotic event not attributable to 
another cause. 
 
Occurrence of a conformed antibody response with high titer to CB2679d and 
whether it is inhibitory and cross-reactive to BeneFIX®.   
 
Change in FIX activity levels, and from pre-dose. 
 
Clinically significant levels of thrombogenicity markers resulting from SC administration 
of CB2679d.  
Statistics 
Primary Analysis Plan:  
Appropriate descriptive statistics of all measured parameters will be reported, including 
95% confidence intervals. 
The dose required to achieve steady-state levels >12% will be reported for daily dosing, 
including 95% confidence intervals. 
Rationale for Number of Subjects: 
6 subjects will provide guidance on dose required to achieve steady-state activity >12% 
and starting SC dose for subsequent studies. 
Name of sponsor: Catalyst Biosciences 
 
 
 
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Catalyst Biosciences, Inc. 
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1.2  
SCHEMA 
FIGURE 1. SCHEMATIC OF STUDY DESIGN 
 
 
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1.3  
SCHEDULE OF ACTIVITIES (SOA) 
 
Study Period 
Screening 
Treatment Period 
Wash-out8 
Unscheduled 
Visit 
End of 
Study9 
Study Day 
Day -28 to 
-1 
Day 1, IV 
Pre-dose 
(-5 min) 
Day 1, SC 
dose, 35 
(±5) min 
Post IV 
Day 2  
Day 3  
Day 7 
(+ 1 
day) 
Day 14 
(+ 1 
day) 
Day 21 
(+ 1 
day) 
Day 28 
(+ 1 
day) 
Days 29, 
30, 31, 32, 
33 
 
 
Informed Consent  
X 
 
 
 
 
 
 
 
 
 
 
 
Demographic Parameters 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical and Hemophilia History2 
X 
 
 
 
 
 
 
 
 
 
X 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Height (screening only) & 
Weight 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
Physical Examination2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Clinical Signs of Thrombosis3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology and Chemistry4 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
X 
Coagulation Assays5 
X 
 
 
 
 
 
 
 
 
 
 
X 
Thrombogenicity Markers5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic Sampling5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity Assays5 
X 
 
 
 
 
X 
X 
X 
X 
 
X 
X 
Genotyping 
X 
 
 
 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
Diary entry training6 
 
X 
 
 
 
 
 
 
 
 
 
 
Diary entry of any bleeding 
episodes, AEs, injection site 
reactions6 
 
 
 
----------------------------------------------------------------------------------------------------------------------------------------- 
Adverse Events 
X 
 
------------------------------------------------------------------------------------------------------------------------------------------------------------ 
Concomitant Medications 
X 
 
------------------------------------------------------------------------------------------------------------------------------------------------------------ 
CB2679d7 Administration8 
 
 
X 
 
------------------------------------------------------------------ 
 
 
 
1. 
As per Standard of Care at hemophilia treatment center. 
2. 
Complete evaluation at Screening followed by interim targeted evaluation, per Investigator’s discretion, as indicated on presentation of subject at study visit. Joint 
evaluation will be performed at Screening.  
3. 
Clinical Signs of Thrombosis per protocol 
4. 
Local Laboratory: Hematology - CBC and platelet count.  Chemistry - Sodium, potassium, chloride, bicarbonate, hepatic enzymes (ALT, AST, GGT), bilirubin, albumin, 
creatinine.  For Days 2, 3, 7, 14, 21, and 28, blood will be collected at Pre-dose (- 5 minutes). 
5. 
Central Laboratory:  Coagulation assays – PT and aPTT.  Thrombogenicity markers – Fibrinogen, D-dimer, F1+2, and TAT.  Pharmacokinetics – FIX activity.  Immunogenicity 
assays – to CB2679d and BeneFIX®. For Days 2, 3, 7, 14, 21, and 28, blood will be collected at Pre-dose (- 5 minutes). 
6. 
Diary entry training and entry consists of investigational drug administration, injection site assessment, adverse events, any bleeding episodes & treatment. 
7. 
IV load dose (50 IU/kg) followed by SC dose (100 IU/kg) 30 minutes (+ 30 mins) after.  Daily SC (100 IU/kg) dosing until Day 28 (28 total SC doses). 
8. 
Daily FIX activity levels needed unless FIX activity level known to be < 5%, as per local lab. 
9. 
End of Study Visit will occur 30 + 2 days after the last dose. 
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2. INTRODUCTION 
 
2.1 STUDY RATIONALE 
 
The rapid clearance of FIX necessitates frequent intravenous (IV) administrations 
to achieve effective prophylaxis for patients with hemophilia B. Subcutaneous 
(SC) administration, a preferred administration route, has historically been limited 
by low bioavailability and potency. CB2679d, formerly known as ISU304, was 
developed using a rational design approach to be the next-generation SC 
coagulation prophylactic FIX therapy.  
2.2 BACKGROUND 
 
Hemophilia B, or sometimes referred to as Christmas disease, is a hereditary X 
chromosomal-linked recessive bleeding disorder caused by Factor IX (FIX) 
deficiency.1 Hemophilia B, especially in severe phenotypes, is characterized by 
frequent and spontaneous bleeding1,2 into joints, muscles and body cavities, and 
can lead to arthropathy with progressive cartilage damage, chronic pain, 
disability, diminished quality of life (QoL) and ultimately joint destruction.1 Disease 
classification of mild (factor activity >5 % and <40%), moderate (1 to 5%) or severe 
phenotype (<1%) is based on residual plasma FIX levels.3,4 The number of patients 
with mild, moderate and severe phenotypes of hemophilia B is not well 
established, however community studies have estimated that 60–70% of patients 
with hemophilia B have a moderate or severe form.5-7 Historically, treatment for 
hemophilia B has been on demand, that is, clotting FIX replacement therapy 
administered when a hemorrhage occurs or before a surgical procedure.8 
Currently, the standard of care treatment for hemophilia B is FIX replacement 
therapy administered prophylactically, at regular intervals to maintain FIX levels 
greater than 1%, to prevent the onset of bleeding episodes.8-11 Routine prophylaxis 
therapy has been demonstrated to substantially reduce the frequency of 
bleeding episodes11-13, prevent joint diseases11,14 and even reduce the risk of 
death. 15,15 Treatment with FIX products, initially purified from plasma-derived factor 
IX product (pdFIX) and subsequently as recombinant human FIX (rFIX), require 2 or 
3 IV infusions per week to achieve effective bleeding prevention due mostly to the 
half-life (t1/2)17-20, rFIX has a t1/2 of approximately 18 hours.21 High frequency of 
infusions can be a major barrier to adhering to the prescribed prophylactic 
regimen, especially in pediatric patients; in those with poor venous access22-24; and 
in those concerned about the associated complications of infection and 
thrombosis.25-27 A FIX product with a longer t1/2 to prolong the protective 
hemostatic effect, would potentially enable fewer injections, thereby reducing 
the need for repeated venous access. This could potentially improve the 
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acceptance of prophylactic regimens by patients with hemophilia. SC 
administration is the preferred route of administration for convenience and less 
pain but has been limited historically by low bioavailability and potency of the 
marketed FIX products.28  
 
2.2.1 Rationale for Prophylaxis with SC Administration of FIX 
 
There is currently no cure for hemophilia.29 The prevention of bleeding episodes in 
hemophilia patients requires life-long prophylaxis.29,30 Due to the short t1/2 of rFIX, 
prophylaxis and treatment for bleeding episodes requires frequent IV dosing (2-3 
IV infusions per week).17-21 IV dosing often requires a medical professional or family 
member to perform the venipuncture, making home prophylaxis cumbersome, 
particularly for pediatric patients.30,31 Other challenges include patient 
adherence, and reliable IV access.32,33 IV administration requires direct 
venipuncture or sterile entry into a central venous access device on a regular 
basis, which makes it time-consuming and negatively influences adherence.32 
SC administration presents a major advantage over IV administration because it 
enables at-home injection, improves quality of life, and reduces health care 
costs.33 While home IV administration has been essential to the provision of 
comprehensive hemophilia care, it nonetheless remains a significant barrier.32 SC 
dosing allows improved ease of self-administration and obviates the need for 
home nursing or a visit to a hemophilia center to provide an IV infusion when a 
patient or a family member has not been able to do so.33  
CB2679d, a novel rFIX variant, is being developed by Catalyst Biosciences (the 
Sponsor) to address the unmet need for medical management of hemophilia B 
patients.  CB2679d was developed using a rational design approach with three-
point mutations in two loops within the FIX protein: (1) arginine-318 is transformed 
into tyrosine (Arg318Tyr) located in ‘loop-150’(also known as the autolysis loop), 
can stabilize the activation structure of activated FIX (FIXa), as well as directly 
interact with factor X (FX), a substrate of FIX and anti-thrombin III (ATIII), a key 
inhibitor; (2) arginine-338 is transformed into glutamic acid (Arg338Glu); and (3) 
threonine-343 is transformed into arginine (Thr343Arg), both located in ‘loop-170’, 
can significantly enhance affinity to the cofactor VIII and stabilize FIXa. These 
mutations in the molecular structure enable CB2679d to increase catalytic activity 
(CB2679d has demonstrated 3 times the catalytic efficiency to factor X 
[substrate]); increase affinity for activated factor VIII (FVIIIa) (CB2679d has a 10 
times higher affinity to cofactor FVIIIa) and improve resistance to inhibition by ATIII 
(CB2679d has 15 times the resistivity to inhibitor ATIII compared to wild-type FIX), 
with a resultant 20-fold enhanced potency in vitro (clotting activity) and in vivo 
(tail clip model) and 8-fold increased duration of aPTT activity in vivo compared 
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with recombinant wild-type FIX dosed at the same mass.34-35 The SC half-life in mini-
pig studies was found to be 33 hours and the bioavailability was 20-42%.36  
These qualities are expected to prolong the interval between doses, improve 
convenience of treatment, and facilitate use of the product for bleeding 
prophylaxis. 
 
2.2.2 Experience with CB2679d in the Clinic 
 
To date, the safety, PK, and PD of CB2679d, is being evaluated in an open-label 
IV to SC cross-over clinical study (NCT03186677), which will recruit 12 adult subjects 
with hemophilia B (all male).37,38 The trial design is provided below. IV PK (antigen 
and activity) was sampled at pre-dose, 0, 0.25, 0.5, 1, 3, 6, 9, 24, 48 and 72 hours. 
SC PK was sampled at pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours. Cohort 5 
has PK sampled before each injection, 6 hours after first and 6th injection and 24 
hours after 6th daily injection. Hematology, chemistry and coagulation was 
measured at Seoul Clinical Laboratories (Yongin-si, South Korea). FIX antigen and 
FIX activity, anti-drug antibody to BeneFIX® and CB2679d and neutralizing 
antibody were measured at Haematologic Technologies Inc (Essex Junction, VT). 
A safety follow-up was done 2 weeks after last visit. FIX antigen was measured 
using VisuLizeTM Factor IX Antigen KitAG (Affinity Biologicals, Inc, Ancaster, ON, 
Canada) and FIX activity was measured using a one-stage clotting assay using 
ACL TOP 700 and Instrumentation Laboratories (Bedford, MA) reagents. The 
calculation of area under the curve (AUC) was based on the trapezoidal rule. To 
calculate the additional AUC from time 0 to the last measurable concentration 
(AUC0-inf), the log-linear regression line for the last three-time points was fit and 
extrapolated to the x-intercept. The calculation of t1/2 was based on the use of 
Demitasse 2000 (version 1.1.3, M. Lee, 2000) which uses an iterative piecewise 
fitting algorithm based on a robust (M-regression) log-linear model. All activity 
data were adjusted for baseline before analysis, assuming exponential falloff after 
IV administration and a t1/2 of 20 hours. Bioavailability was calculated from the 
AUC-time curve (AUC0-t) for the IV and SC data using FIX activity data. 
Subject safety was reviewed by an external Data Safety Monitoring Board and 
also an internal Data Monitoring Committee. 
Interim results showed PK and activity of CB2679d as 22-fold greater potency over 
BeneFIX® and longer mean residence time. Single-dose bioavailability was 18.2-
23.6%, SC beta t1/2 was 66-103 hours and time that CB2679d is present at the 
maximum concentration in serum (Tmax) was 6-24 hours. One subject reported 
transient fever and a mild SC injection site reaction. Cohort 4 was omitted as 
sufficient data had been gained from single dosing SC in Cohorts 2 and 3. The SC 
dose in Cohort 5 was reduced from 300 IU/kg to 150 IU/kg daily. PK and activity 
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levels after 6 daily doses in 5 subjects reached a median of 15.7% [interquartile 
range 14.9% to 16.6%] Four of 5 subjects had levels above 12%. Half-life was 63.2 
hours [interquartile range 60.2 to 64.0 hours]. The interim study results support the 
aim of achieving normal or high mild hemophilia FIX levels in individuals with 
hemophilia B with repeated SC dosing. Mild pain, erythema and redness was 
reported at the injection site in initial injections and not a later injection. One 
subject reported these adverse events to be moderate for the first 2 injections and 
mild thereafter. An IV loading dose has been added to cohort 6 in this study to see 
if it eliminates injection site adverse events as they are believed to be due to low 
FIX levels because of washout of prior treatment (Figure 2). 
The nadir activity after IV plus SC dosing was 20% in both subjects in cohort 6 and 
thereafter levels increased to >30%. It is clear that the IV loading dose increased 
the bioavailability of SC CB2679d by increasing the saturation of the extravascular 
compartment and resulted in greater activity levels than simple addition of SC to 
IV activity. Neutralizing antibodies developed in both subjects (transiently in one 
subject). A root cause analysis determined that the most likely cause was a 3-
month gap between dosing in cohort 5 and cohort 6 in these 2 participants (Figure 
3).  
FIGURE 2. CB2679D PHASE 1/2 OPEN LABEL STUDY DESIGN 
 
IV, intravenous; SC, subcutaneous. 
aFirst SC dose 30 minutes post-IV. 
 
 
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FIGURE 3. CB2679D PHASE 1/2 STUDY: COHORT 5 & 6 FIX ACTIVITY RESULTS 
 
FIX, factor IX; IV, intravenous; SC, subcutaneous. 
 
 
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3.  
OBJECTIVES  
 
3.1  
PRIMARY  
 
The primary objective is: 
 
To evaluate the dose required to achieve steady-state FIX levels >12% of a SC 
prophylaxis treatment regimen of CB2679d, in adult subjects with hemophilia 
B. 
 
3.2  
SECONDARY 
 
The secondary objectives are: 
 To determine the PK of a SC regimen of CB2679d. 
 To determine the PD of a SC regimen of CB2679d. 
 To evaluate the levels of thrombogenicity markers of a SC regimen of 
CB2679d. 
 To evaluate for evidence of the development of antibodies to CB2679d and 
to determine if these are neutralizing antibodies. 
 To monitor and evaluate safety parameters of a SC regimen of CB2679d. 
 
 
 
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4.  
STUDY DESIGN 
  
4.1 
OVERALL DESIGN 
 
This is a single-center, open-label Phase 2b study designed to evaluate the PK, 
PD, efficacy and safety of SC prophylaxis treatment regimens with CB2679d in 
adult subjects with hemophilia B. It is an open-label study, so subjects and 
members of the clinical study team will not be blinded to treatment. It is 
estimated that it will take approximately 6 months from when the study opens 
enrollment until completion of last patient last visit. The study will enroll a total of 6 
adult male subjects with severe congenital hemophilia B. Participants will be 
given SC prophylaxis CB2679d regimens over a 4-week period, with the goal to 
achieve steady-state levels above 12% FIX activity when dosed daily. 
Each subject will participate for approximately 4-weeks (28 days) of SC CB2679d 
drug administrations:  
Treatment: Day 1 to Day 28: Each participant will receive an IV loading dose of 
50 IU/kg followed 35 ± 5 minutes later by a SC dose of 100 IU/kg. Daily SC doses 
of 100 IU/kg will be administered until Day 28 (28 total SC doses). On day 1, PK, 
PD, and safety assessments will be done at pre-IV dose and repeated 35 (± 5) 
minutes later prior to the SC dose. Subsequent PK, PD and safety assessments will 
be performed pre-dose on days 2, 3, 7, 14, 21 and 28.  
Washout Period 
PK, PD, and safety assessments will be done on Days 29, 30, 31, 32 and 33. Daily 
FIX activity levels will be measured, unless FIX activity level is known to be < 5% as 
measured by local laboratory. 
An End of Study visit will occur 30 days (± 2 days) after the last dose of study drug. 
Subjects will sign an ICF at the Screening Visit, prior to any study procedures. 
Eligibility to participate in the study will be determined by inclusion and exclusion 
criteria from medical history, hemophilia history, laboratory investigations and 
ECG. The screening period duration may be up to 4 weeks.  
At enrollment, subjects will receive training and diary entry of self-administered 
investigational drug administration & injection site assessment, bleeding episodes 
& treatment, evaluation & entry of AEs.   
Treatment of a spontaneous or traumatic bleeding episode: Subjects will use 
their current prescribed treatment regimen for any spontaneous or traumatic 
bleed that occurs while on study drug. If treatment for a spontaneous or 
traumatic bleeding episode is needed, then subjects will contact the clinical 
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investigative team immediately to report the event, treatment dose 
administered, and determine follow-up plans for that event including whether to 
arrange for a blood specimen to be drawn (if feasible) before further 
administration of either study drug or the current prescribed treatment regimen 
used.  Decision whether to continue daily study drug administration will also be 
determined by the clinical study team after discussion with the Sponsor.  
Dose interruption: SC study drug injections will be interrupted if any of the 
following occurs: a thrombotic event; clinical evidence of inhibitor formation; or 
laboratory results suggesting a high titer antibody may be developing; trough 
activity levels >80% where subsequent dosing will be determined in consultation 
with the sponsor. 
Surgery: If there is an urgent need for a surgical procedure or an event requiring 
extended (>48 hours) hospitalization, a FIX activity level will be urgently obtained 
and measured prior to the event, and the PI will confer with the Sponsor Medical 
representative regarding the need for any additional treatment and whether 
study drug requires interruption.   
 
Measurements:   
PK, PD, and safety assessments: FIX activity levels, as well as fibrinogen, D-dimer, 
F1+2, and TAT. PT and aPTT will be measured at screening and end of study visit 
only. Genotype testing will be performed at screening. 
Immunogenicity assays: Specimens for immunogenicity testing (antibody to 
CB2679d, BeneFIX®, and neutralizing activity) will be drawn at screening, pre-
dose on days 7, 14, 21, 28 and end of study. 
If the FIX activity level decreases unexpectedly by more than 25%, ie, IU/dL, as 
measured by the central or local lab, FIX activity levels will be drawn for analysis 
within 24 hours and immediately sent to the central laboratory.  Specimens for 
fibrinogen, D-dimer, F1+2, and TAT and immunogenicity testing will also be 
drawn. 
 
4.2  
END OF STUDY DEFINITION 
 
The duration of treatment for each subject is approximately 4 weeks (28 days). 
Up to 4 weeks for screening period; SC prophylaxis treatment regimens over a 4-
week period with the goal to achieve steady-state levels above 12% FIX activity 
when dosed daily. 
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Where interruptions to study drug dosing days occur, study duration may be 
extended to incorporate full dosing schedule. 
The end of study visit will be 30 days ± 2 days after the last dose of study drug 
treatment. 
 
 
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5.  
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
 
An individual must meet all of the following criteria to be eligible to participate in 
this study: 
1. Confirmed diagnosis of severe (<2%) congenital hemophilia B. 
2. Male, age 18 or older. 
3. Agreement to use highly effective birth control throughout the study.  
4. Affirmation of informed consent with signature confirmation before any 
trial-related activities. (Trial related activities are any procedure that would 
not have been performed during normal clinical management of the 
subject). 
5. Stated willingness to comply with all study procedures and availability for 
the duration of the study.  
 
5.2 
EXCLUSION CRITERIA  
 
An individual who meets any of the following criteria will be excluded from 
participation in this study: 
1. Patients with a history or a family history of FIX inhibitors. 
2. Positive antibody to FIX detected by central laboratory at screening. 
3. Previous participation in and subsequent treatment in a clinical trial within 
the previous 30 days or 3-half-lives, whichever is longer, or absence of 
clinical effect.  
4. History of clinically relevant coagulation disorders other than congenital 
hemophilia B including Factor V Leiden or other identified activated 
Protein C resistance. 
5. Platelet count <100,000 based on screening laboratory assessments. 
6. Advanced atherosclerotic disease (ie, known history of CAD, ischemic 
stroke, etc.), or known DVT or considered to be at a high risk of VTE as 
judged by the Investigator. 
7. Known or suspected allergy to trial product or related products. 
8. Known absolute CD4 count <200 cells/μL. 
9. Receiving IMT. 
10. Compromised hepatic or renal function: 
o ALT and AST levels ≥5 x ULN 
o TBIL ≥2 mg/dL (>35 µmol /L) unless there is a known history of GS 
o Serum albumin ≤ LLN 
o Cr level >1.25 x ULN   
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11. Inability or medical, psychosocial, or familial issues that might prevent full 
participation and cooperation with the procedures and requirements of 
the clinical trial as determined by the potential subject and physician 
investigator. 
12. Factor IX gene mutation 128G>A. 
 
5.3  
LIFESTYLE CONSIDERATIONS 
 
There are no specific lifestyle considerations. 
 
5.4  
SCREEN FAILURES 
 
An individual who does not meet the criteria for participation in this trial (screen 
failure) because of an out of range laboratory parameter may be rescreened.  
 
 
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6.  
STUDY INTERVENTION 
 
6.1  
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1  Study Intervention Description 
 
Description and Composition of the Drug Product 
Recombinant Factor IX variant; CB2679d, formerly known as ISU304, will be 
provided as a powder for injection, at a 2.0 mg/vial dosage strength. The drug 
product is supplied in a 5-mL vial that is sealed with a 20mm lyophile stopper and 
20mm aluminum over-seal. CB2679d is supplied in vials which contain excipients 
(stabilizer, buffer, etc.) and packaged in a lyophilized form. Before lyophilization, 
each vial contains 1.42 mg/mL of CB2679d drug substance is filled with 1.4 mL of 
formulation buffer. The lyophilized drug product will be reconstituted for SC 
injection. 
 
6.1.2  Dosing and Administration 
 
This is an open-label study. Each subject will receive the study drug: 
CB2679d loading dose of 50 IU/kg IV, followed 35 ± 5 minutes later with a 100 
IU/kg, with SC administration daily until Day 28 (total 1 IV dose and 28 SC doses). 
 
6.1.2.1  
Guidelines for Treatment Interruption  
 
CB2679d SC study injections will be interrupted, as needed, when: 
 
A surgical procedure is needed 
 
There is a medical event requiring extended (>48 hours) hospitalization 
 
If there is a thrombotic event 
 
If there is clinical evidence of inhibitor formation 
 
If there are laboratory results suggesting an antibody may be developing 
CB2679d SC study injections may be interrupted, as needed, when: 
 
A spontaneous bleeding event occurs 
 
A traumatic bleeding event occurs 
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Subjects will use their current treatment regimen for any spontaneous or 
traumatic bleed that occurs while on study. A spontaneous bleeding episode is 
defined as one that is precipitated by normal activities of daily living (ADL).  If 
treatment for a spontaneous or traumatic bleeding episode is needed, then 
subjects will contact the clinical investigative team immediately to report the 
event; treatment dose administered; and determine follow-up plans for that 
event, including to arrange for a blood specimen to be drawn (if feasible). This 
information will also be recorded in the subjects’ diary. 
 
6.2  
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
6.2.1  Acquisition and Accountability 
 
Upon receipt of the CB2679d shipment, the pharmacist, or a designee, will 
conduct an inventory and return an acknowledgement that all IP was received 
refrigerated and undamaged, thereby maintaining the Good Manufacturing 
Practice (GMP) status of the product during shipment. 
 
All used and unused investigational product (IP) must be returned by the subject 
to the study site. Subjects must return all IP packages and vials (including used, 
empty, and unused vials) for reconciliation of IP. 
The investigator, or approved representative (eg, pharmacist) must maintain 
adequate records documenting the receipt, use, loss, or other disposition of the 
IP. The sponsor will supply drug accountability forms to be used in this study. 
The sponsor or designee will arrange for the return of unused IP.  The IP 
destruction procedure for used vials is to be decided locally to comply with local 
regulations and procedures. 
Drug accountability will be reviewed by the monitor during routine monitoring 
visits.  No IP can be destroyed or returned until the study monitor has reconciled 
all vials of IP. 
 
6.2.2  Product Storage and Stability 
 
The investigator, or an approved representative, eg, pharmacist, will ensure that 
all IPs are stored in a secured area with controlled access under recommended 
storage conditions and in accordance with applicable regulatory requirements.  
The IP and its storage and preparation requirements will be provided by the 
Sponsor, or designee. 
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IP should be stored in its original container and in accordance with the drug 
label.  The Sponsor will provide the Investigator with packaged IP in accordance 
with specific country label requirements.  
Site systems must be capable of measuring and documenting (for example, via 
a log), at a minimum, daily minimum and maximum temperatures for all site 
storage locations (as applicable, including frozen, refrigerated and/or room 
temperature products). This should be captured from the time of IP receipt 
throughout study. Even for continuous monitoring systems, a log or site procedure 
which ensures active daily evaluation for excursions should be available. The 
operation of the temperature monitoring device and storage unit (for example, 
refrigerator), as applicable, should be regularly inspected to ensure it is 
maintained in working order.  
Any excursions from the product storage conditions should be reported upon 
discovery. The site should actively pursue options for returning the product to 
appropriate storage conditions, as soon as possible. Deviations from the storage 
requirements, including any actions taken, must be documented and reported 
to the Sponsor, or designee.  
Once an excursion is identified, the IP must be quarantined and not used until 
the Sponsor, or designee, provides documentation of permission to use the IP. 
Specific details regarding information the site should report for each excursion 
will be provided to the site.  
Receipt of materials, door opening and closing, and other routine handling 
operations where the product(s) are briefly out of labeled temperature range 
are not considered excursions. Site staff will instruct subjects on the storage 
requirements for take home medications including how to report temperature 
excursions.  
 
6.2.3  Preparation 
 
CB2679d will be provided as a powder for injection, at a 2.0 mg/vial dosage 
strength, and is supplied in a 5-mL vial.  The lyophilized drug product will be 
reconstituted with 1.4 mL sterile water for SC injection. 
Details regarding the dosing administration, will be provided by the Sponsor, or 
designee. 
At the study site, the CB2679d SC dose will be prepared and administered by an 
appropriately qualified and experienced member of the study staff (eg, 
physician, nurse, physician assistant, nurse practitioner, or pharmacist) as allowed 
by local, state, and institutional guidance.   
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6.3  
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
The study is an open-label study; subjects and members of the clinical study 
team will not be blinded to treatment.  
 
6.4  
STUDY INTERVENTION COMPLIANCE 
 
Reasonable efforts should be made to ensure that study drug administration is 
administered daily according to the schedule.  However, if an unavoidable 
disruption of the administration occurs, and a dose is not administered on the 
assigned day then the subject should take the dose as soon as possible. In the 
event that the subject does not take study drug for more than 2 days, then the 
subject must contact the research site for instructions on how to proceed prior to 
administering a dose.  
 
6.5  
CONCOMITANT THERAPY 
 
Enrolled subjects will record all concomitant medications administered from the 
Screening Visit to Study termination (including the date and time of 
administration) in their diary. 
For this protocol, a prescription medication is defined as a medication that can 
be prescribed only by a properly authorized/licensed clinician. Medications to 
be reported in the electronic Case Report Form (eCRF) are concomitant 
prescription medications, over-the-counter (OTC) medications and 
supplements.] 
There are no concomitant medication restrictions.   
If an individual has previously been enrolled on a clinical trial evaluating a 
treatment (as specified in exclusion criteria #3) in clinical investigation he will be 
permitted to enroll onto this study, provided it is greater than 30 days since 
exposure to that study drug, or 3-half-lives, whichever is longer, or absence of 
clinical effect. 
The following medications will be permitted during the study: 
 
In the event of spontaneous or traumatic bleeding, treatment for a 
spontaneous or traumatic bleeding episode will be permitted using the 
subject’s current prescribed treatment regimen which could be BeneFIX® or 
Rixubis®. 
 
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7.  
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1  
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Subjects are free to withdraw from participation in the study at any time upon 
request.   
An investigator may discontinue or withdraw a participant from the study for the 
following reasons: 
 
Significant study intervention non-compliance  
 
If any clinical AE, laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be 
in the best interest of the participant 
 
If the participant meets a criterion (either newly developed or not previously 
recognized) that precludes further study participation 
 
Decision by Investigator or Sponsor 
The reason for participant discontinuation or withdrawal from the study and the 
date will be recorded on the eCRF.   
Replacement of a subject occurs for the following reason: 
 
If a subject does not complete 21 days of daily SC dosing, as defined in the 
protocol, another subject may be enrolled. 
If the subject withdraws from the study and also withdraws consent for disclosure 
of future information, no further evaluations should be performed, and no 
additional data should be collected. The sponsor may retain and continue to 
use any data collected before such withdrawal of consent. 
7.2  
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he fails to return for two 
consecutive scheduled visits and is unable to be contacted by the study site 
staff.  
The following actions must be taken if a participant fails to return to the clinic for 
a required study visit: 
The site will attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain if the participant wishes to and/or 
should continue in the study. 
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Before a participant is deemed lost to follow-up, the investigator or designee will 
make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record or study file.  
Should the participant continue to be unreachable, he will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up. 
In any circumstance, every effort should be made to document subject 
outcome, if possible.  The investigator should inquire about the reason for 
withdrawal, request the subject to return all used and unused IP(s), request the 
subject to return for a final visit, if applicable, and follow up with the subject 
regarding any unresolved AEs. 
 
 
 
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8.  
STUDY ASSESSMENTAND PROCEDURES 
 
8.1  
STUDY PROCEDURES 
 
Study procedures and evaluations to be done as part of the study. Please refer 
to Section 1.3, Schedule of Activities (SOA) for the sequence of events.   
 
8.1.1  Screening 
 
Please refer to Section 1.3, Schedule of Activities (SOA) for the sequence of 
events that should occur during the screening process.  Screening should occur 
within 4 weeks prior to enrollment.   
 
Informed consent 
 
Demographic parameters 
 
Joint evaluation (as per SOC at hemophilia treatment center) 
 
Inclusion and Exclusion Criteria review 
 
Medical and hemophilia history 
 
Concomitant medications 
 
Vital signs 
 
Height (screening only) and weight 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Hematology and chemistry: (see Footnote 4 in Section 1.3, Schedule of 
Activities)  
 
Coagulation assays: PT and aPTT (both at screening and end of study visit 
only) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT  
 
PK: FIX activity 
 
Immunogenicity assays: antibody to CB2679d and BeneFIX® 
 
ECG 
 
FIX genotype test 
 
Adverse events  
 
 
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8.1.2  Treatment (Duration 28 days) 
 
Please refer to Section 1.3, Schedule of Activities (SOA) for the sequence of 
events.   
 
8.1.2.1  
Day 1 Pre-dose evaluations  
 
 
Concomitant medications 
 
Vital signs 
 
Weight 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Hematology and chemistry (see Footnote 4 in Section 1.3, SOA) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: FIX activity 
 
Study Subject training on diary entry, drug administration, adverse event 
reporting and injection site assessment 
 
Adverse events 
 
8.1.2.2  
CB2679d administration (Daily from Day 1 to Day 28) 
 
 
Subjects will receive a loading IV dose of 50 IU/kg, followed 35 ± 5 minutes 
later with a 100 IU/kg SC dose of CB2679d  
 
Subjects will then administer a 100 IU/kg daily SC dose of CB2679d from 
Day 2 until Day 28 
 
Daily SC dosing of CB2679d should be self-administered by subjects at 
approximately the same time every day.  
 
 
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8.1.2.3  
Day 1 at SC dose administration (35 minutes post-IV dose) 
 
Blood will be collected at 35-minutes post-IV dose for the following evaluations: 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: FIX activity 
Other evaluations will include: 
 
Concomitant medications 
 
Vital signs 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events 
 
8.1.2.4  
Day 2 and 3 Pre-SC dose evaluations 
 
Blood will be collected pre-dose (- 5 minutes), as close to the timing of the prior 
SC injection, on Day 2 and Day 3 for the following evaluations: 
 
Hematology and chemistry – platelet count only (see Footnote 4 and 5 in 
Section 1.3, SOA): Day 2 ONLY 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: FIX activity  
Other evaluations will include: 
 
Concomitant medications 
 
Vital sign 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
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8.1.2.5  
Day 7, 14, 21 and 28 Pre-dose evaluations  
 
Blood will be collected at pre-dose (-5 minutes) for the following evaluations: 
 
Hematology and chemistry (see Footnote 4 in Section 1.3, SOA) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: FIX activity 
 
Immunogenicity assays to CB2679d and BeneFIX®   
Other evaluations will include: 
 
Concomitant medications 
 
Vital signs 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
8.1.3  Washout Period, Unscheduled Visits and End of Study evaluations 
 
Please refer to Section 1.3, Schedule of Activities (SOA) for the sequence of 
events that should occur during the washout period and end of study process.   
 
8.1.3.1  
Washout period evaluations (Day 29, 30, 31, 32, and 33) 
 
 
Concomitant medications 
 
Clinical signs of thrombosis (see Appendix A) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: FIX activity 
o Daily FIX activity levels will be measured, unless FIX activity level is 
known to be < 5% as measured by local laboratory 
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
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8.1.3.2  
Unscheduled visit evaluations  
 
Should a subject need to be seen at any time while enrolled onto the trial, and 
not on a study scheduled visit, the following assessments may need to be 
conducted based on the judgement of the clinical study team. 
 
Medical and Hemophilia History  
 
Concomitant medications 
 
Vital signs 
 
Weight 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Hematology and chemistry (see Footnote 4 in Section 1.3, SOA) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
 
PK: FIX activity 
 
Immunogenicity assays to CB2679d and BeneFIX®  
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
8.1.3.3  
End of Study visit evaluations (30 days after last dose) 
 
The following procedures will be performed: 
 
Concomitant medications 
 
Vital signs 
 
Physical examination 
 
Clinical signs of thrombosis (see Appendix A) 
 
Hematology and chemistry (see Footnote 4 in Section 1.3, SOA) 
 
Coagulation assays: PT and aPTT (both at screening and end of study visit 
only) 
 
Thrombogenicity markers: Fibrinogen, D-dimer, F1+2, and TAT 
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 
PK: FIX activity 
 
Immunogenicity assays to CB2679d and BeneFIX®   
 
Review of diary entry of investigational drug administration, injection site 
assessment, adverse events, bleeding episodes & treatment  
 
Adverse events  
 
8.2  
STUDY ASSESSMENTS 
 
8.2.1  Efficacy Assessments 
 
Subjects will be asked to record daily SC injections, any injection site reactions, 
any AEs experienced, and all spontaneous or traumatic bleeding episodes and 
concomitant medications administered into the Diary, including (but not limited 
to) the following: 
 
Bleeding episode (date/time of onset and date/time of resolution) 
 
Cause of bleeding (spontaneous or traumatic) 
 
Bleeding site: joint (ankle, knee, elbow, other [right or left]); muscle (iliopsoas, 
calf, forearm, other [right or left]); mucous membranes (mouth, gums, nose, 
genitourinary tract); gastrointestinal (gastric ulcer, fissure, other [requiring 
transfusion – yes, no]), neck/throat, intracranial. 
 
Hemostatic drugs used for treatment of bleeding episodes (time/date of 
administration, type, amount [international units or mg and/or number of 
infusions]) 
A spontaneous bleeding episode is defined as one that is precipitated by normal 
ADL. 
Investigators will document:  
 
Subject demographics (sex, age, race and ethnicity) will be recorded at the 
screening visit.  
 
All ongoing conditions and relevant medical and hemophilia history 
(including all major hospitalizations and surgeries), as well as the subject’s 
current medical status and genotype will be recorded at the screening visit.   
 
Diagnosis of severe congenital hemophilia B will be documented including 
the frequency of spontaneous or traumatic bleeding episodes in the past 6 
months and in the past 50 days.   
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 
Notation will be made regarding history of orthopedic procedures including 
joint aspiration, synovectomy, fusion, or joint replacements or other 
complications of hemophilia including pseudotumors. 
 
Concomitant medication use including treatment used for control of 
spontaneous or traumatic bleeding events (infusion therapies, anti-fibrinolytic 
agents, local agents) and for management of pain and other complications 
related to hemophilia. 
 
Vital signs, height, weight, general physical examination will be performed at 
screening. 
 
8.2.2  Physical Examination 
 
A full physical assessment of the major body systems will be recorded at 
Screening followed by interim targeted evaluation, per Investigator’s discretion, 
as indicated on presentation of subject at study visit. 
 
8.2.3  Vital signs  
 
One measurement of blood pressure, heart rate, respiratory rate, and body 
temperature will be taken after the subject has been sitting quietly for at least 5 
minutes. 
 
8.2.4  Hematology  
 
Complete blood cell count (CBC), and platelet counts will be measured using 
standard laboratory testing methods at a local laboratory. Genotype test will be 
performed at screening. 
 
8.2.5  Chemistry 
 
Sodium, potassium, chloride, bicarbonate, hepatic enzymes (ALT, AST and GGT), 
TBIL, albumin, and creatinine (Cr) will be measured using standard laboratory 
testing methods at a local laboratory. 
 
8.2.6  Coagulation assays  
 
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PT and aPTT (at screening and end of study ONLY) will be performed at a central 
laboratory. 
8.2.7  Thrombogenicity markers  
Fibrinogen, D-dimer, F1+2, and TAT. These evaluations will be performed at a 
central laboratory. 
8.2.8  Immunogenicity Assays 
Antibody response and neutralizing antibodies to Dalcinonacog alfa and 
BeneFIX®. These evaluations will be performed and tested at a central laboratory. 
8.2.9  Pharmacokinetic Sampling  
Evaluations related to PK and PD will include: 

FIX activity levels over time post-dose and calculation of standard PK
parameters. Study evaluations will be performed at a central laboratory.
However, FIX activity levels may be performed at a local laboratory for safety
and during the wash-out period.
8.2.10  Clinical signs of thrombosis (Appendix A)  
This assessment will be included as part of the study subject training, provided as 
a reference in the Diary and will be a scheduled evaluation at clinical study visits. 
8.2.11  Concomitant medications  
Subjects will record concomitant medications (including name of medication, 
dose taken, day and time) they may be taking in their daily diaries. Diaries will be 
reviewed by the clinical staff at each visit.  
8.2.12  ECG 
A12-lead ECG will be performed using local standard methods.  
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For participants that may discontinue or withdraw early, it is important to capture 
the rationale during the final visit. See Section 7, Study Intervention 
Discontinuation and Participant Discontinuation/Withdrawal, for details. 
 
8.3  
SAFETY AND OTHER ASSESSMENTS 
 
Evaluations related to safety will include: 
 
8.3.1  AEs and SAEs 
 
Subjects will record any AEs that occur during the study in their daily diaries. 
Diaries will be reviewed by the clinical staff at each visit.   
 
8.3.2  Injection site reactions 
 
Subjects will record site injection reactions in their daily diaries. Diaries will be 
reviewed by the clinical staff at each visit.   
 
8.4  
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.4.1  Definition of Adverse Events (AE) 
 
Definition of an AE: An AE is any untoward medical occurrence in a patient or 
clinical trial subject administered a medicinal product that may not necessarily 
have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (including a clinically significant laboratory 
abnormality, for example), symptom, or disease temporarily associated with the 
use of a medicinal (investigational) product, whether or not related to the 
medicinal (investigational) product.  
 
Pre-existing conditions, diseases or disorders are not considered AEs unless there 
is a change in the intensity, frequency or quality. 
  
8.4.2  Definition of Serious Adverse Events (SAE) 
 
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Definition of a SAE: Definition of a SAE:  An AE or suspected adverse reaction is 
considered "serious" if, in the view of either the investigator or sponsor, it results in 
any of the following outcomes: death, a life-threatening AE, inpatient 
hospitalization or prolongation of existing hospitalization, a persistent or 
significant incapacity or substantial disruption of the ability to conduct normal life 
functions, or a congenital anomaly/birth defect. Important medical events that 
may not result in death, be life-threatening, or require hospitalization may be 
considered serious when, based upon appropriate medical judgment, they may 
jeopardize the participant and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. Examples of such medical 
events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result 
in inpatient hospitalization, or the development of drug dependency or drug 
abuse. 
 
8.4.3  Classification of an Adverse Event 
 
8.4.3.1  
Severity of Event 
 
All AEs will be assessed by the study clinician using the Common Terminology 
Criteria for Adverse Events (CTCAE) Version 5.0 where applicable.39   
For those AEs that are not included under the CTCAE v5.0, the following 
guidelines will be used to describe severity.  
Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities.  
Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
Severe – Events interrupt a participant’s usual ADL and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-
threatening or incapacitating.  Of note, the term “severe” does not necessarily 
equate to “serious”. 
 
8.4.3.2  
Relationship to Study Drug 
 
All AEs must have their relationship to study drug assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and 
his/her clinical judgment. The degree of certainty about causality will be graded 
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using the categories below. In a clinical trial, the study product must always be 
suspect.  
Related – The AE is known to occur with the study intervention, there is a 
reasonable possibility that the study intervention caused the AE, or there is a 
temporal relationship between the study intervention and event. Reasonable 
possibility means that there is evidence to suggest a causal relationship between 
the study intervention and the AE. 
Not Related – There is not a reasonable possibility that the administration of the 
study intervention caused the event, there is no temporal relationship between 
the study intervention and event onset, or an alternate etiology has been 
established. 
 
8.4.3.3  
Action Taken  
 
None: No changes were made to Study Drug administration and dose  
Permanently discontinued: Study drug was discontinued and not restarted 
Temporarily interrupted, restarted same dose: Dosing was temporarily 
interrupted or delayed due to the AE and restarted at the same dose without 
unblinding to treatment group 
 
8.4.3.4  
Expectedness 
 
The Principle Investigator (or Co-PI) will be responsible for determining whether 
an AE is expected or unexpected.  An AE will be considered unexpected if the 
nature, severity, or frequency of the event is not consistent with the risk 
information previously described for the study intervention. 
 
8.4.4  Time Period and Frequency for Event Assessment and Follow-Up 
 
Subjects will be instructed regarding direct reporting and diary entries of AEs; 
diaries will be reviewed at each visit and subjects queried if evidence of an AE 
recorded. 
The occurrence of an AE or SAE may come to the attention of study personnel 
during study visits and interviews of a study participant presenting for medical 
care, or upon review by a study monitor.   
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All AEs including local and systemic reactions not meeting the criteria for SAEs will 
be captured on the appropriate CRF. Information to be collected includes event 
description, time of onset, clinician’s assessment of severity, relationship to study 
product (assessed only by those with the training and authority to make a 
diagnosis), and time of resolution/stabilization of the event. All AEs occurring 
while on study must be documented appropriately regardless of relationship. All 
AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened 
will be considered as baseline and not reported as an AE. However, if a baseline 
condition deteriorates at any time during the study, it will be recorded at 
minimum as an AE.  
Changes in the severity of an AE will be documented to allow an assessment of 
the duration of the event at each level of severity to be performed. AEs 
characterized as intermittent require documentation of onset and duration of 
each episode. 
Subject Withdrawal from the Study Due to an Adverse Event:  
Every reasonable effort should be made to maintain subject compliance and 
participation in the study. All enrolled subjects who received the study drug must 
be followed through the Follow-Up visit, regardless of the reason for withdrawal. If 
a subject who has a clinically significant laboratory abnormality or AE withdraws 
from the study, every effort must be made to follow these events until satisfactory 
resolution. 
 
8.4.5  Adverse Event Reporting 
 
Members of the study team will record all reportable events with start dates 
occurring any time after informed consent is obtained until study completion, or 
discharge, for non-serious AEs.  At each study visit, the investigator will inquire 
about the occurrence of AE since the last visit.  Events will be followed for 
outcome information until resolution or stabilization. 
The Investigator will categorize the outcome of each AE according to the 
definitions below: 
Resolved: 
 
The subject recovered from the AE.   
Ongoing:  
At the time of the last assessment, the event is ongoing, with 
an undetermined outcome.  Note: Ongoing AEs are not 
considered resolved as a result of death. No AE stop date 
should be recorded with an AE that is ongoing. 
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Chronic/Stable: 
At the time of the last assessment, the event is ongoing and 
stabilized, with no change to the event outcome 
anticipated.  
Unknown:  
There is an inability to access the subject or the subject’s 
records to determine the outcome (ie, subject withdraws 
consent or is lost to follow-up). 
All protocol-defined adverse events will be reported from the time a patient is 
enrolled in the study until the end of study visit. 
Spontaneous or traumatic bleeding events will not be reported as an AE unless 
considered serious and should then be reported per the standard process for 
reporting.   
All bleeds should be entered into the diary including spontaneous bleeds, 
traumatic bleeds or bleeds related to procedure/surgery (see Section 4.1). Only 
bleeds (spontaneous bleeds, traumatic bleeds or bleeds related to 
procedure/surgery) that are considered serious as per definition (see Section 
8.4.6) should be reported as an SAE in the CRF. Non-serious bleeds are not 
considered adverse events for the purpose of this protocol and should not be 
reported as adverse event in the eCRF.  
The study drug has the potential risk of causing the following AEs based on 
information associated with other drugs in the same category, ie, FIX agents for 
treatment of hemophilia; these are: 
Thrombotic events (see Appendix A) 
Based on information associated with other drugs for treatment of hemophilia. 
the study drug has the potential risk of causing thrombotic events.  See Appendix 
A for signs and symptoms listed for the subjects and the study team personnel as 
those requiring urgent reporting and attention.  
Development of Drug Antibodies and Inhibitors 
There is a risk with the study drug of developing an immune response resulting in 
antibody formation and potentially an inhibitory antibody response.  This will also 
be monitored for throughout the study.    
Skin injection site may become reddened or painful.  
Risks associated with blood collection:  
A blood draw may cause faintness, inflammation of the vein, pain, bruising, or 
bleeding at the site of puncture.  There is also a minimal chance of infection at 
the puncture site. 
 
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8.4.6  Serious Adverse Event Reporting 
 
Members of the study team will record all reportable events within 24 hours of 
knowledge of the SAE with start dates occurring any time after informed consent 
is obtained until 30 days after the last day of study participation.  At each study 
visit, the investigator will inquire about the occurrence of SAEs since the last visit.  
Events will be followed for outcome information until resolution or stabilization. 
The Investigator will categorize the outcome of each SAE according to the 
definitions below: 
Resolved: 
 
The subject recovered from the AE.   
Ongoing:  
At the time of the last assessment, the event is ongoing, with 
an undetermined outcome.  Note: Ongoing AEs are not 
considered resolved as a result of death. No AE stop date 
should be recorded with an AE that is ongoing. 
Chronic/Stable: 
At the time of the last assessment, the event is ongoing and 
stabilized, with no change to the event outcome 
anticipated.  
Death:  
 
The AE directly caused death. 
Unknown:  
There is an inability to access the subject or the subject’s 
records to determine the outcome (ie, subject withdraws 
consent or is lost to follow-up). 
Definitions: 
Death: Any event resulting in a subject’s death must be reported as an SAE.  
However, death, in and of itself, is not an AE; it is only an outcome.  The cause of 
death is the AE.  Therefore, the investigator should make every effort to obtain 
and document the cause of death for all subjects who die during the study.  If, 
despite all efforts, the cause of death remains unknown, the AE should be 
documented as an “unspecified fatal event”. 
Life threatening AE:  Any AE that places the patient or subject, in the view of the 
investigator, at immediate risk of death from the reaction as it occurred (ie, it 
does not include a reaction that, had it occurred in a more severe form, might 
have caused death). 
Hospitalization:  It should be noted that hospitalization, in and of itself, does not 
represent an SAE.  It is the AE leading to the subject’s hospitalization that 
becomes “serious” when it requires inpatient care.  Consequently, an SAE should 
not be reported in the case of pre-planned hospitalizations for pre-existing 
conditions that did not worsen during the study. 
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Disability: A substantial disruption of a person’s ability to conduct normal life 
functions. 
 
8.4.7  Adverse Events of Special Interest (AESIs) 
 
The study drug has the potential risk of causing the following AESIs based on 
information associated with other drugs in the same category. These are: 
1. Thromboembolic events (TEs) based on information associated with other 
drugs for treatment of hemophilia. TEs include myocardial infarction (MI); 
venous thrombosis, and pulmonary embolism (PE); and stroke. See 
Appendix A for signs and symptoms listed for the subjects and the study 
team personnel as those requiring urgent reporting and attention.  
2. Immune response resulting in antibody formation and potentially an 
inhibitory antibody response. This will also be monitored for throughout the 
study.  
 
8.4.8  Reporting of Pregnancy 
 
Although pregnancy itself is not considered an adverse event or a serious 
adverse event, the partner of a male participant should be followed until 
termination or to term to ensure absence of congenital anomaly or birth defect 
that may have resulted from maternal exposure or transmission of the study drug 
via semen following paternal exposure. 
All participants must be advised to use a highly effective method of birth control 
from the first dose of study drug through 28 days after dosing to protect the 
health and safety of the mother and/or child. Despite the warnings provided 
and precautions taken, pregnancy may occur during research participation. 
Investigators must be aware of the requirements related to reporting and follow-
up in the event a research participant’s partner becomes pregnant. 
If a participant’s partner becomes pregnant during this study, please provide an 
authorization form to present to the partner. If she is in agreement, that 
authorization will function as consent to approve the study doctor’s access to 
medical information to allow the regulatory required monitoring of the 
pregnancy, and the birth and the health of the child.  
Please report the pregnancy of a participant’s partner to Catalyst Biosciences, or 
it’s designee, and the IRB, and include the following information: expected date 
of delivery, last menstruation, estimated conception date and pregnancy result 
(if known).  
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Pregnancy should be reported as “Information” (not as an “Adverse Event” or 
“Other Problem or Event”). 
 
Pregnancy does NOT have to be reported to the IRB if the subject is receiving 
follow-up only, and conception occurred outside of the time period that the 
study protocol requires contraception (ie, 28 days after the last dose of the 
study drug and the pregnancy occurred after that time). 
 
Subsequent reports containing follow-up information regarding a pregnancy 
is not required unless the pregnancy results in a congenital anomaly. The 
congenital anomaly should be promptly reported.  
 
NOTE: If you suspect that exposure to a medical product prior to conception 
or during pregnancy may have resulted in an adverse outcome in the child, it 
must be reported to the Food and Drug Administration (FDA). 
 
 
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9.  
STATISTICAL CONSIDERATIONS  
 
9.1 
STUDY HYPOTHESIS 
 
The study hypothesis is that a daily SC dose of CB2679d results in levels sufficient 
to provide protection from spontaneous bleeding. 
Primary Analysis Plan:  
Appropriate descriptive statistics of all measured parameters will be reported, 
including 95% confidence intervals. 
The dose required to achieve steady-state levels >12% will be reported for daily 
dosing, including 95% confidence intervals. 
Primary Endpoint 
The primary endpoint will include: 
 
Number of subjects who achieve a steady-state FIX activity level above 12%, 
with daily dosing. 
 
Secondary Endpoints 
The secondary endpoints will include: 
 
Safety assessments: Occurrence of antibody formation resulting in a 
decreased endogenous level of FIX; occurrence of a clinical thrombotic 
event not attributable to another cause. 
 
Occurrence of a conformed antibody response with high titer to CB2679d 
and whether it is inhibitory and cross-reactive to BeneFIX®.   
 
Change in FIX activity levels. 
 
Occurrence of clinically significant levels of thrombogenicity markers resulting 
from SC administration of CB2679d.  
 
 
 
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9.2 
SAMPLE SIZE DETERMINATION 
 
6 subjects are sufficient to provide guidance on range of dose required to 
achieve steady-state activity >12% and starting SC dose for subsequent studies. 
As this study is not inferential, no formal sample size calculation is required. 
 
9.3 
POPULATIONS FOR ANALYSES 
 
Safety population: any patient who receives at least one dose. 
Efficacy/PD population: any patient who receives at least one week of daily SC 
dosing and PK specimens obtained. 
 
If a subject does not complete the study as defined in the protocol another 
subject will need to be enrolled in replacement. 
 
9.4 
STATISTICAL ANALYSIS 
 
9.4.1 General Approach 
 
Various pharmacokinetic parameters will be calculated, including area under 
the time curve (o-t and 0-infinity), clearance, volume of distribution at steady-
state, Tmax and Cmax, and terminal (beta phase) t1/2, will be calculated. A semi-
parametric model described by Lee et al40 will be used to calculate the terminal 
t1/2. Other parameters will be calculated using a standard noncompartmental 
approach. Descriptive statistics will be reported for each parameter and will 
include mean ± standard deviation and median ± interquartile range.  
The evaluation of the primary endpoint is descriptive, but 95% confidence 
intervals will be calculated as appropriate. 
There will be a formal Statistical Analysis Plan (SAP) completed prior to database 
lock.  
 
 
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9.4.2  Analysis of the Primary Efficacy Endpoint(s) 
 
The analysis of the primary endpoint will include: 
 
Number of subjects who achieve a steady-state FIX activity level above 12% 
with daily dosing. 
 
9.4.3  Analysis of the Secondary Endpoint(s) 
 
Study drug exposure and compliance will be provided.  
The following parameters will be documented: 
 
Occurrence of clinical thrombotic event not attributable to another cause, 
and occurrence of antibody formation resulting in a decreased endogenous 
level of FIX. 
 
Change in coagulation parameters (fibrinogen, and FIX activity levels) from 
pre-dose. 
 
Occurrence of an antibody response to CB2679d and whether it is inhibitory 
and cross-reactive to BeneFIX®. 
 
Clinically significant levels of thrombogenicity markers resulting from SC 
administration of CB2679d  
The frequencies of these events will be summarized as proportions and counts. 
Protocol deviations will be listed.  All major protocol deviations (in particular 
those regarding entry criteria) will be summarized in the study report.  
 
9.4.4  Safety Analysis  
 
Adverse Events 
All AEs will be listed, documenting the course, outcome, severity, and causality 
to study drug. Verbatim terms on CRFs will be mapped to preferred terms and 
related system organ class using the Medical Dictionary for Regulatory Activities 
(MedDRA).  
Incidence rates of AEs and the proportion of subjects prematurely withdrawn 
from the study due to AEs will be shown for. Incidence rates will also be displayed 
based on severity and relationship to study drug. AEs with a relationship of 
“possibly” or “probably” related will be considered by the Sponsor as “related” 
to the study drug. Events assessed as “unrelated”, “unlikely” related, or where the 
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relationship was not reported will be considered by the Sponsor as “not related” 
to the study drug. The incidence of SAEs will be provided. All incidence rates will 
be categorized and displayed by system organ class and preferred term. 
Vital Signs  
Safety analyses will include descriptive statistical summaries of shifts in vital signs 
(blood pressure, heart rate, respiratory rate) and in laboratory values. 
 
9.4.5  Baseline Descriptive Statistics  
 
Demographic and baseline measurement variables will be summarized using 
descriptive statistics.  
 
9.4.6  Planned Interim Analyses 
 
Not applicable to this study. 
 
9.4.7  Sub-Group Analyses 
 
Not applicable to this study. 
 
9.4.8  Tabulation of Individual Participant Data 
 
Individual participant data will be listed by measure and time point. 
 
 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1  
Informed Consent Process 
 
The written informed consent documents will be prepared in the language(s) of 
the potential subject population, based on an English version provided by the 
Sponsor and should be easy to understand.   
Before a subject’s participation in the trial, the investigator is responsible for 
obtaining written information consent from the subject after adequate 
explanation of the aims, methods, anticipated benefits, and potential hazards of 
the study and before any protocol specific screening procedures or any study 
drugs are administered. Sufficient time must be given to consider whether to 
participate in the study. 
The informed consent form should be signed and personally dated by the 
subject and by the study person who conducted the informed consent 
discussion. The original signed informed consent form should be retained in the 
Study Master File and in any other locations required by institutional policy, and a 
copy of the signed consent form should be provided to the subject. 
 
10.1.2  Institutional Review Board/Independent Ethics Committee 
 
Before initiation of the study, the investigator must submit for approval the 
protocol, ICF, Investigator’s Brochure, and any advertisements to an IRB/IEC for 
written approval. The Investigator must ensure IRB/IEC compliance with the 
applicable regulations. A copy of written IRB/IEC approval of the protocol, ICF, 
and all advertisements must be provided to Sponsor or designee prior to initiation 
of the study and shipment of study drug.  The Investigator is responsible for 
obtaining continued review of the clinical research at intervals not exceeding 
one year or at more frequent intervals if specified by the IRB/IEC. The Investigator 
must supply Sponsor or designee with written documentation of continued 
review of the clinical research. 
The Investigator is responsible for reporting the following to the IRB/IEC: 
 
All SAEs (including deaths) regardless of cause and whether anticipated or 
unanticipated (reported immediately) 
 
Significant findings that become known in the course of the study that might 
affect the willingness of subjects to continue to participate  
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 
Protocol, or consent amendments prior to the implementation of the change 
 
Study progress reports at least once a year, if applicable 
 
Notification of study completion or termination. 
Sponsor may amend the protocol as needed to ensure that the clinical 
investigation is being conducted as intended. Sponsor will initiate protocol 
amendments in writing if any change significantly affects the safety of subjects, 
the scope of the investigation, or the scientific quality of the study. Protocol 
changes must be submitted to the IRB/IEC as a protocol amendment. If 
necessary, the ICF will be revised to reflect the changes in the amendment and 
will be submitted to the IRB/IEC for review and approval. A copy of the 
amendment must be signed by the Investigator and returned to Sponsor or 
designee. Written documentation of IRB/IEC approval is required before the 
amendment is implemented. Investigators may not perform study-specific 
assessments that are not included in the protocol unless agreed to by Sponsor.  
 
10.1.3  Study Discontinuation and Closure  
 
This study may be temporarily suspended or prematurely terminated if there is 
sufficient reasonable cause.  Written notification, documenting the reason for 
study suspension or termination, will be provided by the suspending or 
terminating party to study subjects, investigator, and regulatory authorities.  If the 
study is prematurely terminated or suspended, the PI will promptly inform study 
participants, the IRB/IEC, and sponsor and will provide the reason(s) for the 
termination or suspension.  Study subjects will be contacted, as applicable, and 
be informed of changes to study visit schedule. 
When a study is prematurely terminated, refer to Section 7, Study Intervention 
Discontinuation and Participant Discontinuation/Withdrawal, for handling of 
enrolled study participants. 
 
10.1.4  Confidentiality and Privacy 
 
Participant confidentiality and privacy is strictly held in trust by the participating 
investigators, their staff, and the sponsor, or designee. The study protocol, 
documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study, or the data will be released to 
any unauthorized third party without prior written approval of the sponsor.  
All research activities will be conducted in as private a setting as possible. 
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The study monitor, other authorized representatives of the sponsor, 
representatives of the IRB/IEC, or regulatory agencies may inspect all documents 
and records required to be maintained by the investigator, including but not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for 
the participants in this study. The clinical study site will permit access to such 
records. 
The study participant’s contact information will be securely stored at each 
clinical site for internal use during the study. At the end of the study, all records 
will continue to be kept in a secure location for as long a period as dictated by 
the reviewing IRB/IEC, Institutional policies, or sponsor requirements. 
 
10.1.5  Future Use of Stored Specimens and Data 
 
There is no genetic testing performed in relation to this study. 
 
10.1.6  Clinical Monitoring 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of 
trial participants are protected, that the reported trial data are accurate, 
complete, and verifiable, and that the conduct of the trial is in compliance with 
the currently approved protocol/amendment(s), with ICH GCP, and with 
applicable regulatory requirement(s).  
The Sponsor, or its designee, and regulatory authority inspectors are responsible 
for contacting and visiting the Investigator for the purpose of inspecting the 
facilities and, upon request, inspecting the various records of the trial (e.g., CRFs 
and other pertinent data) provided that subject confidentiality is respected. The 
Sponsor monitor is responsible for inspecting the CRFs at regular intervals 
throughout the study to verify adherence to the protocol; completeness, 
accuracy, and consistency of the data; and adherence to local regulations on 
the conduct of clinical research. The monitor should have access to subject 
medical records and other study-related records needed to verify the entries on 
the CRFs. The Investigator agrees to cooperate with the monitor to ensure that 
any problems detected in the course of these monitoring visits, including delays 
in completing CRFs, are resolved. 
To ensure the quality of clinical data a clinical data management review will be 
performed on subject data received by the Sponsor. During this review, subject 
data will be checked for consistency, omissions, and any apparent 
discrepancies. In addition, the data will be reviewed for adherence to the 
protocol and GCP.  
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Independent audits may be conducted by the Sponsor, or designee, or 
regulatory authority inspectors to inspection the Study Center facilities (e.g., 
pharmacy, drug storage areas, laboratories) and review of study related records 
to evaluate the trial conduct and compliance with the protocol, ICH GCP, and 
applicable regulatory requirements. 
The Principal Investigator will sign and date the indicated places on the CRF. 
These signatures will indicate that the principal Investigator inspected or 
reviewed the data on the CRF, the data queries, and the Study Center 
notifications, and agrees with the content. 
 
10.1.7  Quality Assurance (QA) and Quality Control (QC) 
 
The Sponsor, or designee, will be responsible for data management of this study, 
including quality checking of the data. Sites will be responsible for data entry into 
the electronic data capture (EDC) system (eCRFs). In the event of data 
discrepancy, the Sponsor, or designee, will request data clarification from the 
sites, which the sites will resolve electronically in the EDC system.  
The eCRFs and correction documentation will be maintained in the EDC system 
audit trail.  
Diary data will be entered into the eCRF.  
Following written Standard Operating Procedures (SOPs), the monitors will verify 
that the clinical trial is conducted, and data are generated, and biological 
specimens are collected, documented (recorded), and reported in compliance 
with the protocol, ICH GCP, and applicable regulatory requirements (e.g., Good 
Laboratory Practices [GLP], GMP).  
The investigational site will provide direct access to all trial related sites, source 
data/documents, and reports for the purpose of monitoring and auditing by the 
sponsor, and inspection by local and regulatory authorities. 
 
10.1.8  Data Handling and Record Keeping 
 
10.1.8.1  
Data Collection and Management Responsibilities 
 
Data collection is the responsibility of the clinical trial staff at the site under the 
supervision of the site investigator. The investigator is responsible for ensuring the 
accuracy, completeness, legibility, and timeliness of the data reported. 
 
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All source documents should be completed in a neat, legible manner to ensure 
accurate interpretation of data.   
Clinical data (including AEs, concomitant medications, and expected adverse 
reactions data) and clinical laboratory data will be entered into Medidata Rave 
EDC, a 21 CFR Part 11-compliant data capture system. The data system includes 
password protection and internal quality checks, such as automatic range 
checks, to identify data that appear inconsistent, incomplete, or inaccurate. 
Clinical data will be entered directly from the source documents.] 
 
10.1.8.2  
Study Records Retention 
 
Study documents should be retained as required by local regulations. No records 
will be destroyed without the written consent of the sponsor, if applicable. It is the 
responsibility of the sponsor to inform the investigator when these documents no 
longer need to be retained 
 
10.1.9  Protocol Amendments 
 
Sponsor may amend the protocol as needed to ensure that the clinical 
investigation is being conducted as intended. Sponsor will initiate protocol 
amendments in writing if any change significantly affects the safety of subjects, 
the scope of the investigation, or the scientific quality of the study. Protocol 
changes must be submitted to the IRB/IEC as a protocol amendment. If 
necessary, the ICF and assent form will be revised to reflect the changes in the 
amendment and will be submitted to the IRB/IEC for review and approval. A 
copy of the amendment must be signed by the Investigator and returned to 
Sponsor or designee. Written documentation of IRB/IEC approval is required 
before the amendment is implemented. Investigators may not perform study-
specific assessments that are not included in the protocol unless agreed to by 
Sponsor. Additionally, a site-specific amendment and revised ICF and assent 
form must be generated and submitted for approval to the IRB/IEC. 
 
10.1.10  
Publication and Data Sharing Policy 
 
The final clinical study report is also intended to form the basis for a manuscript 
intended for publication in a peer-reviewed scientific journal. The authorship, 
timetable and any arrangements for review by the participating investigators will 
be coordinated by Catalyst Biosciences.  No partial subset of data from 
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individual investigational sites can be presented or published until after the 
primary manuscript for the entire study has been accepted for publication in a 
peer reviewed scientific journal. 
 
10.2  PROTOCOL AMENDMENT HISTORY 
 
Version 
Date 
Description of Change 
Brief Rationale 
1.0 
23 March 
2018 
 
 
2.0, 
Amendment 
1 
17 October 
2018 
Removed Part 2 and 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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11.  
REFERENCES 
 
1. Mannucci PM, Tuddenham EG. The hemophilias--from royal genes to 
gene therapy. N Engl J Med. 2001;344(23):1773-1779. 
2. Berntorp E, Shapiro AD. Modern haemophilia care. Lancet. 
2012;379(9824):1447-1456.  
3. White GC 2nd, Rosendaal F, Aledort LM, Definitions in hemophilia. 
Recommendation of the scientific subcommittee on factor VIII and factor 
IX of the scientific and standardization committee of the International 
Society on Thrombosis and Haemostasis. Thromb Haemost. 2001;85(3):560. 
4. World Federation of Hemophilia. Guidelines for the Management of 
Hemophilia. 2nd Edition. https://www1.wfh.org/publication/files/pdf-
1472.pdf. Accessed December 18, 2017. 
5. Aznar JA, Lucía F, Abad-Franch L, Jiménez-Yuste V, Pérez R, Batlle J, Balda 
I, Parra R, Cortina VR. Haemophilia in Spain. Haemophilia. 2009;15(3):665-
675. 
6. Katz J. Prevalence of factor IX inhibitors among patients with haemophilia 
B: results of a large-scale North American survey. Haemophilia 
1996;2(1):28–31. 
7. Nerich V, Tissot E, Faradji A, Demesmay K, Bertrand MA, Lorenzini JL, Briquel 
ME, Pouzol P, Woronoff-Lemsi MC. Cost-of-illness study of severe 
haemophilia A and B in five French haemophilia treatment centres. Pharm 
World Sci. 2008;30(3):287-292. 
8. Giangrande P. Haemophilia B: Christmas disease. Expert Opin 
Pharmacother. 2005;6(9):1517-1524. 
9. Fischer K, Van Den Berg M. Prophylaxis for severe haemophilia: clinical 
and economical issues. Haemophilia. 2003;9(4):376-381. 
10. Ljung RC. Prophylactic infusion regimens in the management of 
hemophilia. Thromb Haemost. 1999;82(2):525-530.  
11. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne 
R, Ingram JD, Manco-Johnson ML, Funk S, Jacobson L, Valentino LA, Hoots 
WK, Buchanan GR, DiMichele D, Recht M, Brown D, Leissinger C, Bleak S, 
Cohen A, Mathew P, et al. Prophylaxis versus episodic treatment to 
prevent joint disease in boys with severe hemophilia. N Engl J Med. 
2007;357(6):535-544. 
12. Tagliaferri A, Franchini M, Coppola A, Rivolta GF, Santoro C, Rossetti G, 
Feola G, Zanon E, Dragani A, Iannaccaro P, Radossi P, Mannucci PM.  
Effects of secondary prophylaxis started in adolescent and adult 
haemophiliacs. Haemophilia 2008;14(5):945-951. 
13. Valentino LA, Mamonov V, Hellmann A, Quon DV, Chybicka A, Schroth P, 
Patrone L, Wong WY; Prophylaxis Study Group. A randomized comparison 
of two prophylaxis regimens and a paired comparison of on-demand and 
Dalcinonacog alfa (DalcA) 
Study DLZ-201, Clinical Study Report
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_________________________________________________________________________
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CONFIDENTIAL CATALYST BIOSCIENCES, INC. 
 
 
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                 17 October 2018 
prophylaxis treatments in hemophilia A management. J Thromb Haemost. 
2012;10(3):359-367. 
14. Oldenburg J, Zimmermann R, Katsarou O, Theodossiades G, Zanon E, 
Niemann B, Kellermann E, Lundin B; Cross-sectional MRI study investigators. 
Controlled, cross-sectional MRI evaluation of joint status in severe 
haemophilia A patients treated with prophylaxis vs. on demand. 
Haemophilia. 2015;21(2):171-179. 
15. Andersson NG, Auerswald G, Barnes C, Carcao M, Dunn AL, Fijnvandraat 
K, Hoffmann M, Kavakli K, Kenet G, Kobelt R, Kurnik K, Liesner R, 
Mäkipernaa A, Manco-Johnson MJ, Mancuso ME, Molinari AC, Nolan B, 
Perez Garrido R, Petrini P, Platokouki HE, et al. Intracranial haemorrhage in 
children and adolescents with severe haemophilia A or B - the impact of 
prophylactic treatment. Br J Haematol. 2017;179(2):298. Epub 2017 Jul 12. 
16. Stieltjes N, Calvez T, Demiguel V, Torchet MF, Briquel ME, Fressinaud E, 
Claeyssens S, Coatmelec B, Chambost H; French ICH Study Group. French 
ICH Study Group. Intracranial haemorrhages in French haemophilia 
patients (1991–2001): clinical presentation, management and prognosis 
factors for death. Haemophilia. 2005;11:452–458. 
17. White GC 2nd, Courter S, Bray GL, Lee M, Gomperts ED. A multicenter 
study of recombinant factor VIII (Recombinate) in previously treated 
patients with hemophilia A. The Recombinate Previously Treated Patient 
Study Group. Thromb Haemost. 1997;77(4):660-667. 
18. Santagostino E. Prophylaxis in haemophilia B patients: unresolved issues 
and pharmacoeconomic implications. Haemophilia. 2010;16(Suppl 6):13-
17. 
19. Schulte S. Half-life extension through albumin fusion technologies. Thromb 
Res. 2009;124(Suppl 2):S6-S8. 
20. National Hemophilia Foundation. Fast Facts. Available at 
https://www.hemophilia.org/About-Us/Fast-Facts. Accessed on 
December 18, 2017. 
21. BeneFIX® Coagulation Factor IX (Recombinant) Prescribing Information, 
Wyeth Pharmaceuticals Inc. June 2017. 
22. De Moerloose P, Urbancik W, Van Den Berg HM, Richards M. A survey of 
adherence to haemophilia therapy in six European countries: results and 
recommendations. Haemophilia. 2008;14(5):931-938. 
23. Blanchette P, Rivard G, Israels S, Robinson S, Ali K, Walker I, Stain AM, 
Blanchette V; Association of Hemophilia Clinic Directors of Canada and 
Canadian Association of Nurses in Hemophilia Care. A survey of factor 
prophylaxis in the Canadian haemophilia A population. Haemophilia. 
2004;10(6):679-683. 
24. Hacker MR, Geraghty S, Manco-Johnson M. Barriers to compliance with 
prophylaxis therapy in haemophilia. Haemophilia. 2001;7(4):392-396. 
Dalcinonacog alfa (DalcA) 
Study DLZ-201, Clinical Study Report
Catalyst Biosciences, Inc. 
Final
_________________________________________________________________________
___________________________________________________________________
CONFIDENTIAL
Page 160 of 174
__________________________________________________________________________
__________________________________________________________________________

 
Dalcinonacog alfa_DLZ‐201 VERSION 2.0, Amendment 1 
CONFIDENTIAL CATALYST BIOSCIENCES, INC. 
 
 
77 
 
                 17 October 2018 
25. Gater A, Thomson TA, Strandberg-Larsen M. Haemophilia B: impact on 
patients and economic burden of disease. Thromb Haemost. 
2011;106(3):398-404.  
26. Manco-Johnson MJ. Update on treatment regimens: prophylaxis versus 
on-demand therapy. Semin Hematol. 2003;40(3 Suppl 3):3-9. 
27. Peters RT, Low SC, Kamphaus GD, Dumont JA, Amari JV, Lu Q, Zarbis-
Papastoitsis G, Reidy TJ, Merricks EP, Nichols TC, Bitonti AJ. Prolonged 
activity of factor IX as a monomeric Fc fusion protein. Blood. 
2010;115(10):2057-2064.  
28. Russell KE, Olsen EH, Raymer RA, Merricks EP, Bellinger DA, Read MS, Rup 
BJ, Keith JC Jr, McCarthy KP, Schaub RG, Nichols TC. Reduced bleeding 
events with subcutaneous administration of recombinant human factor IX 
in immune-tolerant hemophilia B dogs. Blood. 2003;102(13):4393-4398.  
29. Nienhuis AW, Nathwani AC, Davidoff AM. Gene Therapy for Hemophilia. 
Mol Ther. 2017;25(5):1163-1167.  
30. Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: 
diagnosis, treatments, and its complications. Lancet. 2016;388(10040):187-
197.  
31. Hartmann J, Croteau SE. 2017 Clinical trials update: Innovations in 
hemophilia therapy. Am J Hematol. 2016;91(12):1252-1260.  
32. Hacker MR, Geraghty S, Manco-Johnson M. Barriers to compliance with 
prophylaxis therapy in haemophilia. Haemophilia. 2001l;7(4):392-396. 
33. Stoner KL, Harder H, Fallowfield LJ, Jenkins VA. Intravenous versus 
Subcutaneous Drug Administration. Which Do Patients Prefer? A 
Systematic Review. The Patient - Patient-Centered Outcomes Research. 
2015;8(2):145–153. 
34. Hong S-B, Levy H, Jung JY, Park M, Seo AR, Seo SH, Madison E. 
Pharmacokinetics of Subcutaneously Administered CB2679d/ISU304 in 
Wild-Type and Hemophilia B Mice. Blood  2016,128(22):1389. 
35. You CW, Shin H-J, Levy H, Lee M, Hong S-B, Siegel JE, Park JY. Phase 1/2 
Trial of Subcutaneously Administered Factor IX Variant CB2679d/ISU304: 
Pharmacokinetics and Activity. Blood 2017 130:87. 
36. Hong S-B, Levy H, Jung JY, Park M, Seo AR, Park JY. Pharmacokinetics of 
Subcutaneously Administered CB2679d/ISU304 in MiniPig Compared With 
BeneFIX. Presented at the European Association for Haemophilia and 
Allied Disorders (EAHAD) in Paris, France. 1-3 February 2017. Poster Number 
P074.  
37. U.S. National Library of Medicine. ClinicalTrials.gov. Dose-escalation Study 
to Investigate the Safety, PK, and PD of ISU304/CB2679d in Hemophilia B 
Patients. NCT03186677. Available at 
https://clinicaltrials.gov/ct2/show/NCT03186677. Accessed on December 
30, 2017. 
Dalcinonacog alfa (DalcA) 
Study DLZ-201, Clinical Study Report
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CONFIDENTIAL CATALYST BIOSCIENCES, INC. 
 
 
78 
 
                 17 October 2018 
38. You CW, Shin H-J, Levy H, Lee M, Hong S-B, Siegel JE, Park JY. Phase 1/2 
Trial of Subcutaneously Administered Factor IX Variant CB2679d/ISU304: 
Pharmacokinetics and Activity. Presented at the 59th Annual Meeting of 
the American Society of Hematology (ASH) in Atlanta, Georgia. 
December 9-12, 2017. Poster Number 87. 
39. Common Terminology Criteria for Adverse Events, Version 5.0. 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/c
tc.htm#ctc_50. November 27, 2017. Accessed December 31, 2017. 
40. Lee ML, Poon Wai-Yin, Kingdon HS. A two-phase linear regression model 
for biologic half-life data. Journal of Laboratory and Clinical Medicine. 
1990;115(6):745-748. 
41. Blanchette VS, Key NS, Ljung LR, et al. Definitions in hemophilia: 
communication from the SSC of the ISTH. J Thromb Haemost 
2014;12:1935−1939. 
 
 
 
 
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APPENDICES 
 
APPENDIX A – CLINICAL SIGNS OF THROMBOSIS 
 
  
http://www.heart.org/HEARTORG/Conditions/VascularHealth/VenousThromboembolism/
Symptoms-and-Diagnosis-of-Venous-Thromboembolism-VTE_UCM_479057_Article.jsp# 
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http://www.heart.org/HEARTORG/Conditions/HeartAttack/WarningSignsofaHeart
Attack/Warning-Signs-of-a-Heart-
Attack_UCM_002039_Article.jsp#.WkkEAWeYpfw  
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http://www.strokeassociation.org/STROKEORG/WarningSigns/Stroke-Warning-
Signs-and-Symptoms_UCM_308528_SubHomePage.jsp  
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Symptoms and Signs of Venous Thromboembolism – Deep Vein Thrombosis (DVT) 
and Pulmonary Embolism (PE): 
 
Leg pain or tenderness of the thigh or calf 
Leg swelling (edema) 
Skin that feels warm to the touch 
Reddish discoloration or red streaks 
 
Unexplained shortness of breath 
Rapid breathing 
Chest pain anywhere under the rib cage (may be worse with deep breathing) 
Fast heart rate 
Light headedness or passing out 
 
 
Common Heart Attack Warning Signs 
 
Pain or discomfort in the chest 
Lightheadedness, nausea, or vomiting 
Jaw, neck, or back pain 
Discomfort or pain in arm or shoulder 
Shortness of breath 
 
Stroke Signs 
 
Face Drooping 
Arm Weakness 
Speech Difficulty 
 
Sudden confusion, trouble speaking or understanding speech 
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Sudden numbness or weakness of face, arm or leg.  Especially on one side of the 
body. 
Sudden trouble seeing in one or both eyes. 
Sudden trouble walking, dizziness, loss of balance or coordination. 
Sudden severe headache with no known cause. 
 
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Signs and Symptoms of Thrombosis 
The clinical spectrum of venous thromboembolism (VTE) ranges from deep vein thrombosis (DVT) to pulmonary 
embolism (PE). The symptoms of VTE depend on the location of the affected vessel and whether the vessel is totally or 
partially occluded by the clot.  
 
Table. Clinical Spectrum of VTE 
 
Type 
Signs and Symptoms 
Physical Examination 
Deep vein thrombosis (DVT) 
•Blood clots may form in the deep blood 
vessels, most commonly in the legs and groin, 
and can block normal blood flow returning from 
the legs to the heart. 
•Venous clots that form in regions of slow to 
moderate flow are composed of a mixture of 
red cells, platelets, and fibrin and are known as 
mixed platelet fibrin thrombi. 
•Partially occlusive venous thrombosis of the 
deep veins in the legs or abdomen may present 
with subtle symptoms and sometimes may not 
present until significant collateral circulation* 
has developed. 
 
 
Pain 
 
Swelling of the affected 
extremity/area with 
erythema and warmth over 
the vicinity of the clot 
 
Discoloration including a 
bluish or suffused color 
 
 
Positive Homan’s sign: pain with 
dorsiflexion of the foot 
 
Swelling 
 
Pain on palpation 
 
Presence of a palpable cord 
 
Evidence of collateral circulation, 
usually manifested by increased 
prominence of superficial veins 
 
Some people with a DVT may be 
asymptomatic 
 
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Pulmonary Embolism (PE) 
•PE results from a piece or all of a blood clot 
that breaks off and is carried by the blood 
stream to the lung where it obstructs the blood 
vessel. 
•The size of the clot and the site of the 
obstruction of blood flow in the vessel 
determine the extent and severity of the 
pulmonary embolus. 
•Proximal vein thrombosis is more likely to lead 
to fatal PE as compared to calf vein thrombosis. 
•The incidence of fatal PE can be markedly 
reduced if DVT is treated with anticoagulant 
therapy.  
 
Pulmonary emboli may present 
subtly with the following 
complaints listed in order of 
frequency: 
 
Dyspnea 
 
Rapid breathing, fast 
heartbeat and chest pain 
especially with inhalation 
 
Pleural pain: Some patients 
notice only a dull ache in 
their chest 
 
Apprehension, anxiety 
 
Cough 
 
Hemoptysis 
 
Sweats 
 
Syncope 
 
Fatigue 
 
Tachypnea 
 
Tachycardia 
 
Rales 
 
Fever 
 
Sweating 
 
Thrombophlebitis 
 
Accentuation of the pulmonary 
closure sound 
 
Gallop heart sound 
 
Cyanosis 
 
Some people with a PE may be 
asymptomatic 
 
Superficial Thrombophlebitis 
•Superficial thrombophlebitis is due to blood 
clots that form in veins that are closer to the 
surface of the skin and are associated with 
inflammation. 
 
These clots often partially block blood flow in affected veins and may 
cause pain and irritation. 
 
Redness and inflammation along the vein may occur; if hard and 
erythematous, the affected vein is often visible and most commonly 
occurs in the legs or arms.  
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•Superficial thrombophlebitis is often observed 
in individuals who are heterozygous or 
homozygous for the factor V Leiden mutation. 
 
 
Other associated symptoms include warmth and tenderness, 
surrounding purities and swelling. 
 
Pain along the vein: patients may report a throbbing or burning 
sensation beneath the skin’s surface; these symptoms may interfere 
with sleep as they progress. 
Fever: Patients with venous inflammation may develop an elevated 
temperature associated with an episode of thrombophlebitis. 
 
Adapted from IHTC. Signs and Symptoms of Thrombosis. Available at http://www.ihtc.org/payors/conditions-we-
treat/clotting-disorders/signs-and-symptoms-of-thrombosis.
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APPENDIX B – DETAILED STUDY SCHEMA 
 
 
 
 
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