Clinical trial NCT04571645
Conditions: Acute Myeloid Leukemia
Keywords: AML
Sponsor: Chimerix
Start date: 2021-04-30; Completion date: 2022-05-16
Enrollment: 9 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Phase 3 study to evaluate the efficacy and safety of dociparstat sodium in adults with newly diagnosed untreated acute myeloid leukemia (AML) with adverse or intermediate genetic risk.

Detailed description:
A Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of dociparstat sodium in combination with standard intensive induction and consolidation chemotherapy for the treatment of newly-diagnosed acute myeloid leukemia (AML) patients.

Arms: arm 1: Treatment with standard intensive induction, reinduction, or consolidation chemotherapy and dociparstat 4 mg/kg intravenous (IV) bolus on Day 1, administered 30 minutes after completion of the first dose of idarubicin or daunorubicin, followed by dociparstat 0.25 mg/kg/hr via continuous IV infusion 24 hours daily for 5 or 7 days. arm 2: Treatment with standard intensive induction, reinduction, or consolidation chemotherapy and placebo intravenous (IV) bolus on Day 1, administered 30 minutes after completion of the first dose of idarubicin or daunorubicin, followed by placebo via continuous IV infusion 24 hours daily for 5 or 7 days.
Interventions: intervention 1: Dociparstat intervention 2: Control
Intervention descriptions: intervention 1: Dociparstat is a glycosaminoglycan derived from porcine heparin. intervention 2: 0.9% Normal Saline

Protocol documents:
Prot_SAP_000.pdf: 
Protocol CMX-DS-003 
Amendment 2; 19 August 2021 
 
 
 
 
Title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and 
Safety of Dociparstat Sodium in Combination With Standard Chemotherapy for the Treatment of 
Newly-Diagnosed Acute Myeloid Leukemia 
ClinicalTrials.gov Identifier: NCT04571645 
Date: 19 August 2021 


Protocol CMX-DS-003 
 
Amendment 2: 19 August 2021 
 
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TITLE PAGE 
 
Protocol Title:  
A randomized, double-blind, placebo-controlled study to evaluate the efficacy 
and safety of dociparstat sodium in combination with standard chemotherapy 
for the treatment of newly-diagnosed acute myeloid leukemia 
Protocol Number: CMX-DS-003 
Compound: Dociparstat sodium (DSTAT; CX-01) 
Study Phase: 3 
Short Title: Dociparstat in AML with Standard Chemotherapy (DASH AML) 
 
Sponsor Name: Chimerix, Inc 
Legal Registered Address: 2505 Meridian Parkway, Suite 100; Durham, NC USA 27713 
 
Regulatory Agency Identifier Number(s): US IND 118960 
 
Protocol Version Date: 19 August 2021 (Amendment 2) 
 
Sponsor Signatory: Allen Melemed, Chief Medical Officer 
 
Medical Monitor Name and Contact Information: Refer to the Study Reference Manual  


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
1. 
PROTOCOL SYNOPSIS .............................................................................................6 
1.1. 
Study Schema .............................................................................................................16 
1.2. 
Schedule of Activities .................................................................................................17 
2. 
INTRODUCTION ......................................................................................................21 
2.1. 
Study Rationale ...........................................................................................................21 
2.2. 
Background .................................................................................................................21 
2.3. 
Benefit/Risk Assessment ............................................................................................22 
2.3.1. 
Risk Assessment .........................................................................................................22 
2.3.2. 
Benefit Assessment .....................................................................................................23 
2.3.3. 
Overall Benefit: Risk Conclusion ...............................................................................23 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................24 
4. 
STUDY DESIGN .......................................................................................................26 
4.1. 
Overall Design ............................................................................................................26 
4.2. 
Scientific Rationale for Study Design ........................................................................26 
4.3. 
Justification for Dose ..................................................................................................27 
4.4. 
End of Study Definition ..............................................................................................28 
5. 
STUDY POPULATION .............................................................................................29 
5.1. 
Inclusion Criteria ........................................................................................................29 
5.2. 
Exclusion Criteria .......................................................................................................30 
5.3. 
Screen Failures ............................................................................................................31 
6. 
STUDY INTERVENTION ........................................................................................32 
6.1. 
Study Intervention(s) Administered ...........................................................................32 
6.2. 
Preparation, Handling, Storage, and Accountability ..................................................35 
6.2.1. 
Dose Preparation .........................................................................................................35 
6.2.2. 
Handling, Storage, and Accountability .......................................................................35 
6.3. 
Dose Modification ......................................................................................................36 
6.4. 
Measures to Minimize Bias: Randomization and Blinding ........................................36 
6.5. 
Study Intervention Compliance ..................................................................................37 
6.6. 
Concomitant Therapy .................................................................................................37 
6.6.1. 
Prohibited Therapies ...................................................................................................38 


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6.6.2. 
Permitted Therapies ....................................................................................................39 
6.7. 
Intervention after the End of the Study .......................................................................39 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL .......................................40 
7.1. 
Interruption of Study Intervention ..............................................................................40 
7.2. 
Discontinuation of Study Intervention........................................................................41 
7.3. 
Participant Withdrawal from the Study ......................................................................41 
7.4. 
Lost to Follow-up .......................................................................................................42 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................43 
8.1. 
Screening ....................................................................................................................43 
8.2. 
Efficacy Assessments .................................................................................................44 
8.2.1. 
Bone Marrow Aspirate/Biopsy and Peripheral Blood Assessments...........................44 
8.2.2. 
Response Criteria and Outcome Measures .................................................................45 
8.2.3. 
Long-Term Follow-up ................................................................................................47 
8.3. 
Safety Assessments .....................................................................................................47 
8.3.1. 
Physical Examinations ................................................................................................47 
8.3.2. 
Vital Signs ..................................................................................................................48 
8.3.3. 
Electrocardiograms .....................................................................................................48 
8.3.4. 
Clinical Safety Laboratory Assessments ....................................................................49 
8.4. 
Adverse Events and Serious Adverse Events .............................................................50 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................50 
8.4.2. 
Method of Detecting AEs and SAEs ..........................................................................51 
8.4.3. 
Follow-up of AEs and SAEs .......................................................................................51 
8.4.4. 
Regulatory Reporting Requirements for SAEs ...........................................................51 
8.4.5. 
Death Events ...............................................................................................................52 
8.4.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
AEs or SAEs ...............................................................................................................52 
8.4.7. 
Adverse Events of Special Interest .............................................................................52 
8.5. 
Treatment of Overdose ...............................................................................................53 
8.6. 
Pharmacokinetics ........................................................................................................53 
8.7. 
Pharmacodynamics .....................................................................................................54 
8.8. 
Genetics ......................................................................................................................54 
8.9. 
Biomarkers ..................................................................................................................55 


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8.10. 
Medical Resource Utilization .....................................................................................56 
9. 
STATISTICAL CONSIDERATIONS .......................................................................57 
9.1. 
Statistical Hypotheses .................................................................................................57 
9.2. 
Sample Size Determination ........................................................................................57 
9.3. 
Analysis Sets ...............................................................................................................57 
9.4. 
Statistical Analyses .....................................................................................................58 
9.4.1. 
Primary Endpoint ........................................................................................................58 
9.4.2. 
Key Secondary Endpoint ............................................................................................58 
9.4.3. 
Other Secondary Endpoints ........................................................................................59 
9.4.4. 
Safety Analyses ..........................................................................................................59 
9.4.4.1. 
Adverse Events ...........................................................................................................59 
9.4.4.2. 
Laboratory Results ......................................................................................................60 
9.4.4.3. 
Safety Subgroup Analyses ..........................................................................................60 
9.4.5. 
Other Analyses ............................................................................................................60 
9.5. 
Interim Analyses .........................................................................................................60 
9.6. 
Data Monitoring Committee .......................................................................................62 
10. 
REFERENCES ...........................................................................................................63 
11. 
APPENDICES: SUPPORTING DOCUMENTATION AND 
OPERATIONAL CONSIDERATIONS .....................................................................64 
11.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ....................64 
11.1.1. 
Regulatory and Ethical Considerations ......................................................................64 
11.1.2. 
Financial Disclosure ...................................................................................................64 
11.1.3. 
Informed Consent Process ..........................................................................................65 
11.1.4. 
Data Protection ...........................................................................................................65 
11.1.5. 
Data Quality Assurance ..............................................................................................66 
11.1.6. 
Source Documents ......................................................................................................67 
11.1.7. 
Study and Site Start and Closure ................................................................................67 
11.1.8. 
Dissemination of Clinical Study Data ........................................................................67 
11.1.9. 
Publication Policy .......................................................................................................68 
11.2. 
Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................69 
11.2.1. 
Definition of an AE ....................................................................................................69 
11.2.2. 
Definition of an SAE ..................................................................................................70 


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11.2.3. 
Recording and Follow-Up of AEs, SAEs, and AEs of Special Interest .....................71 
11.2.4. 
Reporting of SAEs ......................................................................................................72 
11.3. 
Appendix 3: Contraceptive Guidance and Pregnancy Reporting ...............................73 
11.3.1. 
Definitions ..................................................................................................................73 
11.3.2. 
Contraception Guidance .............................................................................................74 
11.3.3. 
Collection of Pregnancy Information .........................................................................76 
11.4. 
Appendix 4: Genetic Risk Categories.........................................................................77 
11.5. 
Appendix 5: ECOG Performance Status (and Associated Karnofsky Grades) ..........78 
11.6. 
Appendix 6: Drugs Known to Prolong the QT Interval .............................................79 
11.7. 
Appendix 7: Definitions of Terms ..............................................................................80 
11.8. 
Appendix 8: Abbreviations .........................................................................................82 
11.9. 
Appendix 9: Protocol Amendment Summary of Changes .........................................84 
SPONSOR’S SIGNATURE PAGE ...............................................................................................87 
INVESTIGATOR AGREEMENT.................................................................................................88 
 
LIST OF TABLES 
Table 1: 
Schedule of Activities/Assessments: Induction Cycle and Reinduction Cycle 
(as applicable) .............................................................................................................17 
Table 2: 
Schedule of Activities/Assessments: Consolidation Cycles .......................................20 
Table 3: 
Dociparstat Details ......................................................................................................32 
Table 4: 
Standard of Care Therapy Details ...............................................................................33 
Table 5: 
Dosing Regimen for Induction and Consolidation Therapy .......................................34 
Table 6: 
Bone Marrow and Peripheral Blood Efficacy Assessments .......................................44 
Table 7: 
Response Criteria and Outcomes Measures ...............................................................45 
Table 8: 
Laboratory Assessments .............................................................................................50 
Table 9: 
Sample Collection Time Points for MRD Analyses and for Biobanking ...................56 
Table 10: Changes Included in Amendment 1 ............................................................................84 
Table 11: Changes Included in Amendment 2 ............................................................................86 
 
LIST OF FIGURES 
Figure 1: 
Treatment Algorithm ..................................................................................................16 
 


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1. 
PROTOCOL SYNOPSIS 
Name of Sponsor:  
Chimerix, Inc; 2505 Meridian Parkway, Suite 100; Durham, NC USA 27713 
Name of Investigational Product: dociparstat sodium (DSTAT; CX-01) 
Name of Active Ingredient: 2-O, 3-O desulfated heparin 
Protocol Number: CMX-DS-003 
Version Date: 19 August 2021 (Amendment 2) 
Phase: 3 
Title of Study: A randomized, double-blind, placebo-controlled study to evaluate the efficacy and 
safety of dociparstat sodium in combination with standard chemotherapy for the treatment of 
newly-diagnosed acute myeloid leukemia 
Short Title: Dociparstat in AML with Standard Chemotherapy (DASH AML)  
Regulatory Agency Identifier Number(s): US IND 118960; NCT04571645 
Study Centers: This study will be conducted at approximately 120 centers in the United States, 
Canada, and other regions (e.g., Australia, Europe) based on feasibility results. 
Number of Participants: Approximately 1000 potential participants are expected to be screened to 
achieve a total of approximately 570 participants randomly assigned to study intervention. 
Rationale: Dociparstat sodium is a glycosaminoglycan compound derived from porcine heparin that 
has low anticoagulant activity, but retains the ability to inhibit activities of key proteins implicated in 
the resistance of acute myeloid leukemia (AML) blasts and leukemic stem cells to chemotherapy 
(e.g., CXCL12, high mobility group box protein 1 [HMGB1], neutrophil elastase). Dociparstat also 
inhibits platelet factor 4, which has been demonstrated to play a key role in the maintenance of 
hematopoietic stem cell quiescence and impairment of platelet recovery after chemotherapy. 
The current study is being conducted to confirm positive results in previous studies of dociparstat for 
the treatment of AML and to show the benefits of adding dociparstat to standard 7+3 chemotherapy 
versus chemotherapy alone for the treatment of newly-diagnosed AML in adults. 
An open-label pilot study of dociparstat plus standard 7+3 chemotherapy showed positive results in 
12 participants with newly-diagnosed AML (NCT02056782). A randomized, controlled, Phase 2b, 
dose-finding study (NCT02873338) evaluated dociparstat (4 mg/kg intravenous [IV] bolus followed by 
either 0.125 or 0.25 mg/kg/hr continuous IV infusion for 7 days) in combination with standard 7+3 
chemotherapy versus chemotherapy alone in 75 participants ≥60 years of age with newly-diagnosed 
AML. Results for combined complete remission with complete hematologic recovery (CR) and 
complete remission with incomplete hematologic recovery (CRi) rates in the dociparstat 0.125 
mg/kg/hr and 0.25 mg/kg/hr groups were generally comparable to the chemotherapy alone control 
group. Observed overall survival (OS) was longer in the dociparstat 0.25 mg/kg/hr group (median not 
reached [median follow-up for survivors was 20 months]) than the control group (median 11.7 months 
[95% confidence interval (CI): 7.6, nc]) (observed hazard ratio [HR] 0.68 [95% CI: 0.29, 1.57]). A 
subset analysis of participants meeting the target inclusion criteria for this Phase 3 study demonstrated 
a favorable observed HR for dociparstat 0.25 mg/kg/hr (N=20) versus control (N=19) for OS of 0.51. 
Combination treatment with 7+3 chemotherapy and dociparstat did not show increased toxicity 
compared with 7+3 chemotherapy alone, nor did it prolong time to platelet or neutrophil recovery. 


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Overall Design: 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to 
evaluate the efficacy and safety of dociparstat sodium in combination with standard intensive induction 
chemotherapy (i.e., cytarabine plus either idarubicin or daunorubicin “7+3” treatment regimen) and 
cytarabine consolidation chemotherapy versus placebo in combination with standard chemotherapy 
(i.e., chemotherapy alone) for the treatment of newly-diagnosed AML. This study will enroll 
approximately 570 adults with de novo AML who are ≥18 years old with intermediate or adverse 
genetic risk (based on European LeukemiaNet [ELN] 2017 criteria), and who are considered fit for 
intensive induction chemotherapy.  
After completion of all screening evaluations, eligible participants will be randomized by an interactive 
response technology system in a 1:1 ratio to receive either dociparstat plus standard chemotherapy or 
placebo plus standard chemotherapy. Randomization will be stratified based upon FMS-like tyrosine 
kinase 3 (FLT3) status (FLT3-internal tandem duplication [ITD] or tyrosine kinase domain [TKD] 
positive vs FLT3 mutation negative), genetic risk (intermediate vs adverse), and age (<65 years vs 
≥65 years). Of the first 80 participants enrolled, the number of participants between 18 to 59 years of 
age with intermediate genetic risk will be limited to 20. 
Under this protocol, participants will receive an initial induction cycle of 7+3 chemotherapy, a 
reinduction cycle if bone marrow at Day 14 to 23 shows persistent disease, and up to 4 cycles of 
consolidation chemotherapy. Treatment response will be assessed by examination of bone marrow 
aspirates/biopsies and complete blood counts during and at the end of each treatment cycle. After 
completion (or discontinuation) of protocol treatment, long-term follow-up information will continue 
to be collected until death or for 5 years after randomization. 
The study treatment algorithm is shown in Figure 1. The schedule of activities/assessments is presented 
in Table 1 for induction cycles and in Table 2 for consolidation cycles. 
Note: For the purposes of this study, blinded “study intervention” refers to IV dociparstat or placebo; 
“standard chemotherapy” and “chemotherapy” refer to the use of cytarabine + anthracycline (either 
daunorubicin or idarubicin) induction/reinduction therapy, followed by cytarabine consolidation 
therapy when indicated (although it is recognized that what is standard in one center may not be the 
same in other regions); “7+3” may specifically refer to the use of 7 days of cytarabine + 3 days of 
anthracycline for induction therapy, but more generally also includes reinduction and consolidation 
therapy that follow induction; and “chemotherapy alone” refers to the combination of placebo plus 
active standard 7+3 chemotherapy. “Induction therapy” is inclusive of the initial induction cycle and a 
reinduction cycle when applicable.  
Objectives and Endpoints 
Objectives 
Endpoints 
Primary Efficacy 
 
• To compare the efficacy of dociparstat 
plus standard chemotherapy versus 
standard chemotherapy alone as upfront 
treatment for newly-diagnosed AML 
• Overall survival (OS).  


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Objectives 
Endpoints 
Key Secondary Efficacy 
 
• To compare the efficacy of dociparstat 
plus chemotherapy versus chemotherapy 
alone with respect to event-free survival 
(EFS). 
• EFS following CR. Defined as time from 
randomization to treatment failure, relapse, or death 
from any cause, whichever occurs first, with 
treatment failure defined as failure to achieve CR 
within 42 days of the start of induction (or start of 
reinduction, when applicable). 
Secondary Efficacy 
 
• To compare the efficacy of dociparstat 
plus chemotherapy versus chemotherapy 
alone with respect to event- and relapse-
free survival. 
• EFS following CR/CRi, with treatment failure 
defined as failure to achieve CR/CRi within 42 days 
of the start of induction (or start of reinduction, when 
applicable). 
• Relapse-free survival (RFS) after CR. 
• RFS after CR/CRi.  
To compare measurable residual disease 
(MRD) status with dociparstat plus 
chemotherapy versus chemotherapy alone.  
• Proportion of participants who achieve CR with 
MRDneg, as determined by multiparameter 
(multicolor) flow cytometry (MFC), at the end of 
induction and consolidation therapy. 
• Proportion of participants who achieve CR/CRi with 
MRDneg, as determined by MFC, at the end of 
induction and consolidation therapy. 
• Proportion of participants who achieve MRDneg 
(regardless of CR), as determined by MFC, at the end 
of induction and consolidation therapy. 
• Association between CR with MRDneg and relapse. 
• Association between MRDneg and relapse. 
• Association between MRDneg and OS.  
• To compare post-induction response 
rates after treatment with dociparstat 
plus chemotherapy versus chemotherapy 
alone. 
• Proportion of participants who achieve CR. 
• Proportion of participants who achieve CR/CRi. 
• Proportion of participants who achieve CR or 
complete remission with partial hematologic recovery 
(CRh). 
• To compare rates of hematopoietic stem 
cell transplant (HCT) after treatment 
with dociparstat plus chemotherapy 
versus chemotherapy alone. 
• Proportion of participants who receive an allogeneic 
HCT during the study. 
• Proportion of participants who receive any HCT 
(allogeneic or autologous) during the study. 
• To compare relapse rates after treatment 
with dociparstat plus chemotherapy 
versus chemotherapy alone. 
 
• Cumulative incidence of relapse after CR.  
• Cumulative incidence of relapse after CR/CRi. 


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• To compare the time to hematologic 
recovery after induction or reinduction 
(if indicated) with dociparstat plus 
chemotherapy versus chemotherapy 
alone. 
• Time to recovery of neutrophil count (absolute 
neutrophil count [ANC] >500/μL and >1000/μL). 
• Time to transfusion-independent platelet recovery 
(>20,000/μL, >50,000/μL, and >100,000/μL). 
• Incidence of prolonged neutropenia (ANC ≤500/μL 
past cycle Day 42 in the absence of active leukemia). 
• Incidence of prolonged thrombocytopenia (platelets 
≤50,000/μL past cycle Day 42 in the absence of 
active leukemia). 
• Other 
 
• To evaluate the consistency of 
dociparstat treatment effects across 
subgroups. 
EFS, OS, and MRDneg across subgroups (e.g., age 
categories, genetic risk categories). 
To evaluate the pharmacokinetic (PK) 
profile of dociparstat. 
Dociparstat PK parameters, including area under the 
concentration-time curve (AUC), maximum observed 
concentration (Cmax), time to maximum observed 
concentration (Tmax), terminal elimination half-life 
(t½), and clearance, and others as data permit. 
• To evaluate the impact of dociparstat on 
medical resource utilization during 
induction and consolidation treatment. 
• Number of days hospitalized. 
• Number of days in intensive care unit setting. 
• Number of blood product (packed red blood cells, 
platelets) units administered. 
• Number of growth factor administrations. 
• Safety 
 
• To assess the safety and tolerability of 
dociparstat plus chemotherapy versus 
chemotherapy alone for the treatment of 
newly-diagnosed AML. 
• Incidence of adverse events (AEs): overall, 
treatment-related, Grade 3 or higher in severity, 
serious, fatal, and those resulting in treatment 
discontinuation. 
• Incidence of AEs of special interest. 
• Change from baseline in clinical laboratory 
parameters. 
• Distribution of graded clinical laboratory results. 
• Proportion of participants who meet defined QT/QTc 
criteria. 
• Incidence of mortality at Day 30 and Day 60. 
Diagnosis and Criteria for Inclusion:  
The medical monitor (or designee) will review key entry criteria to confirm eligibility for 
randomization. 
A potential participant must meet all the following criteria to be eligible to participate in the study: 
1. Newly-diagnosed, previously untreated AML (according to World Health Organization 
criteria) with at least 20% blasts in the peripheral blood or bone marrow.  


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2. Age ≥18 years. 
a. Adverse genetic risk (according to ELN criteria), defined as any of the following genetic 
abnormalities:  
− 
t(6;9)(p23;q34.1); DEK-NUP214 
− 
t(v;11q23.3); KMT2A rearranged 
− 
t(9;22)(q34.1;q11.2); BCR-ABL1 
− 
inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM(EVI1) 
− 
-5 or del(5q); -7; -17/abn(17p) 
− 
Complex karyotype, monosomal karyotype 
− 
Wild-type NPM1 and FLT3-ITDhigh 
− 
Mutated RUNX1, mutated ASXL1, or mutated TP53 
OR 
b. Intermediate genetic risk (according to ELN criteria), defined as any of the following 
genetic abnormalities: 
− 
Mutated NPM1 and FLT3-ITDhigh 
− 
Wild-type NPM1 without FLT3-ITD or with FLT3-ITDlow (without adverse-risk 
genetic lesions) 
− 
t(9;11)(p21.3;q23.3); MLLT3-KMT2A 
− 
Cytogenetic abnormalities not classified as favorable or adverse 
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 
4. Provide written informed consent to participate in the study. 
Criteria for Exclusion: 
A potential participant who meets any of the following criteria is not eligible to participate in the 
study: 
Leukemia exclusions: 
1. Acute promyelocytic leukemia (t(15;17)), myeloid sarcoma without bone marrow 
involvement, or blast transformation of chronic myelogenous leukemia.  
2. Not applicable (criterion removed in Amendment 1). 
3. Not applicable (criterion removed in Amendment 1). 
4. Clinical evidence of active central nervous system leukemia. 
Prior/concomitant therapy: 
5. AML treatment, including Vyxeos (CPX-351, liposomal cytarabine and daunorubicin), 
gemtuzumab ozogamicin, or any other prohibited concomitant AML therapy previously 
received.  
Note: Prior hydroxyurea and emergency leukapheresis to control white blood cell count are 
allowed. All-trans retinoic acid during workup and a single dose of intrathecal cytarabine 
and/or methotrexate is permitted for participants undergoing lumbar puncture to evaluate 
central nervous system involvement. 
6. Receiving any form of anticoagulant therapy (e.g., unfractionated heparin, low molecular 
weight heparin, coumadin, factor Xa inhibitors).  
Note: Heparin flush of indwelling catheters is permitted. 


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7. Treatment with any other investigational agent within 28 days or 5 half-lives, whichever is 
longer, prior to baseline. 
8. Any major surgery or radiation therapy within 28 days prior to baseline. 
Medical conditions: 
9. Immediately life threatening, severe complications of leukemia such as pneumonia with 
hypoxia or shock, and/or disseminated intravascular coagulation. 
10. Active or uncontrolled bleeding at the time of randomization; a bleeding disorder, either 
inherited or caused by disease; history of known arterial-venous malformation, intracranial 
hemorrhage, or suspected or known cerebral aneurysm; or clinically significant (in the 
judgment of the investigator) gastrointestinal bleeding within the 3 weeks prior to 
randomization. 
11. Presence of significant active or uncontrolled infection, including HIV or hepatitis B or C. 
Note: Patients with an infection receiving treatment (antibiotic, antifungal, or antiviral 
treatment) may be entered into the study but must be afebrile and hemodynamically stable for 
≥72 hours. Patients with current evidence of invasive fungal infection (positive blood or tissue 
culture) must have subsequent negative cultures to be eligible. 
12. Active (uncontrolled, metastatic) second malignancy.  
Note: A second malignancy that is in remission may be permitted if there is clinical evidence 
of disease stability for a period of greater than 6 months off cytotoxic chemotherapy that is 
documented by imaging, tumor marker studies, etc. Long-term nonchemotherapy treatment 
(e.g., hormonal therapy) is acceptable. 
13. Psychiatric or neurologic conditions that could compromise participant safety or compliance. 
14. History of severe congestive heart failure or other cardiac disease that contraindicates the use 
of idarubicin or daunorubicin (e.g., cardiac ejection fraction <45%, as determined by 
echocardiography or multigated acquisition scan). 
Diagnostic assessments: 
15. QTc >480 msec (see Section 8.3.3 for details about QTc correction formulas). 
16. Severe renal impairment, as determined by calculated creatinine clearance <30 mL/min 
or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2. 
17. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x upper limit of 
normal (ULN) or total bilirubin >2x ULN. 
Other: 
18. Woman of childbearing potential who is pregnant, breastfeeding, and/or not using a highly 
effective method of contraception (consistent with local regulations regarding the methods of 
contraception for those participating in clinical studies). 
19. History of allergy or hypersensitivity to heparin, pork, or any excipients in the dociparstat 
formulation. 
20. Any other condition, including abnormal laboratory values, that, in the judgement of the 
investigator, could put the participant at increased risk or interfere with the conduct or planned 
analyses of the study. 


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Intervention Groups and Duration: All participants will receive treatment with an initial cycle of 
standard intensive induction chemotherapy (i.e., cytarabine plus either idarubicin or daunorubicin 
“7+3” treatment regimen) in combination with randomized study intervention (i.e., dociparstat or 
placebo). Participants may also receive a reinduction cycle if bone marrow at Day 14 to 23 shows 
persistent disease, and up to 4 cycles of consolidation chemotherapy. The specific visit schedule and 
number of cycles of treatment will be dependent on institutional standard practice and each 
participant’s individual response to treatment. 
Study intervention dosing is calculated based on weight and chemotherapy dosing is calculated based 
on body surface area. 
 
Standard of Care / Background 
Chemotherapy 
Study Intervention 
Induction 
cycle –  
all participants 
    and 
Reinduction 
cycle (as 
indicated) –
participants 
18 to 59 years 
All participants will receive an initial 
induction cycle: 
• Cytarabine 100 mg/m2/day via 
continuous IV infusion 24 hours daily for 
7 days (Day 1 to Day 8) AND 
• Anthracycline once daily for 3 days 
(on Day 1, Day 2, and Day 3): 
o Idarubicin 12 mg/m2 by slow (10 to 
15 minutes) IV injection OR 
o Daunorubicin 60 mg/m2 via rapidly 
flowing IV infusion 
Note: FLT3-positive participants may 
receive cytarabine 200 mg/m2/day. 
When reinduction is indicated, 
participants 18 to 59 years will receive the 
same dosing schedule. 
• Dociparstat 4 mg/kg or placebo IV 
bolus on Day 1, administered 
30 minutes after completion of the 
first dose of idarubicin or 
daunorubicin, followed by  
• Dociparstat 0.25 mg/kg/hr or placebo 
by continuous IV infusion for 
24 hours daily for 7 days (starting on 
Day 1 and ending on Day 8 
[168 hours]) 
Reinduction 
cycle (as 
indicated) –
participants 
≥60 years  
When reinduction is indicated, 
participants ≥60 years will receive a 
modified dosing schedule: 
• Cytarabine 100 mg/m2/day via 
continuous IV infusion for 5 days AND  
• Anthracycline on Day 1 and Day 2:  
o Idarubicin 12 mg/m2 by slow (10 to 
15 minutes) IV injection OR  
o Daunorubicin 60 mg/m2 given via 
rapidly flowing IV infusion 
Note: FLT3-positive participants may 
receive cytarabine 200 mg/m2/day. 
• Dociparstat 4 mg/kg or placebo IV 
bolus on Day 1, administered 
30 minutes after completion of the 
first dose of idarubicin or 
daunorubicin, followed by  
• Dociparstat 0.25 mg/kg/hr or placebo 
by continuous IV infusion for 
24 hours daily for 5 days (starting on 
Day 1 and ending on Day 6 
[120 hours]) 


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Consolidation 
cycles (up to 
4 cycles, as 
applicable) 
Only participants with a documented 
response (CR or CRi) are eligible for 
consolidation. 
• Cytarabine via IV infusion over 3 hours, 
administered twice daily (at 12-hour 
intervals) on Day 1, Day 3, and Day 5 
o Age 18-59 years: 3 g/m2/dose 
o Age ≥60 years: 1.5 g/m2/dose 
• Dociparstat 4 mg/kg or placebo IV 
bolus on Day 1, administered 
30 minutes after completion of the 
first dose of cytarabine, followed by  
• Dociparstat 0.25 mg/kg/hr or placebo 
by continuous IV infusion for 
24 hours daily for 5 days (starting on 
Day 1 and ending on Day 6 
[120 hours]) 
Note: Participants with a FLT3 mutation may also receive treatment with midostaurin at the investigator’s 
discretion and dependent on local availability. 
Interruption of Study Intervention: 
Infusion of study intervention (i.e., dociparstat or placebo) will be interrupted in the following 
situations: 
aPTT: Participants with activated partial thromboplastin time (aPTT) >45 seconds will have repeat 
testing performed as soon as practicable. If aPTT is confirmed >45 seconds, interrupt the study 
intervention infusion. To minimize time that the participant is off therapy, perform repeat testing for 
aPTT approximately 2 to 6 hours after interruption (as practicable). Infusion may be resumed once 
aPTT is <35 seconds. Note: samples are not to be obtained from the same line as study intervention 
infusion (e.g., collect via peripheral venipuncture).  
Grade 3 or higher hemorrhagic AEs: Study intervention infusion will be interrupted for Grade 3 or 
higher hemorrhagic AEs in the setting of aPTT >40 seconds, or Grade 3 or higher hemorrhagic AEs 
that are deemed to be related to study intervention, regardless of aPTT. Study intervention infusion 
may be resumed once the participant is determined to be stable and the aPTT is <35 seconds.  
Note: Grade 3 or higher hemorrhagic AEs are also considered AEs of special interest. 
Renal function: If the calculated creatinine clearance drops below 30 mL/min or eGFR drops below 
30 mL/min/1.73 m2 prior to or during dosing with study intervention, the infusion will be held until the 
creatinine clearance or eGFR rises to ≥30. 
QTc: Study intervention infusion will be interrupted if a participant meets any of the following criteria 
(based on the average of triplicate electrocardiogram [ECG] readings): 
• 
Without underlying bundle branch block: 
− 
Interrupt for QTc >500 msec OR uncorrected QT >600 msec 
• 
With underlying bundle branch block: 
− 
If baseline QTc <450 msec, then interrupt for QTc >500 msec 
− 
If baseline QTc 450 to 480 msec, then interrupt for QTc >530 msec 
In the event of prolonged QTc, the participant should also be assessed for other medications that may 
impact QT interval, with any necessary changes made to concomitant medications. Infusion of study 
intervention may be resumed once QTc is <480 msec. Following resumption of infusion, ECGs are to 
be checked daily until the participant has had 3 consecutive (daily) tracings with QTc <480 msec, after 
which follow-up ECGs will be as per institutional standard of care. 
Bilirubin: If total bilirubin is >2 mg/dL, refer to the daunorubicin/idarubicin product label for dosage 
adjustments. No adjustment to the study intervention dosing is recommended. 
Anticoagulant therapy: If a participant requires short-term anticoagulant therapy, interrupt the 
administration of study intervention. Infusions may be resumed if anticoagulant therapy is discontinued 
and aPTT is <35 seconds. 


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Note: If study intervention is interrupted and not restarted during the same treatment cycle, the 
participant may receive study intervention (bolus and infusion) during the next treatment cycle 
(assuming the participant no longer meets any of the interruption criteria). 
Criteria for Evaluation 
Induction and consolidation treatments are administered as cycles. A complete treatment cycle consists 
of the administration of therapy (i.e., chemotherapy with cytarabine ± anthracycline plus blinded study 
intervention) and all scheduled assessments to evaluate the response to treatment, including bone 
marrow and hematologic recovery. The complete duration of a treatment cycle is dependent on the 
individual participant’s response to treatment. 
Bone marrow assessments include morphology (cytology), cytogenetics (cell culture and banding 
analyses), MRD via MFC, and biobanking for future analyses. 
Efficacy will be evaluated during and at the end of each treatment cycle. PK will be assessed (at sites 
with appropriate capabilities) during the initial induction cycle. Safety will be monitored from the time 
of consent through 42 days after the start of the last treatment cycle (whether or not treatment is 
completed or discontinued early). 
Long-Term Follow-up: 
After completion or discontinuation of study intervention, participants will be followed-up until death 
or for 5 years after randomization. Contact with the participant (or caregiver or treating physician, as 
applicable) will be made every 3 months for the first 24 months, then every 6 months for the remaining 
follow-up period. The following information will be collected as applicable: disease status (relapse 
date), death date, cause of death, and related source documentation. In addition, all AML therapies 
(i.e., for the treatment of AML and/or prevention of relapse) will be collected from 43 days after start 
of the last treatment cycle through the time of last study follow-up. 
Data Monitoring Committee: Study data will be periodically reviewed by an independent, unblinded, 
data monitoring committee (DMC). Details of the DMC membership and review procedures will be 
outlined in a separate charter. 
Interim Analysis: 
Two interim analyses are planned. 
The first interim analysis will be an early unblinded (only to the DMC) assessment of CR, CR with 
MRDneg, and MRDneg. This analysis will be reviewed by the DMC after 80 evaluable participants 
complete induction and reinduction (if applicable) assessments. Evaluable participants for this purpose 
are defined as those who either have a valid MRD result from the induction therapy recovery bone 
marrow (i.e., Day ~22 to 42), discontinue from induction therapy due to an AE or progressive disease, 
or die during induction therapy. The study will continue recruitment and enrollment while the interim 
analyses are being performed; a decision will be made as soon as practicable (targeted within 
3 months) after the last participants’ last assessments to be included in the analysis. 
Three outcomes are possible from this analysis: 
• The observed risk difference for CR is >30%, the observed risk difference for MRDneg is >50%, or 
the combined total of observed risk differences for CR and CR with MRDneg is >40%. The study 
will remain blinded and continue as planned. 
• Observed risk differences for CR, MRDneg, and CR with MRDneg are all <5%. The study will be 
unblinded to all parties and stopped. 
• Criteria are not met for either of the preceding scenarios. The study will be unblinded to the 
sponsor, who, in consultation with the United States Food and Drug Administration, will determine 
whether to continue or stop the study. If the study continues, participants contributing to the interim 
assessment will not be used in subsequent inferential analyses and will be replaced. A summary of 


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the data will be shared with investigators and ethics committees and publicly presented. Participants 
randomized after the interim cutoff and not contributing to the assessment will remain blinded and 
will contribute to subsequent inferential analyses. 
The second interim analysis will be an unblinded (only to the DMC) efficacy assessment. It will be 
completed after approximately 250 OS events are observed. The O’Brien-Fleming alpha spending 
function will be used to control the familywise type I error rate. Therefore, the interim OS test will be 
performed at the 0.0196 nominal two-sided alpha level, and the final OS test will be performed at the 
0.0342 nominal two-sided alpha level. On the condition that the study proceeds beyond the first interim 
analysis, this approach is expected to yield >68% power at the time of this second interim analysis for 
the primary OS endpoint under the sample size assumptions noted. The key secondary EFS endpoint 
will also be tested at this time, with the alpha level determined based on the total number of observed 
EFS events using an alpha spending function that maps to the O’Brien-Fleming boundary. In the event 
that this interim analysis is successful for either endpoint, the database will be unblinded to the sponsor 
to facilitate regulatory submissions. Regardless of conclusions from the second interim analysis, 
participants will continue to be followed as prescribed, with individual group assignments remaining 
blinded at the site level. 
 


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1.1. 
Study Schema 
Figure 1: 
Treatment Algorithm 
 
Abbreviations: BM=bone marrow aspirate; CR=complete remission; CRi=complete remission with incomplete 
hematologic recovery; HCT=hematopoietic cell transplant 
Notes: The postinduction bone marrow aspirate will be collected on approximately Day 14 to 21. 
Participants with a FLT3 mutation may also receive treatment with midostaurin on Days 8 through 21 at the 
investigator’s discretion and dependent on local availability. For these participants, the postinduction bone marrow 
aspirate will be collected on Day 22 or 23.  
Refer to Table 7 for all criteria required to achieve a CR or CRi.


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1.2. 
Schedule of Activities  
Table 1: 
Schedule of Activities/Assessments: Induction Cycle and Reinduction Cycle (as applicable) 
Study Day: 
Screen a 
BL/ 
D1 
D
2 
D
3 
D
4 
D
5 
D
6 
D
7 
D
8 
D 
14-
21 
D22 until 
count recovery 
or Day 42c 
Post-CR 
Early 
Therapy 
DC 
Notes 
Examination / Procedure 
Study day is relative to start of each 
treatment cycle 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Consolidation Therapy, as applicable – see Table 2 
 
 
Eligibility criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
ECOG status (induction only) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical exam and vital signs 
X 
 
 
 
 
 
 
 
 
 
 
 
Predose findings=medical history; 
Findings after first dose=AE 
Height / Weight  
X 
 
 
 
 
 
 
 
 
 
 
 
 
ECG (induction only) 
X 
X 
 
 
 
 
 
 
X 
 
 
 
D1: Before and after bolus dose; 
D8: At the end of infusion 
Echocardiogram / MUGA scan 
X 
 
 
 
 
 
 
 
 
 
 
 
Repeat per standard of care. 
Pregnancy test (as applicable) 
 
X 
 
 
 
 
 
 
 
 
 
 
Women of childbearing potential 
Peripheral blood samples: 
 
 
 
 
 
 
 
 
 
 
 
 
 
– Molecular genetics (central) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
– Immunophenotyping (central) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
– FISH (central) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
– Fibrinogen, D-dimer (local) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
– Clinical chemistry (local) 
X 
X 
X 
 
X 
 
X 
 
X D14 
 
X 
 
– Hematology (local) 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Every other day through recovery. 
– PT/INR, aPTTe,f (local) 
X 
Xf  
X 
X 
X 
X 
X 
X 
X D14 
 
X 
Do not draw from the same line used 
for drug administratione 
– PK blood samplese (central) 
(induction only) (at sites with 
appropriate capabilities) 
 
X 
 
 
X 
 
 
 
X 
 
 
 
(±10min) D1: predose, end of bolus, 
and 1 and 12 hours after bolus; D4: 
morning; D8: end of infusion, and 0.5, 
1, 2, and 4 hours after end of infusion  
– HMGB1e,g (central) 
 
X 
 
 
X 
 
 
 
X D14 At recoveryb,c 
 
 
– Biobanking (central) 
X 
 
 
 
 
 
 
 
 
 
Xc 
 
Optional, per local regulation/approval 


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Study Day: 
Screen a 
BL/ 
D1 
D
2 
D
3 
D
4 
D
5 
D
6 
D
7 
D
8 
D 
14-
21 
D22 until 
count recovery 
or Day 42c 
Post-CR 
Early 
Therapy 
DC 
Notes 
Examination / Procedure 
Study day is relative to start of each 
treatment cycle 
Bone marrow aspirate/ biopsy: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
– MRD analyses (central) 
X 
 
 
 
 
 
 
 
 
 
At recoveryb,c  
 
Required. Use first draw of marrow. 
– Biobanking (central) 
X 
 
 
 
 
 
 
 
 
 
At recoveryb,c  
 
Optional, per local regulation/approval 
– Morphology (local) 
X 
 
 
 
 
 
 
 
 
Xb 
At recoveryb,c  
 
 
– Cytogenetics (local) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Buccal swab or saliva specimen 
(central) (induction only) 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Optional, single sample for germ line 
analysis 
Randomizationa 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Cytarabine – continuous infusion  
 
X 
X 
X 
X 
X 
Xd 
Xd 
 
 
 
 
 
100 mg/m2/day  
(Note: FLT3-positive participants may 
receive 200 mg/m2/day) 
Idarubicin 12 mg/m2/day OR 
Daunorubicin 60 mg/m2/day 
 
X 
X 
Xd 
 
 
 
 
 
 
 
 
 
 
Study intervention – bolus 
 
X 
 
 
 
 
 
 
 
 
 
 
 
4 mg/kg via IV push, begin 30 min 
after anthracycline infusion ends 
Study intervention – continuous 
infusion 
 
X 
X 
X 
X 
X 
Xd 
Xd 
 
 
 
 
 
0.25 mg/kg/hour; Begin after bolus 
dose 
Adverse event assessments 
Procedure-
related SAEs 
All AEs ------------------------------------------------------------ 
X 
Record through 42 days after start of 
the last induction or consolidation 
treatment cycle (regardless of 
completion or discontinuation) 
Concomitant medications 
X 
---------------------------------------------------------------------- 
X 
Medical resource utilization 
 
---------------------------------------------------------------------- 
X 
Abbreviations: AE=adverse event; aPTT=activated partial thromboplastin time; CR=complete response; D=day; D14=Day 14 (only day specified within window); 
DC=discontinuation; ECG=electrocardiogram; ECOG=Eastern Cooperative Oncology Group; FISH=fluorescence in situ hybridization; HMGB1=high mobility 
group box protein 1; MRD=measurable residual disease; MUGA=multigated acquisition scan; PK=pharmacokinetics; PT/INR=prothrombin time/international 
normalized ratio; SAE=serious adverse event 
**Refer to footnotes on the next page** 


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a All prestudy/screening procedures (including cytogenetic and molecular analyses) will ideally be completed within 14 days of randomization. First dose of 
study intervention should be administered as soon as possible after randomization, and must be administered no more than 24 hours after randomization. 
Screening procedures do not need to be repeated prior to reinduction. 
b  Bone marrow aspirate/biopsy will be performed once between approximately Day 14 and Day 21 (Day 22-23 for participants taking midostaurin), when 
peripheral blood is negative for persistent AML, to determine the need for reinduction. (If the ~Day 14 bone marrow is not evaluable or assessment of aplasia is 
equivocal, a repeat evaluation may be performed 5 to 14 days later, at the discretion of the investigator, in order to determine effect and need for second 
induction). Thereafter, additional bone marrow samples will be collected to confirm response/persistence/relapse after second induction and consolidation 
cycles. For participants who achieve CR/CRi, measurable residual disease assays will be performed by the central laboratory on the recovery marrow sample. 
c  Count recovery is defined as an absolute neutrophil count >1000/µL and a platelet count >100,000/µL. If count recovery occurs, perform bone marrow 
aspirate/biopsy within 7 days. If count recovery has not occurred by ~Day 36 after induction or reinduction, perform a bone marrow aspirate/biopsy on or 
before Day 42 to evaluate disease status.  
d Participants who do not achieve leukemia-free state (<5% bone marrow blasts) on bone marrow aspirate performed between ~Days 14-21 (Day 22-23 for 
participants taking midostaurin) may receive a reinduction cycle. Participants 18 to 59 years will receive the same 7+3 regimen; participants ≥60 years will 
receive a modified “5+2” regimen, with cytarabine and study intervention administered on Days 1 through 5 and idarubicin/daunorubicin on Days 1 and 2.  
e Do not draw blood (especially for aPTT or PK analyses) from the same line that is used for study intervention administration. Drawing blood from a 
heparinized line may falsely alter results obtained; if using an indwelling catheter, draw ~5 mL of blood from the line for discard before drawing the aPTT and 
PK samples. 
f Draw blood for aPTT measurements no sooner than 8 hours after the bolus dose. During the continuous infusion, measure aPTT daily. 
g Refer to laboratory manual for instructions on obtaining a separate sample for HMGB1 analyses versus using a biobanked sample. 
Note: All participants will be followed-up for long-term outcomes for 5 years after randomization. See Section 8.2.3.  
 


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Table 2: 
Schedule of Activities/Assessments: Consolidation Cycles 
Study Day: 
D1 
D2 
D3 
D4 
D5 
D6 
D14 
D7 until count 
recovery or D42h 
Follow-up 
Notes 
Examination / Procedure 
Day is relative to start of each treatment cycle 
Weight  
X 
 
 
 
 
 
 
 
Monitor remission status via blood 
counts and bone marrow aspirates per 
institutional standard of care; 
Long-term study follow-up is 5 yearsk 
 
Bone marrow aspirate/ biopsy: 
 
 
 
 
 
 
 
 
After each consolidation cycle and to confirm 
response/ relapse/ persistent disease 
–Morphology (local) 
 
 
 
 
 
 
 
X – at recovery 
 
–MRD analyses (central) 
 
 
 
 
 
 
 
X – at recovery 
After each consolidation cycle 
–Biobanking (central)  
 
 
 
 
 
 
 
X – at recovery  
Optional, per local regulations/approvals 
Peripheral blood samples: 
 
 
 
 
 
 
 
 
 
–Hematology (local) 
X 
X 
 
X 
 
X 
X 
X 
Every other day through recovery 
–Clinical chemistry (local) 
X 
X 
 
X 
 
X 
X 
 
 
–PT/INR, aPTTi,j (local) 
X 
X 
X 
X 
X 
X 
X 
 
 
–HMGB1 g,i (central) 
X 
 
 
 
 
 
 
X – at recovery  
 
–Biobanking (central) 
 
 
 
 
 
 
 
X – at recovery  
 
Cytarabine – Infusion over 3 hours, 
twice daily 
X 
 
X 
 
X 
 
 
 
 
18 to 59 years: 3 g/m2/dose;  
≥60 years: 1.5 g/m2/dose 
Study intervention – bolus 
X 
 
 
 
 
 
 
 
 
4 mg/kg via IV push over 5 minutes, begin 
30 minutes after cytarabine infusion ends 
Study intervention – continuous 
infusion 
X 
X 
X 
X 
X 
 
 
 
 
0.25 mg/kg/hour. Begin after bolus dose 
Adverse event assessments 
--------------------------------------------------------------- 
 
Record through 42 days after the start of last 
cycle (regardless of completion or 
discontinuation) 
Concomitant medications 
--------------------------------------------------------------- 
Medical resource utilization 
--------------------------------------------------------------- 
Abbreviations: aPTT=activated partial thromboplastin time; CR=complete response; D=day; HMGB1=high mobility group box protein 1; MRD=measurable 
residual disease; PT/INR=prothrombin time/international normalized ratio  
g Refer to laboratory manual for instructions on obtaining a separate sample for HMGB1 analyses versus using a biobanked sample.  
Only samples from the last consolidation cycle will be analyzed. 
h Count recovery is defined as an absolute neutrophil count >1000/µL and a platelet count >100,000/µL.  
If count recovery has not occurred by ~Day 36, perform a bone marrow aspirate/biopsy on or before Day 42 to evaluate disease status. 
i Do not draw blood (especially for aPTT analyses) from the same line that is used for study intervention administration. Drawing blood from a heparinized line 
may falsely alter results obtained; therefore, if using an indwelling catheter, draw approximately 5 mL of blood from the line for discard before drawing the 
sample for analysis. 
j Draw blood for aPTT measurements no sooner than 8 hours after the bolus dose. During the continuous infusion, measure aPTT daily. 
k All participants will be followed-up for long-term outcomes for 5 years after randomization. See Section 8.2.3.  


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2. 
INTRODUCTION 
Dociparstat sodium is being developed for the treatment of newly-diagnosed acute myeloid 
leukemia (AML) in combination with standard chemotherapy in adults. 
2.1. 
Study Rationale 
The addition of dociparstat to standard 7+3 chemotherapy is expected to improve overall 
survival (OS) and relapse-free survival (RFS) versus chemotherapy alone, without additive 
toxicity. The current study is being conducted to confirm positive efficacy and safety results in 
previous studies of dociparstat for the treatment of AML and to show the benefits of adding 
dociparstat to standard 7+3 chemotherapy versus chemotherapy alone for the treatment of 
newly-diagnosed AML in adults. 
2.2. 
Background 
AML is the most common type of acute leukemia in adults, with a median age of onset of 
68 years and an increasing risk of significant morbidity and mortality with increasing age. In 
patients suitable for intensive treatment, the standard of care for newly-diagnosed AML remains 
cytarabine and an anthracycline in a 7+3 induction regimen. This combination has been used for 
more than 40 years and there remains an unmet medical need to increase the efficacy of 
treatment by preventing or delaying relapse and improving survival, and to accomplish this goal 
without additive toxicity. 
Dociparstat sodium is a glycosaminoglycan compound derived from porcine heparin that has low 
anticoagulant activity, but retains the ability to inhibit activities of key proteins implicated in the 
resistance of AML blasts and leukemic stem cells to chemotherapy (e.g., CXCL12, high mobility 
group box protein 1 [HMGB1], neutrophil elastase) (Rao 2010; Ziarek 2013; Zhang 2012). 
Dociparstat also inhibits platelet factor 4, which has been demonstrated to play a key role in the 
maintenance of hematopoietic stem cell quiescence and impairment of platelet recovery after 
chemotherapy (Tkaczynski 2018; Lambert 2007; Lambert 2012). Inhibition of these key proteins 
by dociparstat may result in sensitization of low abundance resistant AML blasts and quiescent 
leukemic stem cells, leading to deeper and more durable responses to cell cycle-dependent 
chemotherapies. 
This multimodal mechanism of action would be particularly beneficial in a disease with 
significant heterogeneity like AML, and may provide an advantage relative to other therapies 
with singular targets (e.g., CXCR4 inhibitors, E-selectin inhibitors). 
An open-label pilot study of dociparstat plus standard 7+3 chemotherapy showed positive results 
in 12 participants with newly-diagnosed AML (NCT02056782) (Kovacsovics 2018). Three 
participants were classified as having good risk, 5 had intermediate risk, and 4 had poor-risk 
disease characteristics. Eleven participants (92%) had morphologic complete remission (CR) 
after the initial induction cycle. Eight participants were alive at a median follow-up of 24 months 
(4 participants in CR). Three participants received an allogeneic stem cell transplant after the 
initial induction cycle. Median disease-free survival was 14.8 months; median OS was not 
attained at the maximum follow-up time of 29.4 months. 


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A randomized, controlled, Phase 2b, dose-finding study (NCT02873338) evaluated dociparstat 
(4 mg/kg intravenous [IV] bolus followed by either 0.125 or 0.25 mg/kg/hr continuous IV 
infusion for 7 days) in combination with standard 7+3 chemotherapy versus chemotherapy alone 
in 75 participants ≥60 years of age with newly-diagnosed AML. Results for combined complete 
remission with complete hematologic recovery (CR) and complete remission with incomplete 
hematologic recovery (CRi) rates in the dociparstat 0.125 mg/kg/hr and 0.25 mg/kg/hr groups 
were generally comparable to the chemotherapy alone control group. Observed OS was longer in 
the dociparstat 0.25 mg/kg/hr group (median not reached [median follow-up for survivors was 
20 months]) than the control group (median 11.7 months [95% confidence interval (CI): 7.6, nc]) 
(observed hazard ratio [HR] 0.68 [95% CI: 0.29, 1.57]). A subset analysis of participants 
meeting the target inclusion criteria for this Phase 3 study demonstrated a favorable observed HR 
for dociparstat 0.25 mg/kg/hr (N=20) versus control (N=19) for OS of 0.51. Combination 
treatment with 7+3 chemotherapy and dociparstat did not show increased toxicity compared with 
7+3 chemotherapy alone, nor did it prolong time to platelet or neutrophil recovery. Febrile 
neutropenia was reported as a severe adverse event (AE) more commonly for participants in the 
dociparstat 0.25 mg/kg/hr group (n=3) than control (n=1); the incidence of infections, however, 
was comparable. The activated partial thromboplastin time (aPTT) remained within the normal 
range for most participants in both the dociparstat and control groups; there was no excess in 
hemorrhagic AEs in participants treated with dociparstat 0.25 mg/kg/hr. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of dociparstat is 
provided in the investigator’s brochure. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits, risks, and reasonably 
expected AEs of dociparstat may be found in the investigator’s brochure. Refer to the approved 
product labeling for detailed information about the known and expected risks of cytarabine, 
daunorubicin, and idarubicin. 
2.3.1. 
Risk Assessment 
Potential Risk of 
Clinical Significance 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Study Intervention: Dociparstat 
Bleeding and 
hemorrhagic AEs 
Based on results of 
nonclinical and clinical 
studies and the relationship of 
dociparstat to heparin (refer 
to data in the investigator’s 
brochure). 
Inclusion/exclusion criteria and screening 
assessments are designed to limit 
enrollment to participants who are less 
likely to have confounding conditions that 
could impact their safety (see Section 5).  
Participants will be routinely monitored 
throughout the infusion period. 
Dosing will be interrupted for prolonged 
aPTT or hemorrhagic AEs Grade 3 or 
higher (see Section 7). 


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Potential Risk of 
Clinical Significance 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Study Procedures 
Pain, bleeding, and 
infection at site of bone 
marrow aspiration. 
These are known risks of the 
procedure, which will be 
performed multiple times 
during the study. 
Bone marrow aspiration/biopsy procedures 
are only to be performed by qualified 
medical personnel.  
Participants will receive treatment for any 
adverse effects. 
Other 
Myelosuppression  
Cytarabine reduces blood cell 
production in the marrow.  
Increased risk of bleeding and 
infections. 
Blood counts will be routinely monitored 
during treatment and until hematologic 
recovery.  
Site personnel and study participants will 
use infection prophylaxis practices and 
report the first sign/symptom of infection. 
Cardiotoxicity (severe 
congestive heart 
failure) 
Anthracyclines have been 
associated with a risk of 
cardiotoxicity.  
Inclusion/exclusion criteria and screening 
assessments are designed to prevent 
enrollment of participants with preexisting 
cardiac dysfunction (see Section 5).  
The cumulative anthracycline dose in this 
study is below the threshold for increased 
risk, as specified in the product labels. 
Severe local tissue 
necrosis 
Extravasation during 
anthracycline administration 
has been associated with 
tissue necrosis 
Must be given into a rapidly flowing 
intravenous infusion. 
2.3.2. 
Benefit Assessment 
Treatment with dociparstat in combination with standard 7+3 chemotherapy may result in 
reduced risk for relapse and longer survival than treatment with standard chemotherapy alone. 
The cytogenetic, molecular, and MRD analyses performed during this study may provide 
additional prognostic information that may influence future treatment decisions. 
AML is a rare condition and an area of unmet need for successful treatments; participants in this 
study will contribute to the process of developing a potential new therapeutic treatment option 
and expanding general knowledge about AML treatment. 
2.3.3. 
Overall Benefit: Risk Conclusion 
AML is a serious, life-threatening condition with limited options for successful treatment. 
Considering the measures taken to minimize risk to participants in this study, the potential risks 
identified in association with dociparstat represent a minimal increase in risk of treatment versus 
standard chemotherapy alone. The use of dociparstat is justified by the anticipated benefits that 
may be afforded to participants with AML in this study. 


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3. 
OBJECTIVES AND ENDPOINTS 
For definitions and response and outcomes criteria, refer to Section 8.2.2 and Appendix 7. 
Objectives 
Endpoints 
Primary Efficacy 
 
• To compare the efficacy of 
dociparstat plus standard 
chemotherapy versus standard 
chemotherapy alone as upfront 
treatment for newly-diagnosed AML 
• Overall survival (OS).  
Key Secondary Efficacy 
 
• To compare the efficacy of 
dociparstat plus chemotherapy 
versus chemotherapy alone with 
respect to event-free survival (EFS). 
• EFS following CR. Defined as time from randomization 
to treatment failure, relapse, or death from any cause, 
whichever occurs first, with treatment failure defined as 
failure to achieve CR within 42 days of the start of 
induction (or start of reinduction, when applicable). 
Secondary Efficacy 
 
• To compare the efficacy of 
dociparstat plus chemotherapy 
versus chemotherapy alone with 
respect to event- and relapse-free 
survival. 
• EFS following CR/CRi, with treatment failure defined as 
failure to achieve CR/CRi within 42 days of the start of 
induction (or start of reinduction, when applicable). 
• Relapse-free survival (RFS) after CR. 
• RFS after CR/CRi.  
• To compare MRD status with 
dociparstat plus chemotherapy 
versus chemotherapy alone.  
• Proportion of participants who achieve CR with MRDneg, 
as determined by multiparameter (multicolor) flow 
cytometry (MFC), at the end of induction and 
consolidation therapy. 
• Proportion of participants who achieve CR/CRi with 
MRDneg, as determined by MFC, at the end of induction 
and consolidation therapy. 
• Proportion of participants who achieve MRDneg 
(regardless of CR), as determined by MFC, at the end of 
induction and consolidation therapy. 
• Association between CR with MRDneg and relapse. 
• Association between MRDneg and relapse. 
• Association between MRDneg and OS. 
• To compare post-induction response 
rates after treatment with dociparstat 
plus chemotherapy versus 
chemotherapy alone. 
• Proportion of participants who achieve CR. 
• Proportion of participants who achieve CR/CRi. 
• Proportion of participants who achieve CR or complete 
remission with partial hematologic recovery (CRh). 


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Objectives 
Endpoints 
• To compare rates of hematopoietic 
stem cell transplant (HCT) after 
treatment with dociparstat plus 
chemotherapy versus chemotherapy 
alone. 
• Proportion of participants who receive an allogeneic HCT 
during the study. 
• Proportion of participants who receive any HCT 
(allogeneic or autologous) during the study. 
• To compare relapse rates after 
treatment with dociparstat plus 
chemotherapy versus chemotherapy 
alone. 
• Cumulative incidence of relapse after CR.  
• Cumulative incidence of relapse after CR/CRi. 
• To compare the time to hematologic 
recovery after induction or 
reinduction (if indicated) with 
dociparstat plus chemotherapy 
versus chemotherapy alone. 
• Time to recovery of neutrophil count (ANC >500/μL and 
>1000/μL). 
• Time to transfusion-independent platelet recovery 
(>20,000/μL, >50,000/μL, and >100,000/μL). 
• Incidence of prolonged neutropenia (ANC ≤500/μL past 
cycle Day 42 in the absence of active leukemia). 
• Incidence of prolonged thrombocytopenia (platelets 
≤50,000/μL past cycle Day 42 in the absence of active 
leukemia). 
Other 
 
• To evaluate the consistency of 
dociparstat treatment effects across 
subgroups. 
• EFS, OS, and MRDneg across subgroups (e.g., age 
categories, genetic risk categories). 
• To evaluate the pharmacokinetic 
(PK) profile of dociparstat. 
• Dociparstat PK parameters, including area under the 
concentration-time curve (AUC), maximum observed 
concentration (Cmax), time to maximum observed 
concentration (Tmax), terminal elimination half-life (t½), 
and clearance, and others as data permit. 
• To evaluate the impact of 
dociparstat on medical resource 
utilization during induction and 
consolidation treatment. 
• Number of days hospitalized. 
• Number of days in intensive care unit setting. 
• Number of blood product (packed red blood cells, 
platelets) units administered. 
• Number of growth factor administrations. 
Safety 
 
• To assess the safety and tolerability 
of dociparstat plus chemotherapy 
versus chemotherapy alone for the 
treatment of newly-diagnosed AML. 
• Incidence of AEs: overall, treatment-related, Grade 3 or 
higher in severity, serious, fatal, and those resulting in 
treatment discontinuation.  
• Incidence of AEs of special interest. 
• Change from baseline in clinical laboratory parameters. 
• Distribution of graded clinical laboratory results. 
• Proportion of participants who meet defined QT/QTc 
criteria. 
• Incidence of mortality at Day 30 and Day 60. 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group 
study to evaluate the efficacy and safety of dociparstat sodium in combination with standard 
intensive induction chemotherapy (i.e., cytarabine plus either idarubicin or daunorubicin “7+3” 
treatment regimen) and cytarabine consolidation chemotherapy versus placebo in combination 
with standard chemotherapy (i.e., chemotherapy alone) for the treatment of newly-diagnosed 
AML. This study will enroll approximately 570 adults with de novo AML who are ≥18 years old 
with intermediate or adverse genetic risk (based on European LeukemiaNet [ELN] 2017 criteria; 
see Appendix 4), and who are considered fit for intensive induction chemotherapy. 
After completion of all screening evaluations, eligible participants will be randomized by an 
interactive response technology (IRT) system in a 1:1 ratio to receive either dociparstat plus 
standard chemotherapy or placebo plus standard chemotherapy. Randomization will be stratified 
based upon FMS-like tyrosine kinase 3 (FLT3) status (FLT3-internal tandem duplication [ITD] 
or tyrosine kinase domain [TKD] positive vs FLT3 mutation negative), genetic risk (intermediate 
vs adverse), and age (<65 years vs ≥65 years). Of the first 80 participants enrolled, the number of 
participants between 18 to 59 years of age with intermediate genetic risk will be limited to 20. 
Under this protocol, participants will receive an initial induction cycle of 7+3 chemotherapy, a 
reinduction cycle if bone marrow at Day 14 to 23 shows persistent disease, and up to 4 cycles of 
consolidation chemotherapy. Treatment response will be assessed by examination of bone 
marrow aspirates/biopsies and complete blood counts during and at the end of each treatment 
cycle. After completion (or discontinuation) of protocol treatment, long-term follow-up 
information (e.g., date of HCT if performed, AML therapies received, date of disease 
relapse/recurrence [including results of tests used for diagnosis of recurrence], and vital status) 
will continue to be collected (via medical records and/or phone/email contact with the study 
center) until death or for 5 years after randomization. 
For definitions, response and outcomes criteria, and abbreviations used in this protocol, refer to 
Appendix 7 and Appendix 8. 
4.2. 
Scientific Rationale for Study Design 
A randomized, double-blind, placebo-controlled study design was selected as the most robust 
design to minimize potential bias. 
Adults with newly-diagnosed, previously-untreated AML, who are fit for intensive, potentially 
curative, chemotherapy (and who do not meet any of the exclusion criteria) will be eligible for 
enrollment. This study is focused on the treatment of participants with intermediate or adverse 
genetic risk because the need for more effective treatment options is greater in this population 
than in patients with favorable risk (NCCN 2019). 
The American Society of Hematology 2020 guidelines for treating newly-diagnosed AML in 
older adults recommends offering antileukemic therapy (if a candidate for such therapy) over 
best supportive care only and suggests intensive antileukemic therapy (if considered fit for 
intensive therapy) over less-intensive therapy; the panel also suggests postremission therapy (if 
not a candidate for HCT) over no additional therapy (Sekeres 2020). Consistent with these 


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guidelines the investigator is advised to discuss all options with each potential participant 
(especially older adults) to understand their treatment goals and reach an agreement on the 
choice of pursuing antileukemic treatment with intensive combination therapy and postremission 
consolidation therapy as applicable. 
During initial induction therapy, all participants will receive background treatment with the 
current standard of care, 7+3 regimen of cytarabine + anthracycline chemotherapy; therefore, all 
participants will be actively treated for AML while preserving the ability to identify an additional 
treatment effect from the study intervention (dociparstat versus placebo). Chemotherapy dosing 
was selected to align with NCCN guidelines (NCCN 2019). 
The goal of induction therapy is to clear leukemia, leading to clinical remission, and ultimately 
longer survival; therefore, the primary endpoint is OS, defined as the time from randomization to 
death from any cause. EFS is a clinically-relevant, key secondary endpoint that is expected to 
show a differential treatment benefit for dociparstat plus 7+3 chemotherapy versus chemotherapy 
alone. Despite high rates of remission, more than 50% of adult AML patients relapse after 
attaining morphological CR after induction therapy. MRDneg status at the end of 
induction/consolidation therapy is correlated with improved OS, and may ultimately serve as a 
more independent measure of the activity of up-front chemotherapy than long-term measures 
(e.g., OS and EFS), given the potential confounding effects of HCT and other maintenance and 
salvage therapies on those outcomes. Therefore, negative MRD status after treatment is an 
important secondary endpoint and will be used as a factor in the early interim analysis of 
efficacy. 
4.3. 
Justification for Dose 
Dociparstat will be administered as an IV bolus dose of 4 mg/kg on Day 1, followed by a 
continuous IV infusion of 0.25 mg/kg/hr for 7 days during standard 7+3 induction chemotherapy. 
Selection of the dose of dociparstat for the treatment of AML was based upon the dual 
requirements to achieve a high enough drug concentration to be effective while also minimizing 
the potential for adverse effects related to prolongation of coagulation time.  
In an AML pilot study, this combination of dociparstat dosing (i.e., 4 mg/kg bolus plus 
0.25 mg/kg/hr continuous infusion) added on to the standard 7+3 chemotherapy regimen of 
cytarabine and idarubicin, resulted in 11 of 12 participants (92%) achieving a complete bone 
marrow response after a single induction cycle. Dociparstat did not increase the risk of bleeding; 
anti-factor Xa activity was not significantly changed from baseline and remained below 
published therapeutic anticoagulant reference ranges.  
The randomized Phase 2b AML study also included a fixed bolus dose of 4 mg/kg dociparstat, 
but initially included 3 dose levels (0.125, 0.25, and 0.325 mg/kg/hr) for the continuous infusion. 
The 0.325 mg/kg/hr dose level was discontinued after 1 of 2 participants dosed experienced a 
fatal serious adverse event (SAE) of retroperitoneal hemorrhage and a contributory role of 
dociparstat could not be excluded. During dociparstat 0.25 mg/kg/hr infusion, aPTT levels were 
numerically higher than the 0.125 mg/kg/hr or control groups, but generally remained in the 
normal range. There was no excess of bleeding AEs for dociparstat 0.25 mg/kg/hr versus control. 
The overall safety profile was similar for the 0.125 and 0.25 mg/kg/hr dose groups, but efficacy 
was greater for the 0.25 mg/kg/hr group. 


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This Phase 3 study will administer dociparstat as an IV bolus dose of 4 mg/kg, followed by a 
continuous IV infusion of 0.25 mg/kg/hr. All participants will receive an initial induction cycle. 
A second induction cycle (reinduction) is recommended for participants with a reduction in 
leukemia burden, but persistent blast counts ≥5% on the initial bone marrow assessment 
(~Day 14 to 21, or Day 22 to 23 for participants taking midostaurin; or the initial response 
assessment at approximately Day 22 to 42 after initial induction). The original 7+3 schedule will 
be utilized for reinduction in participants <60 years; a modified 5+2 dosing schedule will be 
utilized for reinduction in participants ≥60 years of age.  
4.4. 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed all phases of the 
study including the long-term follow-up. 
The end of the study is defined as the date of the last visit (or last follow-up contact) of the last 
participant in the study globally. 


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5. 
STUDY POPULATION 
The target study population is adults with de novo AML who are ≥18 years old with intermediate 
or adverse genetic risk (based on ELN 2017 criteria; see Appendix 4), and who are considered fit 
for intensive induction chemotherapy. The investigator is advised to discuss all options with each 
potential participant (especially older adults) to reach an agreement on the choice of pursuing 
antileukemic treatment (versus supportive management only) with intensive combination therapy 
and postremission consolidation therapy as applicable. 
The medical monitor (or designee) will review key entry criteria to confirm eligibility for 
randomization. Prospective approval of protocol deviations to recruitment and enrollment 
criteria, also known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
A potential participant must meet all the following criteria to be included in the study: 
1. Newly-diagnosed, previously untreated AML (according to World Health Organization 
criteria) with at least 20% blasts in the peripheral blood or bone marrow.  
2. Age ≥18 years. 
a. Adverse genetic risk (according to ELN criteria), defined as any of the following 
genetic abnormalities:  
− t(6;9)(p23;q34.1); DEK-NUP214 
− t(v;11q23.3); KMT2A rearranged 
− t(9;22)(q34.1;q11.2); BCR-ABL1 
− inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM(EVI1)  
− -5 or del(5q); -7; -17/abn(17p) 
− Complex karyotype, monosomal karyotype 
− Wild-type NPM1 and FLT3-ITDhigh  
− Mutated RUNX1, mutated ASXL1, or mutated TP53 
OR 
b. Intermediate genetic risk (according to ELN criteria), defined as any of the following 
genetic abnormalities: 
− Mutated NPM1 and FLT3-ITDhigh 
− Wild-type NPM1 without FLT3-ITD or with FLT3-ITDlow (without adverse-risk 
genetic lesions) 
− t(9;11)(p21.3;q23.3); MLLT3-KMT2A 
− Cytogenetic abnormalities not classified as favorable or adverse 
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 
4. Provide written informed consent to participate in the study. 


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5.2. 
Exclusion Criteria  
A potential participant will be excluded from the study if any of the following criteria apply: 
Leukemia exclusions: 
1. Acute promyelocytic leukemia (t(15;17)), myeloid sarcoma without bone marrow 
involvement, or blast transformation of chronic myelogenous leukemia.  
2. Not applicable (criterion removed in Amendment 1).  
3. Not applicable (criterion removed in Amendment 1).  
4. Clinical evidence of active central nervous system leukemia. 
Prior/concomitant therapy: 
5. AML treatment, including Vyxeos (CPX-351, liposomal cytarabine and daunorubicin), 
gemtuzumab ozogamicin, or any other prohibited concomitant AML therapy previously 
received or anticipated to start during the study.  
Note: Prior hydroxyurea and emergency leukapheresis to control white blood cell count 
are allowed. All-trans retinoic acid during workup and a single dose of intrathecal 
cytarabine and/or methotrexate is permitted for participants undergoing lumbar puncture 
to evaluate central nervous system involvement. 
6. Receiving any form of anticoagulant therapy (e.g., unfractionated heparin, low molecular 
weight heparin, coumadin, factor Xa inhibitors). 
Note: Heparin flush of indwelling catheters is permitted. 
7. Treatment with any other investigational agent within 28 days, or 5 half-lives, whichever 
is longer, prior to baseline. 
8. Any major surgery or radiation therapy within 28 days prior to baseline. 
Medical conditions: 
9. Immediately life threatening, severe complications of leukemia such as pneumonia with 
hypoxia or shock, and/or disseminated intravascular coagulation  
10. Active or uncontrolled bleeding at the time of randomization; a bleeding disorder, either 
inherited or caused by disease; history of known arterial-venous malformation, 
intracranial hemorrhage, or suspected or known cerebral aneurysm; or clinically 
significant (in the judgment of the investigator) gastrointestinal bleeding within the 
3 weeks prior to randomization. 
11. Presence of significant active or uncontrolled infection, including HIV or hepatitis B 
or C. Note: Patients with an infection receiving treatment (antibiotic, antifungal, or 
antiviral treatment) may be entered into the study but must be afebrile and 
hemodynamically stable for ≥72 hours. Patients with current evidence of invasive fungal 
infection (positive blood or tissue culture) must have subsequent negative cultures to be 
eligible. 
12. Active (uncontrolled, metastatic) second malignancy.  
Note: A second malignancy that is in remission may be permitted if there is clinical 
evidence of disease stability for a period of greater than 6 months off cytotoxic 


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chemotherapy that is documented by imaging, tumor marker studies, etc. Long-term 
nonchemotherapy treatment (e.g., hormonal therapy) is acceptable. 
13. Psychiatric or neurologic conditions that could compromise participant safety or 
compliance. 
14. History of severe congestive heart failure or other cardiac disease that contraindicates the 
use of idarubicin or daunorubicin (e.g., cardiac ejection fraction <45%, as determined by 
echocardiography or multigated acquisition scan). 
Diagnostic assessments: 
15. QTc >480 msec (see Section 8.3.3 for details about QTc correction formulas). 
16. Severe renal impairment, as determined by calculated creatinine clearance <30 mL/min 
or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2. 
17. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x upper limit of 
normal (ULN) or total bilirubin >2x ULN. 
Other: 
18. Woman of childbearing potential who is pregnant, breastfeeding, and/or not using a 
highly effective method of contraception (consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies). Refer to Appendix 3 
for guidance. 
19. History of allergy or hypersensitivity to heparin, pork, or any excipients in the dociparstat 
formulation. 
20. Any other condition, including abnormal laboratory values, that, in the judgment of the 
investigator, could put the participant at increased risk or interfere with the conduct or 
planned analyses of the study. 
5.3. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomized to study intervention. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, reason(s) for screen 
failure, eligibility criteria, and any study-procedure related SAEs. 
Individuals whose ALT, AST, bilirubin, creatinine clearance, or eGFR results initially do not 
meet the criteria for participation in this study may have the test(s) repeated one time within 
10 days; if the repeat value is not exclusionary, the participant may be eligible for enrollment and 
randomization. 


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6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention, marketed products, or placebo 
intended to be administered to a study participant according to the study protocol. 
6.1. 
Study Intervention(s) Administered 
Induction and consolidation treatments are administered as cycles. A complete treatment cycle 
consists of the administration of therapy (i.e., chemotherapy with cytarabine ± anthracycline plus 
blinded study intervention) and all scheduled assessments to evaluate the response to treatment, 
including bone marrow and hematologic recovery. 
Details of dociparstat solution for injection are listed in Table 3 and standard of care 
chemotherapy agents are listed in Table 4. Details of the dosing regimens for each treatment 
cycle (and age group) are presented in Table 5. 
Table 3: 
Dociparstat Details 
Intervention Name 
Dociparstat sodium 
Type  
Drug 
Dose Formulation 
Solution for injection 
Unit Dose Strength(s) 
50 mg/mL 
Route of Administration 
Intravenous infusion (bolus followed by continuous infusion) 
Use 
Experimental agent 
IMP or Non-IMP 
Investigational medicinal product (IMP)  
Sourcing 
Provided centrally by the sponsor  
Packaging and Labeling 
Provided in 10-mL vials (1 vial per kit). Each kit and vial will be 
labeled in accordance with applicable regulatory requirements. 
Current/ Former Names  
Dociparstat sodium; 2-O, 3-O desulfated heparin; ODSH; DSTAT; 
CX-01 
Normal saline (sodium chloride 0.9%) will be used to dilute dociparstat solution for injection 
before each infusion. In order to maintain blinding of randomized study intervention, normal 
saline will also be used as the de facto placebo. Commercially-available product will be 
purchased and provided (sourced) locally by the study site (or subsidiary or designee); packaging 
and labeling will be per local requirements for commercial products.  


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Table 4: 
Standard of Care Therapy Details 
Group Name 
Standard of Care for the Dociparstat and Placebo Groups 
(cytarabine + an anthracycline will be administered to all participants)  
Intervention Name 
Cytarabine 
Idarubicina 
Daunorubicina 
Type  
Drug 
Drug 
Drug 
Dose Formulation 
Solution for injection 
Unit Dose Strength(s) 
Refer to product label 
Route of Administration 
IV infusion 
Use 
Standard of care chemotherapy 
IMP or Non-IMP 
Non-investigational medicinal product (NIMP) 
Sourcing 
Provided locally by the study site, subsidiary, or designee 
Packaging and Labeling 
Commercial product packaging and labeling 
Current/ Former Names b 
Ara-C, DepoCyt, 
cytosine arabinoside, 
cytarbel, Cytosar, 
aracytidine, Aracytin, 
arabine, 1-beta-d-
arabinofuranosylcytosine 
Idamycin, Idaru, 
Zavedos 
Cerubidine, 
daunomycin, 
rubidomycin, 
rubomycin C, 
daunorrubicina 
leukaemomycin C 
a The use of idarubicin versus daunorubicin is at the discretion of the investigator based on standard institutional 
practice. 
b List is not exhaustive of all product names available in all countries. 
 
Dociparstat sodium solution for injection is supplied as 1-vial kits. Calculate dosing based on 
participant weight and prepare/dilute the drug product before IV infusion. Dociparstat must be 
administered via a dedicated infusion line. Do not mix with other IV medications. 
Dociparstat is administered as an initial IV bolus dose over 5 minutes, immediately followed by 
a continuous IV infusion 24 hours daily for 5 or 7 days (see Table 5). Dociparstat is intended for 
use in combination with standard chemotherapy (i.e., dociparstat should not be used as 
monotherapy).  


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Table 5: 
Dosing Regimen for Induction and Consolidation Therapy 
 
Standard of Care / Background 
Chemotherapy 
Study Intervention 
Induction 
cycle –  
all participants 
    and 
Reinduction 
cycle (as 
indicated) –
participants 
18 to 59 years 
All participants will receive an initial 
induction cycle:  
• Cytarabine 100 mg/m2/day via continuous 
IV infusion 24 hours daily for 7 days (Day 1 
to Day 8) AND 
• Anthracycline once daily for 3 days 
(on Day 1, Day 2, and Day 3): 
o Idarubicin 12 mg/m2 by slow (10 to 
15 minutes) IV injection OR 
o Daunorubicin 60 mg/m2 via rapidly 
flowing IV infusion 
Note: FLT3-positive participants may receive 
cytarabine 200 mg/m2/day. 
When reinduction is indicated, participants 
18 to 59 years will receive the same dosing 
schedule. 
• Dociparstat 4 mg/kg or placebo IV 
bolus on Day 1, administered 
30 minutes after completion of the 
first dose of idarubicin or 
daunorubicin, followed by  
• Dociparstat 0.25 mg/kg/hr or 
placebo by continuous IV infusion 
for 24 hours daily for 7 days 
(starting on Day 1 and ending on 
Day 8 [168 hours]) 
Reinduction 
cycle (as 
indicated) –
participants 
≥60 years  
When reinduction is indicated, participants 
≥60 years will receive a modified dosing 
schedule: 
• Cytarabine 100 mg/m2/day via continuous 
IV infusion for 5 days AND  
• Anthracycline on Day 1 and Day 2:  
o Idarubicin 12 mg/m2 by slow (10 to 
15 minutes) IV injection OR  
o Daunorubicin 60 mg/m2 given via rapidly 
flowing IV infusion 
Note: FLT3-positive participants may receive 
cytarabine 200 mg/m2/day  
• Dociparstat 4 mg/kg or placebo IV 
bolus on Day 1, administered 
30 minutes after completion of the 
first dose of idarubicin or 
daunorubicin, followed by  
• Dociparstat 0.25 mg/kg/hr or 
placebo by continuous IV infusion 
for 24 hours daily for 5 days 
(starting on Day 1 and ending on 
Day 6 [120 hours]) 
Consolidation 
cycles (up to 
4 cycles, as 
applicable) 
Only participants with a documented response 
(CR or CRi) are eligible for consolidation. 
• Cytarabine via IV infusion over 3 hours, 
administered twice daily (at 12-hour 
intervals) on Day 1, Day 3, and Day 5 
o Age 18-59 years: 3 g/m2/dose 
o Age ≥60 years: 1.5 g/m2/dose 
• Dociparstat 4 mg/kg or placebo IV 
bolus on Day 1, administered 
30 minutes after completion of the 
first dose of cytarabine, followed by  
• Dociparstat 0.25 mg/kg/hr or 
placebo by continuous IV infusion 
for 24 hours daily for 5 days 
(starting on Day 1 and ending on 
Day 6 [120 hours]) 
Note: Participants with a FLT3 mutation may also receive treatment with midostaurin at the investigator’s discretion 
and dependent on local availability. 


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6.2. 
Preparation, Handling, Storage, and Accountability 
6.2.1. 
Dose Preparation 
Dosing will be calculated on the basis of each participant’s weight for study intervention and 
body surface area for chemotherapy (cytarabine, daunorubicin, and idarubicin). It is 
recommended that the dosing calculations and preparation of each dose of study intervention be 
confirmed by a second unblinded pharmacist. 
Preparation of randomized study intervention (i.e., dociparstat or placebo) will be performed by 
an unblinded pharmacist within the investigational pharmacy. The pharmacist will prepare study 
intervention to the appropriate calculated dose. Normal saline will be used to dilute the IV bolus 
dose and continuous maintenance infusion of dociparstat. The dociparstat IV bolus dose will be 
diluted to a total infusion volume of 30 mL. The 24-hour continuous infusion will have the 
appropriate volume of dociparstat added to approximately 250 mL or 500 mL of 0.9% normal 
saline. 
The placebo IV bolus dose will be a total infusion volume of 30 mL of 0.9% normal saline only. 
Placebo for the continuous infusion will be 250 mL or 500 mL of 0.9% normal saline only.  
Only participants randomized in the study may receive study intervention and only authorized 
site staff may prepare, supply, or administer study intervention.  
All study intervention syringes and bags need to be blinded (masked) after final preparation and 
prior to leaving the pharmacy. Sites will follow their own labeling procedures to identify 
prepared study intervention (i.e., dociparstat or placebo) for each participant in a blinded manner. 
Refer to the product labels for information on preparation and administration of cytarabine, 
daunorubicin, and idarubicin. 
6.2.2. 
Handling, Storage, and Accountability  
A sufficient quantity of vials of dociparstat solution for injection will be supplied to the 
investigator (or qualified designee) at each study center. Once received at the study center, kits 
of dociparstat should be stored in accordance with the labeled storage conditions, in a securely 
locked area, with access limited to the unblinded pharmacist and authorized site staff.  
[Note: The labeled storage conditions are dependent on the manufactured drug product 
batch/lot.] 
The investigator or qualified designee (e.g., unblinded pharmacist) must confirm appropriate 
temperature conditions have been maintained during transit for all study intervention received 
and must report and resolve any discrepancies before use of the study intervention. 
The investigator or qualified designee (e.g., unblinded pharmacist) is responsible for ensuring 
adequate accountability of all used and unused study intervention. This includes 
acknowledgment of receipt of the shipment(s) of study intervention (date, quantity, condition, 
and vial numbers), participant dispensing records (date, participant number, and vial number), 
and returned or destroyed vials. All study intervention records must be maintained at the site and 
copies must be submitted to Chimerix at the end of the study. The unblinded investigator 
designee should promptly inform the unblinded study monitor of any discrepancies in 
accountability of study intervention. 


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After verification of the study intervention records by the unblinded study monitor, all remaining 
study intervention supplies should be destroyed according to directions provided by Chimerix (or 
its designee) and/or any applicable site-specific standard operating procedures. If necessary, 
unused study intervention supplies may be returned to the appropriate depot with prior approval 
from Chimerix (or its designee). If study intervention is destroyed on site, the investigator must 
maintain accurate records for all study intervention destroyed. Records must show the 
identification and quantity of each unit destroyed, the method of destruction, and person who 
disposed of the drug. 
Refer to the product labels for information on handling and storage of normal saline, cytarabine, 
daunorubicin, idarubicin, and ancillary supplies (e.g., IV bags and tubing). 
6.3. 
Dose Modification 
All participants randomized into the study will be treated with an initial induction cycle of 
blinded study intervention plus standard 7+3 chemotherapy starting on Day 1. The total number 
of treatment cycles administered to each participant is determined by the investigator through 
evaluations of treatment response, potential toxicity or tolerability issues, and suitability for 
alternate treatments (e.g., HCT).  
There are no modifications in the mg/kg dosing of blinded study intervention. Criteria for 
interruption and discontinuation of study intervention are provided in Section 7. 
6.4. 
Measures to Minimize Bias: Randomization and Blinding 
A randomized, double-blind, placebo-controlled study design was selected as the most robust 
design to minimize potential bias.  
Participants who meet all applicable eligibility criteria will be centrally randomized to one of two 
study intervention groups (dociparstat or placebo) in a 1:1 ratio using an automated IRT system 
and a computer-generated randomization code provided by the sponsor or designee. 
Randomization will be stratified based upon FLT3 status (FLT3+ vs FLT3-), genetic risk 
(intermediate vs adverse), and age (<65 years vs ≥65 years). 
Once a randomization number has been assigned, it will not be re-assigned to any other 
participant in the study. The IRT system will also be used to track study intervention dispensing. 
Investigators, participants, and sponsor personnel (to the extent practicable) will be blinded to 
each participant’s assigned study intervention throughout the course of the study. In order to 
maintain this blind, an otherwise uninvolved third party (an unblinded study pharmacist) will be 
responsible for the preparation and dispensation of blinded study interventions (i.e., dociparstat 
and placebo) and will ensure that there are no differences in appearance or time taken to dispense 
study intervention following randomization.  
In the event of a regulatory inspection or quality assurance audit, the auditor(s) will be allowed 
access to unblinded study intervention records at the site(s) to verify that randomization and 
dispensing have been done accurately. Additional roles and responsibilities that require 
unblinding of specified sponsor (and/or designated contract research organization) personnel not 
directly involved in the conduct of the study include supply chain, regulatory reporting of 
expedited safety reports, and data monitoring committee (DMC) reviews.  


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Normal saline (sodium chloride 0.9%) will be used as the study intervention placebo for both the 
loading doses and the continuous infusions. Placebo-controlled studies are the gold standard for 
clinical trials, as they reduce bias in care and conduct during the study. Though the efficacy 
endpoints are objective, safety assessments are less biased when treatment allocation is masked. 
Most importantly, downstream decisions regarding postinduction therapy are best made without 
knowledge of initial treatment assignment to reduce possible bias in this study. 
Modest effects of dociparstat on aPTT have been observed in previous studies. Although the 
Phase 2b mean aPTT values during the continuous infusion were nominally higher for 
dociparstat 0.25 mg/kg than control, the individual participant values were variable and had 
considerable overlap between groups; therefore, individual aPTT measurements are not expected 
to unblind the participant’s treatment assignment. In this Phase 3 study, potential unblinding will 
be mitigated by obtaining initial aPTT measurements no sooner than 8 hours after the IV bolus 
(after the time of peak effect) and by instructions to obtain blood for aPTT measurements from a 
location that is separate from the dociparstat infusion. Specifically, blood should be obtained via 
separate venipuncture and/or a catheter separate from the one used to administer study 
intervention. If the specimen is drawn from a heparinized line, first draw 5 mL of blood from the 
line for discard before drawing the aPTT sample. 
Emergency unblinding: The IRT system will be used for blind-breaking instructions. In case of 
an emergency, the investigator has the sole responsibility for determining if unblinding of a 
participant’s intervention assignment is warranted. Participant safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the sponsor prior to unblinding a 
participant’s intervention assignment unless this could delay emergency treatment. If a 
participant’s intervention assignment is unblinded, the sponsor must be notified within 24 hours 
after breaking the blind. The date and reason that the blind was broken must be recorded in the 
source documentation and electronic case report form (eCRF), as applicable. 
6.5. 
Study Intervention Compliance 
Participants will receive study intervention and standard of care chemotherapy directly from the 
investigator or qualified designee, under medical supervision. The date and start/stop times of 
each dose of study intervention and standard of care chemotherapy administered will be recorded 
in the source documents and in the eCRF.  
Study participant identification and dose of study intervention will be confirmed at the time of 
dosing by a member of the site staff other than the person administering the study intervention. 
6.6. 
Concomitant Therapy 
Information about the participant’s concomitant medications/therapies will be collected in the 
eCRF as specified below. 
Collection time periods:  
 
• Prior medications: All medications taken from 30 days prior to the time of signing the 
informed consent form (ICF) through the time of randomization.  


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• Concomitant medications: All medications and transfusions from the time of first 
dose of study intervention on Day 1 through 42 days after the start of the last 
treatment cycle (induction, reinduction, or consolidation, whichever is later). 
• Follow-up: Only AML therapies (i.e., for the treatment of AML and/or prevention of 
relapse) from 43 days after start of last treatment cycle through the time of last study 
follow-up. 
Information to collect: 
• Names (nonproprietary names are preferred) for all prescription medications and 
growth factors, and details of transfusions (do not need to collect use of vitamins, 
supplements, or IV fluids). 
• Reason for use (indication). 
• Start and end dates of administration. 
• Dosage information, including dose, units, route, and frequency. 
Contact the medical monitor (or designee) if there are any questions regarding concomitant or 
prior therapy. 
6.6.1. 
Prohibited Therapies 
Refer to the exclusion criteria (see Section 5.2) for medications prohibited prior to randomization 
(and the associated time period) in the study. 
The following medications are prohibited throughout the duration of the treatment period 
(i.e., during protocol-specified induction and consolidation treatment cycles, unless otherwise 
specified): 
• AML treatments not specified in the protocol, including (but not limited to) the 
following: 
− Vyxeos (daunorubicin and cytarabine liposome for injection) 
− Myelotarg (gemtuzumab ozogamicin) 
− Venetoclax 
− Decitabine or azacitidine  
− Isocitrate dehydrogenase (IDH) inhibitors (e.g., Tibsovo [ivosidenib], Idhifa 
[enasidenib]) 
− Mitoxantrone  
• Hematopoietic growth factors during induction and reinduction cycles. 
• Anticoagulants (e.g., unfractionated heparin, low molecular weight heparin, warfarin, 
factor Xa inhibitors) [If a participant requires short-term anticoagulant therapy, see 
Section 7.1]. Heparin flush of indwelling catheters is permitted. Discuss use of other 
agents for catheter occlusion with the medical monitor. 
• Investigational agents. 


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6.6.2. 
Permitted Therapies 
The following medications are permitted during the study: 
• Midostaurin: Participants who are known to have a FLT3 mutation may, at the 
investigator’s discretion and dependent on local availability, receive midostaurin in 
accordance with the product label.  
• Infection prophylaxis and treatment, and transfusion support – according to 
institutional standard of care. 
• Granulocyte colony-stimulating factor (G-CSF) following consolidation therapy.  
If used, recommended treatment is a single dose (per package labeling) of 
peg-filgrastim/liposomal G-CSF (Neulasta or biosimilar) administered 
subcutaneously 24 to 48 hours after the last dose of cytarabine consolidation in 
participants who have achieved an MRDneg CR or CRi after induction/reinduction. 
Alternatively, other G-CSF agents may be used after consolidation therapy per 
institutional standard of care and package labeling. 
6.7. 
Intervention after the End of the Study 
Dociparstat is intended for use as up-front treatment in combination with standard induction and 
consolidation chemotherapy in participants with newly-diagnosed AML. Since dociparstat is not 
intended for continued maintenance treatment, the study intervention will not be provided 
beyond the protocol-specified treatment period. 
After the end of the treatment period, the participants’ ongoing medical care and treatment in the 
event of a recurrence will be the responsibility of the participants’ physician(s). 


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Interruption of Study Intervention 
Infusion of study intervention (i.e., dociparstat or placebo) will be interrupted in the following 
situations: 
aPTT: Participants with aPTT >45 seconds will have repeat testing performed as soon as 
practicable. If aPTT is confirmed >45 seconds, interrupt the study intervention infusion. To 
minimize time that the participant is off therapy, perform repeat testing for aPTT approximately 
2 to 6 hours after interruption (as practicable). Infusion may be resumed once aPTT is 
<35 seconds. Note: samples are not to be obtained from the same line as study intervention 
infusion (e.g., collect via peripheral venipuncture). 
Grade 3 or higher hemorrhagic AEs: Study intervention infusion will be interrupted for Grade 3 
or higher hemorrhagic AEs in the setting of aPTT >40 seconds, or Grade 3 or higher 
hemorrhagic AEs that are deemed to be related to study intervention, regardless of aPTT. Study 
intervention infusion may be resumed once the participant is determined to be stable and the 
aPTT is <35 seconds.  
Note: Grade 3 or higher hemorrhagic AEs are also considered AEs of special interest. 
Renal function: If the calculated creatinine clearance drops below 30 mL/min or eGFR drops 
below 30 mL/min/1.73 m2 prior to or during dosing with study intervention, the infusion will be 
held until the creatinine clearance or eGFR rises to ≥30. 
Electrocardiogram (ECG)/QTc: Study intervention infusion will be interrupted if a participant 
meets any of the following criteria (based on the average of triplicate ECG readings; see 
Section 8.3.3 for details about QTc correction formulas):  
• Without underlying bundle branch block: 
− Interrupt for QTc >500 msec OR uncorrected QT >600 msec,  
• With underlying bundle branch block: 
− If baseline QTc <450 msec, then interrupt for QTc >500 msec 
− If baseline QTc 450 to 480 msec, then interrupt for QTc >530 msec 
In the event of prolonged QTc, the participant should also be assessed for other medications that 
may impact QT interval (see Appendix 6: Drugs Known to Prolong the QT Interval), with any 
necessary changes made to concomitant medications. Infusion of study intervention may be 
resumed once QTc is <480 msec. Following resumption of infusion, ECGs are to be checked 
daily until the participant has had 3 consecutive (daily) tracings with QTc <480 msec, after 
which follow-up ECGs will be as per institutional standard of care. Report any new, 
clinically-relevant finding as an AE. 
Bilirubin: If total bilirubin is >2 mg/dL, refer to the daunorubicin/idarubicin product label for 
dosage adjustments. No adjustment to the study intervention dosing is recommended. 


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Anticoagulant therapy: If a participant requires short-term anticoagulant therapy, interrupt the 
administration of study intervention. Infusions may be resumed if anticoagulant therapy is 
discontinued and aPTT is <35 seconds. 
Note: If study intervention is interrupted and not restarted during the same treatment cycle, the 
participant may receive study intervention (bolus and infusion) during the next treatment cycle 
(assuming the participant no longer meets any of the interruption criteria). 
Reasons for dose interruption will be entered into the eCRF. The total daily volume of IV 
solution infused (obtained directly from the IV pump data) will be recorded in the comment 
section of the eCRF for each participant who requires dose interruption. 
7.2. 
Discontinuation of Study Intervention 
In some instances, it may be necessary for a participant to permanently discontinue study 
intervention. Reasons for permanent discontinuation of study intervention may include the 
following: 
• Participant did not achieve CR/CRi at the end of the reinduction treatment cycle. 
• Criteria for restarting study intervention after interruption were not met. 
• Treatment-related AE of unacceptable severity. 
• Participant requests to discontinue study intervention. 
• Investigator determines discontinuation is in the best interests of the participant for safety, 
behavioral, compliance, administrative, or other reasons. 
Participants who discontinue study intervention early will complete the early discontinuation 
assessments (refer to the Schedule of Activities/Assessments; Section 1.2) and will continue to 
be followed-up for outcomes in the long-term follow-up period of the study until death or for 
5 years after randomization. 
7.3. 
Participant Withdrawal from the Study 
• It is expected that all participants randomized in the study, regardless of completion or 
discontinuation of study intervention, will remain in the study for long-term follow-up.  
• Before withdrawing a participant from the study, clarify and document the specific 
expectations of the participant’s request for withdrawal. The following withdrawal scenarios 
may apply: 
− Discontinuation of study intervention, but completes remaining study 
assessments, and agrees to collection of relevant follow-up information 
(i.e., remains in the study; this is the default scenario). 
− Discontinuation of study intervention and/or refuses further study-specific 
assessments, but agrees to collection of relevant follow-up information 
(i.e., remains in the study). 
− Completion or discontinuation of study intervention and/or refuses further 
assessments, AND withdraws consent for any further study communication or 


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follow-up from the study center (i.e., withdraws from the study); the investigator 
must document this in the site study records. 
• A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons.  
• At the time of withdrawing from the study, if possible, an early withdrawal visit will be 
conducted. See the Schedule of Activities/Assessments (Section 1.2) for data to be collected 
at the time of study withdrawal and follow-up and for any further evaluations that need to be 
completed. 
• If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested; the investigator must document this in the site study records. 
Discontinuation of specific sites or of the study as a whole are discussed in Appendix 1. 
7.4. 
Lost to Follow-up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and the study center is unable to contact the participant. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must 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 whether or not the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 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. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. The sponsor may retain and continue to use any data collected. 
• The site should also make every effort to verify the participant’s vital status with the 
participant’s regular/non-study physician(s). 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
Planned time points for all study assessments and procedures are provided in the Schedule of 
Activities/Assessments (see Table 1 for induction cycles and Table 2 for consolidation cycles). 
Adherence to the study design requirements, including all specified assessments, is essential and 
required for study conduct. Protocol waivers or exemptions are not allowed. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with 
sample quality. Record results of any unscheduled assessments or visits related to study 
participation in the eCRF. 
8.1. 
Screening 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure. 
Procedures conducted as part of the participant’s routine clinical management (e.g., blood 
counts) and obtained before signing of the ICF may be utilized for screening or baseline 
purposes, provided the procedures meet protocol-specified criteria and were performed within 
the time frame defined in the Schedule of Activities/Assessments (Table 1). Applicable results 
must be entered into the participant’s eCRF. 
The following examinations and procedures will be conducted as part of the screening process: 
• Informed consent. Written documentation of completion of the informed consent 
process with the potential participant (and legally authorized representative if 
applicable). 
• Demographics, medical history (including family medical history), medication 
history, ECOG status (see Appendix 5), physical examination, vital signs, height, and 
weight. 
• ECG (see Section 8.3.3).  
• Echocardiogram or multigated acquisition (MUGA) scan to identify pre-existing 
cardiac dysfunction that may exclude a participant from enrollment or contraindicate 
use of standard 7+3 chemotherapy. Repeat testing before subsequent cycles of 
chemotherapy will be per institutional standard of care. 
• Clinical chemistry, hematology, fibrinogen, D-dimer, and coagulation (aPTT, 
prothrombin time/international normalized ration [PT/INR]) tests (see Section 8.3.4). 
• Analysis of bone marrow aspirate/biopsy and peripheral blood screening samples 
(see Section 8.2.1) for confirmation of diagnosis, identification of specific 
translocations and inversions, and determination of genetic risk categorization and 
study eligibility. 
• Review of all eligibility criteria to determine if participant qualifies for 
randomization. This includes review of results of all screening assessments and a 
final review for any changes in medical history, concomitant medications, or ECOG 
status at baseline before randomization. 


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8.2. 
Efficacy Assessments 
The anti-leukemic activity of dociparstat in combination with 7+3 chemotherapy will be assessed 
by routine laboratory tests and examination of bone marrow aspirates/biopsies. Response criteria 
and outcome measures are based on definitions from ELN (Döhner 2017; also see Appendix 7). 
8.2.1. 
Bone Marrow Aspirate/Biopsy and Peripheral Blood Assessments 
Bone marrow aspirate/biopsy and peripheral blood samples will be collected for the assessments 
specified in Table 6. Tests such as cytogenetic analyses are commonly performed locally for 
diagnosis of AML; central molecular genetic testing and using fluorescence in situ hybridization 
(FISH) is performed to facilitate rapid turnaround of tests for purposes of determining eligibility 
and stratification. If there is a discrepancy between results from central and local laboratories, 
results from the central laboratory will be used for determination of eligibility and stratification.  
MRD testing of screening bone marrow samples is critical to identify leukemia associated 
phenotypes that are to be followed at each recovery assessment. Due to the need for high quality 
samples that are not hemodiluted, the ELN strongly recommends that the first bone marrow 
aspirate draw be used for MRD assessment. 
Table 6: 
Bone Marrow and Peripheral Blood Efficacy Assessments 
Assessment 
Purpose 
Laboratory 
• Sample Type 
Timing 
Multiparameter 
(multicolor) flow 
cytometry (MFC) 
(also see Table 9) 
MRD analysis 
Central laboratory  
• Bone marrow aspirate 
(*first draw*) 
• Screening 
• Time of hematologic 
recovery for each 
treatment cycle 
Biobanking 
(also see Table 9) 
Storage and future analyses 
Central laboratory 
• Bone marrow aspirate 
• Whole blood 
• Screening 
• Time of hematologic 
recovery for each 
treatment cycle 
Immunological 
phenotyping 
Expression of cell-surface 
and cytoplasmic markers 
Central laboratory a 
• Whole blood 
• Screening 
Fluorescence in 
situ hybridization 
(FISH) 
Identification of 
rearrangements including 
RUNX1-RUNX1T1, 
CBFB-MYH11, KMT2A 
(MLL), and MECOM 
(EVI1) 
Central laboratory a 
• Whole blood  
• Screening 
Molecular 
genetic testing 
Including mutations in 
FLT3, NPM1, CEBPA, 
RUNX1, TP53, and 
ASXL1 
Central laboratory a 
• Whole blood  
• Screening 


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Assessment 
Purpose 
Laboratory 
• Sample Type 
Timing 
Morphology 
(cytology) 
Identification of marrow 
cellularity and blast 
percentage 
Local – Enter results in eCRF 
• Bone marrow aspirate 
• Screening 
• After each treatment 
cycle 
Cytogenetic 
profile (cell 
culture and 
banding analyses) 
Identification of specific 
translocations and 
inversions 
Local – Enter results in eCRF 
• Bone marrow aspirate 
• Screening 
a  In the event the central laboratory is not able to analyze a sample or results are delayed, local laboratory results (if 
available) may be utilized for screening/eligibility. 
Study center staff must enter results of all local/institutional bone marrow analyses into the 
eCRF. Copies of all local pathology reports are to be retained with the participant’s study records 
and to be available for monitoring. 
Instructions for collection, handling, and shipment of samples is included in the laboratory 
manual. 
8.2.2. 
Response Criteria and Outcome Measures  
Response criteria and outcome measures (Table 7) are based on definitions from ELN 
(Döhner 2017). 
Table 7: 
Response Criteria and Outcomes Measures  
Response / Outcome 
Definition 
Response 
Complete 
remission with 
complete 
hematologic 
recovery (CR) 
Defined for all study participants at the end of induction therapy.  
Bone marrow blasts <5%, absence of circulating blasts and blasts with Auer 
rods, absence of extramedullary disease,  
ANC >1.0 x 109/L (1000/μL), and platelet count >100 x 109/L (100,000/μL).  
Recovery of ANC and platelet counts within 7 days before or 7 days after 
bone marrow biopsy showing blasts <5% may be used to assess best response. 
CR with 
incomplete 
hematologic 
recovery (CRi) 
Defined for all study participants at the end of induction therapy.  
All CR criteria (bone marrow blasts <5%; absence of circulating blasts and 
blasts with Auer rods; absence of extramedullary disease), except for  
residual neutropenia (≤1.0 x 109/L [1000/μL]) or  
residual thrombocytopenia (≤100 x 109/L [100,000/μL]). 
[Note: Participants with both residual neutropenia and residual 
thrombocytopenia are not considered to have achieved CRi.]  
CR with partial 
hematologic 
recovery (CRh) 
Defined for all study participants at the end of induction therapy.  
CR criteria (bone marrow blasts <5%; absence of circulating blasts and blasts 
with Auer rods; absence of extramedullary disease), with partial recovery of 
peripheral blood counts (ANC >0.5 x 109/L [500/μL] and partial recovery of 
platelets >50 x 109/L [50,000/μL], but the count recovery criteria for CR are 
not met). 


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Response / Outcome 
Definition 
Measurable 
residual disease 
negative (MRDneg) 
Defined for all study participants at the end of induction and consolidation 
therapy.  
Negative (undetectable) MRD in recovery (~Day 22-42) bone marrow, as 
measured by MFC (0.1% detection limit). 
Failure 
Treatment failure 
(induction failure) 
Failure to achieve CR (or CR/CRi) within 42 days of the start of induction 
therapy (or start of reinduction therapy when applicable). 
Relapse 
Relapse 
(hematologic) 
Defined through 5 years after randomization only for participants achieving 
CR (or CR/CRi) during induction/reinduction. 
After achievement of CR/CRi, bone marrow blasts ≥5%, reappearance of 
blasts in the blood, or development of extramedullary disease. 
Cumulative 
incidence of 
relapse 
Defined through 5 years after randomization only for participants achieving 
CR (or CR/CRi) during induction/reinduction. 
Measured from the date of randomization to the date of relapse. Participants 
not known to have relapsed will be censored on the date they were last known 
to be alive. Participants who die without relapse will be counted as 
competing-risk events. 
Outcome Measure 
Overall survival 
(OS) 
*Primary 
Endpoint 
Defined for all study participants through 5 years after randomization.  
Measured from the date of randomization to date of death from any cause. 
Participants not known to have died at last follow-up contact will be censored 
on the date they were last known to be alive. 
Event-free 
survival (EFS) 
following CR 
*Key Secondary 
Endpoint 
Defined for all study participants through 5 years after randomization.  
Measured from the date of randomization to treatment failure, relapse, or 
death from any cause, whichever occurs first. For this endpoint, treatment 
failure is defined as failure to achieve CR within 42 days of the start of 
induction/reinduction. Participants not known to have relapsed or died will be 
censored on the date they were last known to be alive. 
EFS following 
CRi 
Defined for all study participants through 5 years after randomization.  
Measured from the date of randomization to treatment failure, relapse, or 
death from any cause, whichever occurs first. For this endpoint, treatment 
failure is defined as failure to achieve CRi within 42 days of the start of 
induction/reinduction. Participants not known to have relapsed or died will be 
censored on the date they were last known to be alive. 
Relapse-free 
survival (RFS) 
Defined through 5 years after randomization only for participants achieving 
CR (or CR/CRi) during induction/reinduction. 
Measured from the date of randomization to date of relapse or death from any 
cause. Participants not known to have relapsed or died at last follow-up 
contact will be censored on the date they were last known to be alive. 
Time to recovery 
of neutrophil 
count 
Defined for all study participants.  
Measured as time from date of randomization until the first day the ANC is 
>500/μL and is >1000/μL following induction or reinduction (if indicated).  


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Response / Outcome 
Definition 
 
Time to 
transfusion-
independent 
platelet recovery 
Defined for all study participants. 
Measured as time from date of randomization until the first day the platelet 
count recovers to >20,000/μL, >50,000/μL, and >100,000/μL, without a 
platelet transfusion in the preceding 5 days following induction or reinduction 
(if indicated). 
8.2.3. 
Long-Term Follow-up 
After completion or discontinuation of study intervention, participants will be followed-up until 
death or for 5 years after randomization. Contact with the participant (or caregiver or treating 
physician, as applicable) will be made every 3 months for the first 24 months, then every 
6 months for the remaining follow-up period.  
At (suspected) relapse, a full bone marrow examination should be performed, including 
morphology, cytogenetics, and biobanking; also collect peripheral blood for immunological 
phenotyping, molecular diagnostics, and biobanking. Participants will be asked to notify the 
study center in the event of relapse, even if a different physician/institution will be handling their 
future care. 
The following information will be collected as applicable: disease status (relapse date) (may 
include results of tests used for diagnosis of recurrence), death date, cause of death, and related 
source documentation. In addition, all AML therapies (i.e., for the treatment of AML and/or 
prevention of relapse) will be collected from 43 days after start of the last treatment cycle 
through the time of last study follow-up; this includes HCT and/or CAR T cell date(s) and 
details, other chemotherapy agent start/stop dates (and reasons for the treatment choice), and 
maintenance therapy start/stop dates. 
8.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the Schedule of 
Activities/Assessments (see Table 1 and Table 2).  
The investigator will discuss any immediate safety concerns with the sponsor (or designee) upon 
occurrence or awareness to determine if the participant should continue or discontinue receiving 
study intervention. 
Safety data will be monitored by an independent DMC on a routine basis (see Section 9.6). 
8.3.1. 
Physical Examinations 
Measure height at screening; measure weight (without shoes) at screening and at the start of 
consolidation therapy. 
Determine ECOG status (see Appendix 5 for details) at screening and confirm status at baseline 
before the first dose of study intervention. 
Complete a physical examination at screening as part of the review for eligibility for the study. 
Investigators should pay special attention to clinical signs related to AML and any other previous 
or ongoing serious illnesses. Record any clinically-relevant findings in the eCRF as medical 
history.  


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During the treatment period of the study (i.e., after the first dose of study intervention), record 
any clinically-relevant change(s) in physical examination (obtained during routine standard of 
care) findings in the eCRF as an AE(s). 
8.3.2. 
Vital Signs 
Assess all vital signs (temperature, pulse rate, respiratory rate, and blood pressure) at screening 
as part of the review for study eligibility. Record any clinically-relevant findings as medical 
history in the eCRF.  
During the treatment period of the study, record any clinically-relevant change(s) in vital sign 
measurements (obtained during routine standard of care) in the eCRF as an AE(s). 
8.3.3. 
Electrocardiograms 
ECGs will be obtained using an ECG machine that automatically calculates the heart rate and 
measures PR, QRS, QT, and QTc intervals. 
As specified in the Schedule of Activities, 12-lead ECGs will be obtained at the following time 
points: 
• Screening 
• Baseline/Day 1 predose 
• Day 1 at the end of the study intervention (i.e., dociparstat or placebo) bolus dose 
• Day 8 at the end of the study intervention (i.e., dociparstat or placebo) infusion for the 
initial induction cycle 
• Additional readings may be necessary to monitor AEs and/or changes in ECG 
measurements (e.g., as described in Section 7) 
At screening, 3 individual ECG tracings should be obtained as closely as possible in succession, 
but ideally no more than 2 minutes apart, with the full set of triplicates completed in less than 
4 minutes. At subsequent time points, a single ECG tracing will be obtained, with a repeat 
tracing to confirm QTc intervals >480 msec. 
Refer to Section 5.2 for QTc-related criteria for participant exclusion and Section 7 for 
QTc-related criteria for interruption and discontinuation of study intervention. 
At screening, as part of the review for eligibility for the study, and at baseline prior to the first 
dose of study intervention, record any clinically-relevant ECG findings as medical history in the 
eCRF. During the treatment period of the study, record any clinically-relevant change(s) in 
ECGs (obtained at protocol-specified time points or during routine standard of care) in the eCRF 
as an AE(s). 
It is recommended that QTc be calculated using Fridericia’s formula (QTcF) for all participants. 
If a study center does not have access to an ECG machine capable of calculating QTcF, then 
correction using an alternate formula may be used. All recordings for a single participant must 
use the same correction formula; therefore, if one formula is used at screening to determine 
eligibility for enrollment, that same formula must also be used during treatment to determine if 
criteria have been met for interruption or discontinuation of study intervention. 


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8.3.4. 
Clinical Safety Laboratory Assessments 
All required laboratory assessments must be conducted in accordance with this protocol and the 
laboratory manual. The timing and frequency of laboratory assessments are specified in the 
Schedule of Activities (Table 1 and Table 2).  
• The laboratory tests (clinical chemistry, hematology, and coagulation) listed in 
Table 8) will be performed by the study centers’ usual local laboratory.  
• All laboratory reports will be filed with the source documents.  
• Site personnel must enter results into the eCRF for the specified laboratory 
parameters (with units and relevant reference ranges) at each specified time point.  
• The investigator must document their review of each laboratory report. 
Clinically-relevant abnormal laboratory findings at screening and before the first dose 
of study intervention will be recorded as medical history. 
• Clinically-significant abnormal changes occurring during the treatment period of the 
study or within 42 days after the start of the last cycle of study intervention will be 
recorded in the eCRF as an AE(s). Clinically-significant abnormal laboratory findings 
are those that are not associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
− These laboratory tests will be repeated (and recorded in the eCRF) until the values 
return to normal or baseline or are no longer considered clinically significant by 
the investigator. 
− If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified. 
− The investigator may consult with the medical monitor for any questions. 
Laboratory tests may be performed at additional times during the study as part of standard care, 
as determined necessary by the investigator, or as required by local regulations. Any laboratory 
test(s) performed in response to an AE and any laboratory results that are used for decisions 
regarding participants’ treatment response, study interventions, and/or AML treatments must be 
recorded in the participants’ eCRF (as an unscheduled visit if not at a protocol-specified time 
point). 
Refer to Section 5.2 for laboratory-related criteria for participant exclusion and Section 7 for 
laboratory-related criteria for interruption and discontinuation of study intervention. 


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Table 8: 
Laboratory Assessments 
Laboratory 
Assessments 
Parameters for Routine Monitoring 
Additional Screening 
Parameters 
Hematology 
• Platelet Count  
• Hemoglobin 
• Absolute neutrophil count 
• White blood cell count with differential 
(unless count is too low) 
• Peripheral blast count  
• Blasts with Auer rods 
Screening only: 
Hematocrit,  
red blood cell (RBC) count 
Clinical 
Chemistry 
• Alanine aminotransferase (ALT) 
• Aspartate aminotransferase (AST) 
• Total and direct bilirubin 
• Alkaline phosphatase  
• Blood urea nitrogen 
• Creatinine 
• Lactate dehydrogenase 
• Calcium 
• Magnesium 
• Potassium  
• Sodium  
Screening only:  
Chloride, phosphate, albumin, 
total protein, glucose, uric acid, 
gamma-glutamyl transferase  
 
Coagulation 
• Activated partial thromboplastin time (aPTT) 
• Prothrombin time and international 
normalized ratio (PT/INR) 
Screening only:  
Fibrinogen, D-dimer 
8.4. 
Adverse Events and Serious Adverse Events 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for follow-up. 
AEs will be categorized by system organ class and preferred term using the Medical Dictionary 
for Regulatory Activities dictionary and AE severity will be graded according to the National 
Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE).  
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
Any SAE that is considered related to study procedures will be collected from the time of 
consent until the first dose of study intervention. Any other medical occurrences that begin 
during this time period will be recorded on the medical history/current medical conditions 
section of the eCRF (not as an AE/SAE). 


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All AEs will be collected from the time of first dose through 42 days after the start of the last 
treatment cycle with study intervention (i.e., dociparstat or placebo administered during initial 
induction, reinduction, or consolidation therapy as specified in this protocol). 
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 2: Adverse Events. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of the data being 
available. 
Investigators are not obligated to actively seek new onset AEs or SAEs after the protocol-defined 
reporting period; however, if the investigator learns of any SAE and he/she considers the event to 
be reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor. 
8.4.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.4.3. 
Follow-up of AEs and SAEs 
After an initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. It is important for all SAEs, AEs of special interest (as 
defined in Section 8.4.7), AEs considered related to study intervention, and AEs that resulted in 
discontinuation of study intervention to be followed until resolution, stabilization, the event is 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.4). 
8.4.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification of an SAE by the investigator to the sponsor is essential so that legal and 
regulatory obligations and ethical responsibilities towards the safety of participants and the 
safety of a study intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and sponsor policy and be forwarded to 
investigators as necessary. An investigator who receives an investigator safety report describing 
an SAE or other specific safety information (e.g., summary or listing of SAEs) from the sponsor 
will review and then file it along with the investigator’s brochure and will notify the IRB/IEC, if 
appropriate according to local requirements. 


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8.4.5. 
Death Events 
If a participant dies during participation in the study (at any time from the time of consent 
through long-term follow-up), the investigator will provide the date of death and a determination 
of cause of death (including any supporting information, such as death certificate, pathology or 
autopsy information, as applicable).  
All deaths from events with onset through 42 days after the start of the last treatment cycle with 
study intervention are to be reported as SAEs. Thereafter, the investigator will provide the 
requested information in the eCRF along with requested supporting information. 
8.4.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
The following disease-related events may be serious and life-threatening and are common in 
participants with AML: 
• AML progression 
• Thrombocytopenia 
• Neutropenia 
Because thrombocytopenia and neutropenia are typically associated with the disease under study, 
when the event(s) occurs with active leukemia, it is not to be reported by the investigator as an 
AE/SAE, unless the event meets one or more of the following conditions. If any of these 
conditions apply, then the event must be recorded and reported as an AE/SAE: 
• The event is, in the investigator’s opinion, of greater intensity, frequency, or duration 
than expected for the individual participant. 
• The investigator considers that there is a reasonable possibility that the event is 
related to study intervention. 
8.4.7. 
Adverse Events of Special Interest 
Adverse events of special interest, as listed below, must be recorded and reported to the sponsor 
(or designee) within 24 hours. 
• Prolonged neutropenia: 
Defined as a case of Grade 4 neutropenia that, in the absence of active leukemia, lasts 
past Day 42 of a chemotherapy cycle. 
• Hemorrhagic AEs that are Grade 3 or higher in severity (per CTCAE criteria): 
Additional information about hemorrhagic AEs will be collected to more fully 
describe the participant’s status and assess potential causes and contributing factors; 
this includes, at a minimum, aPTT values, platelet values, possible contributory 
medications (e.g., heparin or other anticoagulants) in the preceding 7 days, and 
treatment(s) administered. 


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8.5. 
Treatment of Overdose 
For this study, any dose of study intervention (i.e., dociparstat or placebo) greater than 8 mg/kg 
as a bolus dose, greater than 0.5 mg/kg/hr infusion, or greater than 20 mg/kg within a 24-hour 
time period will be considered an overdose. 
In the event of an overdose, the investigator should: 
• Contact the medical monitor immediately. 
• If the continuous infusion is ongoing, adjust the rate to administer the correct dose. 
• Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 48 hours after the overdose. 
• Document the quantity of the excess dose and the duration of the overdose in the 
eCRF. 
Interrupt the study intervention infusion if clinically-significant bleeding (e.g., Grade 3 or higher 
hemorrhagic AE) or aPTT >45 seconds occurs after administration of an overdose of dociparstat 
(see Section 7.1). Other decisions regarding dose interruptions will be made by the investigator 
in consultation with the medical monitor based on clinical evaluation of the participant. 
At the discretion of the investigator in consultation with the medical monitor, protamine may be 
used to neutralize the anticoagulation effects of dociparstat overdose. Protamine doses should be 
based on activated clotting time or aPTT plasma values and not based on the milligram dosage of 
dociparstat administered. 
In the event of an overdose of cytarabine, idarubicin, or daunorubicin, refer to the approved 
product label(s) for guidance. 
8.6. 
Pharmacokinetics 
During the initial induction cycle, plasma samples (~2 mL) will be collected for analysis of 
dociparstat concentrations to derive pharmacokinetic parameters, as data permit.  
Plasma samples will be collected at the following time points: 
• Day 1: predose; at the end of the IV bolus; and at 1 hour and 12 hours after the end of 
the IV bolus.  
• Day 4: a single sample will be collected during the infusion (ideally in the morning). 
• Day 8: within ~5 minutes after the end of the infusion, and at 0.5, 1, 2, and 4 hours 
after the end of the infusion. 
Blood samples will ideally be collected within ±10 minutes of the specified time points. The date 
and actual time (24-hour clock time) must be recorded for each blood sample. The timing of 
sampling may be altered during the study based on newly available data and up to 3 samples may 
be collected at additional time points (if warranted and agreed upon between the investigator and 
the sponsor) to ensure appropriate monitoring.  
Note: Do not draw blood from the same line that is used for study intervention administration. 
Drawing blood from a heparinized line may falsely alter the PK results obtained; therefore, if 


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using an indwelling catheter, draw approximately 5 mL of blood for discard before drawing the 
PK sample. Additional information regarding sample collection and handling is provided in the 
laboratory manual. 
Drug concentration information that would unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded. 
Pharmacokinetic parameters to be evaluated include area under the concentration-time curve 
(AUC), maximum observed concentration (Cmax), time to maximum observed concentration 
(Tmax), terminal elimination half-life (t½), and clearance. Plasma samples collected for analyses 
of dociparstat concentrations may also be used to evaluate safety or efficacy aspects related to 
concerns arising during or after the study. 
Genetic analyses will not be performed on these plasma samples. Participant confidentiality will 
be maintained. 
PK samples will be collected at study centers with appropriate capabilities (e.g., centrifuge, staff 
experience and availability). 
8.7. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.8. 
Genetics 
Genetic variation may impact a participant’s response to study intervention and susceptibility to, 
severity of, and progression of disease. An optional saliva specimen or buccal swab will be 
obtained for germ-cell line analysis. Variable response to study intervention may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease being 
treated. 
Cytogenetic Analyses 
Cytogenetic testing of bone marrow samples is a required screening test to appropriately type 
and characterize AML and to determine eligibility for study enrollment based on intermediate or 
adverse/unfavorable genetic risk.  
Biobanking 
Where local regulations and IRB/IEC allow, a 10-mL bone marrow sample and a 10-mL whole 
blood sample will be collected at designated time points for biobanking from participants who 
have consented to participate in this component of the study.  
• Whole blood and bone marrow will be processed at the central lab to isolate cells for 
cryopreservation to maintain viability. 
• Retrospective analysis on cryopreserved cells and/or extracted nucleic acids from 
biobanked samples will be conducted for research related to biomarkers of 
response/resistance to study drugs and mechanism of action for dociparstat. This 
could allow for developing tests/assays to predict response and resistance to the study 
drugs, including dociparstat. 


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• The results of genetic analyses may be reported in the clinical study report or in a 
separate study summary report. 
• The sponsor will store the samples (cells, DNA or RNA) in a secure storage space 
with adequate measures to protect confidentiality. 
• The samples will be retained while research on dociparstat continues, but no longer 
than 15 years or other period as per local requirements. 
Participation in biobanking is strongly encouraged, but optional. Participants who do not wish to 
participate in biobanking may still participate in the study. 
Details on processes for collection, shipment, and destruction of these samples is included in the 
laboratory manual. 
8.9. 
Biomarkers 
• For all participants, bone marrow aspirate/biopsy samples will be collected and tested 
for MRD via MFC at screening and after hematologic recovery for each cycle of 
induction and consolidation chemotherapy (as specified in the Schedule of Activities) 
to evaluate the association with dociparstat treatment and the observed OS and EFS. 
• Blood samples will be collected during induction and consolidation therapy to 
measure plasma levels of HMGB1, which is expressed in tumor tissues and higher 
levels have been correlated with worse clinical prognosis. The association of 
dociparstat with lower HMGB1 levels will be evaluated. See Section 1.2 for 
collection timepoints. For participants who receive multiple consolidation cycles, 
only samples from the last consolidation cycle will be analyzed. Blood samples 
collected for HMGB1 may be reserved for batch analysis. Refer to the laboratory 
manual for instructions on collection of a separate sample, versus using blood from 
the biobanked sample for analysis. 
• Biobanked blood and bone marrow may be used to conduct retrospective analyses of 
biomarkers including, but not limited to, CXCR4, CXCR7, CXCL12, and LSC 
markers to evaluate their association with observed clinical responses and gain insight 
into the mechanism of action of dociparstat in AML treatment. Genetic markers 
known to be related to AML response and or resistance (e.g., clonal selection for 
TP53 and FLT3 variants) may be examined and additional analyses may be 
conducted to advance understanding of potential predictors for response (e.g., gene 
signatures associated with LSCs). 
Details on processes for collection, shipment, and destruction of these samples is included in the 
laboratory manual. 


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Table 9: 
Sample Collection Time Points for MRD Analyses and for Biobanking 
Sample Time 
Analysis 
Sample Material 
Screening 
MRD + Biobanking 
10 mL Bone marrow 
10 mL Whole blood 
Recovery after initial induction (Day ~28-42) 
MRD + Biobanking 
10 mL Bone marrow 
10 mL Whole blood 
Recovery after reinduction (Day ~28-42) 
MRD + Biobanking 
10 mL Bone marrow 
10 mL Whole blood 
After each consolidation cycle 
MRD + Biobanking 
10 mL Bone marrow 
10 mL Whole blood 
Relapse 
MRD + Biobanking 
10 mL Bone marrow 
10 mL Whole blood 
8.10. 
Medical Resource Utilization 
Dates of hospitalization and discharge, and number of days spent in intensive care settings will 
be assessed. Number of blood product units (e.g., red blood cell transfusions, platelet 
transfusions) administered and number of growth factor administrations will also be collected. 


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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
The null hypothesis is that the effect of dociparstat plus standard chemotherapy on OS and EFS 
equals the effect of standard chemotherapy, or: 
H0: Sdstat = Spbo 
The alternative hypothesis is that the effect of dociparstat plus standard chemotherapy on OS and 
EFS does not equal the effect of standard chemotherapy, or: 
HA: Sdstat ≠ Spbo 
9.2. 
Sample Size Determination 
Approximately 1000 potential participants are expected to be screened to achieve a total of 
approximately 570 participants randomly assigned to study intervention. 
Sample size calculations were based on the OS primary and EFS key secondary endpoints. 
Randomized Phase 2 data in the subset of participants matching our proposed Phase 3 population 
show an observed OS HR of 0.51 and control median OS of 16.1 months; however, these 
estimates are associated with substantial uncertainty given the small size of the Phase 2 study as 
well as actual and potential emerging post-induction and post-relapse therapies for patients with 
AML. To account for these factors, we assume a clinically-meaningful OS HR of 0.7 and a 
control median OS of 18 months; this corresponds with a dociparstat median OS of 25.7 months. 
Hence, assuming 24-month accrual, 24-month minimum follow-up time, and accounting for one 
formal interim analysis (see Section 9.5), the planned sample size will have >85% power to 
demonstrate a difference between treatment arms at a two-sided type I error rate of 4%. The 
target number of OS events is 308. 
Similarly, we assume a clinically-meaningful EFS HR of 0.7, and a control median EFS of 
10 months, 24-month accrual, and 24-month minimum follow-up. Hence, the planned sample 
size will have >85% power to demonstrate a difference between treatment arms at a two-sided 
type I error rate of 1%. Under the assumptions of 50% CR rates in both groups and no separation 
of the curves during the first 6 months, this is expected to result in 454 events. 
9.3. 
Analysis Sets 
The following analysis sets are defined: 
Analysis Set 
Description 
Screened 
All participants who sign the ICF. 
Intent to Treat 
(ITT) 
All participants who are randomized. Participants will be analyzed in the group to 
which they were randomized. 
Safety 
All participants who are randomized to and receive at least one dose of blinded 
dociparstat or placebo. Participants will be analyzed in the group corresponding to 
the first blinded dose of study intervention received.  


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Analysis Set 
Description 
Per protocol 
(PP) 
All participants who are randomized to and receive at least one dose of blinded 
dociparstat or placebo, excluding those who have any significant inclusion/exclusion 
criteria violation or noncompliance that would be expected to impact the analysis of 
efficacy. Participants will be analyzed in the group corresponding to the first blinded 
dose of study intervention received. 
The ITT analysis set will be used to summarize all efficacy endpoints. The PP analysis set will 
be determined prior to unblinding and will be used for supportive primary and key secondary 
efficacy analyses and possibly other selected endpoints to be defined in the Statistical Analysis 
Plan (SAP). The safety analysis set will be used for all safety and all other non-efficacy 
(e.g., medical history, medications, exposure) analyses. 
9.4. 
Statistical Analyses 
All analyses will be presented by randomized group (dociparstat, placebo), unless otherwise 
specified. The SAP will be finalized prior to the first interim analysis. It will include a more 
technical and detailed description of the statistical analyses described in this section, which is a 
summary of the planned analyses of the most important endpoints, including primary and key 
secondary endpoints. 
9.4.1. 
Primary Endpoint 
The primary OS inferential analysis will utilize the ITT analysis set and a log-rank test at 
two-sided alpha 0.04 stratified by baseline FLT3 status, cytogenetic risk, and age. Kaplan-Meier 
(KM) methods/plots and Cox models will be used. Log-rank p-values and hazard ratios with 
95% CIs will be presented for each treatment comparison. Median failure times, KM estimates 
every 90 days, and corresponding 95% CIs will be presented for each group. Survival time will 
be measured from randomization. Participants who are not known to have died will be censored 
at the time they were last known to be alive. The final primary analysis will be conducted after 
approximately 308 death events have been observed. 
9.4.2. 
Key Secondary Endpoint 
The key secondary EFS endpoint will be tested using the same method as the primary endpoint at 
two-sided alpha 0.01. A participant with any bone marrow CR assessment between Days 22 and 
42, inclusive, after start of induction or reinduction treatment will be considered an induction 
success; relapse and death events will be assessed following the last CR assessment during this 
time period. A participant with no CR assessments during this window will be considered an 
induction failure and imputed as such at randomization. Participants with induction success and 
no observed relapse or death events will be censored at the time they were last known to be alive. 
Maximum neutrophil and platelet counts within 7 days before or after the bone marrow draw will 
be used to determine count recovery. The key secondary analysis will be supplemented by a 
planned sensitivity analysis (not subject to alpha control), in which participants progressing to 
hematopoietic cell transplant will be censored at the time of transplant. The key secondary 
analysis will be conducted at the same time as the final primary OS analysis. 


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9.4.3. 
Other Secondary Endpoints 
In the event that both the primary and key secondary analysis rejects the null hypothesis, the 
secondary analyses of MRDneg, time to platelet recovery, time to neutrophil recovery, and CR 
will be tested in a fixed sequential manner at two-sided alpha 0.05. If the primary analysis rejects 
the null hypothesis while the key secondary does not, these secondary analyses will be tested in a 
fixed sequential manner at two-sided alpha 0.04; similarly, if the key secondary analysis rejects 
the null hypothesis while the primary analysis does not, these secondary analyses will be tested 
in a fixed sequential manner at two-sided alpha 0.01. No other multiplicity adjustments will be 
made for secondary analyses. 
Time-to-event secondary analyses will use the same methods used for the primary and key 
secondary analyses. 
Dichotomous secondary efficacy analyses will be analyzed using a Cochran-Mantel-Haenszel 
test stratified by each of the stratification factors. Number of successes/failures and 
success/failure rates will be presented for each treatment arm. Cochran-Mantel-Haenszel 
p-values, estimated common odds ratios, and corresponding approximate 95% CIs will be 
presented for each comparison. The Breslow-Day test will be used to test the homogeneity of the 
odds ratios across the strata. Missing data will generally be imputed as failure unless specifically 
defined otherwise in the SAP. 
Cumulative incidence of relapse will be analyzed with death as a competing risk adjusted for 
baseline strata, with corresponding cumulative incidence plots, Fine-Gray models, and cause-
specific and sub distribution hazard ratios with corresponding 95% CIs. 
OS, EFS, and MRD will be analyzed by various subgroups, including, but not limited to, each of 
the stratification factors, anthracycline use, sex, and race (each race contributing >10% to the 
study plus other races grouped). OS and relapse will be analyzed by number of consolidation 
cycles. Multivariate modelling to assess the impact of these factors on key endpoints will be 
considered and defined in the SAP. 
9.4.4. 
Safety Analyses 
All safety analyses will be presented using the safety analysis set. Inferential analyses will 
generally not be performed for safety endpoints unless specified in the SAP. Frequency and 
percentage will be presented for categorical variables. Sample size, mean, standard deviation, 
median, interquartile range, and range will be presented for continuous variables. 
9.4.4.1. 
Adverse Events 
Treatment-emergent AEs (TEAEs) are those that begin on or after the date of the first 
dose of study intervention and on or before 42 days after the start of the last cycle of 
study intervention. 
Summaries (number and percent of participants) of TEAEs (by system organ class and preferred 
term) will be provided as follows: 
• All 
• Severe, life-threatening, and fatal 


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• Treatment-related 
• Severe, life-threatening, and fatal treatment-related 
• Serious 
• Treatment-related serious 
• Those leading to study intervention discontinuation 
• Those leading to study intervention interruption 
• Fatal 
9.4.4.2. 
Laboratory Results 
Descriptive statistics (N, mean, standard deviation, median, Q1, Q3, minimum, and 
maximum) will be provided for each continuous laboratory test as follows: 
• Baseline values 
• Values at each postbaseline analysis window (to be defined in the SAP) 
• Change from baseline at each postbaseline analysis window 
The minimum, maximum, and last postbaseline value / change from baseline will also be 
summarized. Missing data will not be imputed. 
Laboratory tests will be descriptively analyzed by grade and analysis window using counts and 
percentages. The maximum and last postbaseline grade for each participant will also be 
summarized. Denominators will be the number of participants with a graded (or normal) test 
during the window. Laboratory tests with criteria for both increased and decreased levels will be 
analyzed for each direction (i.e., increased and decreased). This analysis will be generated twice 
to count (1) treatment-emergent increases in laboratory grades (i.e., only those above the baseline 
grade) and (2) any grade regardless of baseline. 
9.4.4.3. 
Safety Subgroup Analyses 
TEAEs Grade 3 and above, serious TEAEs, and treatment-emergent increases in laboratory 
grades will be summarized by age (<65, ≥65 years), race/ethnicity (separate categories for 
racial/ethnic groups contributing at least 10% of study enrollment plus “other”), sex (male vs 
female), and weight (tertiles). Other subgroups may be specified in the SAP. 
9.4.5. 
Other Analyses 
Other analyses, including but not limited to participant enrollment, analysis sets, demographics, 
baseline characteristics, prior and concomitant medications, study intervention usage, 
pharmacokinetics, and medical resource utilization will be specified in the SAP or other specific 
analysis plans. 
9.5. 
Interim Analyses  
Two interim analyses are planned. 


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The first interim analysis will be an early unblinded (only to the DMC) assessment of CR, CR 
with MRDneg, and MRDneg. This analysis will be reviewed by the DMC after 80 evaluable 
participants complete induction and reinduction (if applicable) assessments. Evaluable 
participants for this purpose are defined as those who either have a valid MRD result from the 
induction therapy recovery bone marrow (i.e., Day ~22 to 42), discontinue from induction 
therapy due to an AE or progressive disease, or die during induction therapy. The study will 
continue recruitment and enrollment while the interim analyses are being performed; a decision 
will be made as soon as practicable (targeted within 3 months) after the last participants’ last 
assessments to be included in the analysis. 
Three outcomes are possible from this analysis: 
• The observed risk difference for CR is >30%, the observed risk difference for 
MRDneg is >50%, or the combined total of observed risk differences for CR and CR 
with MRDneg is >40%. The study will remain blinded and continue as planned. 
• Observed risk differences for CR, MRDneg, and CR with MRDneg are all <5% The 
study will be unblinded to all parties and stopped. 
• Criteria are not met for either of the preceding scenarios. The study will be unblinded 
to the sponsor, who, in consultation with the United States Food and Drug 
Administration, will determine whether to continue or stop the study. If the study 
continues, participants contributing to the interim assessment will not be used in 
subsequent inferential analyses and will be replaced. A summary of the data will be 
shared with investigators and ethics committees and publicly presented. Participants 
randomized after the interim cutoff and not contributing to the assessment will remain 
blinded and will contribute to subsequent inferential analyses. 
The second interim analysis will be an unblinded (only to the DMC) efficacy assessment. It will 
be completed after approximately 250 OS events are observed. The O’Brien-Fleming alpha 
spending function will be used to control the familywise type I error rate. Therefore, the interim 
OS test will be performed at the 0.0196 nominal two-sided alpha level, and the final OS test will 
be performed at the 0.0342 nominal two-sided alpha level. On the condition that the study 
proceeds beyond the first interim analysis, this approach is expected to yield >68% power at the 
time of this second interim analysis for the primary OS endpoint under the sample size 
assumptions noted. The key secondary EFS endpoint will also be tested at this time, with the 
alpha level determined based on the total number of observed EFS events using an alpha 
spending function that maps to the O’Brien-Fleming boundary. In the event that this interim 
analysis is successful for either endpoint, the database will be unblinded to the sponsor to 
facilitate regulatory submissions. Regardless of conclusions from the second interim analysis, 
participants will continue to be followed as prescribed, with individual group assignments 
remaining blinded at the site level. 
Additional details of the planned interim analyses will be included in the SAP and DMC charter 
(or associated documents). 


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9.6. 
Data Monitoring Committee 
Study data will be periodically reviewed during the study by an independent, unblinded DMC at 
prespecified timepoints: 
• After ~80 evaluable participants complete induction and reinduction (if applicable) 
assessments (safety data and interim analysis for efficacy). 
• After approximately 200, 300, and 400 participants have been randomized and 
completed at least 4 months of follow-up (safety data). 
• After approximately 250 OS events are observed (interim analysis for efficacy). 
The DMC will also be provided with real-time, expedited safety reports. The DMC chair may 
schedule ad hoc safety review meetings at any time during the study as deemed appropriate. 
Details of the DMC membership and review procedures will be outlined in a separate charter.  


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10. 
REFERENCES 
Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN 
recommendations from an international expert panel. Blood. 2017 Jan 26;129(4):424-447. 
doi: 10.1182/blood-2016-08-733196. Epub 2016 Nov 28. 
Kovacsovics TJ, Mims A, Salama ME, et al. Combination of the low anticoagulant heparin 
CX-01 with chemotherapy for the treatment of acute myeloid leukemia. Blood Adv. 
2018;2(4):381-389. doi: https://doi.org/10.1182/bloodadvances.2017013391. 
Lambert MP, Rauova L, Bailey M, et al. Platelet factor-4 is a negative autocrine in vivo regulator 
of megakaryopoiesis: clinical and therapeutic implications. Blood. 2007; 110:1153-60. DOI: 
10.1182/blood-2007-01-067116. 
Lambert MP, Reznikov A, Grubbs A, et al. Platelet factor 4 platelet levels are inversely 
correlated with steady-state platelet counts and with platelet transfusion needs in pediatric 
leukemia patients. J Thromb Haemost. 2012 Jul;10(7):1442-6. doi: 10.1111/j.1538-
7836.2012.04767.x. 
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Acute 
myeloid leukemia. Version 3.2020. 2019. Available at: 
https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed: August 2020. 
Rao NV, Argyle B, Xu X, et al. Low anticoagulant heparin targets multiple sites of 
inflammation, suppresses heparin-induced thrombocytopenia, and inhibits interaction of RAGE 
with its ligands. Am J Physiol Cell Physiol. 2010 Jul;299(1):C97-110. doi: 
10.1152/ajpcell.00009.2010. Epub 2010 Apr 7. Available at: 
https://www.physiology.org/doi/pdf/10.1152/ajpcell.00009.2010. 
Sekeres MA, Guyatt G, Abel G, et al. American Society of Hematology 2020 guidelines for 
treating newly diagnosed acute myeloid leukemia in older adults. Blood Adv. 2020 Aug 
11;4(15):3528-3549. doi: 10.1182/bloodadvances.2020001920. 
Tkaczynski E, Arulselvan A, Tkaczynski J, et al. 2-O, 3-O desulfated heparin mitigates murine 
chemotherapy- and radiation-induced thrombocytopenia. Blood Adv. 2018 Apr 10;2(7):754-761. 
doi: 10.1182/bloodadvances.2017013672. Erratum in: Blood Adv. 2018 May 22;2(10):1129. 
Zhang S, Condac E, Qiu H, Jiang J, Gutierrez-Sanchez G, Bergmann C, Handel T, Wang L. 
Heparin-induced leukocytosis requires 6-O-sulfation and is caused by blockade of selectin- and 
CXCL12 protein-mediated leukocyte trafficking in mice. J Biol Chem. 2012 Feb 
17;287(8):5542-53. doi: 10.1074/jbc.M111.314716. Epub 2011 Dec 22. Available at: 
http://www.jbc.org/content/287/8/5542.full.pdf. 
Ziarek JJ, Veldkamp CT, Zhang F, et al. Heparin oligosaccharides inhibit chemokine (CXC 
motif) ligand 12 (CXC12) cardioprotection by binding orthogonal to the dimerization interface, 
promoting oligomerization, and competing with the chemokine (CXC motif) receptor 4 
(CXCR4) N terminus. J Biol Chem. 2013 Jan 4;288(1):737-46. doi: 10.1074/jbc.M112.394064. 
Epub 2012 Nov 12. Available at: http://www.jbc.org/content/288/1/737.long. 
 


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11. 
APPENDICES: SUPPORTING DOCUMENTATION AND 
OPERATIONAL CONSIDERATIONS 
11.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
11.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines. 
• Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines. 
• Applicable laws and regulations. 
The investigator will submit the protocol, protocol amendments, ICF, and other relevant 
documents (e.g., advertisements) to an IRB/IEC for review and approval by the IRB/IEC before 
the study is initiated. Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to eliminate 
an immediate hazard to study participants.  
The investigator will also be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
• Oversight of the conduct of the study at the site and adherence to requirements of US 
regulations (21 CFR), ICH guidelines, the IRB/IEC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations. 
• Notify the IRB/IEC of protocol deviations, unanticipated problems, and serious 
breaches of GCP according to local guidelines and maintain this documentation in the 
sites’ study file.  
11.1.2. 
Financial Disclosure 
Investigators and subinvestigators will provide the sponsor with enough accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the study and for 1 year after 
study completion. 


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11.1.3. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the 
participant and/or legally authorized representative and will answer all questions 
regarding the study.  
• Participants must be informed that their participation is voluntary.  
• Participants or their legally authorized representative (as defined by local regulations) 
will be required to sign a statement of informed consent that meets the requirements 
of US regulations (21 CFR Part 50), local regulations, ICH guidelines, and the 
IRB/IEC. In some situations, verbal or remote consent may be permissible.  
• The authorized person obtaining the informed consent must also sign the ICF. 
• The medical record must include the date informed consent was obtained and a 
statement that consent was obtained before the participant was enrolled in the study.  
• When the ICF is amended, the investigator must follow all applicable regulatory 
requirements pertaining to approval of the amended ICF document(s) by the IRB/IEC 
prior to use. Participants must be re-consented to the most current version of the 
ICF(s) during their participation in the study.  
• The investigator must maintain the original and any amended signed and dated ICFs. 
A copy of each signed ICF must be provided to the participant and/or the participant’s 
legally authorized representative.  
The ICF shall contain authorization for the use and disclosure of the participant’s protected 
health information in connection with the study. The authorization shall include at a minimum a 
clear description of the following: the duration of the authorization, the right of access to the 
information (or any suspension thereof during the course of the study), type of information to be 
used/disclosed in the study, names or classes of parties that may use or disclose information, 
purpose of the use/disclosure, extent of the right to revoke the authorization, extent to which 
participation in the study is conditioned on signing the authorization, and potential for 
redisclosure of protected health information.  
The ICF will address the optional biobanking of bone marrow and blood samples for exploratory 
research. The investigator or authorized designee will explain to each participant the objectives 
of the exploratory research. Participants will be told that they are free to refuse to participate in 
exploratory research and may withdraw their consent at any time and for any reason during the 
storage period. 
If a prescreening ICF is used for screening assessments (e.g., bone marrow analyses) to 
determine eligibility before a participant consents to the full study, the participant will be clearly 
informed that the purpose for prescreening is to identify participants to enroll in the full study. 
11.1.4. 
Data Protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are transferred to the sponsor will only contain the identifier; any information that 
would make the participant identifiable (e.g., name) will not be transferred. The investigator will 


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keep an enrollment and identification log that contains a record of the personal identification data 
linked to each participant’s study identification number. 
Encoded participant data will be transferred to the sponsor (located in the US) and will be stored 
indefinitely. Encoded data will be used by the sponsor for safety reporting, research and 
development, regulatory purposes, and marketing of dociparstat; encoded data may also be 
shared with other companies or individuals for research purposes. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with US Health Insurance Portability and Accountability Act (HIPAA) 
requirements (where applicable) and/or national data protection/privacy laws (outside of the 
USA), including without limitation the General Data Protection Regulation (GDPR) 2016/679 
(in the European Union). The participant will be required to give consent for their data to be used 
as described in the informed consent document. 
The participant must be informed about the level of disclosure and that his/her medical records 
may be examined by clinical quality assurance auditors or other authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
11.1.5. 
Data Quality Assurance 
All observations relating to the study will be recorded by site personnel in source documents. In 
addition, an eCRF must be completed for every participant entered into the study. The eCRF 
must be completed according to the eCRF completion guidelines. After each participant has 
completed the study, the investigator must review and electronically sign the eCRFs indicating 
that (s)he has reviewed the completed eCRFs and pertinent clinical data for the participant and 
that, to the best of his/her knowledge, all data recorded in the eCRFs accurately reflects the 
participant’s performance in the study. 
Quality controls are incorporated into project management activities conducted by Chimerix (or 
its designee), including the monitoring and verification of clinical and safety data. 
The investigator must permit study-related monitoring, audits, IRB/IEC reviews, and regulatory 
agency inspections and provide direct access to source data documents. Study monitors will 
perform ongoing source data verification to confirm that data entered into the eCRF by 
authorized site personnel are accurate, complete, and verifiable from source documents; that the 
safety and rights of participants are being protected; and that the study is being conducted in 
accordance with the currently approved protocol and any other study agreements, ICH GCP, and 
all applicable regulatory requirements. Remote monitoring will be considered on a site-by-site 
basis and conducted following procedures outlined in the appropriate study-specific plans 
(e.g., monitoring plan), and in accordance with current available guidance regarding regulatory 
authority opinion on remote monitoring. 
Essential documents pertaining to the conduct of the study should be retained for the following 
time period: 
• At least 2 years after approval of the last marketing application. 
OR 
• At least 2 years have elapsed since the formal discontinuation of clinical development 
of the investigational product. 


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These documents should be retained for a longer period (e.g., 15 years or more), however, if 
required by applicable local or country-specific regulatory requirements or by an agreement with 
Chimerix. It is the responsibility of Chimerix to inform the investigator/institution as to when 
these documents no longer need to be retained. If it becomes necessary for Chimerix or any 
regulatory authority to review any documentation relating to the study, the investigator must 
permit access to such records.  
11.1.6. 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of data collected. Source documents are filed at the investigator’s site. 
Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. Participants’ medical records must be 
available for inspection. The investigator may need to request medical records from other 
providers in order to have all relevant data available.  
11.1.7. 
Study and Site Start and Closure 
The study start date is the date on which the first randomized participant signed the ICF (i.e., first 
participant, first visit). 
The clinical study will be open for recruitment of participants when the first site has completed 
site initiation, has study intervention onsite, and has been notified by the sponsor (or designee). 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor’s procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further development of the study intervention. 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, IECs/IRBs, regulatory authorities, and any contract research organization(s) used 
in the study of the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform participants at their study center and should 
ensure appropriate therapy and/or follow-up. 
11.1.8. 
Dissemination of Clinical Study Data 
Results of the study will be posted on the relevant clinical study registration websites 
(e.g., clinicaltrials.gov and the European Union clinical trials register). Results of the study will 


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also be submitted for publication in a peer-reviewed scientific journal, unless the study is 
terminated prematurely and does not yield sufficient data for a publication. 
11.1.9. 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows the sponsor to protect proprietary information and to provide comments.  
The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 


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11.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
11.2.1. 
Definition of an AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally 
associated with the use of study intervention, whether or not considered related to the study 
intervention.  
• 
Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of study intervention. 
Events Meeting the AE Definition  
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (e.g., ECG, radiological scans, vital signs measurements), including those that worsen 
from baseline, considered clinically significant in the medical and scientific judgment of the 
investigator (i.e., not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study intervention administration even though it may 
have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
• 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be reported as an 
AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as an AE or 
SAE if they fulfil the definition of an AE or SAE.  
 
Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which 
are associated with the underlying disease, unless judged by the investigator to be more severe than 
expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s condition or 
is fatal. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen. 


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11.2.2. 
Definition of an SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study). 
SAEs 
An SAE is defined as any untoward medical occurrence that, at any dose: 
1. Results in death 
2. Is life-threatening 
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the participant was 
at risk of death at the time of the event. It does not refer to an event, which hypothetically might have 
caused death, if it were more severe. 
3. Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
In general, hospitalization signifies that the participant has been detained (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting.  
• 
Complications that occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event is an SAE.  
• 
When in doubt as to whether “hospitalization” occurred or was necessary, the AE should be 
considered serious. 
Exceptions:  
• 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. Hospitalization for protocol therapy administration.  
• 
Hospitalization for diagnostic investigations (e.g., scans, endoscopy, sampling for laboratory 
tests, bone marrow sampling) that are not related to an AE. 
• 
Hospitalization for technical, practical, or social reasons, in absence of an AE. 
• 
Hospitalization for a procedure that was planned prior to study participation (i.e., before 
consent or randomization). 
• 
Hospitalization for administration of blood or platelet transfusion as routine treatment of the 
studied indication.  
• 
However, hospitalization or prolonged hospitalization for complications of administration of study 
intervention, diagnostic investigations, planned procedures, or administration of blood or platelet 
transfusion remains reportable as an SAE. 
4. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance such 
as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
5. Is a congenital anomaly/birth defect 


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SAEs 
6. Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately life-
threatening or result in death or hospitalization but may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in the above definition. 
These events should usually be considered serious. 
• 
Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that do 
not result in hospitalization, or development of drug dependency or drug abuse. 
11.2.3. 
Recording and Follow-Up of AEs, SAEs, and AEs of Special Interest 
AEs, SAEs, and AEs of Special Interest (AEOSI)  
Recording 
• 
When an AE/SAE/AEOSI occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) related to 
the event. 
• 
The investigator will then record all relevant AE/SAE/AEOSI information in the eCRF/data 
collection tool, as appropriate. 
• 
The investigator will promptly (preferably within 24 hours) respond to all queries related to an 
SAE/AEOSI. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s medical records to 
the sponsor in lieu of completion of the AE/SAE/AEOSI eCRF/data collection tool. 
• 
There may be instances when copies of medical records for certain cases are requested by the 
sponsor. In this case, all participant identifiers, with the exception of the participant’s study 
number, will be redacted on the copies of the medical records before submission. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) 
will be documented as the AE/SAE/AEOSI. 
Assessment of Intensity 
The investigator will assess the intensity for each AE/SAE/AEOSI reported during the study and assign 
an intensity/severity grade based on the National Cancer Institute Common Terminology Criteria for 
Adverse Events [NCI-CTCAE]). 
Note: An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described 
in the definition of an SAE, NOT when it is of severe intensity. 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE/AEOSI. 
• 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 


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AEs, SAEs, and AEs of Special Interest (AEOSI)  
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study intervention administration will be 
considered and investigated. 
• 
The investigator will also consult the investigator’s brochure for dociparstat and the product 
information for cytarabine, daunorubicin, and idarubicin (as applicable). 
• 
For each AE/SAE/AEOSI, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE/AEOSI and has provided an assessment of causality. 
• 
There may be situations in which an SAE/AEOSI has occurred, and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important that the 
investigator always assess causality for every event before initial transmission of the SAE/AEOSI 
data to the sponsor. 
• 
The investigator may change his/her opinion of causality after follow-up information is available 
and send an SAE/AEOSI follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
Follow-up 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE/SAE/AEOSI as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals. 
• 
If a participant dies during participation in the study (at any time from randomization through 
long-term follow-up), the investigator will provide the date of death and a determination of cause 
of death (including any supporting information, such as death certificate, pathology or autopsy 
information, as applicable). 
• 
The investigator will submit any updated SAE/AEOSI data to the sponsor within 24 hours of 
receipt of the information. 
11.2.4. 
Reporting of SAEs 
SAE Reporting to the Sponsor  
• 
The primary mechanism for reporting an SAE to the sponsor is the eCRF/data collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data collection tool to 
report the event within 24 hours. 
• 
Contact details for SAE reporting are included in the study reference manual. 
 


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11.3. 
Appendix 3: Contraceptive Guidance and Pregnancy Reporting 
11.3.1. 
Definitions 
Woman of childbearing potential 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile. 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered. 
Women in the following categories are not considered a woman of childbearing potential 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above (e.g., mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study eligibility. 
Note: Documentation can come from site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.  
− A high follicle-stimulating hormone level in the postmenopausal range may be 
used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy. However, in the absence of 
12 months of amenorrhea, confirm with more than one follicle stimulating 
hormone measurement.  
• Females on hormone replacement therapy and whose menopausal status is in doubt 
will be required to use one of the non-estrogen hormonal highly effective 
contraception methods if they wish to continue their hormone therapy during the 
study. Otherwise, they must discontinue hormone therapy to allow confirmation of 
postmenopausal status before study enrollment. 


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11.3.2. 
Contraception Guidance 
Males must 
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent.  
OR 
• Agree to use a male condom with spermicide when having sexual intercourse with a 
woman of childbearing potential throughout the study and for at least 90 days after 
the last dose of study intervention or chemotherapy. The participants should also be 
advised of the benefit for his female partner to use a highly-effective method of 
contraception as a condom may break or leak. 
Females must: 
• Be of nonchildbearing potential.  
OR 
• Agree to use a highly-effective method of contraception throughout the study and for 
at least 90 days after the last dose of study intervention or chemotherapy. 


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Contraceptive Methods Allowed During the Study include the Following:  
Highly-Effective Methods That Have Low User Dependency 
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner 
Vasectomized partner is a highly effective contraceptive method provided that the partner is the 
sole sexual partner of the woman of childbearing potential and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
Spermatogenesis cycle is approximately 90 days. 
Highly-Effective Methods That Are User Dependent 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
o oral 
o intravaginal 
o transdermal 
o injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulation 
o oral 
o injectable 
• 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant. 
Notes:  
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
Highly-effective methods have a failure rate of <1% per year when used consistently and correctly.  
Typical use failure rates differ from those when used consistently and correctly. 
 
Contraceptive Methods that are NOT ACCEPTABLE During the Study include the Following:  
• 
Periodic abstinence (calendar, symptothermal, post-ovulation methods). 
• 
Withdrawal (coitus interruptus). 
• 
Spermicides alone.  
• 
Lactational amenorrhea method. 
• 
Use of both male condom and female condom together, because of the risk of failure with friction. 
 


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11.3.3. 
Collection of Pregnancy Information 
Female participants who become pregnant 
• The investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. The initial information will be 
recorded on the appropriate form and submitted to the sponsor within 24 hours of 
learning of a participant’s pregnancy.  
• The participant will be followed to determine the pregnancy outcome. The 
investigator will collect follow-up information on the participant and neonate and the 
information will be forwarded to the sponsor. Generally, follow-up will not be 
required for longer than 6 to 8 weeks beyond the estimated delivery date. Any 
termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. A spontaneous abortion (occurring at <22 weeks 
gestational age) or still birth (occurring at >22 weeks gestational age) is always 
considered to be an SAE and will be reported as such.  
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor. While the investigator 
is not obligated to actively seek this information in former study participants, he or 
she may learn of an SAE through spontaneous reporting. 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention. 


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11.4. 
Appendix 4: Genetic Risk Categories 
Risk Category 
Cytogenetic findings 
Molecular genetic findings 
Favorable 
− t(8;21)(q22;q22.1) 
− inv(16)(p13.1q22) or t(16;16)(p13.1;q22) 
− RUNX1-RUNX1T1 
− CBFB-MYH11 
− NPM1 mutated without FLT3-ITD or 
NPM1 mutated with FLT3-ITDlow 
− Biallelic mutated CEBPA 
Intermediate 
− Normal karyotype 
 
− NPM1 mutated and FLT3-ITDhigh 
− NPM1 wild-type without FLT3-ITD or 
with FLT3-ITDlow  
(without adverse-risk genetics) 
 
− t(9;11)(p21.3;q23.3)  
(takes precedence over rare, concurrent 
adverse-risk gene mutations) 
− MLLT3-KMT2A 
 
− Cytogenetic abnormalities not classified 
as favorable or adverse 
 
Adverse 
− t(6;9)(p23;q34.1) 
− t(v;11q23.3)  
− t(9;22)(q34.1;q11.2) 
− inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)  
− –5 or del(5q); –7; –17/abn(17p) 
− DEK-NUP214 
− KMT2A rearranged 
− BCR-ABL1  
− GATA2, MECOM(EVI1) 
 
− NPM1 wild-type and FLT3-ITDhigh 
− Mutated TP53 
 
 
− Mutated RUNX1 
− Mutated ASXL1 
(Not adverse if co-occur with favorable-risk 
AML subtype) 
 
− Complex karyotype 
− Monosomal karyotype 
 
Source: Döhner 2017 
Low, low allelic ratio (<0.5); high, high allelic ratio (≥0.5); semiquantitative assessment of FLT3-ITD allelic ratio is 
determined as ratio of the area under the curve “FLT3-ITD” divided by area under the curve “FLT3-wild type” 
Monosomal karyotype=Single monosomy (excluding loss of x or y) with at least 1 additional monosomy or 
structural chromosome abnormality (excluding core-binding factor AML). 
Complex karyotype=Three or more unrelated chromosome abnormalities in the absence of 1 of the World Health 
Organization-designated recurring translocations or inversions. 
 


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11.5. 
Appendix 5: ECOG Performance Status (and Associated Karnofsky 
Grades) 
ECOG 
Grade 
ECOG Status Description 
Associated 
Karnofsky 
Grades 
Karnofsky Status Description 
0 
Fully active, able to carry on all 
predisease performance without 
restriction. 
100 
Normal, no complaints. 
1 
Restricted in physically strenuous 
activity but ambulatory and able to 
carry out work of a light or sedentary 
nature, (e.g., light housework, office 
work). 
90 
Able to carry on normal activities. 
Minor signs or symptoms of disease. 
80 
Normal activity with effort. 
2 
Ambulatory and capable of all 
selfcare but unable to carry out any 
work activities. Up and about more 
than 50% of waking hours. 
70 
Care for self. Unable to carry on normal 
activity or to do active work. 
60 
Requires occasional assistance, but able 
to care for most needs. 
3 
Capable of only limited selfcare, 
confined to bed or chair more than 
50% of waking hours. 
50 
Requires considerable assistance and 
frequent medical care. 
40 
Disabled. Requires special care and 
assistance. 
4 
Completely disabled.  
Cannot carry on any selfcare.  
Totally confined to bed or chair. 
30 
Severely disabled. Hospitalization 
indicated though death not imminent. 
20 
Very sick. Hospitalization necessary. 
Active supportive treatment necessary. 
10 
Moribund 
5 
Dead 
0 
Dead 
Source: Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 1982;5(6):649-55.  
 


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11.6. 
Appendix 6: Drugs Known to Prolong the QT Interval 
The following drugs (list is not exhaustive) are known to prolong the QT-interval:  
• amiodarone 
• citalopram 
• flecainide 
• methadone 
• quinidine 
• astemizole 
• clarithromycin 
• fluconazole 
• moxifloxacin 
• sevoflurane 
• azithromycin 
• disopyramide 
• granisetron 
• ondansetron 
• sotalol 
• bepridil 
• dofetilide 
• halofantrine 
• pentamidine 
• sparfloxacin 
• chloroquine 
• domperidone 
• haloperidol 
• pimozide 
• terfenadine 
• chlorpromazine 
• droperidol 
• ibutilide 
• posaconazole 
• thioridazine 
• ciprofloxacin 
• erythromycin 
• levomethadyl 
• probucol 
• voriconazole 
• cisapride 
• escitalopram 
• mesoridazine 
• procainamide 
 
 
 


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11.7. 
Appendix 7: Definitions of Terms 
Term 
Definition for this Study 
Chemotherapy 
Cytarabine + anthracycline (either daunorubicin or idarubicin) 
induction/reinduction therapy, followed by cytarabine consolidation therapy, 
when indicated 
Consolidation therapy 
Inclusive of all consolidation cycles (i.e., 1, 2, 3, or 4 cycles) received under 
this protocol. 
Induction therapy 
Inclusive of the initial induction cycle and a reinduction cycle when 
indicated 
Recovery bone marrow 
The bone marrow aspirate collected on ~Day 22 to 42 of a treatment cycle. 
Generally collected after (at the time of) hematologic count recovery; if 
counts have not recovered, the sample will still be collected on ~Day 36 
to 42 of the cycle. 
Study intervention 
Dociparstat or placebo 
Treatment cycle 
Consists of the administration of therapy (i.e., chemotherapy with cytarabine 
± anthracycline plus blinded study intervention) and all scheduled 
assessments to evaluate the response to treatment, including bone marrow 
and hematologic recovery. 
Treatment period for 
the study 
The time from randomization through the final treatment cycle. 
 
 
Response / Outcome 
Definition (Based on ELN 2017 Recommendations) 
Response 
Complete 
remission with 
complete 
hematologic 
recovery (CR) 
Bone marrow blasts <5%,  
absence of circulating blasts and blasts with Auer rods,  
absence of extramedullary disease,  
ANC >1.0 x 109/L (1000/μL), and  
platelet count >100 x 109/L (100,000/μL).  
CR with 
incomplete 
hematologic 
recovery (CRi) 
All CR criteria (bone marrow blasts <5%; absence of circulating blasts and 
blasts with Auer rods; absence of extramedullary disease), except for  
residual neutropenia (≤1.0 x 109/L [1000/μL]) or  
thrombocytopenia (≤100 x 109/L [100,000/μL]). 
[Note: Participants with both residual neutropenia and residual 
thrombocytopenia are not considered to have achieved CRi.] 
CR with partial 
hematologic 
recovery (CRh) 
Bone marrow blasts <5%; no evidence of disease, and  
partial recovery of peripheral blood counts (ANC >0.5 x 109/L [500/μL] and 
platelets >50 x 109/L [50,000/μL], but the count recovery criteria for CR are 
not met). 
Measurable 
residual disease 
negative (MRDneg) 
Negative (undetectable) MRD in bone marrow, as measured by MFC (0.1% 
detection limit). 


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Failure 
Treatment failure 
(induction failure) 
Failure to achieve CR within 42 days of the start of induction therapy (or 
start of reinduction therapy when applicable). 
Relapse 
Relapse 
(hematologic) 
After achievement of CR/CRi, bone marrow blasts ≥5%, reappearance of 
blasts in the blood, or development of extramedullary disease. 
Cumulative 
incidence of 
relapse 
Measured from the date of randomization until the date of relapse. 
Participants not known to have relapsed will be censored on the date of last 
follow-up contact. 
Outcome Measure 
Overall survival 
(OS) 
Measured from the date of randomization to date of death from any cause.  
Event-free 
survival 
Measured from the date of randomization to treatment failure, relapse, or 
death from any cause, whichever occurs first.  
Relapse-free 
survival (RFS) 
Measured from the date of randomization to date of relapse or death from 
any cause. 
Time to recovery 
Time to recovery of neutrophil count is measured as time from date of 
randomization until the first day the ANC is >500/μL and is >1000/μL 
following induction or reinduction (if indicated).  
Time to transfusion-independent platelet recovery is measured as time from 
date of randomization until the first day the platelet count recovers to 
>20,000/μL, >50,000/μL, and >100,000/μL, without a platelet transfusion in 
the preceding 5 days following induction or reinduction (if indicated). 
 


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11.8. 
Appendix 8: Abbreviations 
7+3 
7-day infusion of cytarabine and 3 days of idarubicin or daunorubicin as AML induction 
or reinduction therapy 
5+2 
5-day infusion of cytarabine and 2 days of idarubicin or daunorubicin as AML 
reinduction therapy  
AE 
adverse event 
AEOSI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BM 
bone marrow 
CI 
confidence interval 
Cmax 
maximum observed concentration 
CR 
complete remission with complete hematologic recovery 
CRh 
complete remission with at least partial hematologic recovery 
CRi 
complete remission with incomplete hematologic recovery 
CTCAE 
Common Terminology Criteria for Adverse Events 
CX-01 
dociparstat sodium, 2-O, 3-O desulfated heparin 
CXCL12 
chemokine SDF-1, and abbreviation for stromal cell derived factor-1 
CXCR4 
receptor for the chemokine SDF-1  
DMC 
data monitoring committee 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF / CRF 
electronic case report form / case report form 
EFS 
event-free survival 
eGFR 
estimated glomerular filtration rate 
ELN 
European LeukemiaNet 
FISH 
fluorescence in situ hybridization 
FLT3 
FMS-like tyrosine kinase 3 
GCP 
good clinical practice 
HCT 
hematopoietic stem cell transplant 


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HMGB1 
high mobility group box protein 1 
HR 
hazard ratio 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IRT 
interactive response technology 
ITD 
internal tandem duplication 
ITT 
intent to treat 
IV 
intravenous  
MFC 
multiparameter (multicolor) flow cytometry  
MRD 
measurable (minimal) residual disease 
MRDneg 
measurable (minimal) residual disease negative 
ODSH 
(previously-used abbreviation for) 2-O, 3-O desulfated heparin 
OS 
overall survival 
PK 
pharmacokinetic 
RFS 
relapse-free survival  
SAE 
serious adverse event 
SAP 
statistical analysis plan 
t½ 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
TKD 
tyrosine kinase domain 
Tmax 
time to maximum observed concentration 
ULN 
upper limit of normal 
 
 
 


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11.9. 
Appendix 9: Protocol Amendment Summary of Changes 
Rationale for protocol Amendment 1: Broaden the eligibility criteria to permit enrollment of 
additional participants in the study. 
Deleted text is shown as strikethrough and new text is shown in bold. The synopsis has been 
updated to align with changes in the protocol body. The amendment includes additional changes 
for clarity that have not been included in Table 10. 
Table 10: 
Changes Included in Amendment 1 
Section(s) 
Change 
Rationale 
1.2: Schedule of 
Activities, Table 1; 
6.1: Study 
Intervention(s) 
Administered, 
Table 5  
FLT3-positive Participants may receive 
cytarabine 200 mg/m2/day according to local 
practices (e.g., for FLT3-positive 
participants) 
Some investigators indicated 
200 mg/m2/day is their 
standard cytarabine dose for 
all patients. 
3: Objectives and 
Endpoints 
Proportion of participants who receive any 
HCT (allogeneic or autologous) during the 
study. 
New endpoint to account for 
participants who may receive 
an autologous HCT if a 
suitable match is not available. 
4: Study Design 
Of the first 80 participants enrolled, the 
number of participants age 18 to 59 years 
with intermediate risk genetic risk will be 
limited to 20. 
To ensure adequate 
representation from the 
original planned population in 
order to assess outcomes from 
the first 80 evaluable subjects 
and inform subsequent 
investigation. 
4: Study Design;  
5: Study 
Population;  
5.1: Inclusion 2b 
… ≥18 years old with adverse genetic risk or 
≥60 years old with either intermediate or 
adverse genetic risk… 
2b. Intermediate genetic risk (≥60 years 
only)… 
Inclusion criteria modified to 
permit enrollment of 
participants 18 to 59 years of 
age with intermediate genetic 
risk to broaden study 
population. 
5.1: Inclusion 3 
Eastern Cooperative Oncology Group (ECOG) 
performance status of 0 to 2 if ≤79 years of age; 
ECOG status of 0 or 1 if ≥80 years of age. 
Criterion modified to broaden 
study population. 
5.2: Exclusion 2 
AML with a history of antecedent 
myelodysplasia that has been previously-
treated (e.g., with a hypomethylating agent).  
Note: Myelodysplasia that has not been 
previously treated is permitted. 
Criterion removed to broaden 
study population. 
5.2: Exclusion 3 
Therapy-related AML after prior radiotherapy 
or chemotherapy for another cancer or disorder. 
Criterion removed to broaden 
study population. 


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Section(s) 
Change 
Rationale 
5.2: Exclusion 15 
QTc >450 >480 msec for a male, >470 msec 
for a female, or >480 msec if underlying bundle 
branch block.  
Criterion modified to broaden 
study population. 
5.2: Exclusion 19 
History of allergy or hypersensitivity to 
heparin, pork, or any excipients in the 
dociparstat formulation. 
Criterion added to as a 
potential risk for participants. 
5.2: Exclusion 20 
Any other condition, including abnormal 
laboratory values, that, in the judgment of 
the investigator, could put the participant at 
increased risk or interfere with the conduct 
or planned analyses of the study. 
Criterion added to cover other 
potential risks not specified as 
individual exclusion criteria. 
6.2.2: Handling, 
Storage, and 
Accountability 
Dociparstat should be stored at controlled room 
temperature (i.e., 15°C to 25°C [59°F to 77°F]), 
with excursions permitted to 30°C (86°F); 
protect from freezing. 
[Note: the labeled storage conditions are 
dependent on the manufactured drug 
product batch/lot.] 
Storage conditions will be 
changing when the next batch 
of drug product is 
manufactured and released. 
7.1: Interruption of 
Study Intervention 
Infusion of study intervention may be resumed 
once QTc is <450 <480 msec. Following 
resumption of infusion, ECGs are to be 
checked daily until the participant has had 3 
consecutive (daily) tracings with QTc <450 
<480 msec, after which follow-up ECGs will 
be as per institutional standard of care. 
Criterion modified to align 
with change in Exclusion 15. 
8.2.2: Response 
Criteria and 
Outcome 
Measures; 
Appendix 7  
Definition of CRh … partial recovery of 
peripheral blood counts (ANC >0.5 x 109/L 
[500/μL] and platelets >50 x 109/L 
[50,000/μL], but the count recovery criteria 
for CR are not met). 
Clarification. 
8.3.3: 
Electrocardiograms At subsequent time points, a single ECG 
tracing will be obtained, with a repeat tracing to 
confirm QTc intervals >450 >480 msec. 
Criterion modified to align 
with changes in Exclusion 15 
and Section 7.1. 
 


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Rationale for protocol Amendment 2: Revert back to the original standardized cytarabine dosing 
to reduce variability. Deleted text is shown as strikethrough and new text is shown in bold. The 
synopsis has been updated to align with changes in the protocol body.  
Table 11: 
Changes Included in Amendment 2 
Section(s) 
Change 
Rationale 
1.2: Schedule of 
Activities, Table 1; 
6.1: Study 
Intervention(s) 
Administered, 
Table 5  
FLT3-positive Participants may receive 
cytarabine 200 mg/m2/day according to local 
practices (e.g., for FLT3-positive participants) 
Revert to the original 
standardized cytarabine dosing 
to reduce variability. 
 


Protocol CMX-DS-003 
Amendment : 
 August 2021 
Confidential 
SPONSOR’S SIGNATURE PAGE 
Protocol Title: 
A randomized, double-blind, placebo-controlled study to evaluate the 
efficacy and safety of dociparstat sodium in combination with standard 
chemotherapy for the treatment of newly diagnosed acute myeloid 
leukemia
Protocol Number: 
CMX-DS-003 
Protocol Date: 
 August 2021 (Amendment ) 
This protocol has been approved by Chimerix, Inc. 
The following signature documents this approval. 
Allen Melemed, MD 
Chief Medical Officer


Protocol CMX-DS-003 
 
Amendment 2: 19 August 2021 
 
Confidential  
 
INVESTIGATOR AGREEMENT 
 
Protocol Title:  
A randomized, double-blind, placebo-controlled study to evaluate the 
efficacy and safety of dociparstat sodium in combination with standard 
chemotherapy for the treatment of newly diagnosed acute myeloid 
leukemia 
Protocol Number:  CMX-DS-003 
Protocol Date:  
19 August 2021 (Amendment 2) 
 
 
I have received and read this protocol, the Investigator Brochure, and all other study-related 
information provided to me.  
I agree to conduct the study in accordance with the protocol, International Council for 
Harmonisation Good Clinical Practice (ICH GCP) guidelines, and all applicable local laws and 
regulations pertaining to the conduct of clinical studies. 
I will ensure that all subinvestigators and other staff members involved with the conduct of the 
study read and understand all aspects of this protocol. 
I agree to maintain the confidentiality of all information received or developed in connection 
with this protocol. All rights of publication of the results reside with Chimerix, Inc., unless made 
in a separate agreement. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date