Clinical trial NCT03715998
Conditions: Myocardial Infarction
Sponsor: Quantum Genomics SA
Start date: 2019-06-04; Completion date: 2021-07-08
Enrollment: 295 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multicenter, randomized, double-blind, active-controlled, dose-titrating phase 2 study to evaluate the safety and efficacy of firibastat administered orally BID (2 daily doses) versus ramipril administered orally BID over 12 weeks after acute anterior MI.

Subjects will be followed for 12 weeks (over 4 study visits). A total of 294 male and female subjects with a diagnosis of first acute anterior MI will be randomized. The subjects will need to have a primary percutaneous coronary intervention (PCI) of the index MI related artery within 24 hours after MI.

Detailed description:
At Inclusion Visit (Visit 2 \[within 72 hours after acute MI\]), subjects will be randomly assigned to 1 of the following 3 treatment groups in a 1:1:1 ratio:

* Group 1: Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks
* Group 2: Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks
* Group 3: Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks

Then subjects will undergo study procedures at Titration Visit (Visit 3 \[Day 14\]), Treatment Visit (Visit 4 Day 42\]) and End-of-Treatment Visit (Visit 5 \[Day 84\]).

Arms: arm 1: Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks. arm 2: Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks. arm 3: Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks.
Interventions: intervention 1: Ramipril intervention 2: Firibastat
Intervention descriptions: intervention 1: 1 or 2 capsules administered orally, twice daily intervention 2: 1 or 2 capsules administered orally, twice daily

Protocol documents:
Prot_000.pdf: 
 
AD-MW-07.07 16-Jul-2018 
Page 1 of 96 
PROTOCOL 
PRODUCT NAME/NUMBER: 
Firibastat (QGC001) 
PROTOCOL NUMBER: 
QGC001-2QG4 
IND NUMBER: 
145271 
NCT NUMBER: 
NCT03715998 
EUDRACT NUMBER: 
2018‐003146‐17 
DEVELOPMENT PHASE: 
2 
PROTOCOL TITLE: 
A Phase 2, Double-blind, Active-controlled, Dose-titrating 
Efficacy and Safety Study of Firibastat (QGC001) 
Compared to Ramipril Administered Orally, Twice Daily, 
Over 12 Weeks to Prevent Left Ventricular Dysfunction 
after Acute Myocardial Infarction 
Short Title: Quantum Genomics Firibastat (QGC001) or 
Ramipril after Acute Myocardial Infarction for Prevention 
of Left Ventricular Dysfunction (QUORUM) 
PROTOCOL DATES: 
Final V1.0: 04-Dec-2018, Local V2.0 for France:  
26-Feb-2019, Local V3.0 for France: 14-Mar-2019,  
Local V2.0 for Germany: 15-Apr-2019,  
Global Amendment V2.0: 09-Aug-2019, Local V4.0 for 
France: 09-Oct-2019, Local V2.0 for United Kingdom:  
09-Oct-2019, Local V5.0 for Germany: 10-Oct-2019, 
Global Amendment V3.0: 10-Oct-2019 
COORDINATING/PRINCIPAL 
INVESTIGATOR: 
Prof. Gilles Montalescot, MD, PhD 
Head of the Medical Cardiology Department 
Cardiology Institute, Hôpital Pitié-Salpêtrière 
47 Boulevard de l’Hôpital 
75013 Paris, France 
Telephone: 
+33 1 42 16 30 07 
SPONSORED BY: 
Quantum Genomics 
33 rue Marbeuf, Paris, 75008, France 
Telephone: 
+33 1 85 34 77 74 
Fax: 
+33 1 85 34 77 78 
CONTRACT RESEARCH 
ORGANIZATION: 
Premier Research Group Ltd 
First Floor, Rubra 2, Mulberry Business Park 
Fishponds Road, Wokingham 
RG41 2G4, United Kingdom 
This study will be performed in compliance with International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use (ICH) Good Clinical Practices (GCP) and applicable regulatory requirements, 
including the archiving of essential documents. Information contained in this protocol is confidential in nature, and 
may not be used, divulged, published, or otherwise disclosed to others except to the extent necessary to obtain approval 
of the institutional review board or independent ethics committee, or as required by law. Persons to whom this 
information is disclosed should be informed that it is confidential and may not be further disclosed without the express 
permission of Quantum Genomics. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 2 of 96 
1. APPROVAL SIGNATURES 
PROTOCOL NUMBER: 
QGC001-2QG4 
PROTOCOL TITLE: 
A Phase 2, Double-blind, Active-controlled, Dose-titrating Efficacy 
and Safety Study of Firibastat (QGC001) Compared to Ramipril 
Administered Orally, Twice Daily, Over 12 Weeks to Prevent Left 
Ventricular Dysfunction after Acute Myocardial Infarction 
I, the undersigned, have read this protocol and confirm that to the best of my knowledge it 
accurately describes the planned conduct of the study. 
SIGNATURE 
 
DATE: 
 
 
 
 
 
 
Bruno Besse, MD 
Chief Medical Officer 
Quantum Genomics 
 
 
 
 
 
 
Prof. Gilles Montalescot, MD, PhD 
Head of the Medical Cardiology Department 
Pitié-Salpêtrière Hospital in Paris 
 
 
 
 
 
 
Ilze Balode, MD 
Senior Medical Director III 
Premier Research 
 
 
 
 
 
 
Celine Fragneaud 
Biostatistics & Medical Writing Manager 
Aixial 
 
 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 3 of 96 
2. PROTOCOL SUMMARY 
2.1. Synopsis 
PRODUCT NAME/ 
NUMBER 
Firibastat (QGC001) 
PROTOCOL 
NUMBER 
QGC001-2QG4 
EUDRACT 
NUMBER 
2018‐003146‐17 
DEVELOPMENT 
PHASE 
2 
PROTOCOL TITLE 
A Phase 2, Double-blind, Active-controlled, Dose-titrating Efficacy and Safety Study of 
Firibastat (QGC001) Compared to Ramipril Administered Orally, Twice Daily, Over 
12 Weeks to Prevent Left Ventricular Dysfunction after Acute Myocardial Infarction 
INDICATION 
Prevention of left ventricular dysfunction after acute anterior myocardial infarction 
OBJECTIVES 
Primary objective: 
The primary objective of this study is to compare the effects of twice daily (bis in die 
[BID]) oral administration of 2 doses of firibastat to those of BID oral administration of 
ramipril on the change from Baseline in left ventricular ejection fraction (LVEF) assessed 
by cardiac magnetic resonance imaging (CMRI) on Day 84. 
Secondary objectives: 
• 
To compare the effects of BID administration of firibastat and ramipril on the 
change from Baseline to Day 84 in left-ventricular end-diastolic and end-systolic 
volumes assessed by CMRI 
• 
To compare the effects of BID administration of firibastat and ramipril on the 
change from Baseline to Day 84 in average peak of longitudinal and 
circumferential strain (assessed by CMRI) in the infarcted segments 
• 
To compare the effects of BID administration of firibastat and ramipril on infarct 
mass (assessed by CMRI) at Day 84 
• 
To compare the effects of BID administration of firibastat and ramipril on major 
cardiac event (MACE): combined clinical endpoint of cardiovascular death, 
myocardial infarction (MI), and cardiac hospitalization over 84 days 
• 
To compare the effects of BID administration of firibastat and ramipril on the 
change from Baseline to Day 84 in N-terminal pro b-type natriuretic peptide 
(NT-proBNP), procollagen type III aminoterminal peptide (PIIINP), and 
C-reactive protein (CRP) 
• 
To compare the effects of BID administration of firibastat and ramipril on the 
slope of decrease in copeptin blood level change between Baseline and Day 84 
• 
To compare the safety of firibastat and ramipril 
RATIONALE 
Heart failure (HF) is considered to be a complex clinical syndrome that could develop 
from multiple structural or functional cardiac and non-cardiac diseases. HF is often the 
result of a myocardial infarction (MI) or hypertension. HF is the leading cause of 
hospitalization for patients over 65 years old in western countries. It affects 1 to 5 persons 
in a thousand persons in industrialized countries, all ages considered, with a prevalence 
of 3 to 20 in a thousand persons. Although a large number of drugs is available to treat 
HF symptoms, half of the patients die in the 3 to 5 years following the onset of symptoms 
of HF. Thus, HF remains one of the major causes of cardiovascular death. The aim of this 
study is to assess the efficacy and the safety of firibastat compared to ramipril to prevent 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 4 of 96 
left ventricular dysfunction in subjects after acute MI. Firibastat targets the brain 
renin-angiotensin system. Through a triple mechanism of action, firibastat induces a 
simultaneous effect on the arteries, heart, and kidneys, offering promising perspectives 
in the treatment of HF. Latest data in post-myocardial infarction in mice and rats treated 
with oral doses of firibastat showed significant cardiac function improvement. 
Furthermore, a favorable safety profile of firibastat was observed in HF patients during a 
phase 2a clinical study (QUID-HF). 
STUDY DESIGN 
This is a multicenter, randomized, double-blind, active-controlled, dose-titrating phase 2 
study to evaluate the safety and efficacy of firibastat administered orally BID (2 daily 
doses) versus ramipril administered orally BID over 12 weeks after acute anterior MI. 
Subjects will be followed for 12 weeks over 5 study visits (about 16 weeks over 6 study 
visits for women of childbearing potential). A total of 294 male and female subjects with 
a diagnosis of first acute anterior MI will be randomized. The subjects will need to have 
a primary percutaneous coronary intervention (PCI) of the index-MI-related artery within 
24 hours after MI. Subjects will be randomly assigned to 1 of the following 3 treatment 
groups in a 1:1:1 ratio: 
• 
Group 1: Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg 
BID for 10 weeks 
• 
Group 2: Subjects will receive 250 mg firibastat BID for 2 weeks and then 
500 mg BID for 10 weeks 
• 
Group 3: Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg 
BID for 10 weeks 
It should be noted that the subjects’ dosage will be up-titrated and/or down-titrated 
according to a specific titration procedure. 
Baseline is defined as the day when the CMRI is performed and the first investigational 
product (IP) dose is taken. Day 84 will be the day of treatment discontinuation (i.e. 
84 days [±3 days] after the Inclusion Visit [Day 1]). 
Screening Visit (Visit 1; within 24 hours after acute MI [Day -2 – Day 1]): 
The Screening Visit will occur within 24 hours after index acute MI, defined as the time 
of onset of symptoms, and after PCI is performed (no earlier than 3 hours after acute MI 
and within 24 hours after MI). Subjects will sign an informed consent form (ICF) prior 
to any study procedures being performed. Any standard-of-care procedures performed 
prior to ICF signature should not be repeated for the purpose of the study if already 
performed. Subjects may be screened even if the exclusion criterion 4 (SBP <100 mmHg) 
is not met at this time. 
Inclusion Visit (Visit 2; within 72 hours after acute MI [Day 1]): This visit can be 
done on the same day as the Screening Visit: 
Subjects who meet all of the inclusion criteria but none of the exclusion criteria 
(excluding exclusion criterion 4 [SBP <100 mmHg]) at the Screening Visit will undergo 
visit-specific procedures, and a baseline CMRI must be performed no later than 72 hours 
after the MI. 
As soon as possible after the CMRI is performed, the subject’s blood pressure will be 
measured. If systolic blood pressure (SBP) is ≥100 mmHg, the subject’s eligibility will 
be confirmed, and the site will connect on the treatment kits allocation web system 
available through the electronic data capture (EDC) system for randomization 
information. Subjects will be randomly assigned on Day 1 in a 1:1:1 ratio to receive either 
50 mg firibastat BID (Group 1), 250 mg firibastat BID (Group 2), or 2.5 mg ramipril BID 
(Group 3). 
The first capsule of the IP will be administered on Day 1 as soon as possible after the 
CMRI, which will be performed no later than 72 hours after MI. Subjects will then take 
1 capsule of the IP BID until the next visit. After the first administration occurring after 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 5 of 96 
the CMRI, next intake must not occur before 6 hours and if not possible, must be done 
on the next morning. 
Safety Check (Day 3): 
A safety check should be performed 3 days after first administration of the IP to ensure 
the good tolerance of the treatment by the subjects. 
In most of the cases, subjects will be still hospitalized at the site 3 days after the first 
IP administration, and the investigator will be able to continuously monitor the tolerance 
of the treatment and immediately react if non-tolerance is suspected. As there is no 
possibility to decrease the dose of the IP at this stage, in case of non-tolerance of the IP 
the subject will be withdrawn from the study. 
For subjects discharged early, i.e., before 3 days after the first IP administration, a phone 
call to the subject should be performed. If the investigator judges that there is a risk of 
non-tolerance according to the subject’s answers (e.g., any suspicion or symptoms related 
to hyper- or hypotension), the subject will be asked to come to the site for an unscheduled 
visit. The investigator will then decide whether the subject should be withdrawn from the 
study. Details provided by the subject should be recorded in the subject’s medical notes. 
In all cases, tolerability of the IP should be checked before subject discharge. 
Titration Visit (Visit 3 [Day 14 ±2 days]): 
Subjects will undergo visit-specific procedures. 
If SBP is ≥110 mmHg without any symptoms of hypotension and/or cardiogenic shock, 
the dose will be increased to 2 capsules of the IP BID. 
If SBP is <110 mmHg, the subject will remain on the same dose (1 capsule BID). 
If symptomatic hypotension, symptomatic orthostatic hypotension, or cardiogenic shock 
occur, the treatment will be discontinued for the remainder of the study, and the event 
will be recorded as an adverse event (AE) leading to discontinuation. 
In case of any suspicion or symptoms related to hyper- or hypotension, the subjects 
should contact the site, attend an unscheduled visit, or visit their general practitioner or 
nearest cardiovascular unit, where a decision on any action with the IP can be made by 
the investigator or other physician seeing the subject. 
Note: the newly allocated dose will be administered as soon as possible after the visit is 
completed (i.e., on the evening of the day of the visit). 
Treatment Visit (Visit 4 [Day 42 ±2 days]): 
Subjects will undergo visit-specific procedures. 
If SBP is ≥110 mmHg without any symptoms of hypotension and/or cardiogenic shock, 
the dose will remain the same if the subject has already been treated with 2 capsules of 
the IP BID, or the dose will be increased to 2 capsules of the IP BID. 
If SBP is <110 mmHg and if the subject was being treated with 2 capsules of the IP BID, 
the dose will be decreased to 1 capsule of the IP BID. 
If SBP is <110 mmHg and if the subject was being treated with 1 capsule of the IP BID, 
the subject will remain on the same dose (1 capsule BID). 
If symptomatic hypotension, symptomatic orthostatic hypotension, or cardiogenic shock 
occur, the treatment will be discontinued for the remainder of the study, and the event 
will be recorded as an AE leading to discontinuation. 
In case of any suspicion or symptoms related to hyper- or hypotension, the subjects 
should contact the site, attend an unscheduled visit, or visit their general practitioner or 
nearest cardiovascular unit, where a decision on any action with the IP can be made by 
the investigator or other physician seeing the subject. 
Note: the newly allocated dose will be administered as soon as possible after the visit is 
completed (i.e., on the evening of the day of the visit). 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 6 of 96 
End-of-Treatment Visit (Visit 5 [Day 84 ± 3 days]): 
Subjects will undergo End-of-Treatment (EOT) Visit-specific procedures, and the IP will 
be discontinued. In case of premature discontinuation (except if consent is withdrawn), a 
CMRI and all Visit 5 procedures, if possible, will be performed as soon as possible and 
no later than 72 hours after treatment discontinuation. 
Follow-up Visit (Visit 6 [Day 114 (±3 days) or 30 Days after IP discontinuation]): 
For females of childbearing potential only, a serum pregnancy test will be performed. 
A schematic presentation of the titration procedure for Groups 1, 2, and 3 is given below: 
 
 
PLANNED NUMBER 
OF SUBJECTS 
A total of 294 subjects will be randomized to reach 264 evaluable subjects (88 subjects 
per group). Evaluable subjects are defined as those subjects who have a CMRI at both 
the Baseline and EOT Visits. 
STUDY ENTRY 
CRITERIA 
The population for this study corresponds to subjects with a first acute anterior MI. 
Inclusion criteria: 
1. 
Subject must provide signed written informed consent. Important Note: Subject 
must be willing and able to give informed consent for participation in the study. 
2. 
Men and women ≥18 years of age at Screening. 
3. 
Diagnosis of first acute anterior MI (ST-elevation myocardial infarction) defined 
as chest pain >30 minutes and ST elevation ≥0.2 mV in at least 2 consecutive 
electrocardiogram (ECG) leads in the anterior area (DI, aVL, V1-V6). 
4. 
Primary PCI of the index-MI-related artery within 24 hours after the MI. 
5. 
Women of childbearing potential and non-surgically sterile male subjects who 
are sexually active must agree to use an approved highly effective form of 
contraception from the time of informed consent until 30 days post-dose. 
Approved forms of contraception include hormonal intrauterine devices, 
hormonal contraceptives (oral birth control pills, depot, patch, or injectable), 
together with supplementary double-barrier methods such as condoms or 
diaphragms with spermicidal gel or foam. 
Note: The following categories define women who are NOT considered to be of 
childbearing potential: 
o 
Premenopausal women with 1 of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
OR 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 7 of 96 
o 
Postmenopausal women, defined as having amenorrhea for at least 
12 months without an alternative medical cause. 
6. Women of childbearing potential must have a negative serum pregnancy test result 
at the Screening Visit. 
Exclusion criteria: 
1. 
Body mass index >45 kg/m². 
2. 
Subject is hemodynamically unstable or has cardiogenic shock. 
3. 
Subjects with clinical signs of HF (Kilipp III and IV corresponding to severe 
HF). 
4. 
Systolic blood pressure <100 mmHg at Inclusion Visit. 
5. 
Early primary PCI of the index-MI-related artery performed within 3 hours after 
MI. Important Note: the time of the PCI MUST NOT be delayed because of the 
protocol; if PCI is performed within 3 hours after MI, the subject is not eligible. 
6. 
Subjects who require treatment with angiotensin-converting-enzyme inhibitor 
(ACE-I), angiotensin-receptor blocker (ARB), or sacubitril/valsartan after the 
index magnetic resonance imaging. Note: if treatment was for HTN, ACE-I/ARB 
should be stopped right before index magnetic resonance imaging, and, if 
necessary, another therapeutic class can be prescribed for HTN. If the 
ACE-I/ARB was prescribed for congestive HF, the subject is not considered 
eligible; if the ACE-I/ARB prescribed for another reason cannot be stopped, the 
subject is not eligible for study inclusion. 
7. 
Subjects scheduled for implantable cardioverter defibrillator (ICD), cardiac 
resynchronization therapy, or pacemaker within the next 3 months. If an ICD is 
indicated for ventricular arrhythmia during the course of the study, a life vest, 
when possible, should be prescribed and the ICD scheduled after study 
completion. 
8. 
Subjects with any contraindication related to the CMRI procedure (devices or 
metal foreign bodies, including pacemaker, defibrillator) including severe 
claustrophobia according to the lists/safety rules of the local MRI departments. 
9. 
Female who is breast-feeding, pregnant, or planning to become pregnant during 
the study. 
10. 
Medical history of cancer (except for basal cell carcinoma) and/or treatment for 
cancer within the last 5 years. 
11. 
Alkaline phosphatase >3 × upper limit of normal (ULN), total bilirubin 
≥1.5 × ULN, or direct bilirubin >ULN in subjects with Gilbert’s syndrome at the 
Screening Visit. 
12. 
Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, as calculated 
using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 
formula at the Screening Visit. 
13. 
History of any blood disorder, other than sickle cell trait, causing hemolysis or 
unstable red blood cells (e.g., malaria, babesiosis, hemolytic anemia, 
thalassemia, or sickle cell anemia). 
14. 
Clinical evidence of thyroid disease, thyroid hormone therapy that is not stable 
≥4 weeks prior to Screening, or a thyroid-stimulating hormone (TSH) level 
<0.75 × lower limit of normal or >1.5 × ULN. 
15. 
History of alcohol or drug abuse within the 3 months prior to the Screening Visit 
that would interfere with study participation or lead to decreased compliance 
with study procedures or IP intake in the investigator’s opinion. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 8 of 96 
16. 
Participation in another clinical study involving an investigational drug within 
30 days prior to Screening, or if a subject plans to participate in another clinical 
study within 30 days of discontinuation of the IP. 
17. 
Any condition that in the opinion of the investigator would interfere with study 
participation, may pose a risk to the subject, or would make study participation 
not in the best interest of the subject. 
18. 
Subjects with a life expectancy of less than 1 year per investigator’s discretion. 
19. 
Any subject who, in the opinion of the investigator, will not be able to follow the 
protocol. 
The contraindications of Ramipril as given in the summary of product characteristics 
must be checked before any inclusion to ensure that the subject has no contraindication 
to the administration of Ramipril; otherwise, the subject should be excluded from the 
study. 
TEST PRODUCT 
Name: firibastat (QGC001) 
Dose, route, and frequency: 
Subjects will receive either: 
• 
Group 1: 1 capsule of firibastat as 50 mg capsule orally BID (1 capsule in the 
morning and 1 capsule in the evening) from Day 1 to Day 14 (Day 14 morning 
only) and then 2 capsules BID (2 capsules in the morning and 2 capsules in the 
evening) from Day 14 (Day 14 evening only) to Day 84 (the subjects’ dosage 
will be up-titrated and/or down-titrated according to a specific titration 
procedure) 
OR 
• 
Group 2: 1 capsule of firibastat as 250 mg capsule orally BID (1 capsule in the 
morning and 1 capsule in the evening) from Day 1 to Day 14 (Day 14 morning 
only) and then 2 capsules BID (2 capsules in the morning and 2 capsules in the 
evening) from Day 14 (Day 14 evening only) to Day 84 (the subjects’ dosage 
will be up-titrated and/or down-titrated according to a specific titration 
procedure) 
CONTROL 
PRODUCT 
Name: ramipril 
Dose, route, and frequency: 
Subjects will receive: 
Group 3: 1 capsule of ramipril as 2.5 mg capsule orally BID (1 capsule in the morning 
and 1 capsule in the evening) from Day 1 to Day 14 (Day 14 morning only) and then 
2 capsules BID (2 capsules in the morning and 2 capsules in the evening) from Day 14 
(Day 14 evening only) to Day 84 (the subjects’ dosage will be up-titrated and/or 
down-titrated according to a specific titration procedure). 
TREATMENT 
REGIMENS 
The IP will be administered orally as 1 capsule BID (1 capsule in the morning and 
1 capsule in the evening) from Day 1 to Day 14. The dose will then be increased to 
2 capsules BID (2 capsules in the morning and 2 capsules in the evening) from Day 14 if 
the subject has an SBP ≥110 mmHg without any symptoms of hypotension and/or 
cardiogenic shock. If the SBP is <110 mmHg, the subject will remain on the same dose 
(1 capsule BID). If symptomatic hypotension, symptomatic orthostatic hypotension, or 
cardiogenic shock occur, the treatment will be discontinued for the remainder of the 
study. SBP will be calculated as the average of 3 measurements (with intervals of 1 to 
2 minutes), which will be performed after the subject has been sitting for 5 minutes at 
rest. In case of any suspicion or symptoms related to hyper- or hypotension, the subjects 
should contact the site, attend an unscheduled visit, or visit their general practitioner or 
nearest cardiovascular unit, where a decision on any action with the IP can be made by 
the investigator or other physician seeing the subject. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 9 of 96 
On Day 42, if SBP is ≥110 mmHg without any symptoms of hypotension and/or 
cardiogenic shock, the dose will remain the same if the subject has already been treated 
with 2 capsules of the IP BID, or will be increased to 2 capsules of the IP BID. If SBP is 
<110 mmHg and if the subject was being treated with 2 capsules of the IP BID, the dose 
will be decreased to 1 capsule of the IP BID. If SBP is <110 mmHg and if the subject 
was being treated with 1 capsule of the IP BID, the subject will remain on the same dose 
(1 capsule BID). If symptomatic hypotension, symptomatic orthostatic hypotension, or 
cardiogenic shock occur, the treatment will be discontinued for the remainder of the 
study. 
COORDINATING/ 
PRINCIPAL 
INVESTIGATOR 
Prof. Gilles Montalescot, MD, PhD 
Head of the Medical Cardiology Department 
Cardiology Institute, Hôpital Pitié-Salpêtrière 
47 Boulevard de l’Hôpital 
75013 Paris, France 
Telephone: 
+33 1 42 16 30 07 
Fax: 
+33 1 42 16 29 31 
PLANNED STUDY 
SITES 
Approximately 38 study sites in Europe and the United States 
CRITERIA FOR 
EVALUATION 
Efficacy endpoints: 
Primary efficacy endpoint: 
The primary efficacy endpoint is the change from Baseline to Day 84 in LVEF assessed 
by CMRI (centralized reading). 
Secondary endpoints: 
• 
Change from Baseline to Day 84 in left-ventricular end-diastolic and 
end-systolic volumes assessed by CMRI (centralized reading). 
• 
Change from Baseline to Day 84 in average peak of longitudinal and 
circumferential strain in the infarcted segments assessed by CMRI (centralized 
reading). 
• 
Infarct mass at EOT (Day 84) assessed by CMRI (centralized reading). 
• 
MACE (i.e., cardiovascular deaths, new MIs, and cardiac hospitalizations) as 
adjudicated by an independent committee 
• 
Change from Baseline in NT-proBNP, PIIINP, and CRP levels to Day 84 
• 
Slope of decrease in copeptin over time 
Safety endpoints: 
Safety assessments will include all AEs, adverse events of special interest, which include 
allergic reactions and diabetes insipidus, and clinical laboratory evaluations and 
specifically: 
• 
Change from Baseline in clinic SBP, diastolic blood pressure (DBP), and heart 
rate (HR) at each visit 
• 
Change from Baseline in sodium, potassium, aspartate aminotransferase (AST), 
and ALT blood levels and eGFR 
Every effort should be made to follow up subjects who continue to experience an AE or 
a serious adverse effect (SAE) on completion of the study until the AE stabilizes or 
resolves. 
INDEPENDENT 
DATA 
MONITORING 
COMMITTEE 
An independent data monitoring committee (IDMC), consisting of independent 
physicians qualified to treat the study population will be established for the regular 
unblinded review of emerging safety data. The IDMC will also include an independent 
statistician who will be in charge of the interim analysis corresponding to efficacy and 
safety data. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 10 of 96 
STATISTICAL 
METHODS 
Analysis populations: 
The following analysis populations will be considered: 
• 
Safety population: The safety population will consist of all subjects who receive 
at least 1 dose of the IP. This population will be based on the treatment actually 
received by the subject and will be used for the analysis of the safety endpoints. 
• 
Intent-to-treat (ITT) population: The ITT population will consist of all 
randomized subjects. This population will be based on the treatment to which the 
subject was randomized. Any subject who receives a randomization number will 
be considered to have been randomized. 
• 
Modified intent-to-treat (mITT) population: The mITT population will consist of 
all randomized subjects who receive at least 1 dose of the IP and who have at 
least 1 baseline and 1 post-randomization efficacy assessment (CMRI) on 
treatment. This population will be based on the treatment to which the subject 
was randomized and will be the primary population for the analysis of the 
efficacy endpoints. 
• 
Per-protocol (PP) population: The PP population will consist of all subjects from 
the mITT population without any major protocol deviation. This population will 
be considered for sensitivity analysis of the primary endpoint. 
A single futility interim analysis (IA) is planned for the primary efficacy endpoint for the 
comparison of firibastat 50 mg against ramipril when approximately 50% of the 
maximum number of subjects have completed the Day 84 primary endpoint assessment. 
Subject characteristics and disposition: 
The number of subjects in each analysis population will be provided overall and by 
treatment group. Demographics and baseline characteristics will be summarized overall 
and by treatment group on the mITT population. 
Efficacy analyses: 
The primary efficacy endpoint will be primarily analyzed on the mITT population. 
Sensitivity analyses will be performed on the ITT and PP populations. The secondary 
efficacy endpoints will be analyzed on the mITT population. 
Primary analysis of the primary efficacy endpoint: 
The change from Baseline in LVEF will be primarily analyzed using an analysis of 
covariance (ANCOVA). The ANCOVA will include treatment group as factor and 
baseline LVEF and country as covariates. For subjects who prematurely discontinue the 
study, measurements made at the time of study withdrawal will be considered in the 
analysis. Pattern of study premature discontinuations, including the profile of subjects 
and reason and time to withdrawal, will be presented to assess potential impact of 
dropouts on treatment comparisons. 
The adjusted mean will be presented by treatment group. Difference in adjusted mean 
between treatment groups, associated 95% confidence interval, and P value will be also 
presented using a hierarchical step-down testing procedure to control the overall type I 
error. 
Sensitivity analysis of the primary efficacy endpoint: 
A sensitivity analysis will be performed to explore possible impact of dropout pattern on 
treatment comparisons. 
Secondary efficacy endpoints: 
As for the primary efficacy endpoint, a hierarchical step-down testing procedure will be 
applied for each of the secondary efficacy endpoints in order to control the overall type I 
error due to multiplicity of treatment comparisons. 
Safety analyses: 
All safety analyses will be descriptive and performed on the safety population. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 11 of 96 
Vital signs: 
The SBP, diastolic blood pressure (DBP), and heart rate (HR), as well as the 
corresponding changes from Baseline, will be described at each visit by treatment group. 
Clinical laboratory data: 
The blood level of sodium, potassium, AST, ALT, and the eGFR calculated value, as well 
as the corresponding changes from Baseline, will be described at each visit by treatment 
group. 
Adverse events: 
All AEs, whether serious or non-serious, will be reported from signing the ICF until 
7 days (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation. 
For AE reporting, the verbatim term recorded in the electronic case report form by the 
investigators to identify AEs will be coded using the latest version of Medical Dictionary 
for Regulatory Activities. 
Treatment-emergent AEs are defined as: 
• 
Adverse events with onset at the time of or following the start of treatment with 
IP through the EOT Visit 
• 
Adverse events starting prior to the start of treatment but increasing in severity 
or relationship at the time of, or following, the start of treatment with IP through 
the EOT Visit 
The following AEs of clinical and special interest will be summarized separately: 
• 
Allergic reactions 
• 
Diabetes insipidus 
SAMPLE SIZE 
DETERMINATION 
The sample size determination is based on the primary efficacy endpoint (i.e., the change 
from Baseline in LVEF assessed by CMRI on Day 84) on an equal randomization, using 
a 2-sided 5% nominal level of significance. 
The standard deviation of the primary efficacy variable is estimated to 10%. 
Based on an estimated difference of 5% between the treatment groups on the primary 
efficacy variable, approximately 88 evaluable subjects per group are needed to achieve 
90% power (accounting for the futility IA at 50% of the maximum information). 
Assuming an approximate 10% of dropout/non-evaluable rate, 98 subjects per group are 
expected to be randomized, i.e., a total of 294 subjects. 
STUDY AND 
TREATMENT 
DURATION 
The overall study duration is expected to be 19 months (16 months of active enrollment 
and 3 months of treatment). 
The sequence and maximum duration of the study periods will be as follows: 
1. Screening: 1 day (+1 day) 
2. Inclusion: 1 day 
3. Titration Period: 42 days (±2 days) 
4. Treatment Period: 42 days (±3 days) 
5. Follow-up Visit for women of childbearing potential only: 1 day 
The maximum study duration is 119 days for women of childbearing potential and 
89 days for all other subjects. 
The maximum treatment duration for each subject is 87 days. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 12 of 96 
2.2. Schedule of Events 
Table 2-1: 
Schedule of Events 
 
Screeninga 
Inclusiona 
Safety checkb 
Titration 
Treatment 
EOTc 
Follow-upm 
Visit 
Visit 1 
Visit 2 
On-site or via 
Telephone Call 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Study Day 
Assessment 
Day -2 to  
Day 1 
Day 1 
Day 3 
Day 14 
(±2 days) 
Day 42 
(±2 days) 
Day 84 
(±3 days) 
Day 114  
(±3 days) or 
30 Days after 
Treatment 
Discontinuation 
Written informed consentd 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
Clinical examinatione 
X 
 
 
X 
X 
X 
 
12-lead ECGf 
X 
 
 
X 
X 
X 
 
Blood pressure and HR measurementg 
X 
X 
 
X 
X 
X 
 
Capture of troponin peak 
X 
 
 
 
 
 
 
CMRIh 
 
X 
 
 
 
X 
 
Blood samples for local laboratory 
assessment (hematology and clinical 
chemistry)i,j 
X 
 
 
 
X 
X 
 
Blood samples for central laboratory 
assessment (biomarkers)k 
 
X 
 
Xl 
Xl 
X 
 
Pregnancy testm 
X 
 
 
 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
Dispense IPn 
 
X 
 
X 
X 
 
 
Discontinue IP 
 
 
 
 
 
X 
 
IP compliance check 
 
 
 
X 
X 
X 
 
Concomitant medications 
X 
X 
 
X 
X 
X 
 
AEs 
 
X 
X 
X 
X 
X 
 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 13 of 96 
Abbreviations: AE = adverse event; CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; CMRI = cardiac magnetic resonance imaging; 
CRP = C-reactive protein; ECG = electrocardiogram; EOT = end of treatment; GFR = glomerular filtration rate; HR = heart rate; ICF = informed consent form; 
IP = investigational product; MI = myocardial infarction; NT-proBNP = N-terminal pro b-type natriuretic peptide; PCI = percutaneous coronary intervention; 
PIIINP = procollagen type III aminoterminal peptide; TSH = thyroid-stimulating hormone 
a. The Screening Visit will occur within 24 hours after index acute MI, defined as the time of onset of symptoms and after PCI is performed (no earlier than 
3 hours after acute MI and within 24 hours after MI). If possible, the Screening (Visit 1) and the Inclusion (Visit 2) Visits could be performed on the same 
day; procedures applicable for both visits should not be duplicated. 
b. A safety check should be performed 3 days after first administration of the IP to ensure the good tolerance of the treatment by the subjects. If a subject is 
discharged early (i.e., before 3 days after the first IP administration), the site will contact the subject by telephone. If the investigator judges that there is a risk 
of non-tolerance such as any suspicion or symptoms related to hyper- or hypo-tension, the subject will be asked to come to the site for an unscheduled visit. 
The investigator will then decide whether the subject should be withdrawn from the study. 
c. For subjects completing the study, EOT will be at Visit 5. For subjects who are withdrawn from the study prior to completion, all Visit 5 procedures will be 
performed at an Early Termination Visit that should be conducted as early as possible after treatment discontinuation. 
d. The subject will sign an ICF before any study-specific procedures are performed. Any standard-of-care procedures performed prior to ICF signature should 
not be repeated for the purpose of the study if already performed. 
e. Clinical examination will also include the measurement of height (at Screening only) and weight. If the subject provided consent for this, the subject’s 
coronary angiography performed after MI at Screening will be captured using the CMRI electronic repository as part of the subject’s study documentation. 
f. The subject must rest in a supine position for at least 5 minutes before the 12-lead ECG recording. 
g. The blood pressure will be calculated as the average of 3 measurements (with intervals of 1 to 2 minutes), which will be performed after the subject has been 
sitting for 5 minutes at rest. 
h. The CMRI must be performed within 72 hours after MI. 
i. Blood sample analysis for hematology will include red blood cell count, hemoglobin, hematocrit, white blood cell count with differential (neutrophils, 
lymphocytes, monocytes, eosinophils, and basophils), and platelet count. 
j. Blood sample analysis for clinical chemistry will include sodium, chloride, potassium, blood urea nitrogen, creatinine, alanine aminotransferase, aspartate 
aminotransferase, alkaline phosphatase, glucose, albumin, bicarbonate, creatinine kinase, TSH, direct bilirubin, and total bilirubin. Estimated GFR will be 
calculated using the CKD-EPI formula. 
k. The blood samples should be shipped to the central laboratory for analysis of biomarkers (NT-proBNP, copeptin, PIIINP, and CRP). 
l. At Visits 3 and 4, assessment of copeptin only. 
m. For females of childbearing potential only; serum pregnancy tests will be performed at the Screening Visit, Treatment Visit 4, EOT Visit, and Follow-up Visit 
(or 30 days after treatment discontinuation). 
n. The first capsule of the IP will be administered on Day 1 as soon as possible after CMRI is performed, with a maximum of 72 hours after MI. 
 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 14 of 96 
3. TABLE OF CONTENTS 
1. 
APPROVAL SIGNATURES .............................................................................................2 
2. 
PROTOCOL SUMMARY .................................................................................................3 
2.1. Synopsis ...................................................................................................................3 
2.2. Schedule of Events ................................................................................................. 12 
3. 
TABLE OF CONTENTS ................................................................................................. 14 
3.1. List of In-Text Tables ............................................................................................. 18 
3.2. List of In-Text Figures ............................................................................................ 18 
REASONS FOR AMENDMENT ......................................................................................... 19 
SUMMARY OF AMENDED SECTIONS ............................................................................ 20 
AMENDED PROTOCOL .................................................................................................... 22 
4. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................................ 23 
5. 
INTRODUCTION ........................................................................................................... 25 
5.1. Background and Rationale ...................................................................................... 25 
5.1.1 Heart Failure ............................................................................................... 25 
5.1.2 ST-segment Elevation Myocardial Infarction ................................................ 26 
5.2. Firibastat ................................................................................................................ 26 
5.2.1 Preclinical Experience.................................................................................. 27 
5.2.2 Clinical Experience...................................................................................... 28 
5.2.3 Phase 1 Studies in Healthy Volunteers .......................................................... 28 
5.2.4 Phase 2 Studies ............................................................................................ 29 
5.2.5 Rationale for Using Firibastat after Acute Myocardial Infarction and for the 
Conduct of the Study ................................................................................... 30 
5.3. Summary of Potential Risks and Benefits ................................................................ 30 
6. 
OBJECTIVES ................................................................................................................. 33 
6.1. Primary Objective ................................................................................................... 33 
6.2. Secondary Objectives.............................................................................................. 33 
7. 
STUDY DESIGN ............................................................................................................ 34 
7.1. Overall Study Design and Plan ................................................................................ 34 
7.2. Rationale and Discussion of Study Design ............................................................... 38 
7.3. Selection of Doses in the Study ............................................................................... 38 
7.4. Study Sites ............................................................................................................. 39 
7.5. Point of Contact ...................................................................................................... 39 
7.6. End of Study Definition .......................................................................................... 39 
8. 
SUBJECT POPULATION ............................................................................................... 40 
8.1. Selection of Study Population and Diagnosis ........................................................... 40 
8.2. Study Entry Criteria ................................................................................................ 40 
8.2.1 Inclusion Criteria ......................................................................................... 40 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 15 of 96 
8.2.2 Exclusion Criteria ........................................................................................ 41 
8.3. Premature Subject Withdrawal ................................................................................ 42 
8.4. Discontinuation of Study Intervention ..................................................................... 42 
8.5. Subject Discontinuation/Withdrawal from the Study ................................................ 43 
8.6. Subject Replacement Criteria .................................................................................. 44 
9. 
TREATMENTS............................................................................................................... 45 
9.1. Identification of Investigational Products ................................................................. 45 
9.1.1 Test Product ................................................................................................ 45 
9.1.2 Reference Product........................................................................................ 45 
9.2. Selection of Timing of Dose for Each Subject.......................................................... 45 
9.3. Dose Adjustment Criteria ........................................................................................ 45 
9.4. Treatment Compliance ............................................................................................ 46 
9.5. Method of Assigning Subjects to Treatment Groups................................................. 46 
9.6. Blinding and Unblinding Treatment Assignment...................................................... 46 
9.7. Permitted and Prohibited Therapies ......................................................................... 47 
9.7.1 Permitted Therapies ..................................................................................... 47 
9.7.2 Prohibited Therapies .................................................................................... 47 
9.7.3 Restrictions ................................................................................................. 48 
9.8. Treatment after End of Study .................................................................................. 48 
9.9. Dispensing and Storage ........................................................................................... 48 
9.10. Drug Accountability ............................................................................................... 48 
9.11. Labeling and Packaging .......................................................................................... 49 
9.11.1 Labeling ...................................................................................................... 49 
9.11.2 Packaging .................................................................................................... 49 
10. STUDY PROCEDURES.................................................................................................. 50 
10.1. Study Duration ....................................................................................................... 50 
10.2. Study Visits ............................................................................................................ 50 
10.2.1 Screening Visit (Visit 1; within 24 Hours after Acute Myocardial Infarction 
[Day -2 - Day 1]) ......................................................................................... 51 
10.2.2 Inclusion Visit (Visit 2; within 72 Hours after Acute Myocardial Infarction [Day 
1]) ............................................................................................................... 52 
10.2.3 Safety Check (Day 3) ................................................................................... 52 
10.2.4 Titration Visit (Visit 3 [Day 14 ± 2 days]) .................................................... 53 
10.2.5 Treatment Visit (Visit 4 [Day 42 ± 2 days]) .................................................. 53 
10.2.6 End-of-Treatment Visit (Visit 5 [Day 84 ± 2 days])....................................... 54 
10.2.7 Follow-up Visit (Visit 6 [Day 114 ± 3 days] or 30 days after Treatment 
Discontinuation) .......................................................................................... 54 
10.3. Assessments ........................................................................................................... 54 
10.3.1 Efficacy Variables ....................................................................................... 54 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 16 of 96 
10.3.1.1 
Cardiac Magnetic Resonance Imaging............................................... 54 
10.3.1.2 
Major Cardiac Events ....................................................................... 56 
10.3.1.3 
Assessment of Biomarkers................................................................ 56 
10.3.2 Safety Variables .......................................................................................... 56 
10.3.2.1 
Clinical Laboratory Safety Assessments ............................................ 57 
10.3.2.2 
Clinical Assessments ........................................................................ 59 
11. ADVERSE EVENTS ....................................................................................................... 60 
11.1. Definitions.............................................................................................................. 60 
11.1.1 Adverse Events............................................................................................ 60 
11.1.2 Adverse Drug Reaction ................................................................................ 60 
11.1.3 Unexpected Adverse Event/Adverse Drug Reaction ...................................... 60 
11.1.4 Serious Adverse Events/Drug Reaction......................................................... 60 
11.1.5 Significant Adverse Events .......................................................................... 61 
11.1.6 Treatment-emergent Adverse Events ............................................................ 61 
11.2. Event Assessment and Follow-up of Adverse Events ............................................... 61 
11.2.1 Assessment.................................................................................................. 62 
11.2.2 Evaluation ................................................................................................... 62 
11.2.2.1 
Severity of Adverse Events............................................................... 62 
11.2.2.2 
Seriousness ...................................................................................... 62 
11.2.2.3 
Actions Taken .................................................................................. 63 
11.2.2.4 
Outcome at the Time of Last Observation ......................................... 63 
11.2.2.5 
Adverse Event Relationship to Investigational Product ...................... 63 
11.2.3 Documentation ............................................................................................ 64 
11.2.4 Treatment of Adverse Events ....................................................................... 64 
11.2.5 Follow-up.................................................................................................... 65 
11.2.6 Reporting .................................................................................................... 65 
11.2.6.1 
Serious Adverse Events .................................................................... 65 
11.2.6.2 
Adverse Drug Reactions ................................................................... 66 
11.2.6.3 
Non-serious Adverse Events ............................................................. 66 
11.3. Special Considerations ............................................................................................ 66 
11.3.1 Adverse Events of Special Interest................................................................ 66 
11.3.1.1 
Allergic Reactions ............................................................................ 67 
11.3.1.2 
Diabetes Insipidus ............................................................................ 68 
11.3.2 Pregnancy.................................................................................................... 68 
11.3.3 Overdose ..................................................................................................... 68 
12. INDEPENDENT DATA MONITORING COMMITTEE.................................................. 70 
13. STATISTICS................................................................................................................... 71 
13.1. Statistical Analysis.................................................................................................. 71 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 17 of 96 
13.1.1 Analysis Populations.................................................................................... 71 
13.1.2 Study Subjects and Demographics ................................................................ 72 
13.1.2.1 
Disposition and Withdrawals ............................................................ 72 
13.1.2.2 
Protocol Deviations .......................................................................... 72 
13.1.2.3 
Demographics and Other Baseline Characteristics ............................. 72 
13.1.3 Exposure and Compliance ............................................................................ 73 
13.1.4 Efficacy Analysis......................................................................................... 73 
13.1.4.1 
Efficacy Endpoints ........................................................................... 73 
13.1.4.2 
Primary Efficacy Endpoint Analysis ................................................. 73 
13.1.4.3 
Secondary Efficacy Endpoints Analyses............................................ 74 
13.1.5 Safety and Tolerability Analyses .................................................................. 75 
13.1.5.1 
Adverse Events ................................................................................ 75 
13.1.5.2 
Clinical Laboratory Evaluations ........................................................ 76 
13.1.5.3 
Vital Signs ....................................................................................... 76 
13.1.5.4 
Twelve-lead Electrocardiograms ....................................................... 76 
13.1.5.5 
Clinical Examination Findings .......................................................... 77 
13.1.6 Interim Analysis .......................................................................................... 77 
13.2. Sample Size Determination ..................................................................................... 77 
14. STUDY CONDUCT ........................................................................................................ 78 
14.1. Sponsor and Investigator Responsibilities ................................................................ 78 
14.1.1 Sponsor Responsibilities .............................................................................. 78 
14.1.2 Investigator Responsibilities......................................................................... 78 
14.1.3 Confidentiality and Privacy .......................................................................... 78 
14.2. Site Initiation .......................................................................................................... 79 
14.3. Screen/Randomization Failures ............................................................................... 79 
14.4. Study Documents.................................................................................................... 79 
14.4.1 Informed Consent ........................................................................................ 80 
14.4.2 Investigator’s Regulatory/Good Clinical Practice Documents ........................ 80 
14.4.3 Case Report Forms ...................................................................................... 81 
14.4.4 Source Documents ....................................................................................... 81 
14.5. Data Quality Control............................................................................................... 81 
14.5.1 Monitoring Procedures................................................................................. 81 
14.5.2 Data Management ........................................................................................ 82 
14.5.3 Quality Assurance/Audit .............................................................................. 82 
14.6. Study Termination .................................................................................................. 83 
14.6.1 Regular Study Termination .......................................................................... 83 
14.6.2 Premature Study Termination ....................................................................... 83 
14.7. Study Site Closure .................................................................................................. 84 


Quantum Genomics 
Confidential 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 18 of 96 
14.7.1 Record Retention ......................................................................................... 84 
14.7.2 Sample Retention......................................................................................... 84 
14.8. Changes to the Protocol .......................................................................................... 85 
14.9. Use of Information and Publication ......................................................................... 85 
15. FINAL CLINICAL STUDY REPORT ............................................................................. 86 
16. ETHICAL AND LEGAL CONSIDERATIONS................................................................ 87 
16.1. Declaration of Helsinki and Good Clinical Practice.................................................. 87 
16.2. Subject Information and Informed Consent and/or Assent ........................................ 87 
16.3. Approval by Institutional Review Board and Independent Ethics Committee ............ 88 
16.4. Finance and Insurance............................................................................................. 88 
17. REFERENCES ................................................................................................................ 89
18. ATTACHMENTS ........................................................................................................... 93 
18.1. Investigator’s Agreement ........................................................................................ 93 
APPENDICES ....................................................................................................................... 94 
A.
Study-specific Requirements ................................................................................... 95 
B.
Regulations and Good Clinical Practice Guidelines .................................................. 96 
3.1. List of In-Text Tables 
Table 2-1: 
Schedule of Events ...................................................................................... 12 
Table 10-1: 
Blood Sample Collection Volumes (mL) ...................................................... 58 
3.2. List of In-Text Figures 
Figure 5-1: 
Mechanism of Action of Firibastat................................................................ 27 
Figure 7-1: 
Timing of Study Procedures at Screening and Inclusion Visits ...................... 35 
Figure 7-2: 
Study Titration Scheme ................................................................................ 37 
Figure 10-1: 
Timing of Study Procedures at Screening and Inclusion Visits ...................... 51 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 19 of 96 
REASONS FOR AMENDMENT 
The following changes were introduced due to a deficiency letter of the Medicines and Healthcare 
Products Regulatory Agency: 
1. 
Exclusion criterion 11 was modified to exclude any subjects with severe liver impairment 
(total bilirubin ≥1.5 upper limit of normal [ULN]) or Gilbert’s syndrome (direct bilirubin 
>ULN). Furthermore, the restriction regarding alanine aminotransferase (ALT) was 
removed from exclusion criterion 11 since following acute MI as a result of myocardium 
cytolysis, a transient increase in ALT is frequently observed. Therefore, it does not make 
sense to exclude patients with an elevation of ALT at Screening or randomization visits 
(within 72 hours after acute MI). 
2. 
Section 10.3.2.1.1 and Table 10-1, which describe blood collection volumes, was updated 
to clarify expected blood draws during Visit 6. 
 
 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 20 of 96 
SUMMARY OF AMENDED SECTIONS 
This is a substantial protocol amendment. 
Section 2.1 
Synopsis – Study Entry Criteria 
Text formerly read: 
Exclusion criteria: 
11. Alanine aminotransferase (ALT) or alkaline phosphatase >3 x 
upper limit of normal (ULN) or a total bilirubin ≥2 x ULN (unless 
secondary to Gilbert’s syndrome) at the Screening Visit. 
Now reads: 
Exclusion criteria: 
11. Alkaline phosphatase >3 x upper limit of normal (ULN), total 
bilirubin ≥1.5 x ULN, or direct bilirubin >ULN in subjects with 
Gilbert’s syndrome at the Screening Visit. 
Section 8.2.2 
Exclusion Criteria 
Text formerly read: 
Exclusion criteria: 
 
11. Alanine aminotransferase (ALT) or alkaline phosphatase >3 × 
upper limit of normal (ULN) or a total bilirubin ≥2 × ULN (unless 
secondary to Gilbert’s syndrome) at the Screening Visit. 
Now reads: 
Exclusion criteria: 
 
11. Alkaline phosphatase >3 × upper limit of normal (ULN), total 
bilirubin ≥1.5 × ULN, or direct bilirubin >ULN in subjects with 
Gilbert’s syndrome at the Screening Visit. 
Section 10.3.2.1.1 
Clinical Laboratory Tests to be Performed 
Text formerly read: 
Each blood sample will be 3.0 to 21.5 mL in volume. The total amount 
of blood to be drawn during the study will be 55.0 mL per subject, 
including samples for assessment of hematology, clinical chemistry, 
biomarkers, and pregnancy testing. The blood volumes to be collected 
at each visit are specified in Table 10 1. 
Now reads: 
Each blood sample will be 3.0 to 21.5 mL in volume. The total amount 
of blood to be drawn during the study will be 60.0 mL per subject, 
including samples for assessment of hematology, clinical chemistry, 
biomarkers, and pregnancy testing. The blood volumes to be collected 
at each visit are specified in Table 10 1. 
Addition: 
Table 10-1: Blood Sample Collection Volumes 
A 5.0 mL blood sample for pregnancy test was added at the Follow-up 
Visit 6 (Day 114 [±3 days] or 30 days after treatment discontinuation). 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 21 of 96 
Footnotes a (referring to clinical chemistry) and c (referring to 
pregnancy test) were added to the table: 
a.  The pregnancy test for females of childbearing potential will be 
performed from the blood samples collected for clinical 
chemistry at Visits 1, 4, and 5, but a separate blood sample for 
pregnancy testing will be collected at Visit 6. 
c. For females of childbearing potential only; a serum pregnancy 
test will be performed at the Follow-up Visit (or 30 days after 
treatment discontinuation). The blood volume will depend on 
the site standard up to a maximum of 5.0 mL. 
 
 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 22 of 96 
AMENDED PROTOCOL 
The following are the amended protocol and appendices, including all revisions specified above. 
 
 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 23 of 96 
4. LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
ABBREVIATION 
EXPLANATION 
ACE-I 
angiotensin-converting-enzyme inhibitor 
ADR 
adverse drug reaction 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
AOBP 
automatic office blood pressure 
APA 
aminopeptidase A 
ARB 
angiotensin receptor blocker 
AST 
aspartate aminotransferase 
BAPAI 
brain aminopeptidase A inhibitor 
BID 
bis in die 
BP 
blood pressure 
CI 
confidence interval 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CMRI 
cardiac magnetic resonance imaging 
CRA 
clinical research associate 
CRO 
contract research organization 
CRP 
C-reactive protein 
CSR 
clinical study report 
DBP 
diastolic blood pressure 
DI 
diabetes insipidus 
DOCA 
deoxycorticosterone acetate 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate 
EOT 
end-of-treatment 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GFR 
glomerular filtration rate 
HF 
heart failure 
HR 
heart rate 
HTN 
hypertension 
IA 
interim analysis 
IB 
investigator brochure 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 24 of 96 
ABBREVIATION 
EXPLANATION 
ICD 
implantable cardioverter defibrillator 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IDMC 
independent data monitoring committee 
IEC 
independent ethics committee 
IND 
Investigational New Drug 
IP 
investigational product 
IRB 
institutional review board 
ITT 
intent-to-treat 
LV 
left ventricular 
LVEF 
left ventricular ejection fraction 
MACE 
major cardiac event 
MI 
myocardial infarction 
MMRM 
mixed model for repeated measures 
MR 
mineralocorticoid receptor 
NT-proBNP 
N-terminal pro b-type natriuretic peptide 
PCI 
percutaneous coronary intervention 
PD 
pharmacodynamics 
PIIINP 
procollagen type III aminoterminal peptide 
PK 
pharmacokinetics 
PT 
preferred term 
RAAS 
renin-angiotensin aldosterone 
REML 
restricted maximum likelihood 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
SD 
standard deviation 
SHR 
spontaneously hypertensive rat 
STEMI 
ST-elevation myocardial infarction 
SUSAR 
suspected unexpected serious adverse reaction 
T½ 
plasma elimination half-life 
Tmax 
time to reach the maximum plasma concentration 
TSH 
thyroid-stimulating hormone 
UADR 
unexpected adverse drug reaction 
UAE 
unexpected adverse event 
ULN 
upper limit of normal 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 25 of 96 
5. INTRODUCTION 
5.1. Background and Rationale 
5.1.1 
Heart Failure 
Heart failure (HF) is considered to be a complex clinical syndrome that could develop from 
multiple structural or functional cardiac and non-cardiac diseases. From a population-based study 
in 220 patients with new onset of HF, primary etiologies were reported as coronary heart disease 
(36%), unknown (34%), hypertension (HTN) (14%), valve disease (7%), atrial fibrillation alone 
(5%), and other (5%).1 In western developed countries, coronary artery disease and HTN seem to 
be the most common causes of HF. HF is often the result of a myocardial infarction (MI). In the 
Framingham Heart Study, coronary artery disease and HTN (either alone or in combination) were 
implicated as the cause in over 90% of the cases of HF. HTN has been associated with an increased 
risk of HF; it was reported as the cause of HF (either alone or in association with other factors) in 
over 70% of the cases.2 HF is the leading cause of hospitalization for patients over 65 years old in 
western countries. It affects 1 to 5 persons in a thousand in industrialized countries, all ages 
considered, with a prevalence of 3 to 20 in a thousand. The total estimated direct and indirect cost 
of HF in the US for 2010 was $39.2 billion.3 
HF is characterized by increased activity of the renin-angiotensin aldosterone system (RAAS), by 
enhanced sympathetic tonus, and withdrawal of parasympathetic control. This autonomic 
imbalance is recognized as an important mediator of increased mortality and morbidity in HF.4 
The sustained increase of sympathetic drive, along with reduced parasympathetic activity and 
activation of the RAAS in HF, also contribute to progressive left ventricular (LV) dysfunction, 
progressive LV remodeling, end-organ damage, and ultimately death.5,6 In addition, several studies 
have shown a significant elevation in mean values of plasma vasopressin in populations of patients 
with HF and/or LV dysfunction.7-9 
Very few pharmacological innovations have been recorded in the past decade for HF. The current 
evidence-based guideline interim analysis (IA) recommended medicines for HF with reduced 
ejection fraction are mainly RAAS-acting molecules such as angiotensin-converting enzyme 
(ACE) inhibitors or angiotensin II receptor blockers (ARB), mineralocorticoid receptor (MR) 
antagonists, 
β-adrenergic 
receptor blocking 
agents, 
and 
diuretics. 
The combination 
valsartan/sacubitril (brand name Entresto™, previously known as LCZ696) consists of the 
ARB valsartan and the neprilysin inhibitor sacubitril in a 1:1 ratio by molecule count. It is also 
available for the treatment of symptomatic HF with reduced ejection fraction if HF is still 
symptomatic and if left ventricular ejection fraction (LVEF) is ≤35% despite therapy combining 
an ACE inhibitor, a β-adrenergic receptor blocker, and a MR antagonist. 
Although a large number of drugs is available, HF has still a poor prognosis as the 1-year survival, 
all stages considered, is about 65%. HF remains one of the first causes of cardiovascular death. 
Consequently, there is still an unmet medical need to develop new efficient and safe classes of 
drugs acting on alternative pathways, specifically those preventing activation of brain 
neuromodulatory pathways that may lead to more optimal and specific strategies to improve the 
treatment of HF. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 26 of 96 
5.1.2 
ST-segment Elevation Myocardial Infarction 
ST-segment elevation myocardial infarction (STEMI) is a very serious type of heart attack, which 
is characterized by a blockade of one of the heart’s major arteries detected as an abnormality on 
the 12-lead electrocardiogram (ECG). It is considered as a cardiology emergency requiring 
immediate recognition and treatment aimed at successful and early reperfusion to ensure optimal 
outcomes. It is a significant public health problem in both industrialized and developing countries, 
which is associated with significant morbidity and mortality. The annual incidence of STEMI 
ranged between 44 and 142/100 000 in European countries in 201010, and it was shown to be 
73/100 000 in the United States in 2011.11 
Rapid and timely reperfusion is recommended after STEMI for all eligible patients, presenting 
within 12 hours of symptom onset to LVEF deterioration and remodeling. Primary percutaneous 
coronary intervention (PCI) is considered the reperfusion strategy of choice. After acute MI, 
cardiac remodeling can lead to changes in size, shape, and function of the heart, which is 
recognized as an important aspect of cardiovascular disease progression. 
Activation of the renin-angiotensin system (RAS) is considered to play an important role in 
remodeling since its inhibition improves the long-term clinical outcomes after a successful PCI.12 
In patients following acute MI, ACE-inhibitors were successfully studied: The results from the 
Survival And Ventricular Enlargement (SAVE) study showed a benefit of captopril, suggesting 
that ACE inhibitors should be routinely administered to patients with impaired left ventricular 
function after MI.13 In the TRAndolapril Cardiac Evaluation (TRACE) study, the long-term 
treatment of patients with reduced left ventricular function with trandolapril resulted in a 
significantly reduced the risk of overall mortality, mortality from cardiovascular causes, sudden 
death, and the development of severe HF.14 The effect of ramipril on mortality and morbidity of 
survivors of acute MI with clinical evidence of HF was analyzed in the Acute Infarction Ramipril 
Efficacy (AIRE) study. The investigators showed that the treatment resulted in a substantial 
reduction in premature death from all causes.15 Based on these studies, ACE-inhibitors are 
recommended after MI in patients with low LVEF and/or clinical signs of HF. Nevertheless, all of 
these drugs were tested before the era of early revascularization, and it is unclear if the benefit 
remains the same when used after early PCI. 
5.2. Firibastat 
Quantum Genomics is developing the molecule firibastat as the first drug candidate of a new class 
of centrally acting agents, brain aminopeptidase A inhibitors (BAPAIs). 
Firibastat ([3S,3'S]-4,4'-dithiobis-[3-aminobutane-1-sulfonic acid]), previously named RB150 or 
QGC001) is a prodrug of EC33 ([3S]-3-amino-4-sulfanylbutane-1-sulfonic acid, a specific and 
selective inhibitor of aminopeptidase A (APA), a membrane-bound zinc metalloprotease of the 
RAS that generates angiotensin III from angiotensin II. The design of firibastat is based on a 
previously demonstrated approach that causes an increase of the brain penetration of free 
sulfide-containing molecules by blocking the thiol group under a disulfide form.16 Firibastat, 
obtained by disulfide bridge-mediated dimerization of EC33, is known to be stable in plasma but 
to be reduced in the brain by a physiologically dependent process, releasing 2 active molecules of 
EC33 into the brain. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 27 of 96 
The mechanism of action of firibastat is displayed in Figure 5-1. Following oral administration, 
firibastat crosses the intestinal, hepatic, and blood-brain barriers. On entry into the brain, it is 
cleaved by brain reductases to generate 2 active molecules of EC33, which inhibit brain 
APA activity and block the formation of brain angiotensin III, and this process further results in a 
decrease in sympathetic tone and a reduction in arginine-vasopressin release from the posterior 
pituitary into the bloodstream in experimental animal models of HTN and HF. 
Because there is supportive evidence that overactivity of the brain RAS plays a major role in the 
activation of peripheral mechanisms contributing to progressive cardiac remodeling and 
dysfunction after a MI and that targeting vasopressin release and sympathetic tone could be of 
interest for the treatment of HF, firibastat appears to be a reasonable drug candidate to treat patients 
with HF. Thus, firibastat represents a new therapeutic approach that may specifically prevent 
activation of brain neuromodulatory pathways and lead to a more optimal and specific strategy to 
improve the treatment of HF. 
 
Figure 5-1: 
Mechanism of Action of Firibastat  
(Firibastat = QGC001/RB150; adapted from Gao et al., 2014)17 
 
5.2.1 
Preclinical Experience 
When administered intravenously to deoxycorticosterone acetate (DOCA)-salt rats, firibastat can 
penetrate into the brain, block the brain RAS activity through APA inhibition, and markedly reduce 
blood pressure (BP) in conscious hypertensive DOCA-salt rats.17 The antihypertensive effect of 
firibastat was further demonstrated in hypertensive DOCA-salt and in spontaneously hypertensive 
rats (SHRs) after single oral dosing at 15 mg/kg.19,1 Firibastat was found to act as an 
antihypertensive drug and not as a hypotensive drug since it has no significant effect on BP and 
heart rate (HR) in normal normotensive rats at 15 mg/kg. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 28 of 96 
In acute MI animal models (coronary artery ligation in rats and mice), APA activity rapidly 
increases. When infused intracerebroventricularly early after MI in rats, firibastat prevents the 
MI-induced increase in APA activity, improves baroreflex function and LV function, prevents 
enhanced sympatho-excitatory and pressor responses to air stress, and seems to be more effective 
than losartan.21 Firibastat was also found to improve the left ventricular end diastolic pressure and 
the LVEF without lowering BP levels after 4 weeks in post-MI rats treated daily by oral route with 
firibastat.22 
Similarly, firibastat oral treatment given in mice post MI was found to normalize brain 
APA hyperactivity to control values measured in sham-operated animals after 2 weeks. After 
6 weeks post MI, mice treated daily by oral route with firibastat exhibited significant lower 
LV end-diastolic pressure, LV end-systolic diameter and volume, and higher LVEF (data on file). 
Firibastat treatment (150 mg/kg/day) was found to be as effective as enalapril (1 mg/kg/day) alone. 
However, oral treatment combining firibastat (150 mg/kg/day) with enalapril (1mg/kg/day) was 
found less effective on LVEF improvement in mice post MI than the treatment of each compound 
alone, suggesting that dual blockade of brain RAS and systemic RAS may not be optimal after MI 
(data on file). Firibastat treatment (150 mg/kg/day) alone was found to also reduce significantly 
messenger ribonucleic acid expressions of several HF biomarkers (β-myosin heavy chain, brain 
natriuretic peptide, and atrial natriuretic factor) and the fibrosis biomarkers connective tissue 
growth factor, collagen type I and collagen type III in the peri-infarct area (data on file). 
In conclusion, experimental data support that chronic oral administrations of firibastat in mice and 
rats post MI normalize brain APA activity, prevent cardiac dysfunction, attenuate cardiac 
hypertrophy, and potentially reduce fibrosis. 
5.2.2 
Clinical Experience 
Five clinical studies evaluating the safety, tolerability, efficacy, pharmacokinetics (PK), and/or 
pharmacodynamics (PD) of firibastat have been completed so far.23 
5.2.3 
Phase 1 Studies in Healthy Volunteers 
Study QGC001/1QG1 was a phase 1, double-blind, placebo-controlled, ascending single-dose, 
safety, tolerability, and PK study of firibastat in 56 healthy male volunteers. Study QGC001/1QG2, 
was a phase 1, double-blind, placebo-controlled, ascending, repeated-dose study. Firibastat was 
administered orally as a single ascending dose (Part 1) or as multiple ascending doses (Part 2) to 
69 healthy male volunteers to assess the safety, tolerability, PK, and PD. In these 2 phase 1 studies, 
the administration of a single oral dose of firibastat up to 2000 mg was found to be safe and 
well-tolerated. No withdrawal due to adverse events (AEs) occurred; no serious adverse events 
(SAEs) or important medical events were recorded. A total of 5 treatment-emergent adverse events 
(TEAEs) of mild or moderate intensity and possibly related to treatment were reported by 
3 subjects of the firibastat groups; the other TEAEs were considered to be unlikely related to the 
investigational product (IP). All the subjects recovered without sequelae. 
After repeated doses, the most common TEAEs were diarrhea in 4 patients (44%) and rash in 
4 patients (44%). These events occurred at the highest tested dose (1000 mg twice daily [bis in die, 
BID]). All the subjects recovered without sequelae. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 29 of 96 
All firibastat doses (500 mg, 750 mg, and 1000 mg BID) were rapidly absorbed (time to reach the 
maximum plasma concentration [Tmax] range: 3-5 hours) and converted to EC33 within 3-5 hours. 
The peak plasma concentrations and area under the curve of firibastat and EC33 increased with 
the dose. There was a mild accumulation of firibastat and EC33 and increase in plasma elimination 
half-life (T½) with time. When compared to placebo, firibastat did not significantly change renin, 
aldosterone, and cortisol plasma concentrations, or levels of plasma copeptin in any treatment 
group. No change in heart rate, nor in systolic/diastolic blood pressure was observed. 
Food intake had no influence on the safety and the tolerability of firibastat after single oral 
administration of 1000 mg in healthy male subjects in study QGC001/1QG2. There was no 
significant influence of food intake on the Tmax. The T½ of firibastat remained around 2.5 hours 
and 2 hours in fed and fasted conditions, respectively. A moderate decrease in the firibastat plasma 
peak (30%) and exposure (15%) was observed when the IP was taken with food, while food intake 
had no influence on the PK parameters of EC33. 
5.2.4 
Phase 2 Studies 
The phase 2a study QGC001/2QG1 compared the oral administration of firibastat with placebo 
over 4 weeks in a multicenter, randomized, double-blind, 2-period, placebo controlled, forced 
titration, proof-of-concept crossover design in 34 patients with Grade I or II HTN. The dose of 
firibastat in this study was 250 mg BID for 1 week followed by 500 mg BID for 3 weeks. The 
ambulatory daytime systolic blood pressure (SBP) (primary endpoint) was decreased, by 
2.69 mmHg compared to placebo (P = 0.16), and clinic SBP by 4.65 mmHg (P = 0.15). The 
decrease was directly correlated with the initial BP level, i.e., a higher initial BP was associated 
with a larger decrease in SBP. The non-significant BP-lowering effect of firibastat may be of 
multifactorial origin, including the small sample size of the study, the short duration of exposure 
to firibastat (4 weeks), the relatively low level of HTN (mean baseline clinic SBP of 144 mmHg), 
and the large between-patient variability in BP levels. 
Firibastat administration in this study did not influence the HR, or plasma/urine hormones, 
including renin, aldosterone, copeptin, apelin, and adrenocorticotrophic hormone. No significant 
laboratory abnormalities were reported, particularly no change in sodium and potassium blood 
levels, and no change in renal function were observed. Firibastat administration was well tolerated, 
with the exception of occurrence of 3 SAEs: 1 episode of macular rash and periorbital oedema 
each, which were considered to be probably related to firibastat and AEs of special interest 
(AESIs), and a case of vestibular disorder, considered to be possibly related to firibastat. The case 
of macular rash was the only TEAE that occurred during the treatment with firibastat that was 
considered to be probably related to the IP. Other than the case of vestibular disorder, TEAEs 
occurring during treatment with firibastat and considered possibly related to the IP were arthralgia 
(leading to study withdrawal), 
blood creatinine increased, chest pain, headache, and 
hypertriglyceridemia, reported only in 1 patient each. All these AEs were of mild intensity, except 
the arthralgia and vestibular disorder, which were of moderate intensity. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 30 of 96 
Study QGC001/2QG3 NEW-HOPE is “A Phase 2, Open-Label, Dose-Titrating Safety and 
Efficacy Study of QGC001 Administered Orally, Twice Daily, Over 8 Weeks in Hypertensive 
Overweight Subjects of Multiple Ethnic and Racial Groups in the United States”. The aim of the 
study was to assess the safety and efficacy of firibastat administered orally BID over 8 weeks in 
overweight patients with HTN of multiple ethnic groups. 256 patients were enrolled in this study. 
Results showed that 8 weeks of treatment with firibastat (250 mg twice-a-day orally for 2 weeks, 
then 500 mg twice-a-day if automatic office blood pressure [AOBP] was >140/90 mmHg; 
hydrochlorothiazide 25 mg once daily could be added after 1 month if systolic AOPB was 
≥160 mmHg and/or diastolic AOBP was ≥100 mmHg) led to a statistically significant decrease of 
9.7 mmHg in systolic AOBP from Baseline (P <0.0001), which was the primary endpoint of the 
trial. Overall, firibastat was well-tolerated. The most common side effects were skin reactions and 
headaches, with occurrence frequencies of 4% and 3%, respectively. No angioedema was reported. 
No changes in serum potassium or sodium levels were observed. Blood glucose levels and renal 
function remained stable. 
Study QGC001/QUID-HF is “A Phase II randomized, placebo controlled, double-blind, 
multi-centre study to assess safety and efficacy of incremental doses of QGC001 in patients with 
NYHA class II/III chronic heart failure with left ventricular systolic dysfunction”. Recruitment 
was completed, and 23 patients were enrolled in this study. No efficacy results were available at 
the time of protocol writing for this study, QGC001-2QG4, but no major safety concerns occurred 
during the study. 
5.2.5 
Rationale for Using Firibastat after Acute Myocardial Infarction and for the 
Conduct of the Study 
• 
The RAS is activated after acute MI and has deleterious effects on remodeling. Blockade 
of the RAS demonstrated efficacy (ACE-I, angiotensin receptor-neprilysin inhibitors). 
Firibastat is a RAS inhibitor at the brain level. 
• 
Animal data showed a rapid increase in brain APA activity after MI, and firibastat (as the 
first APA inhibitor) prevents this activation. 
• 
After MI in animal models (rats and mice), firibastat improves LVEF, as compared to 
sham, increases contractility and decreases filing pressures without any decrease in 
systemic blood pressure. 
• 
There is no evidence that a dual blockade of both cerebral and peripheral RAS is useful. 
Some data suggest that, since this is an adaptive mechanism, indeed a high blockade of the 
RAS may be deleterious. Some experimental data with combination of enalapril and 
firibastat may support this hypothesis. 
• 
It is currently unclear if a beneficial effect of ACE inhibitors after acute MI remains when 
an early revascularization is performed. 
5.3. Summary of Potential Risks and Benefits 
During the phase 1 clinical study (QGC001/1QG2) conducted in healthy normotensive adult male 
subjects, the administration of a multiple oral doses of QGC001 (500 mg BID, 750 mg BID, and 
1000 mg BID) for 7 consecutive days was safe and well-tolerated up to 750 mg BID. At the 
1000 mg BID dose, 4 subjects had liquid stools, and 4 cases of probable skin allergy were 
observed. All cases remained of mild intensity and regressed spontaneously. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 31 of 96 
Following this observation, the French competent authority, the Agence Nationale de Sécurité du 
Médicament et des Produits de Santé, requested that all allergic reactions should be collected and 
analyzed as AESIs by Quantum Genomics. This additional special safety-related reporting 
requirement was put in place in the frame of the Phase 2a clinical study in HTN (QGC001/2QG1). 
No other actions have been taken by Quantum Genomics and/or any regulatory authority during 
the reporting period up to 13-Nov-2016. 
Cumulatively, 12 SAEs, collected in 9 different SAE case reports, occurred during the clinical 
studies program: 
• 
Three SAEs were reported from study QGC001/2QG1, among which 2 SAEs were 
experienced by the same subject and during treatment with QGC001. There was 1 case of a 
vestibular disorder, considered possibly related to the IP, which led to treatment 
discontinuation and hospitalization; the patient recovered with 48 hours. The 2 other SAEs 
were experienced by the same subject and were a macular rash and periorbital oedema, 
thought to be a drug-induced toxidermia and probably related to the IP. The treatment was 
discontinued, and the subject was hospitalized and treated with an antihistamine. The 
subject recovered within 4 days. These 2 SAEs were classified as AESIs. Two other AESIs 
of pruritic rash occurred in another subject in Study 2QG1, but both events occurred whilst 
the subject was treated with placebo. 
• 
Three SAEs were experienced by the same subject from study QGC001/QUID-HF: 
ventricular tachycardia, cardiac failure, and pneumonia. These events were assessed as 
unrelated and were not unblinded. 
• 
Six SAEs occurred during the NEW-HOPE study (QGC001/2QG3) and were all 
experienced by different subjects. There were 4 cases assessed as unrelated, 1 case of 
squamous cell carcinoma, 1 case of umbilical hernia, 1 case of myocardial infarction, and 
1 case of lung nodule. Two cases of erythema multiforme occurred and were also reported 
as AESIs: the first was assessed as reasonable possibility to be related to the IP and the 
second as related to the IP. The subjects recovered. 
Cumulatively, 14 AESIs were collected from all studies during the clinical studies program: 
• 
Four AESIs were collected from study QGC001/2QG1, among which 2 nonserious AESIs 
of pruritic rash occurred during the placebo treatment phase, and 2 serious AESIs of rash 
macular and periorbital oedema occurred in the same subject during the IP treatment phase 
and were also considered as a suspected unexpected serious adverse reaction (SUSAR). 
• 
Ten AESIs were collected from study QGC001/2QG3, among which 2 reports of erythema 
multiforme were serious and considered as SUSARs. The 8 nonserious AESIs included 
3 AEs of rash, 2 AEs of eczema, and 3 AEs of drug hypersensitivity, all experienced by 
different subjects. 
Data obtained from a non-clinical 13-week toxicity study conducted in dogs suggest that high 
doses of QGC001 (100 mg/kg or more) could affect hematological parameters, such as the platelet 
count. However, available clinical safety data from clinical studies (phase 1 study QGC001/1QG2: 
exposure to QGC001 in humans dosed at 500 mg BID for 7 consecutive days; phase 2 study 
QGC001/2QG1: exposure to QGC001 in humans dosed at 250 mg BID for 1 week and then 
500 mg BID for 3 weeks) did not put in evidence any effect on hematological parameters in 
humans. Based on the PK analysis of the phase 1 clinical study QGC001/1QG2, QGC001 exposure 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 32 of 96 
in humans dosed for 7 consecutive days with QGC001 500 mg BID is below 200 ng h/mL, which 
is more than 100-times lower than the exposure found in the 13-week non-clinical study in dogs, 
which were dosed at 100 mg/kg. 
As mentioned above, the clinical development is currently limited to 2 phase 1 studies, conducted 
in 125 healthy male volunteers, a completed phase 2a study in 34 hypertensive patients, a 
completed phase 2b study in 256 hypertensive patients, and a completed phase 2 study in 
23 patients with HF. Currently, 438 patients and healthy volunteers have been enrolled into the 
QGC001 clinical development program; and 398 subjects have received QGC001. 
The data obtained so far imply a good safety profile of QGC001 for the treatment of HTN and HF. 
As mentioned earlier, allergic reactions have been identified as a potential risk for QGC001, 
although 4 allergic reactions that occurred in clinical studies were considered as serious. Due to 
the low number of subjects treated so far in the development program, no frequency calculation 
has been established for allergic reactions. The sponsor has put in place relevant measures to 
closely monitor, collect, and assess all allergic reactions occurring in the development program. 
Any allergic skin reaction must be reported as an AESI. 
The subjects participating in the clinical studies should be informed by the investigator at site that, 
as noted in the informed consent form (ICF), in case of occurrence of skin lesions, they must 
inform their site investigator as soon as possible. In cases where a skin reaction is concomitant to 
fever or blisters on the skin and/or the mucous membranes of the mouth, nose, eyes, and genitals, 
and peeling and shedding skin, which may suggest erythema multiforme or Stevens-Johnson 
syndrome, subjects must immediately stop their investigational treatment and inform their site 
investigator. In this case, the subject should be managed by an experienced team and receive the 
appropriate symptomatic treatment. All subjects with skin reactions must be referred to a 
dermatologist as soon as possible for precise diagnosis, to document the case, to take pictures, and 
to perform a skin biopsy (for central reading). Skin biopsy samples should be sent to the referent 
for central reading. In addition, all the cases will be reviewed by a referent dermatologist. 
Overall, although the efficacy data are currently limited, accumulating safety data from the 
completed clinical studies suggest that the overall risk-benefit balance for QGC001 remains 
favorable and supports the continued development of QGC001. 
A summary of the pharmaceutical properties and known potential risks of firibastat is provided in 
the current version of the IB.23 The investigator must become familiar with all sections of the IB 
and the prescribing information for ramipril before the start of the study. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 33 of 96 
6. OBJECTIVES 
6.1. Primary Objective 
The primary objective of this study is to compare the effects of BID oral administration of 2 doses 
of firibastat to those of BID oral administration of ramipril on the change from Baseline in left 
ventricular ejection fraction (LVEF) assessed by cardiac magnetic resonance imaging (CMRI) on 
Day 84. 
6.2. Secondary Objectives 
Secondary objectives include the following: 
• 
To compare the effects of BID administration of firibastat and ramipril on the change from 
Baseline to Day 84 in left-ventricular end-diastolic and end-systolic volumes assessed by 
CMRI 
• 
To compare the effects of BID administration of firibastat and ramipril on the change from 
Baseline to Day 84 in average peak of longitudinal and circumferential strain (assessed by 
CMRI) in the infarcted segments 
• 
To compare the effects of BID administration of firibastat and ramipril on infarct mass 
(assessed by CMRI) at Day 84 
• 
To compare the effects of BID administration of firibastat and ramipril on major cardiac 
event (MACE): combined clinical endpoint of cardiovascular death, new MIs, and cardiac 
hospitalization over 84 days 
• 
To compare the effects of BID administration of firibastat and ramipril on the change from 
Baseline to Day 84 in N-terminal pro b-type natriuretic peptide (NT-proBNP), procollagen 
type III aminoterminal peptide (PIIINP), and C-reactive protein (CRP) 
• 
To compare the effects of BID administration of firibastat and ramipril on the slope of 
decrease in copeptin blood level change between Baseline and Day 84 
• 
To compare the safety of firibastat and ramipril 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 34 of 96 
7. STUDY DESIGN 
7.1. Overall Study Design and Plan 
This phase 2, multicenter, randomized, double-blind, active-controlled, dose-titration clinical 
study is designed to compare the efficacy and safety of firibastat with ramipril in the prevention of 
LV dysfunction after acute anterior MI. A total of 294 male and female subjects will be randomized 
to obtain 264 evaluable subjects. Subjects must be at least 18 years of age and have a diagnosis of 
first acute anterior MI with primary PCI of the index-MI-related artery no earlier than 3 hours after 
acute MI and within 24 hours after the MI. The definition of MI is chest pain >30 minutes and 
ST elevation ≥0.2 mV in at least 2 consecutive ECG leads in the anterior area (DI, aVL, V1-V6). 
Subjects will not be eligible if they have a body mass index of >45 kg/m², are hemodynamically 
unstable or have cardiogenic shock, or have clinical signs of HF (Kilipp II and III). 
Subjects will be randomly assigned to 1 of the following 3 treatment groups in a 1:1:1 ratio: 
• 
Group 1: Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 
10 weeks 
• 
Group 2: Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 
10 weeks 
• 
Group 3: Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 
10 weeks 
Approximately 98 subjects will be randomized into each treatment group. The maximum treatment 
duration for each subject is 87 days. Women of childbearing potential will have an additional 
Follow-up Visit with a pregnancy test on Day 114 (±3 days). For all other subjects, the last study 
visit will be the EOT Visit (Visit 5) on Day 84 (±3 days). 
It should be noted that the subjects’ dosage will be up-titrated and/or down-titrated according a 
specific titration procedure. 
Baseline is defined as the day when the CMRI is performed and the first IP dose is taken. Day 84 
will be the day of treatment discontinuation (i.e. 84 days [±3 days] after the Inclusion Visit 
[Day 1]). A schematic representation of the timing of study procedures and assessments is 
provided in Figure 7-1. 
 


Quantum Genomics 
Confidential 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 35 of 96 
Figure 7-1: 
Timing of Study Procedures at Screening and Inclusion Visits 
Screening Visit (Visit 1; within 24 hours after acute MI [Day -2 -Day 1]): 
The Screening Visit will occur within 24 hours after index acute MI defined as the time of onset 
of symptoms and after primary PCI is performed (no earlier than 3 hours after acute MI and within 
24 hours after MI). Subjects will sign an informed consent form (ICF) prior to any study 
procedures being performed. Any standard-of-care procedures performed prior to ICF signature 
should not be repeated for the purpose of the study if already performed. Subjects may be screened 
even if excluding exclusion criterion 4 (SBP <100 mmHg) is not met at this time (see 
Section 8.2.2). 
Inclusion Visit (Visit 2, within 72 hours after acute MI [Day 1]): This visit can be done on the 
same day as the Screening Visit: 
Subjects who meet all of the inclusion criteria but none of the exclusion criteria (excluding 
exclusion criterion 4 [SBP <100 mmHg]) at the Screening Visit will undergo visit-specific 
procedures, and a baseline CMRI must be performed no later than 72 hours after the MI. 
As soon as possible after the CMRI is performed, the subject’s blood pressure will be measured. 
If SBP is ≥100 mmHg, the subject’s eligibility will be confirmed, and the site will connect on the 
treatment kits allocation web system available through the electronic data capture (EDC) system 
for randomization information. Subjects will be randomly assigned on Day 1 in a 1:1:1 ratio to 
receive either 50 mg firibastat BID (Group 1), 250 mg firibastat BID (Group 2), or 2.5 mg ramipril 
BID (Group 3). 
The first capsule of the IP will be administered on Day 1 as soon as possible after the CMRI, which 
will be performed no later than 72 hours after MI. Subjects will then take 1 capsule of the IP BID 
until the next visit. After the first administration occurring after the CMRI, the next intake must 
not occur within 6 hours, and if not possible, must be done on the next morning. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 36 of 96 
Safety Check (Day 3): 
A safety check should be performed 3 days after first administration of the IP to ensure the good 
tolerance of the treatment by the subjects. 
In most of the cases, the subjects will be still hospitalized at the site 3 days after first administration 
of the IP. The investigator will be able to continuously monitor the tolerance of the IP and 
immediately react if non-tolerance is suspected. As there is no possibility to decrease the dose of 
the IP at this stage, in case of non-tolerance of the IP, the subject will be withdrawn from the study. 
For subjects discharged early, i.e., before 3 days after the first IP administration, a telephone call 
to the subject should be performed. If the investigator judges that there is a risk of non-tolerance 
according to the subject’s answers e.g. any suspicion or symptoms related to hyper- or 
hypotension, the subject will be asked to come to the site for an unscheduled visit. The investigator 
will then decide whether the subject should be withdrawn from the study. 
In all cases, tolerability of the IP should be checked before subject discharge. 
Titration Visit (Visit 3 [Day 14 ±2 days]): 
Subjects will undergo visit-specific procedures. 
If SBP is ≥110 mmHg without any symptoms of hypotension and/or cardiogenic shock, the dose 
will be increased to 2 capsules of the IP BID. The BP will be calculated as the average of 
3 measurements (with intervals of 1 to 2 minutes), which will be performed after the subject has 
been sitting for 5 minutes at rest. 
If SBP is <110 mmHg, the subject will remain on the same dose (1 capsule BID). 
If symptomatic hypotension, symptomatic orthostatic hypotension, or cardiogenic shock occur, the 
treatment will be discontinued for the remainder of the study, and the event will be recorded as an 
AE leading to discontinuation. 
In case of any suspicion or symptoms related to hyper- or hypotension, the subjects should contact 
the site, attend an unscheduled visit, or visit their general practitioner or nearest cardiovascular 
unit, where a decision on any action with the IP can be made by the investigator or other physician 
seeing the subject. 
Note: the newly allocated dose will be administered as soon as possible after the visit is completed 
(i.e., on the evening of the day of the visit). 
Treatment Visit (Visit 4 [Day 42 ±2 days]): 
Subjects will undergo visit-specific procedures. 
If SBP is ≥110 mmHg without any symptoms of hypotension and/or cardiogenic shock, the dose 
will remain the same if the subject has already been treated with 2 capsules of the IP BID, or the 
dose will be increased to 2 capsules of the IP BID. 
If SBP is <110 mmHg and if the subject was being treated with 2 capsules of the IP BID, the dose 
will be decreased to 1 capsule of the IP BID. 
If SBP is <110 mmHg and if the subject was being treated with 1 capsule of the IP BID, the subject 
will remain on the same dose (1 capsule BID). 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 37 of 96 
If symptomatic hypotension, symptomatic orthostatic hypotension, or cardiogenic shock occur, the 
treatment will be discontinued for the remainder of the study, and the event will be recorded as an 
AE leading to discontinuation. 
In case of any suspicion or symptoms related to hyper- or hypotension, the subjects should contact 
the site, attend an unscheduled visit, or visit their general practitioner or nearest cardiovascular 
unit, where a decision on any action with the IP can be made by the investigator or other physician 
seeing the subject. 
Note: the newly allocated dose will be administered as soon as possible after the visit is completed 
(i.e., on the evening of the day of the visit). 
End-of-Treatment Visit (Visit 5 [Day 84 ± 3 days]): 
Subjects will undergo End-of-Treatment (EOT) Visit-specific procedures, and the IP will be 
discontinued. In case of premature discontinuation (except if consent is withdrawn), a CMRI and 
all Visit 5 procedures, if possible, will be performed as soon as possible and no later than 72 hours 
after treatment discontinuation. 
Follow-up Visit (Visit 6 [Day 114 (±3 days) or 30 days after IP discontinuation]): 
For females of childbearing potential only, a serum pregnancy test will be performed. 
A schematic presentation of the titration procedure for Groups 1, 2, and 3 is given in Figure 7-2. 
 
Figure 7-2: 
Study Titration Scheme 
 
 
Efficacy will be assessed by measurement of LVEF, left-ventricular end-diastolic and end-systolic 
volumes, average peak of longitudinal and circumferential strain in the infarcted segments, and 
infarct mass by respectively cine and late gadolinium enhancement CMRI all measured with 
centralized core laboratory reading. In addition, blood levels of biomarkers (NT-proBNP, PIIINP, 
and CRP) and the slope of decrease in copeptin will be measured, and any MACE (cardiovascular 
death, new MIs, and cardiac hospitalization) will be documented. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 38 of 96 
Safety will be assessed by evaluating TEAEs and AESIs (allergic reactions and diabetes insipidus 
[DI]), clinical laboratory test results (including sodium and potassium blood levels and estimated 
glomerular filtration rate [eGFR]), vital sign measurements (SBP, diastolic blood pressure [DBP], 
and HR), 12-lead ECGs, and clinical examination findings. 
All AEs observed by the study personnel or reported by the subject during the study (from the time 
of the signing of the informed consent through Visit 5) will be documented. 
A single futility IA is planned for the primary efficacy endpoint for the comparison of firibastat 
50 mg against ramipril when approximately 50% of the maximum number of subjects have 
completed the Day 84 primary endpoint assessment. 
7.2. Rationale and Discussion of Study Design 
This is a randomized, double-blind, active-controlled, dose-titrating study to compare the efficacy 
and safety of 2 doses of the test product firibastat against that of the approved ACE inhibitor 
ramipril. 
The study population will consist of subjects following first acute anterior MI. It is planned that 
294 subjects within 24 hours after acute MI will be randomized at about 38 sites in Europe and in 
the US. 
The primary endpoint of the study will be the change from Baseline in LVEF assessed by CMRI; 
secondary endpoints will include CMRI regional strain in the infarcted segments and infarct mass, 
cardiac events, functional status, and change in HF biomarkers. The efficacy and safety 
assessments in this study are considered as standard in this subject population. 
The study is designed to show superiority of the test treatment to the active control. A hierarchical 
testing procedure will be applied to control the type I error rate since failure to appropriately 
control the type I error rate can lead to false-positive conclusions.24 
7.3. Selection of Doses in the Study 
According to the clinical studies conducted in healthy subjects, PK results demonstrated good dose 
proportional exposure to firibastat after repeated oral administration. 
The maximal dose of 500 mg BID is expected to be safe since no SAE, no TEAEs, and no 
important medical event were recorded after repeated oral administrations up to 500 mg BID for 
7 consecutive days in healthy male subjects. Firibastat was safe and well-tolerated following oral 
administration of multiple doses up to 750 mg BID to healthy subjects for 7 consecutive days. 
Furthermore, in post-MI animal models, after coronary artery ligation, rats were treated daily for 
4 weeks with vehicle (peanut butter 5 to 6 g) or QGC001 (150 mg/kg/day) on peanut butter. At 
4 weeks post-MI, the left ventricular end diastolic pressure was increased and EF, and the 
maximum rate of pressure change in the left ventricle (dP/dtmax) and left ventricular pulse systolic 
pressure were decreased as compared to sham-operated rats. The dose of 150 mg/kg of firibastat, 
which was pharmacologically active in this model, corresponds to a human-equivalent dose of 
1440 mg daily normalized to the body surface area and using a conversion factor of 0.16 and a 
mean body weight in humans of 60 kg. The sponsor, therefore, proposes a maximal dose of 500 mg 
BID (1000 mg daily), which was a safe diose in healthy volunteers and which was the dose used 
in phase 2 clinical studies in hypertensive patients.23 


Quantum Genomics 
Confidential 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 39 of 96 
Ramipril dosing will be done according to the approved summary of product characteristics. The 
drug is considered to have a favorable cost profile compared to other ACE inhibitors and belongs 
the preferred ACE inhibitors recommended for the treatment of HF by the European Society of 
Cardiology25,26 
and the American College 
of Cardiology 
Foundation/American 
Heart 
Association.27 
7.4. Study Sites 
The study will take place at approximately 38 sites in Europe and in the US. Each site is anticipated 
to screen a sufficient number of subjects to randomize a total of 294 subjects. A study site with a 
high recruitment rate may be allowed to recruit more subjects if other sites have slow enrollment. 
7.5. Point of Contact 
A point of contact will be identified to provide guidance to subjects about where to obtain 
information on the study, the rights of subjects, and whom to contact in case of a study-related 
injury. This information will be provided in the ICF. 
7.6. End of Study Definition 
This clinical study is considered completed when the last subject’s last study visit has occurred. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 40 of 96 
8. SUBJECT POPULATION 
8.1. Selection of Study Population and Diagnosis 
As specified in Section 13.2, 294 total subjects (98 subjects per treatment group) with a first acute 
anterior MI will be randomized to achieve a total of 264 evaluable subjects (88 subjects per 
treatment group). 
Subjects who do not meet all of the eligibility criteria will not be enrolled. 
A screening log of potential study candidates and an enrollment log must be maintained at each 
study site. 
8.2. Study Entry Criteria 
8.2.1 
Inclusion Criteria 
A subject will be eligible for study participation if he or she meets all of the following criteria: 
1. 
Subject must provide signed written informed consent. Important Note: Subject must be 
willing and able to give informed consent for participation in the study. 
2. 
Men and women ≥18 years of age at Screening. 
3. 
Diagnosis of first acute anterior MI (STEMI) defined as chest pain >30 minutes and 
ST elevation ≥0.2 mV in at least 2 consecutive ECG leads in the anterior area (DI, aVL, 
V1-V6). 
4. 
Primary PCI of the index-MI-related artery within 24 hours after the MI. 
5. 
Women of childbearing potential and non-surgically sterile male subjects who are sexually 
active must agree to use an approved highly effective form of contraception from the time 
of informed consent until 30 days postdose. Approved forms of contraception include 
hormonal intrauterine devices, hormonal contraceptives (oral birth control pills, depot, 
patch, or injectable), together with supplementary double-barrier methods such as condoms 
or diaphragms with spermicidal gel or foam. 
Note: The following categories define women who are NOT considered to be of childbearing 
potential: 
o 
 
Premenopausal women with 1 of the following: 
• 
 
Documented hysterectomy 
• 
 
Documented bilateral salpingectomy 
• 
 
Documented bilateral oophorectomy 
OR 
o 
 
Postmenopausal women, defined as having amenorrhea for at least 12 months 
without an alternative medical cause. 
6. 
Women of childbearing potential must have a negative serum pregnancy test result at the 
Screening Visit. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 41 of 96 
8.2.2 
Exclusion Criteria 
A subject will be excluded from the study if he or she meets any of the following criteria: 
1. 
Body mass index >45 kg/m². 
2. 
Subject is hemodynamically unstable or has cardiogenic shock. 
3. 
Subjects with clinical signs of HF (Kilipp III and IV corresponding to severe HF). 
4. 
Systolic blood pressure <100 mmHg at Inclusion Visit. 
5. 
Early primary PCI of the index-MI-related artery performed within 3 hours after MI. 
Important Note: the time of the PCI MUST NOT be delayed because of the protocol; if PCI 
is performed within 3 hours after MI, the subject is not eligible. 
6. 
Subjects who require treatment with angiotensin-converting-enzyme inhibitor (ACE-I), 
ARB, or sacubitril/valsartan after the index magnetic resonance imaging. Note: if treatment 
was for HTN, ACE-I/ARB should be stopped right before index magnetic resonance 
imaging, and, if necessary, another therapeutic class can be prescribed for HTN. If the 
ACE-I/ARB was prescribed for congestive HF, the subject is not considered eligible; if the 
ACE-I/ARB prescribed for another reason cannot be stopped, the subject is not eligible for 
study inclusion. 
7. 
Subjects scheduled for implantable cardioverter defibrillator (ICD), cardiac 
resynchronization therapy, or pacemaker within the next 3 months. If an ICD is indicated 
for ventricular arrhythmia during the course of the study, a life vest, when possible, should 
be prescribed and the ICD scheduled after study completion. 
8. 
Subjects with any contraindication related to the CMRI procedure (devices or metal foreign 
bodies, including pacemaker, defibrillator) including severe claustrophobia according to the 
lists/safety rules of the local MRI departments. 
9. 
Female who is breast-feeding, pregnant, or planning to become pregnant during the study. 
10. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer 
within the last 5 years. 
11. Alkaline phosphatase >3 × upper limit of normal (ULN), total bilirubin ≥1.5 × ULN, or 
direct bilirubin >ULN in subjects with Gilbert’s syndrome at the Screening Visit. 
12. Estimated glomerular filtration rate <30 mL/min/1.73 m2, as calculated using the Chronic 
Kidney Disease Epidemiology Collaboration formula at the Screening Visit. 
13. History of any blood disorder, other than sickle cell trait, causing hemolysis or unstable red 
blood cells (e.g., malaria, babesiosis, hemolytic anemia, thalassemia, or sickle cell anemia). 
14. Clinical evidence of thyroid disease, thyroid hormone therapy that is not stable ≥4 weeks 
prior to Screening, or a thyroid-stimulating hormone (TSH) level <0.75 × lower limit of 
normal or >1.5 × ULN. 
15. History of alcohol or drug abuse within the 3 months prior to the Screening Visit that 
would interfere with study participation or lead to decreased compliance with study 
procedures or IP intake in the investigator’s opinion. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 42 of 96 
16. Participation in another clinical study involving an investigational drug within 30 days 
prior to Screening or if a subject plans to participate in another clinical study within 
30 days of discontinuation of the IP. 
17. Any condition that in the opinion of the investigator would interfere with study 
participation, may pose a risk to the subject, or would make study participation not in the 
best interest of the subject. 
18. Subjects with a life expectancy of less than 1 year per investigator’s discretion. 
19. Any subject who, in the opinion of the investigator, will not be able to follow the protocol. 
Section 9.7.3 provides a listing of the contraindications of Ramipril as given in the summary of 
product characteristics. These restrictions must be checked before any inclusion to ensure that the 
subject has no contraindication to the administration of Ramipril; otherwise, the subject should be 
excluded from the study. 
8.3. Premature Subject Withdrawal 
All subjects will be informed that they are free to withdraw from participation in this study at any 
time, for any reason, and without prejudice. The investigator should make every reasonable 
attempt to keep subjects in the study; however, subjects must be withdrawn from the study if they 
withdraw their consent to participate. Investigators must attempt to contact subjects who fail to 
attend scheduled visits by telephone or other means to exclude the possibility of an AE being the 
cause of withdrawal. Should this be the cause, the AE must be documented, reported, and followed 
as described in Section 11.2. 
The sponsor reserves the right to request the withdrawal of a subject due to protocol deviations or 
other reasons. 
The investigator also has the right to withdraw subjects from the study at any time for lack of 
therapeutic effect that is intolerable or otherwise unacceptable to the subject, for intolerable or 
unacceptable AEs, intercurrent illness, non-compliance with study procedures, administrative 
reasons, or in the investigator’s opinion, to protect the subject’s best interest. 
If a subject is withdrawn before completing the study, the reason for withdrawal and the date of 
discontinuation will be recorded on the appropriate page of the electronic case report form (eCRF). 
Whenever possible and reasonable, the evaluations that were to be conducted at the completion of 
the study should be performed at the time of premature discontinuation. 
8.4. Discontinuation of Study Intervention 
If symptomatic hypotension, symptomatic orthostatic hypotension, or cardiogenic shock occur, the 
treatment will be discontinued for the remainder of the study, and the event will be recorded as an 
AE leading to discontinuation. 
In case a skin reaction is concomitant to fever, blisters on the skin, and/or the mucous membranes 
of the mouth, nose, eyes and genitals, peeling and shedding skin, which may suggest erythema 
multiforme or Stevens-Johnson syndrome, the treatment must be immediately discontinued. In this 
case, the subject should be managed by an experienced team and receive the appropriate 
symptomatic treatment. All subjects with a skin reaction must be referred to a dermatologist as 
soon as possible for precise diagnosis, to document the case, to take pictures, and to perform a skin 
biopsy (for central reading). Skin biopsy samples should be sent to the referent for central reading. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 43 of 96 
In addition, all the cases will be reviewed by a referent dermatologist. Any allergic skin reaction 
must be reported as an AESI. 
Discontinuation from treatment with firibastat or ramipril does not necessitate discontinuation 
from the study, and remaining study procedures and all future visits should be completed as 
indicated in the schedule of events in Section 2.2. If a clinically significant finding is identified 
(including, but not limited to changes in the subject’s health status from Day 1 after enrollment), 
the investigator or qualified designee will determine whether any change in subject management 
is needed. Any new clinically relevant finding will be reported as an AE. 
The data to be collected at the time of study intervention discontinuation are detailed in the 
schedule of events in Section 2.2. 
8.5. Subject Discontinuation/Withdrawal from the Study 
Subjects are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a subject from the study for the following reasons: 
• 
Pregnancy 
• 
Significant study intervention non-compliance 
• 
If any clinical AE, laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interest of the 
subject 
• 
Disease progression that requires discontinuation of the study intervention 
• 
If the subject meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Subject is unable to receive firibastat/ramipril for a total of 14 consecutive or 
non-consecutive days during the study 
If an allergic reaction, symptomatic hypotension, symptomatic orthostatic hypotension, or 
cardiogenic shock occur, the treatment with firibastat or ramipril will be immediately discontinued 
for the remainder of the study. 
A safety check should be performed 3 days after first administration of the IP to ensure the good 
tolerance of the treatment by the subjects. 
In most of the cases, the subjects will be still hospitalized at the site 3 days after first administration 
of the IP. The investigator will be able to continuously monitor the tolerance of the treatment and 
immediately react if non-tolerance is suspected. As there is no possibility to decrease the dose of 
the IP at this stage, in case of non-tolerance of the IP, the subject will be withdrawn from the study. 
For subjects discharged early, i.e., before 3 days after the first IP administration, a telephone call 
to the subject should be performed. If the investigator judges that there is a risk of non-tolerance 
according to the subject’s answers e.g. any suspicion or symptoms related to hyper- or 
hypotension, the subject will be asked to come to the site for an unscheduled visit. The investigator 
will then decide whether the subject should be withdrawn from the study. 
In all cases, tolerability of the IP should be checked before subject discharge. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 44 of 96 
The reason for subject discontinuation or withdrawal from the study will be recorded on the eCRF. 
Subjects who sign the ICF and are randomized but do not receive the IP may be replaced. Subjects 
who sign the ICF, are randomized, and receive the IP, and subsequently withdraw or are withdrawn 
or discontinued from the study, will not be replaced. 
Whenever possible and reasonable, the evaluations that were to be conducted at the completion of 
the study should be performed at the time of premature discontinuation. Details on subject 
replacement criteria are provided in Section 8.6. 
A subject will be considered lost to follow-up if he or she fails to return for 2 consecutive scheduled 
visits and is unable to be contacted by the study site staff. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• 
The site will attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain if the subject wishes to and/or should continue in the study 
• 
Before a subject is deemed lost to follow up, the investigator or designee will make every 
effort to regain contact with the subject (where possible, 3 telephone calls and, if 
necessary, a certified letter to the subject’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the subject’s medical record or 
study file 
• 
Should the subject continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up 
8.6. Subject Replacement Criteria 
Withdrawn subjects will not be replaced. If a substantial number of subjects are withdrawn from 
the study, the sponsor will evaluate the need for developing replacement criteria. 
Randomized subjects withdrawn from the study must not reenter. The subject number for a 
withdrawn subject will not be reassigned to another subject. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 45 of 96 
9. TREATMENTS 
9.1. Identification of Investigational Products 
9.1.1 
Test Product 
Firibastat (QGC001), is a prodrug, a dimer of EC33 ([3S]-3-amino-4-sulfanylbutane-1-sulfonic 
acid), a selective inhibitor of APA. Firibastat (50 mg or 250 mg) will be provided in opaque white 
hard hydroxypropyl methylcellulose size-1 capsules. It has been mixed with the following 
well-known excipients that are all described in the current edition of the European Pharmacopoeia 
and the US Pharmacopoeia: 
• 
Lactose anhydrous (specific grade “direct tableting high velocity”) as diluent 
• 
Povidone 90 (Kollidon 90) as a binder in wet granulation 
• 
Magnesium stearate as lubricant 
• 
Silica, dental type (specific grade RxCIPIENTS GL100, precipitated) as glidant 
9.1.2 
Reference Product 
The active comparator ramipril (Triatec, manufacturer: Sanofi S.p.A., Scoppito [AQ], Italy) will 
be provided in the form of opaque white hard hydroxypropyl methylcellulose size-1 capsules 
capsules (2.5 mg each) by the sponsor. The active substance is ramipril; the other ingredients are: 
• 
Hypromellose 
• 
Pregelatinised maize starch 
• 
Microcrystalline cellulose 
• 
Sodium stearyl fumarate 
• 
Yellow ferric oxide (E172) 
9.2. Selection of Timing of Dose for Each Subject 
Firibastat and ramipril should be taken twice daily, i.e., in the morning and in the evening around 
the same time each day, with or without food. Details on the IP dosing are provided in Sections 7.1 
and 7.3. 
9.3. Dose Adjustment Criteria 
The IP dose will be increased to 200 mg firibastat daily (Group 1), 1000 mg firibastat daily 
(Group 2), and 10 mg ramipril daily (Group 3), respectively, if the subject is tolerating the IP and 
the following criteria are met: 
• 
At Visit 3, if SBP is ≥110 mmHg without any symptoms of hypotension and/or cardiogenic 
shock 
• 
At Visit 4, if SBP is ≥110 mmHg without any symptoms of hypotension and/or cardiogenic 
shock (if the subject is already treated with 2 capsules of the IP BID, the dose will remain 
the same) 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 46 of 96 
If symptomatic hypotension, symptomatic orthostatic hypotension, or cardiogenic shock occur, the 
treatment with firibastat or ramipril will be discontinued for the remainder of the study. 
Note: the newly allocated dose will be administered as soon as possible after the visit is completed 
(i.e., on the evening of the day of the visit). 
9.4. Treatment Compliance 
Study personnel will assess treatment compliance with IP regimens via capsule counts of returned 
IP and by questioning the subject, if necessary, at every post-randomization visit. A subject who 
is not compliant (taken <80% or >120% of IP) will be counseled at each visit on the importance 
of taking the IP as instructed. 
9.5. Method of Assigning Subjects to Treatment Groups 
In this parallel-group randomized study, subjects who meet study entry criteria will be randomly 
assigned in a 1:1:1 ratio to initially receive either 100 mg firibastat daily (Group 1), 500 mg 
firibastat daily (Group 2), or 5 mg ramipril daily (Group 3), respectively. The randomization 
schedule will be computer-generated using a permuted block algorithm and will randomly allocate 
IP to randomization numbers. The randomization numbers will be assigned sequentially through a 
web-allocation system as subjects are entered into the study. 
The randomization schedule will be prepared by a subcontracted company before the start of the 
study. No one involved in the study performance will have access to the randomization schedule 
before official unblinding of treatment assignment. No subject will be randomized into this study 
more than once. 
9.6. Blinding and Unblinding Treatment Assignment 
All subjects, investigators, and study personnel involved in the conduct of the study, including 
data management, will be blinded to treatment assignment with the exception of a specified 
independent, unblinded statistician and programmer, who will have access to the randomization 
code for interim analysis needs. The unblinded study personnel will not participate in study 
procedures or data analysis prior to unblinding of the study data to all study-related personnel with 
exception of the independent statistician. A single futility interim analysis is planned for the 
primary efficacy endpoint for the comparison of firibastat 50 mg against ramipril when 
approximately 50% of the maximum number of subjects have completed the Day 84 primary 
endpoint assessment. Unblinded personnel who are not otherwise involved in the study will 
prepare the data for review. 
Study personnel will make every effort to safeguard the integrity of the study blind to minimize 
bias in the conduct of the study. Treatment unblinding is discouraged if knowledge of the treatment 
assignment will not materially change the planned management of a medical emergency. 
Unblinding will be permitted in a medical emergency that requires immediate knowledge of the 
subject’s treatment assignment. 
Unblinding should be discussed in advance with the medical monitor, if possible. For emergency 
unblinding, the study personnel will use the treatment kits allocation web-system available through 
the EDC system. If the investigator is not able to discuss treatment unblinding in advance with the 
medical monitor, then he/she must notify the medical monitor as soon as possible about the 
unblinding incident without revealing the subject’s treatment assignment. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 47 of 96 
The investigator or designee must record the date and reason for treatment unblinding on the 
appropriate CRF for that subject. In all cases that are not emergencies, the investigator must discuss 
the event with the medical monitor prior to unblinding the subject’s treatment assignment. 
If treatment assignment is unblinded for an individual subject, study personnel will be notified of 
that subject’s treatment assignment without unblinding the treatment assignments for the 
remaining subjects in the study. Thus, the overall study blind will not be compromised. If a 
subject’s treatment assignment is unblinded, he/she may or may not be asked to withdraw from 
the study. The investigator will make this decision after consultation with the medical monitor. 
Overall unblinding will take place at the end of the study only after database lock has been 
achieved. 
9.7. Permitted and Prohibited Therapies 
All concomitant 
medications 
used (including 
over-the-counter medications 
and herbal 
supplements) will be recorded in the source document and on the appropriate eCRF. 
9.7.1 
Permitted Therapies 
Subjects can continue to receive treatment and management for their condition(s) unless the drug 
and procedure is prohibited by the protocol. Concomitant medications should be limited to those 
medications considered necessary. Gadolinium 
chelates will be administered during the 
CMRI examination for infarct imaging and mass quantification at doses and protocols 
recommended in standard-of-care CMRI procedures. 
9.7.2 
Prohibited Therapies 
The following therapies are prohibited during the study: 
• 
Subjects who have had treatment with ACE-Is, ARBs, or sacubitril/valsartan prior to index 
MRI are not allowed to participate in the study. If the treatment was for HTN, ACE-I/ARB 
should be stopped, and, if necessary, another therapeutic class can be prescribed for HTN. 
If the ACE-I/ARB or sacubitril/valsartan was prescribed for congestive HF, the subject is 
not considered eligible; if the ACE-I/ARB prescribed for another reason cannot be stopped, 
the subject is not eligible for study inclusion. There are no other prohibited concomitant 
medications to treat HTN other than ACE-I/ARB. 
• 
Subjects who are scheduled for an ICD, cardiac resynchronization therapy, or pacemaker 
within the next 3 months are not allowed to participate in the study. If an ICD is indicated 
for ventricular arrhythmia during the course of the study, a life vest, when possible, should 
be prescribed and the ICD scheduled after study completion. 
Subjects receiving excluded therapies will be ineligible for study enrollment or for continuation in 
the study, at the discretion of Quantum Genomics, the investigator, and the medical monitor. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 48 of 96 
9.7.3 
Restrictions 
The following contraindications as given in the ramipril summary of product characteristics should 
be taken into account: 
• 
Hypersensitivity to the active substance, to any of the excipients, or any other ACE inhibitors 
• 
History of angioedema (hereditary, idiopathic, or due to previous angioedema with 
ACE inhibitors or angiotensin II receptor antagonists) 
• 
Concomitant use of sacubitril/valsartan therapy 
• 
Extracorporeal treatments leading to contact of blood with negatively charged surfaces 
• 
Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning 
kidney 
• 
Second and third trimesters of pregnancy 
• 
Ramipril must not be used in patients with hypotensive or hemodynamically unstable states 
• 
The concomitant use of ramipril with aliskiren-containing products is contraindicated in 
patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m2) 
Investigators and study teams should refer to the section “Contraindications” and “Special 
warnings and precautions for use” of the current Summary of Product Characteristics. 
9.8. Treatment after End of Study 
After the end of the study, each subject will be treated according to standard clinical practice. 
9.9. Dispensing and Storage 
The IP is to be used exclusively in the clinical study according to the instructions of this protocol. 
The investigator or designee (e.g., site pharmacist) is responsible for dispensing the IP according 
to the dosage scheme described in this protocol and for ensuring proper storage of the IP. The 
acknowledgement of receipt of the IP will be managed via the IP-allocation system. 
Until the IP is dispensed to the subjects, it must be stored in a securely locked area, only accessible 
to authorized personnel, at room temperature (15 to 25°C/59 to 77°F). 
9.10. Drug Accountability 
The investigator or designee must maintain adequate records showing the receipt, dispensing, 
return, or other disposition of the IP, including the date, quantity, batch or code number, and 
identification of subjects (subject number and initials) who received the IP. The investigator or 
designee will not supply the IP to any person except those named as sub-investigators, designated 
study personnel, and subjects in this study. The investigator will not dispense the IP from any study 
sites other than those listed. The IP may not be relabeled or reassigned for use by other subjects. 
If any of the not dispensed IPs, are lost, stolen, unusable, or are received in a damaged condition, 
this information must be documented and reported to the sponsor and appropriate regulatory 
agencies, as required. 
Upon completion of the study, the IP (partly used, unused, and empty packaging, e.g., empty 
bottles) must be left in the original packaging and returned to the sponsor or designee for 
destruction. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 49 of 96 
9.11. Labeling and Packaging 
Labeling and packaging of the IPs will be performed by Amatsigroup SAS (Saint-Gély-du-Fesc, 
France). 
9.11.1 Labeling 
The following information will be included on the label; other information may be included as 
needed. 
• 
Protocol number 
• 
Unique bottle identifier 
• 
Subject number (record at the time of dispensing) 
• 
Expiry date 
• 
Directions for use 
• 
Package contents (quantity) 
• 
Storage instructions 
• 
Caution: “For clinical trial use only”, “Keep out of reach of children” and “New Drug – 
Limited by United States Law to Investigational Use” (US-specific information). 
• 
Sponsor name and address 
Sites should keep all empty packaging and unused IP for accountability and final disposition by 
the sponsor or site pharmacy. 
9.11.2 Packaging 
Investigational products will be packaged in white high-density polyethylene child-resistant 
closure 50 mL bottles of 35 capsules each. In this double-blind study, firibastat and ramipril will 
be packaged so as to be blinded to the investigator, the study clinic personnel, and subjects. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 50 of 96 
10. STUDY PROCEDURES 
Subjects must provide written informed consent before any study-related procedures are initiated, 
including the cessation of prohibited concomitant therapy. 
For the timing of assessments and procedures throughout the study, refer to the schedule of events 
(Section 2.2). Throughout the study, every reasonable effort should be made by study personnel to 
follow the timing of assessments and procedures in the schedule of events for each subject. If a 
subject misses a study visit for any reason, the visit should be rescheduled as soon as possible. 
10.1. Study Duration 
The overall study duration is expected to be 19 months (16 months of active enrollment and 
3 months of treatment for the last subject included). 
The planned sequence and maximum duration of the study periods will be as follows: 
1. Screening: 1 day (+1 day) 
2. Inclusion: 1 day 
3. Titration Period: 42 days (±2 days) 
4. Treatment Period: 42 days (±3 days) 
5. Follow-up Visit for women of childbearing potential only: 1 day 
The maximum study duration for each subject is 119 days for women of childbearing potential and 
89 days for all other subjects. 
The maximum treatment duration for each subject is 87 days. 
10.2. Study Visits 
Procedures and assessments will be performed at each visit as given in the schedule of assessments 
in Section 2.2. 


Quantum Genomics 
Confidential 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 51 of 96 
Figure 10-1: Timing of Study Procedures at Screening and Inclusion Visits 
10.2.1 Screening Visit (Visit 1; within 24 Hours after Acute Myocardial Infarction 
[Day -2 - Day 1]) 
The Screening Visit will occur within 24 hours after index acute MI, defined as the time of onset 
of symptoms and after primary PCI is performed (no earlier than 3 hours after acute MI and within 
24 hours after MI). The subject will sign an ICF before any study-specific procedures are 
performed. Any standard-of-care procedures performed prior to ICF signature should not be 
repeated for the purpose of the study if already performed. Subject may be screened even if 
exclusion criterion 4 (SBP <100 mmHg) is not met at this time (see Section 8.2.2). The following 
procedures will be performed: 
1.
Obtain written informed consent and record concomitant medications
2.
Assess inclusion/exclusion criteria
3.
Collect demographic information
4.
Record medical history, including current therapies (e.g., prescription and non-prescription
medications)
5.
If the subject provided consent for this, capture the subject’s coronary angiography
performed after MI using the CMRI electronic repository as part of the subject’s study
documentation
6.
Perform a clinical examination, including measurement of height and weight
7.
Perform a 12-lead ECG


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 52 of 96 
8. 
Measure vital signs (SBP, DBP, and HR); the blood pressure will be calculated as the 
average of 3 measurements (with intervals of 1 to 2 minutes), which will be performed 
after the subject has been sitting for 5 minutes at rest 
9. 
Blood samples for local laboratory assessments (hematology and clinical chemistry, 
including capture of troponin peak) 
10. Conduct a serum pregnancy test for females of childbearing potential 
10.2.2 Inclusion Visit (Visit 2; within 72 Hours after Acute Myocardial Infarction [Day 1]) 
This visit can be done on the same day as the Screening Visit. If the Screening (Visit 1) and the 
Inclusion (Visit 2) are performed on the same day, procedures applicable for both visits should not 
be duplicated. 
Subjects who meet all the inclusion criteria but none of the exclusion criteria (excluding exclusion 
criterion 4 [SBP <100 mmHg]) (see Section 8.2.2) will undergo visit-specific procedures, and a 
baseline CMRI must be performed no later than 72 hours after the MI. 
As soon as possible after the CMRI is performed, the subject’s blood pressure will be measured, 
and after confirmation that the subject is eligible (SBP ≥100 mmHg), the site will connect on the 
treatment kits allocation web system available through the EDC system for randomization 
information. Subjects will be randomly assigned (Day 1) in a 1:1:1 ratio to receive either 50 mg 
firibastat BID (Group 1), 250 mg firibastat BID (Group 2), or 2.5 mg ramipril BID (Group 3). 
The first capsule of the IP will be administered on Day 1 as soon as possible after CMRI, which 
will be performed no later than 72 hours after MI. Subjects will then take 1 capsule of the IP BID 
until the next visit. The following procedures will be performed: 
1. 
Re-assess inclusion/exclusion criteria 
2. 
Measure vital signs (SBP, DBP, and HR); the blood pressure will be calculated as the 
average of 3 measurements (with intervals of 1 to 2 minutes), which will be performed 
after the subject has been sitting for 5 minutes at rest 
3. 
Conduct CMRI for LVEF, left-ventricular end-diastolic and end-systolic volumes 
longitudinal and circumferential strain, and infarct mass assessment no later than 72 hours 
after primary MI 
4. 
Blood samples for central laboratory assessments (biomarkers NT-proBNP, copeptin, 
PIIINP, and CRP) 
5. 
Connect on the treatment kits allocation web system available through the EDC system for 
randomization information and treatment kit allocation after CMRI is performed 
6. 
Dispense IP 
7. 
Assess and record AEs and concomitant medications 
10.2.3 Safety Check (Day 3) 
A safety check should be performed 3 days after first administration of the IP to ensure the good 
tolerance of the treatment by the subjects. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 53 of 96 
In most of the cases, subjects will be still hospitalized at the site 3 days after first administration 
of the IP, and the investigator will be able to continuously monitor the tolerance of the treatment 
and immediately react if non-tolerance is suspected. As there is no possibility to decrease the dose 
of the IP at this stage, in case of non-tolerance of the IP the subject will be withdrawn from the 
study. 
For subjects discharged early, i.e., before 3 days after the first IP administration, a phone call to 
the subject should be performed. If the investigator judges that there is a risk of non-tolerance 
according to the subject answers to his/her investigation such as any suspicion or symptoms related 
to hyper- or hypotension, the subject will be asked to come to the site for an unscheduled visit. 
The investigator will then decide whether the subject should be withdrawn from the study. 
In all cases, tolerability of the IP should be checked before subject discharge. 
10.2.4 Titration Visit (Visit 3 [Day 14 ± 2 days]) 
Titration of the IP dose will be done as described in Section 7.1. In addition, the following 
procedures will be performed: 
1. 
Perform a clinical examination, including measurement of weight 
2. 
Perform a 12-lead ECG 
3. 
Measure vital signs (SBP, DBP, and HR) 
4. 
Blood samples for central laboratory assessments (biomarker copeptin only) 
5. 
Connect on the treatment kits allocation web system available through the EDC system for 
treatment kits allocation 
6. 
Dispense IP 
7. 
Perform IP compliance check 
8. 
Assess and record AEs and concomitant medications 
10.2.5 Treatment Visit (Visit 4 [Day 42 ± 2 days]) 
Titration of the IP dose will be done as described in Section 7.1. In addition, the following 
procedures will be performed: 
1. 
Perform a clinical examination, including measurement of weight 
2. 
Perform a 12-lead ECG 
3. 
Measure vital signs (SBP, DBP, and HR) 
4. 
Blood samples for local laboratory assessments (hematology and clinical chemistry) 
5. 
Blood samples for central laboratory assessments (biomarker copeptin only) 
6. 
Connect on the treatment kits allocation web system available through the EDC system for 
treatment kits allocation 
7. 
Dispense IP 
8. 
Perform IP compliance check 
9. 
Assess and record AEs and concomitant medications 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 54 of 96 
10. Conduct a serum pregnancy test for females of childbearing potential only 
10.2.6 End-of-Treatment Visit (Visit 5 [Day 84 ± 2 days]) 
The following procedures will be performed: 
1. 
Perform a clinical examination, including measurement of weight 
2. 
Perform a 12-lead ECG 
3. 
Measure vital signs (SBP, DBP, and HR) 
4. 
Conduct CMRI for LVEF, left-ventricular end-diastolic and end-systolic volumes, 
longitudinal and circumferential strain, and infarct mass assessment as soon as possible and 
no later than 72 hours after treatment discontinuation 
5. 
Blood samples for local laboratory assessments (hematology and clinical chemistry) 
6. 
Blood samples for central laboratory assessments (biomarkers NT-proBNP, copeptin, 
PIIINP, and CRP) 
7. 
Conduct a serum pregnancy test for females of childbearing potential 
8. 
Discontinuation of IP 
9. 
Perform IP compliance check 
10. Assess and record AEs and concomitant medications 
10.2.7 Follow-up Visit (Visit 6 [Day 114 ± 3 days] or 30 days after Treatment 
Discontinuation) 
The visit will be performed for females of childbearing potential only. The following procedures 
will be performed: 
1. 
Conduct a serum pregnancy test for females of childbearing potential 
10.3. Assessments 
The efficacy variables selected are standard for this indication/subject population. 
10.3.1 Efficacy Variables 
10.3.1.1 Cardiac Magnetic Resonance Imaging 
Cardiac magnetic resonance imaging is a non-invasive imaging technique in cardiovascular 
disease that allows a clear delineation of the cardiac anatomy, detailed tissue characterization, and 
a comprehensive evaluation of global and regional cardiac function. It is considered as the gold 
standard for evaluating cardiac structure and function along with non-invasive 
tissue 
characterization. More specifically, it is widely established as a reference method for the diagnosis 
and management of ischemic heart disease thanks to its ability to precisely study regional cardiac 
deformation and provide non-invasive infarct depiction and quantification in clinical practice and 
research.28 CMRI has demonstrated the best inter-study reproducibility of all methods for 
measurement of chamber volumes, ejection fraction and mass, making it an important tool now 
considered as the gold standard for clinical studies.29 


Quantum Genomics 
Confidential 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 55 of 96 
CMRI reading and quantitative image post-processing will be performed centrally in a CMRI Core 
Laboratory. The measurement of LVEF, left-ventricular end-diastolic and end-systolic volumes, 
longitudinal and circumferential strain, and infarct mass by CMRI will be conducted at the time 
points detailed in the schedule of events in Section 2.2. 
10.3.1.1.1 
Left Ventricular Ejection Fraction Measurement by Cardiac Magnetic 
Resonance Imaging 
LVEF is considered as the main imaging prognostic marker after a STEMI. The measurement of 
LVEF is a strong predictor of mortality in patients with LV dysfunction and has become one of the 
most common primary endpoints in cardiovascular studies after STEMI.30 LVEF measurement 
with CMRI is considered as the gold standard in care and clinical research.31,32 LVEF will be 
calculated from end-diastolic and end-systolic LV volumes measured with a semi-automated 
method and expert validation reading and manual adjustments as necessary. 
10.3.1.1.2 
Measurement of Left-ventricular End-diastolic and End-systolic Volumes by 
Cardiac Magnetic Resonance Imaging 
The difference between end-diastolic and end-diastolic volumes determine the stroke volume or 
output of blood by the heart during the cardiac cycle. Impairment of global systolic LV function is 
the major predictor of mortality after acute MI, which is also indicated by changes in the end-
systolic and end-diastolic volumes. End-systolic and end-diastolic volumes have also been related 
to mortality after MI.33 To quantify LV volumes and mass, cine acquisitions will be made using 
retrospectively ECG steady-state free-precession sequences. Two- and 4-chamber long axis cine 
magnetic resonance images will be acquired and used to prescribe a complete stack of 12 to 14 
short axis cine loops, acquired from above the mitral valve plane to the left ventricular apex. LV 
end-diastolic and end-systolic endocardial and epicardial contours will be semi-automatically traced 
using 
established methods with expert validation 
reading and manual 
adjustments 
as 
necessary. Measurements and readings will be centralized in the CMRI core laboratory. 
10.3.1.1.3 
Strain Measurement by Cardiac Magnetic Resonance Imaging 
Estimating the cardiac ejection fraction is a widely performed global assessment of myocardial 
function, but many cardiac diseases initially affect the myocardium regionally rather than globally. 
Myocardial strain analysis is a widely performed technique to quantify the regional myocardial 
wall motion as a normalized measure of deformation. Initially, tagged-CMRI methods have been 
considered the non-invasive gold standard to measure myocardial deformation34, but they require 
specific and not widely available acquisition sequences. Recently, CMRI feature tracking methods have 
been proposed to measure strain and were validated in the general population including by our 
group (REFS).35,36 This method may be considered as a practical reference for the 
measurement of regional myocardial strain free from issues related to echogenicity.37 
The validated CARDIO-TRACK (Sorbonne University license) software will be used to study regional 
average peak longitudinal and circumferential strain in the infarcted segments. Measurements and 
readings will be centralized in the CMRI core laboratory. 


Quantum Genomics 
Confidential 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 56 of 96 
10.3.1.1.4 
Measurement of Infarct Mass by Cardiac Magnetic Resonance Imaging 
Following MI, multiple large studies have demonstrated that infarct mass measured by CMRI is a 
stronger predictor of outcome than either LV volumes or ejection fraction.38,39 Infarct size, 
measured within 1 month after primary PCI, was shown to be strongly associated with all-cause 
mortality and hospitalization for HF within 1 year. Therefore, infarct size may be useful as an 
endpoint in clinical studies and as an important prognostic measure when caring for patients with 
STEMI.40 CMRI is the reference non-invasive method to detect and quantify myocardial infarction 
using late gadolinium enhancement in T1-weighted inversion recovery images. A segmental 
classification of MI transmurality will be provided as well as infarcted mass in grams and mass 
indexed to global LV mass in %.41 Measurements and readings will be centralized in the CMRI 
core laboratory. 
10.3.1.2 Major Cardiac Events 
The term ‘MACE’ is a commonly used endpoint for cardiovascular research. Generally, MACE 
are defined in studies as a composite of various secondary outcomes, including death, cardiac 
death, MI, Q-wave MI, stent thrombosis, target lesion revascularization; 
target vessel 
revascularization, coronary artery bypass graft surgery, and stroke, whichever occurred first.42 
For the purpose of this trial, MACE will be defined as cardiovascular deaths, new MIs, and cardiac 
hospitalizations and will be recorded in the eCRF and adjudicated by an independent committee 
between the treatment groups. 
10.3.1.3 Assessment of Biomarkers 
Cardiac biomarkers are cardiac enzymes and cell contents (e.g., troponin I, troponin T, and 
myoglobin), which are released into the bloodstream after myocardial cell necrosis. The markers 
appear at different times after injury, and the levels decrease at different rates. Sensitivity and 
specificity for myocardial cell injury vary significantly among these markers, but the troponins 
(cTn) are the most sensitive and specific and are now the markers of choice.43 The consensus 
guidelines from the European Society of Cardiology and the American College of Cardiology 
recommend that cardiac markers should be measured at presentation in patients with suspected MI 
and cardiac troponin should be used for diagnosis of acute MI due to its superior sensitivity and 
accuracy.1,44-45
Blood samples for the determination of biomarkers (NT-proBNP, PIIINP, CRP, and copeptin) will 
be collected at the specified time points in the schedule of events in Section 2.2 and shipped to the 
central laboratory for analysis. Details are provided in the laboratory manual. 
10.3.2 Safety Variables 
Safety will be assessed by evaluating TEAEs and AESIs (allergic reactions, and DI), clinical 
laboratory test results (including sodium, potassium, AST, and ALT blood levels and eGFR), vital 
sign measurements (SBP, DBP, and HR), 12-lead ECGs, and clinical examination findings. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 57 of 96 
10.3.2.1 Clinical Laboratory Safety Assessments 
10.3.2.1.1 
Clinical Laboratory Tests to be Performed 
Samples for the following laboratory tests will be collected at the time points specified in the 
schedule of events (Section 2.2). 
Hematology: 
Red blood cell count, hemoglobin, hematocrit, white blood cell count with 
differential (neutrophils, 
lymphocytes, 
monocytes, eosinophils, 
and 
basophils), and platelet count 
Clinical chemistry: 
Sodium, chloride, potassium, blood urea nitrogen, creatinine, ALT, 
aspartate aminotransferase (AST), alkaline phosphatase, glucose, albumin, 
bicarbonate, creatinine kinase, TSH, direct bilirubin, and total bilirubin; 
eGFR will be calculated using the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) formula 
Biomarkers 
NT-proBNP, PIIINP, copeptin, and CRP 
Pregnancy test 
(serum) 
For women of childbearing potential only, a serum pregnancy test will be 
performed at the Screening Visit, Treatment Visit 4 (Day 42), EOT Visit 
(Day 84), and Follow-up Visit (or 30 days after treatment discontinuation) 
If possible, all blood samples for the clinical chemistry tests must be taken in a fasting state, 
approximately 8 hours after the previous meal. 
Each blood sample will be 3.0 to 21.5 mL in volume. The total amount of blood to be drawn during 
the study will be 60.0 mL per subject, including samples for assessment of hematology, clinical 
chemistry, biomarkers, and pregnancy testing. The blood volumes to be collected at each visit are 
specified in Table 10-1. 
 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 58 of 96 
Table 10-1: Blood Sample Collection Volumes (mL) 
 
Screening 
Inclusion 
Titration 
Treatment 
EOT 
Follow-up 
Visit 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Study Day 
 
Panel 
Day -2 to 
Day 1 
Day 1 
 
Day 14 
(± 2 days) 
Day 42 
(± 2 days) 
Day 84 
(± 3 days) 
Day 114  
(±3 Days) or 30 Days 
after Treatment 
Discontinuation 
Hematology 
3.0 
- 
- 
3.0 
3.0 
- 
Clinical 
chemistrya 
5.0 
- 
- 
3.0 
5.0 
- 
NT-proBNP 
- 
3.0 
- 
- 
3.0 
- 
PIIINP 
- 
5.0 
- 
- 
5.0 
- 
Copeptinb 
- 
3.0 
3.0 
3.0 
3.0 
- 
CRP 
- 
2.5 
- 
- 
2.5 
- 
Pregnancy testc 
- 
- 
- 
- 
 
5.0 
Total blood 
volume 
8.0 
13.5 
3.0 
9.0 
21.5 
5.0 
Abbreviations: CRP = C-reactive protein; EOT = end-of-treatment; NT-proBNP = N-terminal pro b-type natriuretic 
peptide; PIIINP = procollagen type III aminoterminal peptide 
a. The pregnancy test for females of childbearing potential will be performed from the blood samples collected for 
clinical chemistry at Visits 1, 4, and 5, but a separate blood sample for pregnancy testing will be collected at 
Visit 6. 
b. The volume required for copeptin assay may need to be updated. The central laboratory will provide the final 
volume requirement upon validation of the assay. 
c. For females of childbearing potential only; a serum pregnancy test will be performed at the Follow-up Visit (or 
30 days after treatment discontinuation). The blood volume will depend on the site standard up to a maximum of 
5.0 mL. 
 
Laboratory specimens for hematology, clinical chemistry, and pregnancy tests will be analyzed at 
local laboratories, according to the site’s procedures. Blood samples for biomarker measurement 
will be sent to a central laboratory for analysis, as specified in the central laboratory manual. 
10.3.2.1.2 
Specimen Handling Requirements 
The transmission of infectious agents may occur through contact with contaminated needles and 
blood or blood products. Consequently, appropriate blood and body fluid precautions should be 
employed by all study personnel involved in the collection of blood and handling of specimens in 
both the clinic and laboratory settings. Refer to current recommendations of the appropriate 
authorities. 
In addition to appropriate handling of subject samples, specific regulations exist regarding the 
shipment of biologic samples. Procedures and regulations for the packaging and shipping of 
infectious samples should follow the site’s procedures and will be detailed in the central laboratory 
manual (biomarkers). The investigator or designee is responsible for ensuring that all study 
samples that are to be transported to another location are packed and shipped appropriately 
according to the applicable regulations. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 59 of 96 
Samples for assessment of biomarkers will be transported to the central laboratory (for address, 
see laboratory manual). 
10.3.2.1.3 
Evaluation of Clinical Laboratory Values 
The normal ranges of values for the clinical laboratory assessments in this study will be provided 
by the responsible laboratory and submitted to Quantum Genomics prior to the beginning of the 
study. They will be regarded as the reference ranges on which decisions will be made. 
If a laboratory value is out of the reference range, it is not necessarily clinically relevant. The 
investigator must evaluate the out-of-range values and record his or her assessment of the clinical 
relevance in the appropriate eCRF. 
All clinical laboratory values that in the investigator’s opinion show clinically relevant or 
pathological changes during or after termination of treatment must be reported as AEs and 
followed, as described in Section 11.2.5. 
All measurements described in this section are recognized standard methods. 
10.3.2.2 Clinical Assessments 
10.3.2.2.1 
Vital Signs 
The SBP and DBP, together with the HR, will be measured at each visit and recorded in the eCRF. 
The blood pressure will be calculated as the average of 3 measurements (with intervals of 1 to 
2 minutes), which will be performed after the subject has been sitting at 5 minutes at rest. 
10.3.2.2.2 
Twelve-lead Electrocardiogram 
A standard 12-lead ECG will be performed after the subject has been supine for at least 5 minutes. 
All ECG recordings will be identified with the subject number, initials, date, and time of the 
recording and will be attached to the subject’s notes. 
10.3.2.2.3 
Clinical Examination 
A complete clinical examination (excluding the genitourinary examination) will be performed at 
each visit and recorded in the eCRF. In addition, height (at Screening only) and weight will be 
measured. 
10.3.2.2.4 
Other Safety Variables 
The definitions and management of AEs, and any special considerations for AEs, are provided in 
Section 11. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 60 of 96 
11. ADVERSE EVENTS 
11.1. Definitions 
11.1.1 Adverse Events 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom, or disease temporally associated with the 
use of a medicinal product, whether or not related to the medicinal product. 
Preexisting diseases or conditions will not be considered AEs unless there is an increase in the 
frequency or severity or a change in the quality of the disease or condition (worsening of a 
preexisting condition is considered an AE). 
11.1.2 Adverse Drug Reaction 
All noxious and unintended responses to an IP related to any dose should be considered adverse 
drug reactions (ADRs). 
The phrase “responses to an investigational product” means that a causal relationship between an 
IP and an AE is at least a reasonable possibility, i.e., the relationship cannot be ruled out. All AEs 
judged by either the reporting investigator or the sponsor as having a reasonable causal relationship 
to an IP qualify as ADRs. 
All AEs for which the judgment of relationship to IP is “possible” or higher will be considered 
ADRs. If a relationship to IP is not provided, then the AE must be treated as if it were “possible”. 
11.1.3 Unexpected Adverse Event/Adverse Drug Reaction 
An expected AE or ADR is one for which the nature or severity is consistent with the known 
AE profile of the product. For a preapproval test product, the known information is contained in 
the IB. For a marketed product, the known information is contained in the current package insert 
for the product. 
An unexpected adverse event (UAE) or unexpected adverse drug reaction (UADR) is one for 
which the nature or severity of which is not consistent with the applicable product information 
(e.g., IB for an unapproved IP or package insert/summary of product characteristics for an 
approved product). 
Furthermore, reports that add significant information on specificity or severity of a known, already 
documented adverse reaction constitute unexpected events. 
11.1.4 Serious Adverse Events/Drug Reaction 
An SAE is any untoward medical occurrence that at any dose: 
• 
Results in death 
• 
Is life-threatening 
NOTE: The term “life-threatening” in the definition of “serious” refers to an event in 
which the patient was at risk of death at the time of the event; it does not refer to an event 
that hypothetically might have caused death if it were more severe. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 61 of 96 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
NOTE: Inpatient hospitalization is defined as 24 hours in a hospital or an overnight stay. 
An elective hospital admission to treat a condition present before exposure to the IP, or a 
hospital admission for a diagnostic evaluation of an AE, does not qualify the condition or 
event as an SAE. Further, an overnight stay in the hospital that is only due to 
transportation, organization, or accommodation problems and without medical background 
does not need to be considered an SAE. 
• 
Results in persistent or significant disability/incapacity 
• 
Is a congenital anomaly 
NOTE: A congenital anomaly in an infant born to a mother who was exposed to the IP 
during pregnancy is an SAE. However, a newly diagnosed pregnancy in a subject that has 
received an IP is not considered an SAE unless it is suspected that the IP(s) interacted with 
a contraceptive method and led to the pregnancy.  
• 
Is an important medical event 
NOTE: Medical and scientific judgment should be exercised in deciding whether it is 
appropriate to consider other situations serious, such as important medical events that may 
not be immediately life-threatening or result in death or hospitalization but may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition above. Examples of such events are intensive treatment in an emergency room or 
at home for allergic bronchospasm, blood dyscrasias, or convulsions that do not result in 
hospitalization, development of drug dependency, or drug abuse. The occurrence of 
malignant tumors is also to be considered serious. 
11.1.5 Significant Adverse Events 
Other significant AEs are defined as marked hematological and other laboratory abnormalities 
(other than those meeting the definition of serious) and any events that led to an intervention, 
including withdrawal of test drug, dose reduction, or significant additional concomitant therapy. 
11.1.6 Treatment-emergent Adverse Events 
An AE is defined as treatment-emergent if the first onset or worsening is after the first 
administration of IP (firibastat and/or ramipril) and not more than 30 days after the last 
administration of IP. 
11.2. Event Assessment and Follow-up of Adverse Events 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits 
and interviews of a study subject presenting for medical care or upon review by a study monitor. 
All AEs, including local and systemic reactions not meeting the criteria for SAEs, will be captured 
on the appropriate eCRF. Information to be collected includes event description, time of onset, 
clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All 
AEs occurring while on study must be documented appropriately, regardless of relationship. All 
AEs will be followed to adequate resolution. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 62 of 96 
Any medical condition that is present at the time that the subject is screened will be considered as 
baseline and not reported as an AE. However, if the study subject’s condition deteriorates at any 
time during the study, it will be recorded as an AE. 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
The investigator will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation. At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit. Events will be followed for outcome information until resolution or 
stabilization. 
11.2.1 Assessment 
The investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE described previously. At each visit, the subject will be allowed 
time to spontaneously report any issues since the last visit or evaluation. The investigator will then 
monitor and/or ask about or evaluate AEs using non-leading questions, such as: 
• 
“How are you feeling?” 
• 
“Have you experienced any issues since your last visit?” 
• 
“Have you taken any new medications since your last visit?” 
Any clinically relevant observations made during the visit will also be considered AEs. 
11.2.2 Evaluation 
11.2.2.1 Severity of Adverse Events 
The clinical severity of an AE will be classified as: 
Mild 
Usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of 
daily living. 
Moderate 
Usually alleviated with additional specific therapeutic intervention. The event 
interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the subject. 
Severe 
Interrupts usual activities of daily living, or significantly affects clinical status, 
or may require intensive therapeutic intervention. 
It is important to distinguish between severe AEs and SAEs. Severity is a classification of intensity 
whereas an SAE is an AE that meets serious criteria, as described in Section 11.1.4. 
11.2.2.2 Seriousness 
The investigator is to evaluate whether the AE meets serious criteria, as described in 
Section 11.1.4. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 63 of 96 
11.2.2.3 Actions Taken 
Actions taken may consist of: 
Dose increased 
An indication that a medication schedule was modified by addition; either 
by changing the frequency, strength, or amount. 
Dose not changed 
An indication that a medication schedule was maintained. 
Dose reduced 
An indication that a medication schedule was modified by subtraction, 
either by changing the frequency, strength, or amount. 
Drug interrupted 
An indication that a medication schedule was modified by temporarily 
terminating a prescribed regimen of medication. 
Drug withdrawn 
An indication 
that a medication schedule was modified through 
termination of a prescribed regimen of medication. 
Not applicable 
Determination of a value is not relevant in the current context. 
Unknown 
Not known, not observed, not recorded, or refused. 
11.2.2.4 Outcome at the Time of Last Observation 
The outcome at the time of last observation will be classified as: 
• Recovered/resolved 
• Recovered/resolved with sequelae 
• Recovering/resolving 
• Not recovered/not resolved 
• Fatal* 
• Unknown 
*Only select fatal as an outcome when the AE results in death. If more than 1 AE is judged to be 
possibly related to the subject’s death, the outcome of death should be indicated for each such AE. 
Although “fatal” is usually an event outcome, events such as sudden death or unexplained death 
should be reported as SAEs. 
11.2.2.5 Adverse Event Relationship to Investigational Product 
The investigator must make an assessment of each AE’s relationship to the IP. The categories for 
classifying the investigator’s opinion of the relationship are as follows: 
Not related 
An AE with sufficient evidence to accept that there is no causal relationship 
to IP administration (e.g., no temporal relationship to drug administration, 
because the drug was administered after onset of event; investigation shows 
that the drug was not administered; another cause was proven). 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 64 of 96 
Unlikely 
related 
An AE, including laboratory test abnormality, with a temporal relationship to 
IP administration that makes a causal relationship improbable, and in which 
other drugs, events, or underlying disease provide plausible explanations. 
Potentially 
related 
An AE with a reasonable time sequence to administration of the IP, but that 
could also be explained by concurrent disease or other drugs or events. 
Information on drug withdrawal may be lacking or unclear. 
Probably 
related 
An AE with evidence to suggest a causal relationship, and the influence of 
other factors is unlikely. The clinical event, including an abnormal laboratory 
test result, occurs within a reasonable time after administration of the study 
intervention, is unlikely to be attributed to concurrent disease or other drugs 
or chemicals, and follows a clinically reasonable response on withdrawal 
(dechallenge). Rechallenge information 
is not required to fulfill this 
definition. 
Definitely 
related 
An AE occurring in a plausible time relationship to IP administration and that 
cannot be explained by a concurrent disease or other drugs or events. The 
response to withdrawal of the drug (dechallenge) is clinically reasonable. 
11.2.3 Documentation 
All AEs that occur within the period of observation for the study must be documented in the eCRF 
with the following information, where appropriate (the period of observation for the study is 
described in Section 11.2). 
• 
AE name or term 
• 
When the AE first occurred (start date and time) 
• 
When the AE stopped (stop date and time or an indication of “ongoing”) 
• 
Severity of the AE 
• 
Seriousness (hospitalization, death, etc.) 
• 
Actions taken 
• 
Outcome 
• 
Investigator opinion regarding the AE relationship to the IP 
11.2.4 Treatment of Adverse Events 
Adverse events that occur during the study will be treated, if necessary, by established standards 
of care. The decision about whether the subject may continue in the study will be made by the 
sponsor after consultation with the investigator and/or medical monitor. 
If AEs occur in a subject that are not tolerable, the investigator must decide whether to stop the 
subject’s involvement in the study and/or treat the subject. Special procedures may be 
recommended for the specific IP, such as the collection of a serum sample for determining blood 
concentrations of IP, specific tapering procedures, or treatment regimens, as appropriate. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 65 of 96 
For double- or triple-blinded studies, it is not necessary to unblind a subject’s treatment assignment 
in most circumstances, even if an SAE has occurred. If unblinding is necessary, see Section 9.6 
for a description of the unblinding procedures. 
11.2.5 Follow-up 
Any AE will be followed to a satisfactory resolution, until it becomes stable, or until it can be 
explained by another known cause(s) (i.e., concurrent condition or medication) and clinical 
judgment indicates that further evaluation is not warranted. Every effort should be made to follow 
up subjects who continue to experience an AE or an SAE on completion of the study until the AE 
stabilizes or resolves. All findings relevant to the final outcome of an AE must be reported in the 
subject’s medical record and recorded on the eCRF page. 
11.2.6 Reporting 
11.2.6.1 Serious Adverse Events 
The investigator or designee must report all SAEs promptly to the contract research organization 
(CRO) within 24 hours of first becoming aware of the event by completing, signing and dating the 
Serious Adverse Event Report Form, verifying the accuracy of the information recorded in the 
form with the source documents and eCRF, and sending the SAE form to the CRO by one of the 
following methods: 
European contact details for 24-hours immediate reporting: 
Fax number: +1 215 972 8765 
Email: globalPV-US@premier-research.com 
US contact details for 24-hours immediate reporting: 
Fax number: +421 2 6820 3713 
Email: PVDS-ROW@premier-research.com 
This written report should be submitted on the SAE form provided for this purpose. At the time of 
first notification, the investigator or designee should provide the following information, if 
available: 
• 
Protocol number 
• 
Reporter (study site and investigator) 
• 
Suspect IP 
• 
Subject’s study number 
• 
Subject’s year of birth 
• 
Subject’s gender 
• 
Date of first dose of IP 
• 
Date of last dose of IP, if applicable 
• 
AE term 
• 
Date of occurrence of the event 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 66 of 96 
• 
A brief description of the event, outcome to date, and any actions taken 
• 
The seriousness criteria(on) that were met 
• 
Concomitant medication at onset of the event 
• 
Relevant medical history information 
• 
Relevant laboratory test findings 
• 
Investigator’s opinion of the relationship to IP(s) (“Is there a reasonable possibility that the 
IP caused the SAE? Yes or No?”) 
• 
Whether and when the investigator was unblinded as to the subject’s treatment assignment 
Any missing or additional relevant follow-up information concerning the SAE should be sent to 
the sponsor representative via the same contact details above as soon as possible on a follow-up 
SAE Report Form, together with the following minimal information (initial report, AE, date of 
occurrence, subject identification (ID), study ID, IP, and site number); this will allow the follow-up 
information to be linked to the initial SAE report. 
Specific information may be requested by the CRO Pharmacovigilance Department using a 
follow-up request form or via email communication. 
The investigator is required to comply with applicable regulations (including local laws and 
guidances) regarding the notification of his or her health authorities, institutional review board 
(IRB)/independent ethics committee (IEC), principal and coordinating investigators, study 
investigators, and institutions. Each investigator is obligated to learn about the reporting 
requirements for investigators in his/her country. The study monitor may be able to assist with 
this. 
11.2.6.2 Adverse Drug Reactions 
All ADRs should be reported by the investigator in the eCRF. 
Suspected serious ADRs must be reported to the sponsor immediately, regardless of the time 
elapsed since the end of the observation period. 
11.2.6.3 Non-serious Adverse Events 
A non-serious AE is any AE that does not fulfill the definition of an SAE. All non-serious AEs 
will be recorded in the eCRF. 
11.3. Special Considerations 
11.3.1 Adverse Events of Special Interest 
For AESIs with immediate notification, the sponsor is to be informed immediately (i.e., within 
24 hours of the investigator’s first knowledge), as per SAE notification guidelines, even if a 
seriousness criterion is not met and whatever its severity grade is. Subjects that report an AESI 
will be followed until the full disappearance of symptoms. The events described in the following 
subsections are considered AESIs for this study. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 67 of 96 
11.3.1.1 Allergic Reactions 
Drug reactions deemed to be allergic or have an allergic component that require consultation with 
another physician for further evaluation of hypersensitivity/allergy, as per the investigator’s 
medical judgment, should be reported as an AESI with immediate notification. 
Adverse events that may constitute an allergic reaction could be generalized as itch, nasal itch, 
flushing, hives, swelling at lips, eyes, face, tongue, hands, or feet, lump in throat, difficulty 
swallowing, hoarseness, change in pitch of voice, inability to speak, wheezing, chest tightness, 
stridor, cutaneous reaction, pruritus, etc. 
The subjects participating in the clinical studies should be informed by the investigator at site that, 
as noted in the informed consent form (ICF), in case of occurrence of skin lesions, they must 
inform their site investigator as soon as possible. In cases where a skin reaction is concomitant to 
fever or blisters on the skin and/or the mucous membranes of the mouth, nose, eyes, and genitals, 
and peeling and shedding skin, which may suggest erythema multiforme or Stevens-Johnson 
syndrome, subjects must immediately stop their investigational treatment and inform their site 
investigator. In this case, the subject should be managed by an experienced team and receive the 
appropriate symptomatic treatment. All subjects with skin reactions must be referred to a 
dermatologist as soon as possible for precise diagnosis, to document the case, to take pictures, and 
to perform a skin biopsy (for central reading). Skin biopsy samples should be sent to the referent 
for central reading. Any allergic skin reaction must be reported as an AESI. 
The investigator should evaluate the subject for possible etiologies and extra-cutaneous symptoms 
and signs. Additional blood tests will be performed if necessary according to the guidance of the 
dermatologist or allergist. 
In the setting of skin lesions, whenever possible, the site will take photographs of the skin lesions 
after receiving the subject’s consent. If photos are obtained, then copies should be kept as source 
documents that may later be collected by the sponsor, and these photos will be forwarded to the 
dermatologist by the sponsor for a specific opinion. The identity of the subject will be preserved, 
and his/her face will not be shown on photographs, except for lesions occurring at the level of the 
subject’s face. In this case, the subject’s face will be partly masked to avoid identification. 
Adverse events with cutaneous involvement that are obviously of allergic origin should be 
evaluated by a dermatologist as soon as possible and preferably within 7 days of the investigator’s 
first knowledge. 
The full report of the dermatologist should include at least a detailed description of the rash (such 
as the morphology [lesion type], shape of individual lesions, arrangement of multiple lesions 
[e.g., scattered, grouped, or linear], distribution, color, consistency, presence of pruritus or pain, 
and other clinical signs), and, if a skin biopsy (including histopathology and immunofluorescence) 
is performed (if deemed necessary as per the dermatologist’s or investigator’s medical judgment), 
the results of this investigation with, if applicable, a specific diagnosis for the biopsy. The full 
report should be sent by the dermatologist to the investigator. Skin biopsy samples should be sent 
to the referent for central reading. 
In case of potential allergic reactions (including delayed hypersensitivity), whatever the intensity 
of the observed symptoms is, the administration of the tested drug will be immediately stopped, 
and a symptomatic treatment will be started if needed. This treatment may include oral 
antihistaminic drugs, oral or intravenous steroids, β2-agonists, or adrenaline if needed. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 68 of 96 
11.3.1.2 Diabetes Insipidus 
One consequence of the inhibition of APA is the decrease of vasopressin. Although not observed 
in any animal or human subject during the study of firibastat, the suppression of vasopressin holds 
a theoretical risk for the development of central DI. Symptoms of DI include polyuria, nocturia, 
and polydipsia. In the setting of suspected DI, the investigator should proceed with a diagnostic 
evaluation to establish the diagnosis as well as any subsequent management at their discretion. All 
suspected DI, as per the investigator’s medical judgment, should be reported as an AESI with 
immediate notification. 
11.3.2 Pregnancy 
Fertility and teratology studies with firibastat have been conducted, and the results indicate that 
women of childbearing potential could participate provided that they are using an appropriate form 
of contraception (as defined in inclusion criterion 5 in Section 8.2.1). 
All women of childbearing potential who participate in the study should be counseled on the need 
to practice adequate birth control and on the importance of avoiding pregnancy during study 
participation. Women should be instructed to contact the investigator or study staff immediately if 
pregnancy occurs or is suspected. 
Pregnancy testing will be conducted prior to administration of the IP on every woman of 
childbearing potential at Screening, Visit 4 (Day 42), EOT Visit, and Follow-up Visit (or 30 days 
after treatment discontinuation). A woman who is found to be pregnant at the Screening Visit will 
be excluded from the study and considered to be a screening failure. 
A female subject who becomes pregnant during IP treatment or within 30 days of discontinuing 
the IP will be immediately discontinued from study participation. The investigator must report the 
pregnancy of a female study subject, as well as a male subject’s female partner, as if it were an 
SAE within 24 hours of learning of the pregnancy to the CRO Pharmacovigilance using the 
Pregnancy Data Collection Form via the same fax number and/or email address as for 
SAE reporting. The investigator should contact the designated individual(s) who receive 
SAE notification and record information related to the pregnancy on an Exposure in Utero 
form/SAE and AE form (entering the event temporarily as non-serious on both forms)/other 
designated form provided by the CRO. 
Early Termination Visit assessments are required as soon as possible after learning of the 
pregnancy. The investigator is also responsible for following the pregnancy until delivery or 
termination. These findings must be reported on the Exposure in Utero form/SAE and 
AE form/other designated form and forwarded to the designated individual(s). The event meets 
the SAE criterion only if it results in a spontaneous abortion or a congenital anomaly. 
11.3.3 Overdose 
At present, there are no data available for overdose in humans. If overdose does occur in humans, 
administration of firibastat should be discontinued, and necessary measures should be taken for 
support of vital functions. 
The maximal dose of firibastat should not be exceeded during the study. Overdose that occurs 
during the study will be treated and documented as an AE/UAE/SAE if it fulfills the criteria. If the 
overdose does not result in an AE, it should be reported in written form to the designated 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 69 of 96 
individual(s) who receive SAE notification. The information contained therein should include 
study site identification, reporter identification, subject identification, IP, dose, action taken 
(e.g., supportive measures or therapy), and any comments. 


Quantum Genomics 
Confidential 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 70 of 96 
12. INDEPENDENT DATA MONITORING COMMITTEE
Safety oversight will be under the direction of an independent data monitoring committee (IDMC), 
composed of individuals with the appropriate expertise, including cardiology. It will also include an 
independent statistician who will be in charge of the interim analysis corresponding to efficacy and 
safety data. Members of the IDMC will be independent from the study conduct and free of conflict 
of interest, or measures will be in place to minimize perceived conflict of interest. The 
IDMC will meet at least semi-annually to assess safety data on each arm of the study (unblinded 
for treatment). The IDMC will operate under the rules of an approved charter that will be written and 
reviewed at the organizational meeting of the IDMC prior to the start of the study. At this time, each 
data element that the IDMC needs to assess will be clearly defined. The interim analysis, 
planned to assess futility, will be performed when approximately 50% of the maximum number of 
subjects have completed the Day 84 primary endpoint assessment, for the comparison of firibastat 
50 mg against ramipril. Details are provided in Section 13.1.6. 
The IDMC will provide its input to Quantum Genomics. In case of significant safety concerns, the 
IDMC may recommend stopping recruitment in a particular dose group. The IDMC may also 
recommend dropping the firibastat 50 mg arm if a substantially low treatment effect compared to 
ramipril is demonstrated as the outcome of futility interim analysis. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 71 of 96 
13. STATISTICS 
13.1. Statistical Analysis 
This section presents a summary of the planned statistical analyses. A statistical analysis plan 
(SAP) that describes the details of the analyses to be conducted will be written prior to database 
lock. Any changes from the planned analyses will be described and justified in the final clinical 
study report (CSR). 
Unless otherwise indicated, all testing of statistical significance will be 2-sided, and a difference 
resulting in a P value of ≤ 0.05 will be considered statistically significant. 
The acceptable risk of error for the statistical tests will be set at 5%, except for 
treatment-by-covariates interactions. For those interactions, the level of significance will be set at 
10%. 
There is a single primary efficacy endpoint in the study – the change from Baseline in LVEF 
assessed by CMRI on Day 84. The other efficacy endpoints are defined to be of secondary 
importance. Due to multiple treatment comparisons, a hierarchical step-down testing procedure 
will be applied for the primary and secondary criteria to control the overall type I error rate. Only 
if superiority of firibastat 250 mg against ramipril is demonstrated at the 2-sided 5%-level, 
superiority of firibastat 50 mg against ramipril can be tested. Likewise, only if superiority of 
firibastat 50 mg against ramipril is demonstrated at the 2-sided 5%-level, superiority of firibastat 
250 mg against firibastat 50 mg can be tested. The testing procedure stops as soon as a comparison 
is found to be not statistically significant at the 2-sided 5%-level. 
Continuous variables will be summarized using descriptive statistics (number of observations, 
mean, standard deviation (SD), median, Q1, Q3, minimum, and maximum). Frequency distribution 
(counts and percentages) will be summarized for the categorical variables. When applicable, 
95% confidence interval (CI) of the mean (or the median) will be provided for continuous 
variables, and the 95% CI of the proportion will be displayed for each modality of categorical 
variables. 
For each analyzed parameter, the normality assumption of model residuals distribution will be 
checked using graphical methods, skewness and kurtosis values, and Shapiro-Wilk’s statistic. If 
there is a strong violation of the normality assumption (or violation of homogeneity of variances 
for analysis of covariance [ANCOVA]), a rank transformation will be primarily done, and the 
statistical analysis model will be applied to ranks. 
13.1.1 Analysis Populations 
The following 4 analysis populations are planned for this study: 
• 
Safety population: The safety population will consist of all subjects who receive at least 
1 dose of the IP. This population will be based on the treatment actually received by the 
subject and will be used for the analysis of the safety endpoints. 
• 
Intent-to-treat (ITT) population: The ITT population will consist of all randomized 
subjects. This population will be based on the treatment to which the subject was 
randomized. Any subject who receives a randomization number will be considered to have 
been randomized. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 72 of 96 
• 
Modified intent-to-treat (mITT) population: The mITT population will consist of all 
randomized subjects who receive at least 1 dose of the IP and who have at least 1 baseline 
and 1 post-randomization efficacy assessment (CMRI) on treatment. This population will 
be based on the treatment to which the subject was randomized and will be the primary 
population for the analysis of the efficacy endpoints. 
• 
Per-protocol (PP) population: The PP population will consist of all subjects from the 
mITT population without any major protocol deviation. This population will be considered 
for sensitivity analysis of the primary endpoint. 
13.1.2 Study Subjects and Demographics 
13.1.2.1 Disposition and Withdrawals 
The numbers of subjects randomized, completing, and withdrawing, along with reasons for 
withdrawal, will be tabulated overall and by treatment group. The number of subjects in each 
analysis population will be reported. 
13.1.2.2 Protocol Deviations 
A protocol deviation is any non-compliance with the clinical study protocol or International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 
Good Clinical Practice (GCP) requirements. The non-compliance may be either on the part of the 
participant, the investigator, or the study site staff. As a result of deviations, corrective actions are 
to be developed by the site and implemented promptly. 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 5 working days of identification of the protocol deviation or within 5 working 
days of the scheduled protocol-required activity. All deviations must be addressed in study source 
documents, reported to the relevant regulatory bodies as applicable and sponsor. Protocol 
deviations must be sent to the reviewing IRB/IEC per their policies. The site investigator is 
responsible for knowing and adhering to the reviewing IRB/IEC requirements. Further details 
about the handling of protocol deviations will be included in the protocol deviation guidance plan. 
Deviations from the protocol including violations of inclusion/exclusion criteria will be defined 
and assessed as minor or major in cooperation with the sponsor during a blind review meeting 
before the database lock, together with the determination of inclusion in the analysis populations. 
13.1.2.3 Demographics and Other Baseline Characteristics 
Demographics and baseline characteristics will be summarized overall and by treatment group on 
the mITT population. 
Demographic variables will include age, gender, height, and weight. 
Baseline subject characteristics will include medical history, clinical examination findings, and 
results of the coronary angiography defining the success or not of the procedure (TIMI 3 or not). 
If the subject provided consent for this, the subject’s coronary angiography performed after MI at 
Screening will be captured using the CMRI electronic repository as part of the subject’s study 
documentation. Coronary angiography reading will be performed centrally in a core laboratory. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 73 of 96 
Prior and concomitant medications will be summarized by treatment group, by the number and 
percentage of subjects taking each medication, classified using World Health Organization Drug 
Dictionary Anatomical Therapeutic Chemical classes and preferred terms (PTs). 
13.1.3 Exposure and Compliance 
Investigational product administration will be summarized in terms of each subject’s mean and 
final dose and in terms of duration of exposure. Descriptive statistics for these quantities, including 
the mean, median, SD, minimum, maximum, and quartiles, will be provided by treatment group. 
All intake details per subject will be provided in data listings. 
13.1.4 Efficacy Analysis 
The primary efficacy endpoint, i.e., the change from Baseline in LVEF assessed by CMRI, will be 
primarily analyzed on the mITT population. Sensitivity analyses will be performed on the ITT and 
PP populations. Secondary efficacy endpoints will be analyzed on the mITT population. 
For efficacy variables, descriptions will be given by treatment group at each assessment time. The 
change from Baseline will be also presented if applicable. 
13.1.4.1 Efficacy Endpoints 
Primary efficacy endpoint: 
The primary efficacy endpoint is the change from Baseline to Day 84 in LVEF assessed by 
CMRI (centralized reading). 
Secondary endpoints: 
• 
Change from Baseline to Day 84 in left-ventricular end-diastolic and end-systolic volumes 
assessed by CMRI 
• 
Change from Baseline to Day 84 in average peak of longitudinal and circumferential strain 
in the infarcted segments assessed by CMRI 
• 
Infarct mass at EOT (Day 84) assessed by CMRI 
• 
MACE (i.e., cardiovascular deaths, new MIs, and cardiac hospitalizations) as adjudicated 
by an independent committee 
• 
Change from Baseline in NT-proBNP, PIIINP, and CRP levels to Day 84 
• 
Slope of decrease in copeptin over time 
13.1.4.2 Primary Efficacy Endpoint Analysis 
The analysis of the primary efficacy endpoint will be based on the mITT population. 
Primary analysis of the primary efficacy endpoint: 
The change from Baseline in LVEF will be primarily analysed using an ANCOVA. The ANCOVA 
will include treatment group as factor, baseline LVEF and country as covariates. For subjects who 
prematurely discontinue the study, measurements made at the time of study withdrawal will be 
considered in the analysis. Pattern of study premature discontinuations including the profile of 
subjects and reason and time to withdrawal will be presented to assess potential impact of dropouts 
on treatment comparisons. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 74 of 96 
The adjusted mean will be presented by treatment group. The difference in adjusted mean between 
the treatment groups, associated 95% CI and P value will be also presented using a hierarchical 
step-down testing procedure to control the overall type I error. 
Model assumptions checking: 
Assumptions underlying ANCOVA (residuals distribution normality, heteroscedasticity, etc.) will 
be checked using graphical methods, skewness and kurtosis values, and Shapiro-Wilk’s statistic. 
Possible treatment-by-covariate interactions will be investigated including the interaction term in 
the model for ANCOVA (1 separated model for each interaction). 
Sensitivity analyses of the primary efficacy endpoint: 
While subjects missing Day 84 data but having earlier data will be included in the primary analysis, 
the interpretability of the results from the primary model will depend on the missing data satisfying 
the missing at random. To support the validity of the conclusions drawn from this analysis, 
sensitivity analyses will be performed to explore possible impact of dropout pattern on treatment 
comparisons. 
1. 
An ANCOVA will be performed on the value recorded on Day 84 (i.e., the measurement 
made at the time of the study premature discontinuation will not be considered in the 
analysis) 
2. 
A sensitivity analysis will be performed using a multiple imputation method that will be 
further detailed in the SAP 
The primary analysis and the sensitivity analyses presented here above will be repeated on the 
ITT and PP populations. 
13.1.4.3 Secondary Efficacy Endpoints Analyses 
Secondary efficacy endpoints will be analyzed on the mITT population. 
As for the primary efficacy endpoint, a hierarchical step-down testing procedure will be applied 
for each of the secondary efficacy endpoints in order to control the overall type I error due to 
multiplicity of treatment comparisons. 
Change from baseline in left-ventricular end-diastolic and end-systolic volumes: 
The change from Baseline in left-ventricular end-diastolic and end-systolic volumes assessed by 
CMRI will be analyzed using an ANCOVA as for the primary efficacy endpoint, i.e., considering 
the treatment group as factor, baseline value and country as covariates. 
Change from baseline in average peak of longitudinal and circumferential strain: 
The change from Baseline in the average peak of longitudinal and circumferential strain in the 
infarcted segments assessed by CMRI will be analyzed using an ANCOVA as for the primary 
efficacy endpoint, considering the treatment group as factor and baseline value and country as 
covariates. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 75 of 96 
Infarct mass: 
The infarct mass assessed by CMRI at the end of the treatment will be analyzed using an 
ANCOVA. The ANCOVA will include treatment group as factor and country as covariate. 
MACE: 
The MACE (i.e., cardiovascular deaths, new MIs, and cardiac hospitalizations) which occurred 
during the course of the study will be adjudicated by an independent committee. The number of 
committee-confirmed events per subject will be described per category. The time to first confirmed 
MACE will be tested using censored data analysis. Median time with 95% CI will be estimated 
using the Kaplan-Meier method. Number and percentage of subjects who had an event or were 
censored will also be reported. A Kaplan-Meier survival curve will be generated by treatment 
group. 
Changes from Baseline in NT-proBNP, PIIINP, and CRP: 
The change from Baseline in NT-proBNP, PIIINP, and CRP will be analyzed using an ANCOVA 
as for the primary efficacy endpoint, considering the treatment group as factor and baseline value 
and country as covariates. 
Slope of decrease in copeptin: 
Copeptin will be assessed at each visit. The change from Baseline in copeptin will be analyzed 
using a mixed model for repeated measures (MMRM) where intercept and slope will be considered 
as random. The model will include treatment group as fixed factor, Baseline value and country as 
covariates, and time, treatment group by time interaction, and Baseline by time interaction. Time 
will be calculated in days as date of copeptin assessment - date of first study treatment intake. The 
restricted maximum likelihood (REML) estimation approach will be used, and the default 
covariance structure will be unstructured. 
Estimate of slope will be presented by treatment group. Difference in slopes between the treatment 
groups and associated 95% CI will be also presented. Comparison of slopes between the treatment 
groups will be performed using the hierarchical step-down testing procedure. 
The decrease of copeptin will be graphically illustrated. The mean change at each time point used 
for the figure will be estimated from the model. 
13.1.5 Safety and Tolerability Analyses 
Safety analyses will be conducted using data from the safety population (as defined in 
Section 13.1.1). Safety variables include TEAEs, clinical laboratory values, vital signs (SBP, DBP, 
and HR measurement), 12-lead ECG readings, and clinical examination results. No formal 
inferential analyses will be conducted for safety variables, unless otherwise noted. 
13.1.5.1 Adverse Events 
All AEs, whether serious or non-serious, will be reported from signing the ICF until 7 days (for 
non-serious AEs) or 30 days (for SAEs) after the last day of study participation. For AE reporting, 
the verbatim term recorded in the eCRF by the investigators to identify AEs will be coded using 
the Medical Dictionary for Regulatory Activities, Version 21.1 or higher. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 76 of 96 
Treatment-emergent AEs are defined as: 
• 
Adverse events with onset at the time of or following the start of treatment with IP through 
the EOT Visit (Day 84) or Early Termination Visit, whichever occurs first, or 
• 
Adverse events starting prior to the start of treatment but increasing in severity or 
relationship at the time of, or following, the start of treatment with IP through the 
Follow-up Visit or Early Termination Visit, whichever occurs first 
The AEs will be summarized by frequency and proportion of subjects by treatment group, by SOC, 
and PT. Separate summaries will be given for all AEs, treatment-related AEs, SAEs, and AEs 
leading to discontinuation of study treatment. 
The following AEs of clinical and special interest will be summarized separately: 
• 
Allergic reactions 
• 
Diabetes insipidus 
Individual subject data listings of AEs including outcome, action taken, severity, relationship to 
IP, and seriousness will be performed for overall AEs, SAEs, and drug-related SAEs. 
13.1.5.2 Clinical Laboratory Evaluations 
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual (absolute) values 
and changes from baseline values will be presented for clinical laboratory values for each treatment 
group at each time point. 
The number of subjects with clinical laboratory values categorized as below, within, or above 
normal ranges, will be tabulated showing the change from Baseline (shift tables) for each clinical 
laboratory analyte by treatment group and by study visit. 
Laboratory values that are outside the normal range will also be flagged in the data listings and 
presented with the corresponding normal ranges. Any out-of-range values that are identified by 
the investigator as being clinically significant will also be shown in a data listing. 
Blood level in sodium, potassium, AST, and ALT and the eGFR calculated value, as well as 
corresponding changes from Baseline, will be described at each visit by treatment group. 
13.1.5.3 Vital Signs 
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual values and 
changes from baseline will be presented at each visit and by treatment group for SBP, DBP, and 
HR. 
The number of subjects with vital signs values categorized as below, within, or above normal 
ranges will be tabulated showing change from Baseline (shift tables) for each parameter by 
treatment group and by study visit. 
13.1.5.4 Twelve-lead Electrocardiograms 
The number and percentage of subjects with normal and abnormal ECG findings will be 
summarized for each treatment group at each time point. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 77 of 96 
13.1.5.5 Clinical Examination Findings 
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual values and 
changes from Baseline in weight will be presented at each visit and by treatment group. 
13.1.6 Interim Analysis 
One single futility IA is planned for the primary efficacy endpoint for the comparison of firibastat 
50 mg against ramipril when approximately 50% of the maximum number of subjects have 
completed the Day 84 primary endpoint assessment. However, if the dynamic of subject inclusion 
in the study is faster than expected, it could be decided to not perform the IA if the time of delivery 
of IA results is deemed too close to the end of the recruitment period. 
This futility IA was put in to allow for dropping firibastat 50 mg arm if a substantially low 
treatment effect compared to ramipril is demonstrated. The futility stopping rule is based on a 
group-sequential design using the beta-spending O’Brien-Fleming approach. If firibastat 50 mg 
does not pass the futility boundaries (i.e., if futility of firibastat 50 mg against ramipril is 
demonstrated), then the treatment arm will be dropped due to lack of efficacy. 
The IA to assess futility of firibastat 50 mg will be performed by an independent data monitoring 
committee (IDMC) using the primary model of analysis. Additional details of the IA will be 
provided in an IDMC charter that will be written and validated before the IA database lock. 
13.2. Sample Size Determination 
The sample size determination is based on the primary efficacy endpoint (i.e., the change from 
Baseline in LVEF assessed by CMRI on Day 84), on an equal randomization, using a 2-sided 
5% nominal level of significance. 
The SD of the primary efficacy variable is estimated to 10%. 
Based on an estimated difference of 5% between the treatment groups on the primary efficacy 
variable, around 88 evaluable subjects per group are needed to achieve 90% power (accounting 
for the futility IA at 50% of the maximum information). Assuming of a dropout/non-evaluable rate 
of about 10%, 98 subjects per group are expected to be randomized, namely a total of 294 subjects. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 78 of 96 
14. STUDY CONDUCT 
Steps to ensure the accuracy and reliability of data include the selection of qualified investigators 
and appropriate study sites, review of protocol procedures with the investigator and associated 
personnel before the study, periodic monitoring visits, and meticulous data management. 
14.1. Sponsor and Investigator Responsibilities 
14.1.1 Sponsor Responsibilities 
The sponsor is obligated to conduct the study in accordance with strict ethical principles 
(Section 16). The sponsor reserves the right to withdraw a subject from the study (Section 8.3), to 
terminate participation of a study site at any time (Section 14.7), and/or to discontinue the study 
(Section 14.6). 
Quantum Genomics agrees to provide the investigator with sufficient material and support to 
permit the investigator to conduct the study according to the study protocol. 
14.1.2 Investigator Responsibilities 
By signing the Investigator’s Agreement (Section 18.1), the investigator indicates that he or she 
has read the protocol carefully, fully understands the requirements, and agrees to conduct the study 
in accordance with the procedures and requirements described in this protocol. 
The study will be conducted in accordance with ICH GCP and applicable regulations. The 
principal investigator will assure that no deviation from, or changes to, the protocol will take place 
without prior agreement from the Investigational New Drug (IND) sponsor, documented approval 
from the IRB/IEC, except where necessary to eliminate an immediate hazard(s) to the study 
subjects. All personnel involved in the conduct of this study have completed human subject’s 
protection and ICH GCP training. 
Investigators should ensure that all persons who are delegated study-related responsibilities are 
adequately qualified and informed about the protocol, the IPs, and their specific duties within the 
context of the study. Investigators are responsible for providing Quantum Genomics with 
documentation of the qualifications, GCP training, and research experience for themselves and 
their staff as required by the sponsor and the relevant governing authorities. 
To ensure compliance with the guidelines, the study may be audited by an independent person. 
The investigator agrees, by written consent to this protocol, to cooperate fully with compliance 
checks by allowing access to all study documentation by authorized individuals. 
14.1.3 Confidentiality and Privacy 
Subject confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor and their interventions. This confidentiality is extended to cover testing of 
biological samples in addition to the clinical information relating to subjects. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in strict confidence. 
No information concerning the study or the data will be released to any unauthorized third party 
without prior written approval of the sponsor. 
All research activities will be conducted in as private a setting as possible. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 79 of 96 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB/IEC, 
regulatory agencies, or pharmaceutical company supplying study product may inspect all 
documents and records required to be maintained by the investigator, including, but not limited to, 
medical records (office, clinic, or hospital) and pharmacy records for the subjects in this study. 
The clinical study site will permit access to such records. 
The study subject’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by the reviewing IRB/IEC, institutional policies, or sponsor 
requirements. 
Study subject research data, which is for purposes of statistical analysis and scientific reporting, 
will be stored at Aixial. This will not include the subject’s contact or identifying information. 
Rather, individual subjects and their research data will be identified by a unique study 
identification number. The study data entry and study management systems used by clinical sites 
and by Aixial research staff will be secured and password protected. 
14.2. Site Initiation 
Study personnel may not screen or enroll subjects into the study until after receiving notification 
from the sponsor or its designee that the study can be initiated at the study site. The study site will 
not be authorized for study initiation until: 
1. 
The study site has received the appropriate IRB/IEC approval for the protocol and the 
appropriate ICF 
2. 
All regulatory/GCP documents have been submitted to and approved by the sponsor or its 
designee 
3. 
The study site has a clinical trial agreement in place 
4. 
Study site personnel, including the principal investigator, have participated in a study 
initiation visit or have been trained appropriately if visit attendance is not possible 
14.3. Screen/Randomization Failures 
Due to the nature of the study population (subjects to be randomized at a maximum of 24 hours 
after acute MI), rescreening will not be possible. 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently randomly assigned to the study intervention or entered in the study. Randomization 
failures are defined as subjects who were randomized but not treated. A minimal set of information 
is required to ensure transparent reporting of those subjects to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any SAE. 
14.4. Study Documents 
All documentation and material provided by Quantum Genomics for this study are to be retained 
in a secure location and treated as confidential material. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 80 of 96 
14.4.1 Informed Consent 
Consent forms describing in detail the study intervention, study procedures, and risks are given to 
the subject, and written documentation of informed consent is required prior to starting 
intervention/administering study intervention. The ICF and subject’s card are submitted as consent 
materials with this protocol. 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be 
IRB/IEC-approved, and the subject will be asked to read and review the document. The 
investigator will explain the research study to the subject and answer any questions that may arise. 
A verbal explanation will be provided in terms suited to the subject’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research subjects. 
Subjects will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The subjects should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The subject will sign the informed 
consent document prior to any procedures being done specifically for the study. Subjects must be 
informed that participation is voluntary and that they may withdraw from the study at any time, 
without prejudice. A copy of the informed consent document will be given to the subjects for their 
records. The informed consent process will be conducted and documented in the source document 
(including the date) and the form signed before the subject undergoes any study-specific 
procedures. The rights and welfare of the subjects will be protected by emphasizing to them that 
the quality of their medical care will not be adversely affected if they decline to participate in this 
study. 
14.4.2 Investigator’s Regulatory/Good Clinical Practice Documents 
The regulatory/GCP documents are listed below: 
• 
Signed original protocol (i.e., investigator’s agreement) 
• 
Curricula vitae of all investigators and sub-investigators 
• 
Name and address of the local and central laboratories 
• 
List of laboratory reference ranges, and if available, a quality certificate 
• 
Any other relevant GCP documents 
The regulatory and GCP documents must be received from the investigator and reviewed and 
approved by Quantum Genomics or its designee before the study site can initiate the study and 
before Quantum Genomics will authorize shipment of IP to the study site. Copies of the 
investigator’s regulatory and GCP documents must be retained at the study site in a secure location. 
Additional documents, including a copy of the protocol and applicable amendment(s), the firibastat 
IB, eCRF completion guidelines, copies of regulatory correspondence and approvals, copies of 
IRB/IEC correspondence and approvals, and IP accountability records should also be retained as 
part of the investigator’s regulatory and GCP documents. It is the investigator’s responsibility to 
ensure that copies of all required regulatory and GCP documents are organized, current, and 
available for inspection. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 81 of 96 
14.4.3 Case Report Forms 
By signing the investigator’s agreement (Section 18.1), the investigator agrees to maintain 
accurate eCRFs and source documentation as part of the case histories for all subjects who sign an 
ICF. 
Case report forms are considered confidential documents and should be handled and stored 
accordingly. The sponsor or its designee will provide the necessary training on the use of the 
specific eCRF system used during the study to ensure that the study information is captured 
accurately and appropriately. 
To ensure data accuracy, eCRF data for individual subject visits should be completed as soon as 
possible after the visit. All requested information must be entered in the eCRF/EDC system 
according to the completion guidelines provided by the sponsor or its designee. 
The eCRFs must be signed by the investigator or a sub-investigator. These signatures serve to 
attest that the information contained in the eCRF is accurate and true. 
14.4.4 Source Documents 
Information recorded in the eCRF/EDC system should be supported by corresponding source 
documentation. Examples of acceptable source documentation include, but are not limited to, 
hospital records, clinic and office charts, laboratory notes, and recorded data from automated 
instruments, memoranda, and pharmacy dispensing records. 
The following data are to be recorded directly on the eCRFs (i.e., no prior written or electronic 
record of data) and considered to be source data: hospital records, clinic and office charts, 
laboratory notes, and recorded data from automated instruments, memoranda, and pharmacy 
dispensing records. 
Clinical laboratory data required by the protocol will be electronically transferred from the 
central/local laboratory to the sponsor or its designee. A paper copy of the laboratory results will 
be provided to the study site and should be retained with each subject’s source data. 
14.5. Data Quality Control 
Quantum Genomics and its designees will perform quality control checks on this clinical study. 
14.5.1 Monitoring Procedures 
Quantum Genomics and/or its designee will conduct site visits to monitor the study and ensure 
compliance with the protocol, GCP, and applicable regulations and guidelines. The assigned 
clinical research associate(s) (CRA[s]) will visit the investigator and study site at periodic intervals 
and maintain periodic communication. The investigator agrees to allow the CRA(s) and other 
authorized Quantum Genomics personnel access. The CRA(s) will maintain current personal 
knowledge of the study through observation, review of study records and source documentation, 
and discussion of the conduct of the study with the investigator and staff. While on site, the CRA(s) 
will review the following items: 
• 
Regulatory documents, directly comparing entries in the eCRF system with the source 
documents 
• 
Consenting procedures 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 82 of 96 
• 
AE procedures 
• 
Storage and accountability of IP and study materials 
The CRA will ask for clarification and/or correction of any noted inconsistencies. Procedures for 
correcting eCRF are described in the study plan. As representatives of the sponsor, CRAs are 
responsible for notifying project management of any noted protocol deviations. 
By signing the investigator’s agreement (Section 18.1), the investigator agrees to meet with the 
CRA(s) during study site visits; to ensure that study staff is available to the CRA(s) as needed; to 
provide the CRA(s) access to all study documentation, to the clinical supplies dispensing and 
storage area; and to assist the monitors in their activities, if requested. Further, the investigator 
agrees to allow Quantum Genomics or designee auditors or inspectors from regulatory agencies to 
review records and to assist the inspectors in their duties, if requested. 
For additional information, please refer to the clinical monitoring plan. 
14.5.2 Data Management 
Quantum Genomics or designee will be responsible for activities associated with the data 
management of this study. The standard procedures for handling and processing records will be 
followed per GCP. A comprehensive data management plan will be developed, including a data 
management overview, description of database contents, annotated CRF, pre-entry review list, 
self-evident correction conventions, query contacts, and consistency checks. 
Study site personnel will be responsible for providing resolutions to all data queries. The 
investigator will be required to document electronic data review to ensure the accuracy of the 
corrected and/or clarified data. Procedures for soliciting and documenting resolution to data 
queries are described in the study plan. 
14.5.3 Quality Assurance/Audit 
This study will be subject to audit by Quantum Genomics or its designee. Audits may be performed 
to check compliance with GCP guidelines and can include: 
• 
Site audits 
• 
Trial Master File audits 
• 
Database audits 
• 
Document audits (e.g., protocol and/or CSR) 
Quantum Genomics or its designee may conduct additional audits on a selection of study sites, 
requiring access to subject notes, study documentation, and facilities or laboratories used for the 
study. 
The study site, facilities, all data (including source data), and documentation will be made available 
for audit by quality assurance auditors and for IRB/IEC or regulatory authorities according to 
GCP guidelines. The investigator agrees to cooperate with the auditor during the visit and will be 
available to supply the auditor with eCRFs or other files necessary to conduct that audit. Any 
findings will be strictly confidential. 
If a regulatory authority informs the investigator that it intends to conduct an inspection, the 
investigator shall notify Quantum Genomics immediately. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 83 of 96 
14.6. Study Termination 
The study may be terminated at Quantum Genomics’ discretion at any time and for any reason. 
The IDMC may recommend discontinuation of the study if they find evidence of unacceptable risk 
to subjects. 
14.6.1 Regular Study Termination 
The end of this study is defined as the date of the last visit of the last subject (last subject out or 
last subject last visit) participating in the study. Within 90 days of the end of the clinical study, 
Quantum Genomics or designee will notify the IRBs/IECs and regulatory authorities on the regular 
termination of the study as required according to national laws and regulations. 
14.6.2 Premature Study Termination 
The study may be temporarily suspended or terminated prematurely if there is sufficient reasonable 
cause at any time by Quantum Genomics, IRBs/IECs, regulatory authorities, respective steering 
committees, or the coordinating investigator. A decision to prematurely terminate the study is 
binding to all investigators of all study sites. 
Within 15 days of premature termination of a clinical study, Quantum Genomics or its designee 
will notify the IRBs/IECs and regulatory authorities on the premature termination as required 
according to national laws and regulations. Quantum Genomics or its designee must clearly 
explain the reasons for premature termination. 
Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to study subjects, investigator, funding agency, the 
IND sponsor and regulatory authorities. If the study is prematurely terminated or suspended, the 
principal investigator will promptly inform study subjects, the IRB/IEC, and sponsor and will 
provide the reason(s) for the termination or suspension. Study subjects will be contacted, as 
applicable, and be informed of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to subjects 
• 
Demonstration of efficacy that would warrant stopping 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
If the study is terminated prematurely, all investigators have to inform their subjects and take care 
of appropriate follow up and further treatment of the subjects to ensure protection of the subjects’ 
interests. Study sites may be asked to have all subjects currently participating in the study complete 
all of the assessments for the Early Termination Visit. 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB/IEC and/or regulatory authority. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 84 of 96 
14.7. Study Site Closure 
At the end of the study, all study sites will be closed. Quantum Genomics may terminate 
participation of a study site at any time. Examples of conditions that may require premature 
termination of a study site include, but are not limited to, the following: 
• 
Non-compliance with the protocol and/or applicable regulations and guidelines 
• 
Inadequate subject enrollment 
14.7.1 Record Retention 
After completing the study, Quantum Genomics will receive the original CRFs or at least a legible 
copy and retain the documents for at least 5 years after the completion of the study. 
One copy will remain with the investigator. The investigator shall arrange for the retention of the 
subject identification codes, subject files and other source data until at least 5 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or until at least 2 years have elapsed since 
the formal discontinuation of the clinical development of the product. These documents need to be 
retained for a longer period of time if required by applicable regulatory authorities or by agreement 
with the sponsor. 
At the end of such period, the investigator shall notify the sponsor in writing of his or her intent to 
destroy all such material. The sponsor shall have 30 days to respond to the investigator’s notice, 
and the sponsor shall have a further opportunity to retain such materials at the sponsor’s expense. 
Copies of these study records (and all study-related documents, including source data) shall be 
kept by the investigator for the maximum period of time permitted by the hospital, institution, or 
private practice. 
14.7.2 Sample Retention 
Samples may be used for purposes related to this research. The samples will be stored until the 
sponsor has determined that specimens are no longer needed, and the decision has been made that 
none of the samples needs to be reanalyzed. In addition, identifiable samples can be destroyed at 
any time at the request of the subject. 
Data collected for this study will be analyzed and stored at the central laboratory either in Europe 
or the USA, depending on the biomarker to be analyzed. After the study is completed, the archived 
data will be transmitted to and stored at Quantum Genomics for use by other researchers, including 
those outside of the study. Permission to transmit data to Quantum Genomics will be included in 
the informed consent. 
These samples could be used to provide information on the diagnosis of MI and risk stratification, 
to assess the degree of damage and assist in deciding management, as well as to reflect the repair 
process and scar formation after MI. 
During the conduct of the study, an individual subject can choose to withdraw consent to have 
biological specimens stored for future research. However, withdrawal of consent with regard to 
biosample storage may not be possible after the study is completed. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 85 of 96 
14.8. Changes to the Protocol 
This protocol cannot be altered or changed except through a formal protocol amendment, which 
requires the written approval of Quantum Genomics. The protocol amendment must be signed by 
the investigator and approved by the IRB or IEC before it may be implemented. Protocol 
amendments will be filed with the appropriate regulatory agency(s) having jurisdiction over the 
conduct of the study. 
14.9. Use of Information and Publication 
All information concerning firibastat, Quantum Genomics’ operations, patent applications, 
formula, manufacturing processes, basic scientific data, and formulation information supplied by 
Quantum Genomics or its designee to the investigator, and not previously published, is considered 
confidential and remains the sole property of Quantum Genomics. Electronic case report forms 
also remain the property of Quantum Genomics. The investigator agrees to use this information 
for purposes of study execution through finalization and will not use it for other purposes without 
the written consent of the sponsor. 
The information developed in this study will be used by Quantum Genomics in connection with 
the continued development of firibastat and thus may be disclosed as required to other clinical 
investigators or government regulatory agencies. 
The information generated by this study is the property of Quantum Genomics. Publication or 
other public presentation of firibastat data resulting from this study requires prior review and 
written approval of Quantum Genomics. Abstracts, manuscripts, and presentation materials should 
be provided to Quantum Genomics for review and approval at least 30 days prior to the relevant 
submission deadline. Data from individual study sites must not be published separately. 
It is agreed that the results of the study will not be submitted for presentation, abstract, poster 
exhibition, or publication by the investigator until Quantum Genomics has reviewed and 
commented on such a presentation or manuscript for publication. This study will be registered at 
ClinicalTrials.gov and ClinicalTrialsRegister.eu, and results information from this study will be 
submitted to both databases. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 86 of 96 
15. FINAL CLINICAL STUDY REPORT 
Quantum Genomics will retain ownership of the data. 
The final CSR will be written within 1 year of completion of the clinical part of the study. This 
report will include a summary of the study results, based on a statistical evaluation and clinical 
assessment of the protocol-defined endpoints. 
The final CSR will be submitted to the regulatory authorities. 


Quantum Genomics 
Confidential 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 87 of 96 
16. ETHICAL AND LEGAL CONSIDERATIONS
16.1. Declaration of Helsinki and Good Clinical Practice 
This study will be conducted in compliance with the April 1996 ICH Guidance for Industry GCP 
E6 (including archiving of essential study documents), the Integrated Addendum to ICH E6 (R2) 
of November 2016, the Declaration of Helsinki, the applicable regulations of the country(ies) in 
which the study is conducted, and with the Commission Directives 2001/20/EC and 2005/28/EC. 
See Appendix B for regulation and guidelines. 
16.2. Subject Information and Informed Consent and/or Assent 
A properly constituted, valid IRB or IEC must review and approve the protocol, the investigator’s 
ICF, and related subject information and recruitment materials before the start of the study. 
It is the responsibility of the investigator to ensure that written informed consent is obtained from 
the subject before any activity or procedure is undertaken that is not part of routine care. 
According to the Declaration of Helsinki and ICH GCP, subjects must provide their written 
informed consent prior to enrollment in a clinical study and before any protocol-specified 
procedures are performed. Subjects must declare their consent by personally signing and dating 
the ICF. The written ICF will embody the elements of informed consent and/or assent as described 
in the Declaration of Helsinki and will also comply with local regulations. 
Each subject should be made aware by the investigator of the nature of the study (objectives, 
methods, and potential hazards and benefits) and the procedures involved, using the information 
on the ICF. Information should be given in both oral and written form whenever possible and 
deemed appropriate by the IRB/IEC. Subjects, their relatives, or, if necessary, legal representatives 
must be given ample opportunity to inquire about details of the study. 
Subject information and the ICF must be in a language fully comprehensible to the prospective 
subject. The written information must be provided to the subject to give him or her sufficient time 
to understand the information and to prepare questions before being asked for his or her consent. 
The investigator must confirm that the text was understood by the subject. The subject will then 
sign and date the IRB/IEC-approved consent form indicating that he or she has given his or her 
consent to participate in the study. The signature confirms that the consent is based on information 
that has been understood. The form will also be signed by the investigator obtaining the consent 
and annotated with the study subject number. Each subject’s signed ICF must be kept on file by 
the investigator for possible inspection by regulatory authorities, Quantum Genomics, and/or the 
sponsor’s designee. Collection of informed consent has to be documented on the eCRF. 
Furthermore, the subject will be informed that if he or she wishes to dropout or withdraw (see 
Section 8.3) at any time during the study, this will not have any negative consequences. Subjects 
may be withdrawn by the investigator if any change related to safety or ethics precludes further 
participation in the study. Subjects will be asked to agree to a final assessment in the event of an 
early termination of the study. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 88 of 96 
Subjects will be informed that data from their case may be stored in a computer without inclusion 
of their name and that such data will not be revealed to any unauthorized third party. Data will be 
reviewed by the monitor, an independent auditor, and possibly by representatives of regulatory 
authorities and/or IRBs/IECs. The terms of the local data protection legislation will be applied as 
appropriate. 
16.3. Approval by Institutional Review Board and Independent Ethics Committee 
For IND studies, the minimum standards of conduct and requirements for informed consent and/or 
assent are defined in the Food and Drug Administration (FDA) regulations. 
A valid IRB/IEC must review and approve this protocol before study initiation. Written 
notification of approval is to be provided by the investigator to the sponsor’s monitor before 
shipment of investigational drug supplies, and will include the date of the committee’s approval 
and the chairperson’s signature. This written approval must consist of a completed sponsor form, 
IRB/IEC approval form, or written documentation from the IRB/IEC containing the same 
information. 
Until written approval by the IRB/IEC has been received by the investigator, no subject may 
undergo any procedure not part of routine care for the subject’s condition. 
Protocol amendments must also be reviewed and approved by the IRB/IEC. Written approval from 
the IRB/IEC, or a designee, must be received by Quantum Genomics before implementation. This 
written approval will consist of a completed IRB/IEC approval form or written documentation 
from the IRB/IEC containing the same information. 
16.4. Finance and Insurance 
Details on finance and insurance will be provided in a separate agreement between the investigator 
and the sponsor. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 89 of 96 
17. REFERENCES 
1. 
Mahmood SS, Wang TJ. The epidemiology of congestive heart failure: the Framingham 
Heart Study perspective. Glob Heart. 2013;8(1):77–82. 
2. 
Cowie MR, Wood DA, Coats AJ, et al. Incidence and aetiology of heart failure; a 
population-based study. Eur Heart J. 1999;20(6):421–428. 
3. 
Klersy C, De Silvestri A, Gabutti G, et al. Economic impact of remote patient monitoring: 
an integrated economic model derived from a meta-analysis of randomized controlled trials 
in heart failure. Eur J Heart Failure. 2011;13(4):450–459. 
4. 
Mortara A, La Rovere MT, Pinna GD, et al. Arterial baroreflex modulation of heart rate in 
chronic heart failure: clinical and hemodynamic correlates and prognostic implications. 
Circulation. 1997;96(10):3450–3458. 
5. 
Packer M. Neurohumoral interactions and adaptations in congestive heart failure. 
Circulation. 1988;77(4):721–730. 
6. 
Brunner-La Rocca HP, Esler MD, Jennings GL, Kaye DM. Effects of cardiac sympathetic 
nervous activity on mode of death in congestive heart failure. Eur Heart J. 
2001;22(13):1136–1143. 
7. 
Lee CR, Watkins ML, Patterson JH, et al. Vasopressin: a new target for the treatment of 
heart failure. Am Heart J. 2003;146(1):9–18. 
8. 
Goldsmith SR, Francis GS, Cowley AW Jr, Levine TB, Cohn JN. Increased plasma arginine 
vasopressin levels in patients with congestive heart failure. J Am Coll Cardiol. 
1983;1(6):1385–1390. 
9. 
Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in 
patients with left ventricular dysfunction with and without congestive heart failure: 
a substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation. 
1990;82(5):1724–1729. 
10. Widimsky P, Wijns W, Fajadet J, et al. Reperfusion therapy for ST elevation acute 
myocardial infarction in Europe: description of the current situation in 30 countries. Eur 
Heart J. 2010;31:943–957. doi:10.1093/eurheartj/ehp492. 
11. Ward MJ, Kripalani S, Zhu Y, et al. Incidence of Emergency Department Visits for 
ST-Elevation Myocardial Infarction in a Recent 6-Year Period in the United States. Am J 
Cardiol. 2015;115(2): 167–170. doi:10.1016/j.amjcard.2014.10.020. 
12. Park H, Kim HK, Jeong MH, et al. Clinical impacts of inhibition of renin–angiotensin system 
in patients with acute ST-segment elevation myocardial infarction who underwent successful 
late percutaneous coronary intervention. J Cardiol. 2017;69(1):216–221. 
13. Tokmakova MP, Skali H, Kenchaiah S et al. Chronic kidney disease, cardiovascular risk, 
and response to angiotensin-converting enzyme inhibition after myocardial infarction - the 
Survival 
And 
Ventricular 
Enlargement 
(SAVE) 
study. 
Circulation. 
2004;110(24):3667-3673. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 90 of 96 
14. Kober 
L, 
Torp-Pedersen 
C, 
Carlsen 
JE, 
et 
al. 
A 
clinical 
trial 
of 
the 
angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular 
dysfunction after myocardial infarction: Trandolapril Cardiac Evaluation (TRACE) study 
group. New Engl J Med. 1995;333(25):1670–1676. 
15. The Acute Infarction Ramipril Efficacy (AIRE) study investigators. Effect of ramipril on 
mortality and morbidity of survivors of acute myocardial infarction with clinical evidence 
of heart failure. The Lancet. 1993;342(8875):821–828. 
16. Fournie-Zaluski MC, Coric P, Turcaud S, et al. “Mixed inhibitor-prodrug” as a new approach 
toward systemically active inhibitors of enkephalin-degrading enzymes. J Med Chem. 
1992;35(13):2473–2481. 
17. Gao J, Marc Y, Iturrioz X, Leroux V, Balavoine F, Llorens-Cortes C. A new strategy for 
treating hypertension by blocking the activity of the brain renin-angiotensin system with 
aminopeptidase A inhibitors. Clin Sci (Lond). 2014;127(3):135–148. 
18. Fournie-Zaluski MC, Fassot C, Valentin B, et al. Brain renin-angiotensin system blockade 
by systemically active aminopeptidase A inhibitors: a potential treatment of salt-dependent 
hypertension. Proc Natl Acad Sci U S A. 2004;101(20):7775–7780. 
19. Bodineau L, Frugière A, Marc Y, et al. Orally active aminopeptidase A inhibitors reduce 
blood 
pressure: 
a 
new 
strategy 
for 
treating 
hypertension. 
Hypertension. 
2008;51(5):1318-1325. 
20. Marc Y, Gao J, Balavoine F, et al. Central antihypertensive effects of orally active 
aminopeptidase A inhibitors in spontaneously hypertensive rats. Hypertension 2012; 60, 
411-418. 
21. Huang BS, Ahmad M, White RA, et al. Inhibition of brain angiotensin III attenuates 
sympathetic hyperactivity and cardiac dysfunction in rats post-myocardial infarction; 
Cardiovascular Research. 2013; 97, 424–431. 
22. Leenen FHH, Ahmad M, Marc Y, et al. Specific Inhibition of Brain Angiotensin III 
formation as a new strategy for prevention of heart failure after myocardial infarction. 
Journal of Cardiovascular Pharmacology (In press). 
23. Quantum Genomics, QGC001 Investigator’s Brochure. Edition Number QGC001IBPIIA5. 
Release date 11-Jan-2018. 
24. U.S. Food & Drug Administration. Multiple endpoints in clinical trials – guidance for 
industry. https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/ 
document/ucm536750.pdf. Updated January 2017. Accessed 24 Aug 2018. 
25. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and 
treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and 
Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. 
Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart 
J. 2012;33(14):1787–1847. 
26. McMurray J, Cohen-Solal A, Dietz R, et al. Practical recommendations for the use of 
ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in 
heart failure: putting guidelines into practice. Eur J Heart Fail. 2005;7(5):710–721. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 91 of 96 
27. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 
ACCF/AHA Guideline for the Management of Heart Failure: a report of the American 
College of Cardiology/American Heart Association task force on clinical practice guidelines 
and the Heart Failure Society of America. Circulation. 2017;136(6):e137–e161. 
28. Manning WJ, Pennell DJ. Cardiovascular Magnetic Resonance. 2nd ed. Philadelphia, PA: 
Saunders; 2010. 
29. Grothues F, Moon JC, Bellenger NG, Smith GS, Klein HU, Pennell DJ. Interstudy 
reproducibility of right ventricular volumes, function, and mass with cardiovascular 
magnetic resonance. Am Heart J. 2004;147(2):218–223. 
30. Sackner-Bernstein J, Pecora A. Comparison of infarct size and left ventricular ejection 
fraction as surrogate endpoints for STEMI trials: evaluating the strength of the evidence. Eur 
Heart J. 2013;34, Issue suppl_1:5309. 
31. Greupner J, Zimmermann E, Grohmann A, Dübel HP, Althoff T, Borges AC, Rutsch W, 
Schlattmann P, Hamm B, Dewey M. Head-to-head comparison of left ventricular function 
assessment with 64-row computed tomography, biplane left cineventriculography, and both 
2- and 3-dimensional transthoracic echocardiography: comparison with magnetic resonance 
imaging as the reference standard. J Am Coll Cardiol, 2012;59(21): 1897-1907. 
32. Bellenger NG, Davies LC, Francis JM, Coats AJS, Pennell DJ. Reduction in sample size for 
studies of remodelling in heart failure by the use of cardiovascular magnetic resonance. J 
Cardiovasc Magn Reson. 2000;2(4):271-278. 
33. Burns RJ, Gibbons RJ, Yi Q, et al. The relationships of left ventricular ejection fraction, 
end-systolic volume index and infarct size to six-month mortality after hospital discharge 
following 
myocardial 
infarction 
treated by thrombolysis. 
J Am Coll Cardiol. 
2002;39(1):30-36. 
34. Venkatesh BA, Donekal S, Yoneyama K, Wu C, Fernandes VR, Rosen BD, Shehata ML, 
McClelland R, Bluemke DA, Lima JA. Regional myocardial functional patterns: 
Quantitative tagged magnetic resonance imaging 
in an adult population 
free of 
cardiovascular risk factors: The multi-ethnic study of atherosclerosis (MESA). J Magn 
Reson Imaging. 2015;42(1):153-159. doi: 10.1002/jmri.24749. Epub 2014 Sep 15. 
35. Taylor RJ, Moody WE, Umar F, Edwards NC, Taylor TJ, Stegemann B, Townend JN, Hor 
KN, Steeds RP, Mazur W, Leyva F. Myocardial strain measurement with feature-tracking 
cardiovascular magnetic resonance: normal values. Eur Heart J Cardiovasc Imaging. 
2015;16(8):871-881. doi: 10.1093/ehjci/jev006. Epub 2015 Feb 23. 
36. Lamy J, Soulat G, Evin M, Huber A, de Cesare A, Giron A, Diebold B, Redheuil A, 
Mousseaux E, Kachenoura N. Scan-rescan reproducibility of ventricular and atrial MRI 
feature 
tracking 
strain. 
Comput 
Biol 
Med. 
2018;92:197-203. 
doi: 
10.1016/j.compbiomed.2017.11.015. Epub 2017 Nov 24. 
37. Tee M, Noble A, Bluemke DA. Imaging techniques for cardiac strain and deformation: 
comparison of echocardiography, cardiac magnetic resonance and cardiac computed 
tomography. Expert Rev Cardiovasc Ther. 2013;11(2):221–231. 
38. Kelle S, Roes SD, Klein C, et al. Prognostic value of myocardial infarct size and contractile 
reserve using magnetic resonance imaging. J Am Coll Cardiol. 2009;54(19):1770–1777. 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 92 of 96 
39. Eitel I, de Waha S, Wöhrle J, et al. Comprehensive prognosis assessment by CMR imaging 
after 
ST-segment 
elevation 
myocardial 
infarction. 
J 
Am 
Coll 
Cardiol. 
2014;64(12):1217-1226. 
40. Stone GW, Selker HP, Thiele H, et al. Relationship between infarct size and outcomes 
following primary PCI: patient-level analysis from 10 randomized trials. J Am Coll Cardiol. 
2016;67(14):1674–1683. 
41. Baron N, Kachenoura N, Cluzel P, Frouin F, Herment A, Grenier P, Montalescot G, Beygui 
F. Comparison of various methods for quantitative evaluation of myocardial infarct volume 
from magnetic resonance delayed enhancement data. Int J Cardiol. 2013;167(3):739-744. 
doi: 10.1016/j.ijcard.2012.03.056. Epub 2012 Mar 27. 
42. Kip KE, Hollabaugh, K, Marroquin OC, Williams DO. The problem with composite end 
points in cardiovascular studies: the story of major adverse cardiac events and percutaneous 
coronary intervention. J Am Coll Cardiol. 2008;51(7):701–707. 
43. Schreiber D, Miller SM. Cardiac markers. In: Brenner BE, chief editor. Medscape. 
https://emedicine.medscape.com/article/811905-overview. Updated 08 Jan 2017. Accessed 
11 Sep 2018. 
44. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the 
management of patients with non–ST-elevation acute coronary syndromes: a report of the 
American College of Cardiology/American Heart Association Task Force on practice 
guidelines. J Am Coll Cardiol. 2014;64(24):e139–e228. 
45. Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute 
coronary syndromes in patients presenting without persistent ST-segment elevation: task 
force for the management of acute coronary syndromes in patients presenting without 
persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 
2016;37(3):267–315. 
46. Lee KL, Woodlief LH, Topol EJ, et al. Predictors of 30-day mortality in the era of 
reperfusion for acute myocardial infarction. Results from an international trial of 41,021 
patients. GUSTO-I Investigators. Circulation. 1995;91(6):1659–1668. 
 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 93 of 96 
18. ATTACHMENTS 
18.1. Investigator’s Agreement 
PROTOCOL NUMBER: 
QGC001-2QG4 
PROTOCOL TITLE: 
A Phase 2, Double-blind, Active-controlled, Dose-titrating 
Efficacy and Safety Study of Firibastat (QGC001) Compared 
to Ramipril Administered Orally, Twice Daily, Over 12 Weeks 
to Prevent Left Ventricular Dysfunction after Acute 
Myocardial Infarction 
FINAL PROTOCOL: 
Global Amendment V3.0, 10-Oct-2019 
The undersigned acknowledges possession of and has read the product information (e.g., the IB) 
on the IP and has discussed these data with the study monitor. Having considered fully all the 
available information, the undersigned considers that it is ethically justifiable to give the IP to 
selected subjects in his/her care, according to the study protocol. 
He or she agrees to use the study material, including IP, only as specified in the protocol. He or 
she understands that changes cannot be made to the protocol without prior written approval of 
Quantum Genomics. 
He or she understands that any deviation from the protocol may lead to early termination of the 
study. 
He or she agrees to report to Quantum Genomics within time any clinical AE or abnormal 
laboratory value that is serious, whether or not considered related to the administration of IP. 
He or she agrees to comply with Quantum Genomics and regulatory requirements for the 
monitoring and auditing of this study. 
In addition, he or she agrees that the study will be carried out in accordance ICH, the Declaration 
of Helsinki, and the local laws and regulations relevant to the use of new therapeutic agents. 
I, the undersigned, have carefully read this protocol and agree that it contains all the necessary 
information required to conduct the study. 
Principal Investigator: 
Printed Name: 
 
 
 
Signature: 
 
 
 
 
Date: 
 
 
 
Investigator’s name and address (stamp) 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 94 of 96 
APPENDICES 
A. 
Study-specific Requirements 
B. 
Regulations and Good Clinical Practice Guidelines 
 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 95 of 96 
A. Study-specific Requirements 
Killip Classification for HF 
The Killip classification46 is widely used in patients presenting with acute MI for the purpose of 
risk stratification, as follows: 
• 
Killip class I includes individuals with no clinical signs of heart failure 
• 
Killip class II includes individuals with rales or crackles in the lungs, an S 3 gallop, and 
elevated jugular venous pressure 
• 
Killip class III describes individuals with frank acute pulmonary edema 
• 
Killip class IV describes individuals in cardiogenic shock or hypotension (measured as 
systolic blood pressure <90 mmHg), and evidence of low cardiac output (oliguria, 
cyanosis, or impaired mental status) 
 
 
 


Quantum Genomics 
Confidential 
 
QGC001-2QG4 
10-Oct-2019 
Global Amendment Final V3.0 
AD-MW-07.07 16-Jul-2018 
Page 96 of 96 
B. Regulations and Good Clinical Practice Guidelines 
1. Regulations 
Refer to the following United States Code of Federal Regulations (CFR): 
• 
FDA Regulations 21 CFR, Parts 50.20 – 50.27 
Subpart B – Informed Consent of Human Subjects 
• 
FDA Regulations 21 CFR, Parts 56.107 – 56.115 
Part 56 – Institutional Review Boards 
Subpart B – Organization and Personnel 
Subpart C – IRB Functions and Operations 
Subpart D – Records and Reports 
• 
FDA Regulations 21 CFR, Parts 312.50 – 312.70 
Subpart D – Responsibilities of Sponsors and Investigators 
Refer to the following European Directives (and applicable regulations/guidances): 
• 
European Directive 2001/20/EC and related guidance documents 
• 
European Directive 2005/28/EC and related guidance documents 
2. Good Clinical Practice Guidelines 
ICH GCP guidelines can be found at the following URLs: 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_ 
Guideline.pdf 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__
Step_4.pdf 
 

SAP_001.pdf: 
 
STATISTICAL ANALYSIS PLAN 
 
 
Confidential 
TMPL-SOP-STAT-001a-V1-30-OCT-2018 
 Page 1/31 
 
 
 
Sponsor: Quantum Genomics 
Protocol: QGC001-2QG4 
EudraCT number: 2018‐003146‐17 
  
A Phase 2, Double-blind, Active-controlled, Dose-titrating Efficacy and Safety Study of Firibastat 
(QGC001) Compared to Ramipril Administered Orally, Twice Daily, Over 12 Weeks to Prevent Left 
Ventricular Dysfunction after Acute Myocardial Infarction 
VERSION: Final 2.0 
DATE: 20JUL2021 
 
 
 
 
Signatures: 
AIXIAL : 
 Isabelle Josse (Project Manager / Senior statistician) 
 
 
 
 
 
 Signature 
 Date 
 
 
 
Quantum 
Genomics: 
 
Bruno Besse (Chief Medical Officer) 
 
 
 
 
 
 Signature 
 
Date 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 2/31 
TMPL-SOP-STAT-001a 
 
TABLE OF CONTENTS 
ABBREVIATIONS .............................................................................................................................. 4 
INTRODUCTION ............................................................................................................................... 6 
1. PLANNED CHANGES FROM STUDY PROTOCOL ............................................................................ 6 
2. STUDY OBJECTIVES ..................................................................................................................... 6 
2.1 PRIMARY OBJECTIVE ........................................................................................................................ 6 
2.2 SECONDARY OBJECTIVES ................................................................................................................. 6 
3. STUDY DESIGN ............................................................................................................................ 7 
3.1 BRIEF DESCRIPTION OF STUDY DESIGN ............................................................................................ 7 
3.2 RANDOMIZATION ............................................................................................................................. 8 
4. STUDY ENDPOINTS ..................................................................................................................... 8 
4.1 DEMOGRAPHY AND BASELINE DATA .................................................................................................. 8 
4.2 PRIMARY ENDPOINT ......................................................................................................................... 8 
4.3 SECONDARY ENDPOINTS .................................................................................................................. 8 
5. DEFINITIONS .............................................................................................................................. 9 
5.1 STUDY DATABASE AND EXTERNAL DATA ........................................................................................... 9 
5.2 LABELS USED IN SAP AND IN STATISTICAL OUTPUTS ........................................................................ 9 
5.3 BASELINE VALUES ............................................................................................................................ 9 
6. ANALYSIS SETS ........................................................................................................................... 9 
6.1 SAFETY POPULATION ....................................................................................................................... 9 
6.2 ITT POPULATION ............................................................................................................................ 10 
6.3 mITT POPULATION ......................................................................................................................... 10 
6.4 PP POPULATION ............................................................................................................................. 10 
6.5 PROTOCOL DEVIATIONS ................................................................................................................. 10 
6.6 EXPLORATORY SUBGROUPS ............................................................................................................ 10 
7. STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE ........................................... 10 
7.1 GENERAL PRINCIPLES ..................................................................................................................... 11 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 3/31 
TMPL-SOP-STAT-001a 
 
7.1.1 Descriptive statistics .......................................................................................................... 11 
7.1.2 Rounding procedures ......................................................................................................... 11 
7.1.3 Unscheduled/ repeated assessments ................................................................................... 11 
7.1.4 Missing data ...................................................................................................................... 11 
7.1.5 Methods for handling of incomplete dates/ times ................................................................. 12 
7.1.6 Validation of statistical programming................................................................................... 12 
7.2 STUDY SUBJECTS ........................................................................................................................... 12 
7.3 DESCRIPTION OF BASELINE CHARACTERISTICS .............................................................................. 12 
7.4 EXPOSURE AND COMPLIANCE ......................................................................................................... 14 
7.5 ANALYSES OF EFFICACY ................................................................................................................. 15 
7.5.1 Primary efficacy endpoint ................................................................................................... 15 
7.5.2 Secondary efficacy endpoint ............................................................................................... 18 
7.6 ANALYSES OF SAFETY ..................................................................................................................... 19 
7.6.1 Adverse events .................................................................................................................. 19 
7.6.2 Clinical examination findings ............................................................................................... 20 
7.6.3 Vital signs ......................................................................................................................... 20 
7.6.4 Clinical laboratory evaluations ............................................................................................ 20 
7.6.5 Twelve-lead electrocardiogram ........................................................................................... 20 
7.7 INTERIM ANALYSES ........................................................................................................................ 21 
7.8 DETERMINATION OF SAMPLE SIZE .................................................................................................. 21 
8. LIST OF TABLES, FIGURES AND LISTINGS ................................................................................ 22 
8.1 Section 10 of CSR (STUDY SUBJECTS) ............................................................................................. 22 
8.3 Section 11 of CSR (EFFICACY EVALUATION) ..................................................................................... 23 
8.4 Section 12 of CSR (SAFETY EVALUATION) ........................................................................................ 26 
8.5 Appendix 16.2 of CSR (SUBJECT DATA LISTINGS) ............................................................................ 28 
REFERENCES .................................................................................................................................. 30 
DOCUMENT HISTORY ..................................................................................................................... 31 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 4/31 
TMPL-SOP-STAT-001a 
 
ABBREVIATIONS 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
ATC 
Anatomic, Therapeutic, Chemical (Classification System for Drugs) 
BID 
Bis in die (twice daily) 
CI 
Confidence Interval 
DBP 
Diastolic blood pressure 
eCRF 
Electronic Case Report Form 
eGFR 
Estimated Glomerular Filtration Rate 
CMRI 
Cardiac Magnetic Resonance Imaging 
CRP 
C-reactive Protein 
CSR 
Clinical Study Report 
DB 
Database 
EOT 
End-of-Treatment 
ICH 
International Conference of Harmonization 
IA 
Interim Analysis 
IP 
Investigational Product 
ITT 
Intent-To-Treat  
mITT 
Modified Intent-To-Treat 
LVEF 
Left Ventricular Ejection Fraction 
MACE 
Major Cardiac Event 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Myocardial Infarction 
NT-proBNP 
N-terminal Pro B-type Natriuretic Peptide 
PIIINP 
Procollagen Type III Aminoterminal Peptide 
PCI 
Percutaneous Coronary Intervention 
PP 
Per-protocol 
PT 
Preferred Term 
Q1 
The first quartile 
Q3 
The third quartile 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 5/31 
TMPL-SOP-STAT-001a 
 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Systems 
SBP 
Systolic blood pressure 
SD 
Standard Deviation 
SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 6/31 
TMPL-SOP-STAT-001a 
 
INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the statistical analyses to be performed on the study, contains the 
definition of analysis populations and protocol deviations, specifies the primary and secondary endpoints to be 
analyzed and outlines the outputs (tables, listings and figures) to be compiled in the Clinical Study Report (CSR). 
This analysis plan is based on the final versions of Study Protocol Final Version 1.0 dated 04-DEC-2018 (including 
local final versions: Final Version 4.0 for France dated 09-OCT-2019, Final Version 5.0 for Germany dated  
10-OCT-2019, and Final Version for UK dated 09-OCT-2019) and the Global Amendment to the Study Protocol 
Version 3.0 dated 10-OCT-2019 and the electronic case report from (eCRF) Final Version 1.0 dated  
12-JUL-2019. The analyses closely follow the ICH guidelines for industry on topic E3 (Structure and Content of 
CSRs) and E9 (Statistical Principles for Clinical Trials).   
The SAP has to be finalized and approved before database (DB) lock and executed after DB lock. Protocol 
deviations have to be defined and subjects’ disposition into analysis populations has to be approved before DB 
lock. 
1. PLANNED CHANGES FROM STUDY PROTOCOL 
A single futility interim analysis (IA) performed by the independent statistician of the independent data 
monitoring committee was to be planned for the primary efficacy endpoint for the comparison of firibastat 50 
mg against ramipril when approximately 50% of the maximum number of subjects have completed the Day 84 
primary endpoint assessment. Due to the dynamic of subject inclusion in the study, the time of delivery of IA 
results is deemed too close to the end of the recruitment period. Therefore, it was decided to not perform IA. 
To complete the primary objective, several exploratory subgroups were added. 
2. STUDY OBJECTIVES 
2.1 
PRIMARY OBJECTIVE 
The primary objective of this study is to compare the effects of BID (bis in die) oral administration of 2 doses 
of firibastat to those of BID oral administration of ramipril on the change from Baseline in left ventricular ejection 
fraction (LVEF) assessed by cardiac magnetic resonance imaging (CMRI) on Day 84. 
2.2 
SECONDARY OBJECTIVES 
Secondary objectives include the following: 
• 
To compare the effects of BID administration of firibastat and ramipril on the change from baseline to 
Day 84 in left-ventricular end-diastolic and end-systolic volumes assessed by CMRI 
• 
To compare the effects of BID administration of firibastat and ramipril on the change from baseline to 
Day 84 in average peak of longitudinal and circumferential strain (assessed by CMRI) in the infarcted 
segments 
• 
To compare the effects of BID administration of firibastat and ramipril on infarct mass (assessed by 
CMRI) at Day 84 
• 
To compare the effects of BID administration of firibastat and ramipril on major cardiac event (MACE): 
combined clinical endpoint of cardiovascular death, new myocardial infarctions (MIs), and cardiac 
hospitalization over 84 days 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 7/31 
TMPL-SOP-STAT-001a 
 
• 
To compare the effects of BID administration of firibastat and ramipril on the change from Baseline to 
Day 84 in N-terminal pro b-type natriuretic peptide (NT-proBNP), procollagen type III aminoterminal 
peptide (PIIINP), and C-reactive protein (CRP) 
• 
To compare the effects of BID administration of firibastat and ramipril on the slope of decrease in 
copeptin blood level change between baseline and Day 84 
• 
To compare the safety of firibastat and ramipril 
3. STUDY DESIGN 
3.1 
BRIEF DESCRIPTION OF STUDY DESIGN 
This phase 2, multicenter, randomized, double-blind, active-controlled, dose-titration clinical study is designed 
to compare the efficacy and safety of firibastat with ramipril in the prevention of left ventricular dysfunction 
after acute anterior MI. A total of 294 male and female subjects are randomized at about 38 sites in Europe 
and in the US to obtain 264 evaluable subjects. Subjects must be at least 18 years of age and have a diagnosis 
of first acute anterior MI with primary percutaneous coronary intervention (PCI) of the index-MI-related artery 
no earlier than 3 hours after acute MI and within 24 hours after the MI.  
Subjects are randomly assigned to 1 of the following 3 treatment groups in a 1:1:1 ratio: 
• 
Group 1: Subjects receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks 
• 
Group 2: Subjects receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks 
• 
Group 3: Subjects receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks 
98 subjects are randomized into each treatment group. The first capsule of the investigational product (IP) is 
administered on Day 1 as soon as possible after the CMRI, which is performed no later than 72 hours after MI. 
Subjects then take 1 capsule of the IP BID until the next visit. The maximum treatment duration for each subject 
is 87 days. 
It should be noted that the subjects’ dosage is up-titrated and/or down-titrated according a specific titration 
procedure described in the study protocol.  
This clinical study is considered completed when the last subject’s last study visit has occurred.  
All subjects are informed that they are free to withdraw from participation in this study at any time, for any 
reason, and without prejudice. The sponsor reserves the right to request the withdrawal of a subject due to 
protocol deviations or other reasons. The investigator also has the right to withdraw subjects from the study at 
any time for lack of therapeutic effect that is intolerable or otherwise unacceptable to the subject, for intolerable 
or unacceptable adverse events (AEs), intercurrent illness, non-compliance with study procedures, 
administrative reasons, or in the investigator’s opinion, to protect the subject’s best interest.  
If a subject is withdrawn before completing the study, the reason for withdrawal and the date of discontinuation 
are recorded on the appropriate page of the eCRF form. Whenever possible and reasonable, the evaluations 
that were to be conducted at the completion of the study should be performed at the time of premature 
discontinuation. 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 8/31 
TMPL-SOP-STAT-001a 
 
3.2 
RANDOMIZATION 
In this parallel-group randomized study, subjects who meet study entry criteria are randomly assigned in a 
1:1:1 ratio to initially receive either 100 mg firibastat daily (Group 1), 500 mg firibastat daily (Group 2), or 5 
mg ramipril daily (Group 3), respectively. The randomization schedule is computer-generated using a permuted 
block algorithm and randomly allocates IP to randomization numbers. The randomization numbers are assigned 
sequentially through a web-allocation system as subjects are entered into the study. 
The randomization schedule is prepared by a subcontracted company before the start of the study. No one 
involved in the study performance has access to the randomization schedule before official unblinding of 
treatment assignment. No subject is randomized into this study more than once. 
All subjects, investigators, and study personnel involved in the conduct of the study, including data 
management, are blinded to treatment assignment with the exception of a specified independent, unblinded 
statistician and programmer, who has access to the randomization code for interim analysis needs. The 
unblinded study personnel do not participate in study procedures or data analysis prior to unblinding of the 
study data to all study-related personnel with exception of the independent statistician. Unblinded personnel 
who are not otherwise involved in the study prepare the data for review. 
Overall unblinding takes place at the end of the study only after DB lock has been achieved. 
4. STUDY ENDPOINTS 
4.1 
DEMOGRAPHY AND BASELINE DATA 
Demographic data include age, gender, height and weight. Baseline subject characteristics include medical 
history, clinical examination findings at Screening, results of the coronary angiography, acute MI details, and 
troponin peak test. 
4.2 
PRIMARY ENDPOINT 
The primary efficacy endpoint is the change from baseline to Day 84 in LVEF assessed by CMRI (centralized 
reading). 
4.3 
SECONDARY ENDPOINTS 
Secondary efficacy endpoints: 
• 
Change from baseline to Day 84 in left-ventricular end-diastolic and end-systolic volumes assessed by 
CMRI (centralized reading) 
• 
Change from baseline to Day 84 in average peak of longitudinal and circumferential strain in the 
infarcted segments assessed by CMRI (centralized reading) 
• 
Infarct mass at end-of-treatment (EOT) (Day 84) assessed by CMRI (centralized reading) 
• 
MACE (i.e., cardiovascular deaths, new MIs, and cardiac hospitalizations) as adjudicated by an 
independent committee 
• 
Change from baseline in NT-proBNP, PIIINP, and CRP levels to Day 84 
• 
Slope of decrease in copeptin over time 
Safety endpoints: 
• 
All AEs, AEs of special interest, which include allergic reactions and diabetes insipidus, and clinical 
laboratory evaluations 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 9/31 
TMPL-SOP-STAT-001a 
 
• 
Change from baseline in clinic systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart 
rate at each visit 
• 
Change from baseline in sodium, potassium, aspartate aminotransferase, and alanine aminotransferase 
blood levels and estimated glomerular filtration rate (eGFR) 
5. DEFINITIONS 
Day 84 is the day of treatment discontinuation (i.e. 84 days [±3 days] after the Inclusion Visit [Day 1]) as long 
treatment discontinuation was not premature. 
MACEs are defined as cardiovascular deaths, new MIs, and cardiac hospitalizations. 
5.1 
STUDY DATABASE AND EXTERNAL DATA 
Data collected and validated in a study DB are analyzed.  
The external data are transformed into format suitable for analysis (SAS datasets) and analyzed. The provider 
of external data is responsible for the quality of those data. 
5.2 
LABELS USED IN SAP AND IN STATISTICAL OUTPUTS 
Labels used for study visits: 
SCR 
  
Screening 
BAS 
 
Baseline 
V1 - V6 
Visit 1 - Visit 6 
EOT 
  
End-of-treatment 
5.3 
BASELINE VALUES 
For CMRI data, baseline is defined as the last value reported before or within 8 hours of taking the first IP. For 
other data, baseline is defined as the last value before first IP. 
6. ANALYSIS SETS 
The following 4 analysis populations are defined in the study protocol (section 13.1.1): 
• 
Safety population 
• 
Intent-to-treat (ITT) population 
• 
Modified intent-to-treat (mITT) population 
• 
Per-protocol (PP) population 
6.1 
SAFETY POPULATION 
The safety population consists of all subjects who receive at least 1 dose of the IP. This population is based on 
the treatment actually received by the subject and is used for the analysis of the safety endpoints. 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 10/31 
TMPL-SOP-STAT-001a 
 
6.2 
ITT POPULATION 
The ITT population consists of all randomized subjects. This population is based on the treatment to which the 
subject was randomized. Any subject who receives an allocated kit number is considered to have been 
randomized. Individual subject data listings will be generated on ITT population if all treated subjects are 
randomized, else these listings will be generated on randomized or treated subjects. 
6.3 
mITT POPULATION 
The mITT population consists of all randomized subjects who receive at least 1 dose of the IP and who have at 
least 1 baseline (before or within 8 hours of taking the first IP) and 1 post-baseline efficacy assessment (LVEF). 
This population is based on the treatment to which the subject was randomized and is the primary population 
for the analysis of the efficacy endpoints. 
6.4 
PP POPULATION 
The PP population consists of all subjects from the mITT population without any major protocol deviation. This 
population is considered for sensitivity analysis of the primary endpoint. 
6.5 
PROTOCOL DEVIATIONS  
Details about handling of protocol deviations are included in the protocol deviation guidance plan. 
Deviations from the protocol including violations of inclusion/exclusion criteria are defined and assessed as 
minor or major in cooperation with the sponsor during a blind review meeting before the DB lock, together with 
the determination of inclusion in the analysis populations.  
6.6 
EXPLORATORY SUBGROUPS 
Exploratory Subgroups for the analysis of primary endpoint are defined as follows: 
- 
Gender (male /female); 
- 
Age group ( ≤65 years/ >65 years ); 
- 
Baseline eGFR level ( ≤60 mL/min/1.73m²/ >60 mL/min/1.73m²); 
- 
PCI successful ( Yes = TIMI 3/ No = TIMI 0, 1 or 2); 
- 
Time from onset of MI to PCI (2 options to define categories: either  ≤ median/> median or if not too 
imbalanced : <6h/ ≥ 6h); 
- 
Baseline LVEF ( <50%/ ≥50%); 
- 
Diabetes mellitus ( Yes / No, Yes= diabetes mellitus in medical history or any intake of anti-diabetic drug 
at baseline.). 
Theses exploratory analyses will be performed only if the sample size in each category of subgroup is enough. 
7. STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
This section describes the data analysis in details. The statistical methods are planned in accordance with 
the study protocol (section 13) and in accordance with ICH Topic E9 Statistical Principles for Clinical Trials. 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 11/31 
TMPL-SOP-STAT-001a 
 
7.1 
GENERAL PRINCIPLES 
Statistical package SAS (version 9.4) is used for analysis and for generation of tables, figures and listings. 
Unless otherwise indicated, all testing of statistical significance is 2-sided, and a difference resulting in a p-value 
of ≤ 0.05 is considered statistically significant. 
The acceptable risk of error for the statistical tests is set at 5%, except for treatment-by-covariates interactions. 
For those interactions, the level of significance is set at 10%. 
Individual subject data listings are generated by treatment group, subject identifier, country and visit (if 
applicable). 
7.1.1 Descriptive statistics 
Continuous variables are summarized using descriptive statistics (number of observations, mean, standard 
deviation (SD), median, the first quartile (Q1), the third quartile (Q3), minimum, and maximum). Frequency 
distribution (counts and percentages) are summarized for the categorical variables (to be noted percentages 
are calculated on available data). When applicable, 95% confidence interval (CI) of the mean (or the median) 
is provided for continuous variables, and the 95% CI of the proportion is displayed for each modality of 
categorical variables. 
Where appropriate, results are presented by treatment group as well as overall.  
7.1.2 Rounding procedures 
The following rounding procedures are used for all variables: 
- for minimum and maximum the same number of decimal places as the original value is used; 
- for mean, SD, median, Q1 and Q3, and 95% CI one more decimal place than the original value is used; 
- p-values are displayed with four decimal places; 
- all values reported as percentage are displayed with 1 decimal place (except no decimal place for 100%). 
7.1.3 Unscheduled/ repeated assessments 
For screening data, the last valid value is used for the analyses. For baseline data, the last valid value which 
meets the baseline definition is used for the analyses. For all other time points, the values at scheduled time 
points are used for calculation of summary statistics. Both unscheduled and scheduled measurements are listed 
in chronological order. 
7.1.4 Missing data 
In general, missing data are not imputed, i.e. complete case analyses are performed.  
For the analysis of primary efficacy endpoint, a sensitivity analysis is performed using a multiple imputation 
method in subjects who discontinued the study prior to Day 84. If the potential impact of the missing data (i.e., 
data recorded at premature discontinuation visit) is substantial and may result into a biased outcome, i.e., the 
proportion of missing data is more than 40%, then the imputation and the corresponding sensitivity analysis is 
not performed. 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 12/31 
TMPL-SOP-STAT-001a 
 
7.1.5 Methods for handling of incomplete dates/ times 
In general, if date and time are missing no imputation is applied. 
If a start time is missing for AE, it is imputed with the time of the first IP intake if the start date equals the first 
IP intake date, otherwise “00:00”. 
If the start day is missing for MACE, it is imputed with the first day of the month. 
7.1.6 Validation of statistical programming 
Outputs and programs are to be reviewed by a second AIXIAL statistician.  
Disposition of subjects into analysis populations is agreed with the sponsor. 
Logs of all programs used for the analysis and data preparation are checked for errors and unexpected warnings. 
Any undocumented updating of study data in statistical programs instead of change in clinical DB (or source 
data) is not allowed. Specifically, this refers to the cases where subjects or the data are added/ changed using 
a statistical program rather than updating the DB. This kind of hard coding can be proposed to correct 
deficiencies (missing values, wrong values, and wrong measurement units) in the DB when these errors are 
detected after DB lock.  
No hard coding is done in any programs used for the creation of analysis data sets, tables, listings, or analyses 
that are intended for external reporting after DB lock.   
This policy ensures integrity of clinical data, since no changes are made to the study data without appropriate 
documentation from the investigator sites and appropriate audit trails within the clinical trial DB. 
7.2 
STUDY SUBJECTS 
The numbers of subjects randomized, treated, completing, and withdrawing, along with reasons for withdrawal, 
are tabulated overall and by treatment group. 
The number of subjects randomized is also tabulated by country, treatment group and overall. Pattern of study 
premature discontinuations including the profile of subjects and reason and time to withdrawal are presented 
in listings to assess potential impact of dropouts on treatment comparisons. The number of subjects in each 
analysis population is reported and tabulated overall and by treatment group. 
Identified protocol deviations are listed together with indication whether they lead to exclusion from analysis 
populations. Major protocol deviations are summarized overall and by treatment group. 
7.3 
 DESCRIPTION OF BASELINE CHARACTERISTICS 
Demographic variables include calculated age, gender, height, and weight measured at Screening. The age is 
calculated in years as follows: 
- 
year of screening – year of birth if month of birth is missing or if month of birth lower or equal to month 
of screening 
- 
year of screening – year of birth -1 if month of birth higher than month of screening 
Baseline subject characteristics include medical history, clinical examination findings, and results of the coronary 
angiography defining the success or not of the procedure (TIMI 3 or not), the MI-related data, and troponin 
peak test measured/performed at Screening. 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 13/31 
TMPL-SOP-STAT-001a 
 
Time between onset of pain and PCI is calculated as the difference between the date of PCI and the date of 
onset of MI symptoms in hours.  
Demographics and baseline characteristics are listed and summarized overall and by treatment group on the 
mITT population using the standard sets of summary statistics as defined in Section 7.1.1.  
Medical history is listed and summarized by treatment group, by the number and percentage of subjects 
having each medical history, classified using MedDRA dictionary (system organ class (SOC) and preferred 
term (PT)) on the mITT population. Previous medication is defined as any treatment taken and stopped prior 
to the first IP dose intake (the day before the first IP dose intake or the same day). 
 
Concomitant medication is defined as any treatment taken at least once between the first IP dose intake and 
EOT Visit (Day 84) or Early Termination Visit, whichever occurs first (including those which started prior to the 
first IP dose intake and continued after that). 
Prior and concomitant medications are listed and summarized by treatment group, by the number and 
percentage of subjects taking each medication, classified using World Health Organization Drug Dictionary ATC 
classes (pharmacological subgroup – ATC level 3) and PTs on the mITT population. 
The status of active smoking, hypertension, diabetes and dyslipidemia are considered to be present at baseline 
if the medical history and concomitant medication meet the following conditions: 
 
MH 
Concomitant medication 
 
Preferred Term name 
Start date 
End date 
ATC code 3 
Start date 
Active 
smocking 
Tobacco user 
Nicotine dependence 
Missing date 
Before or the same 
day first intake of IP 
Missing 
After First IP 
Ongoing 
 
 
Hypertension 
Essential hypertension 
Hypertension 
 
 
 
Diabetes 
Diabetes mellitus 
Diabetic nephropathy 
Diabetic neuropathy 
Type 1 diabetes mellitus 
Type 2 diabetes mellitus 
 
Blood Glucose Lowering 
Drugs, Excl. Insulins 
Insulins And Analogues 
 
Dyslipidaemia 
Dyslipidaemia 
 
Lipid Modifying Agents, 
Combinations 
Lipid Modifying Agents, Plain 
Not Statin*: 
- 
Missing date 
- 
Before or the 
same day first 
intake of IP 
Statin*: 
Before the MI 
*Statins are the treatment with the following PT name  
- 
"Ezetimibe;Rosuvastatin Calcium"  
- 
"Ezetimibe;Simvastatin" 
- 
"Atorvastatin Calcium;Ezetimibe 
- 
"Atorvastatin" 
- 
"Atorvastatin Calcium" 
- 
"Pravastatin Sodium" 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 14/31 
TMPL-SOP-STAT-001a 
 
- 
"Rosuvastatin"  
- 
"Rosuvastatin Calcium" 
- 
"Simvastatin" 
7.4 
EXPOSURE AND COMPLIANCE  
For each subject mean and final dose, and the duration of exposure is calculated.  
The duration of exposure is calculated in days as the number of days between the first and the last 
administration of IP (date of last intake – date of first intake + 1). 
Final dose is considered to be the theoretical dose (see below the definition for the theoretical dose) of the last 
IP administered prior to EOT Visit (Day 84) or Early Termination Visit, whichever occurs first. 
Mean dose is calculated according to the following algorithm: 
Theoretical dose P1 = 50 mg of firibastat or 250 mg of firibastat or 2.5 mg of ramipril according to study group 
Theoretical dose P2 =  
- 
Theoretical dose P1 if no titration at V3  
- 
Theoretical dose P1 * 2 if up titration 
- 
0 mg if treatment discontinuation 
Theoretical dose P3 =  
- 
Theoretical dose P2 if no titration at V4  
- 
Theoretical dose P2 / 2 if down titration 
- 
Theoretical dose P2 * 2 if up titration 
- 
0 mg if treatment discontinuation 
Dose the day of V3 =  
- 
Theoretical dose P1 if no titration or if up-titration and first dose of up/down titration equal morning 
- 
Theoretical dose P1 / 2 + Theoretical dose P2 / 2 if up-titration and first dose of up/down titration equal 
evening 
Dose the day of V4 =  
- 
Theoretical dose P2 if no titration or if up-titration or down titration and first dose of up/down titration 
equal morning 
- 
Theoretical dose P2 / 2 + Theoretical dose P3 / 2 if up-titration or down titration and first dose of 
up/down titration equal evening 
Total dose =  
Theoretical Dose P1 * (Date of [V3-1] – Date of first intake + 1) + Dose the day of V3 + Theoretical dose P2 
* (Date of [V4-1] – Date of [V3+1] + 1) + Dose the day of V4 + Theoretical dose P3 * (Date of last intake – 
Date of [V4+1] +1). 
Note: The day of first intake, this calculation considered that the full dose was taken. In case of withdrawal 
premature, the calculation will be performed until the last intake 
Mean dose = Total dose / Duration of exposure 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 15/31 
TMPL-SOP-STAT-001a 
 
Investigational product administration is summarized in terms of each subject’s mean and final dose and in 
terms of duration of exposure. Descriptive statistics for these quantities, including the mean, median, SD, 
minimum, maximum, and quartiles, are provided by treatment group. Number of subjects who reached 
predefined/target doses at EOT Visit (Day 84) or Early Termination Visit, whichever occurs first and the schema 
of titration (No titration + No titration, No titration + Up titration, Up titration + No titration, Up titration + 
Down titration) are summarized by counts and percentages. 
All intake details per subject are provided in data listings. 
7.5 
ANALYSES OF EFFICACY 
The primary efficacy endpoint, i.e., the change from baseline in LVEF assessed by CMRI, is primarily analyzed 
on the mITT population. Sensitivity analyses is performed on the ITT and PP populations. Secondary efficacy 
endpoints are analyzed on the mITT population. 
For efficacy variables, descriptive statistics are given by treatment group at each assessment time point. The 
change from baseline is also presented if applicable (both listed and summarized). 
There is a single primary efficacy endpoint in the study – the change from baseline in LVEF assessed by CMRI 
on Day 84. The other efficacy endpoints are defined to be of secondary importance. Due to multiple treatment 
comparisons, a hierarchical step-down testing procedure is applied for the primary and secondary criteria to 
control the overall type I error rate. Only if superiority of firibastat 250 mg against ramipril is demonstrated at 
the 2-sided 5%-level, superiority of firibastat 50 mg against ramipril can be tested. Likewise, only if superiority 
of firibastat 50 mg against ramipril is demonstrated at the 2-sided 5%-level, superiority of firibastat 250 mg 
against firibastat 50 mg can be tested. The testing procedure stops as soon as a comparison is found to be not 
statistically significant at the 2-sided 5%-level. 
For each analyzed efficacy parameter, the normality assumption of model residuals distribution is checked using 
graphical methods, skewness and kurtosis values, and Shapiro-Wilk’s statistic. If there is a strong violation of 
the normality assumption (or violation of homogeneity of variances for analysis of covariance [ANCOVA]), a 
rank transformation is primarily done, and the statistical analysis model is applied to the ranks except for 
copeptin analysis. For copeptin analysis, a log base 10 transformation is preferred. 
7.5.1 Primary efficacy endpoint 
The absolute values and changes from baseline in LVEF are listed by subject and summarized with descriptive 
statistics. The changes from baseline are primarily analyzed using an ANCOVA. The ANCOVA includes treatment 
group as factor, baseline LVEF and country as covariates. For subjects who prematurely discontinue the study, 
measurements made at the time of study withdrawal are considered in the analysis. 
The adjusted mean is presented by treatment group. The difference in adjusted mean between the treatment 
groups, associated 95% CI and p-value are also presented using a hierarchical step-down testing procedure to 
control the overall type I error. 
Possible treatment-by-covariate interactions are investigated including the interaction term in the model for 
ANCOVA (1 separated model for each interaction). The adjusted mean difference between treatment groups 
will be computed. If the p-value is lower than 10% and the interaction is qualitative, then the main model will 
be performed by level of the covariate (in classes). 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 16/31 
TMPL-SOP-STAT-001a 
 
Sensitivity analyses of the primary efficacy endpoint: 
While subjects missing Day 84 data but having earlier data are included in the primary analysis, the 
interpretability of the results from the primary model depends on the missing data satisfying the missing 
completely at random. This signifies that data is missing independently of observed (or unobserved) variables. 
To support the validity of the conclusions drawn from this analysis, sensitivity analyses are performed to explore 
possible impact of dropout pattern on treatment comparisons. 
1. A complete case ANCOVA is performed on the values recorded on Day 84 (i.e., the measurement made at 
the time of the study premature discontinuation is not considered in the analysis) 
2. A sensitivity analysis is performed on the values recorded on Day 84 and the data imputed using a multiple 
imputation method in subjects who prematurely discontinued the study. This means that the data from 
premature discontinuation visits are considered as missing and are discarded from the analysis. Multiple 
imputation is used to impute missing Day 84 data in subjects who prematurely discontinued the study.  
The multiple imputation technique is a stepwise procedure. First, a plausible multivariable distribution for the 
missing values is estimated based on observed data. Missing values are then randomly drawn from this 
distribution resulting in a complete dataset. This procedure is repeated multiple times generating multiple 
datasets. The number of imputations is set to the proportion of missing data multiplied by 100. Second, the 
datasets are then analyzed separately producing multiple estimates, and third, the multiple estimates are pooled 
resulting in one single estimate. 
The multiple imputation technique is a stepwise procedure. First, a plausible multivariable distribution for the 
missing values is estimated based on observed data. Missing values are then randomly drawn from this 
distribution resulting in a complete dataset. This procedure is repeated multiple times generating multiple 
datasets. The number of imputations is set to the proportion of missing data multiplied by 100. Second, the 
datasets are then analyzed separately producing multiple estimates, and third, the multiple estimates are pooled 
resulting in one single estimate.  
The PROC MI procedure from SAS 9.4 is used under the MONOTONE REG option. The missing Day 84 data is 
imputed according to all the variables in the VAR statement. The number of imputations is automatically 
determined with the NIMPUTE = PCTMISSING option. A SEED value is used to guarantee the reproducibility of 
the multiple imputation. Lastly, PROC MIANALYZE is used to combine the adjusted means by treatment group 
and the adjusted mean differences.  To be noted type III p-values cannot be combined with PROC MIANALYZE.  
At the minimum, the regression model used to impute missing Day 84 data includes the baseline value, 
treatment group, and country as covariates. This imputation is performed under the assumption that Day 84 
values are missing at random, meaning that their missingness depends on observed variables. To improve the 
accuracy of imputed values as well as of the efficiency of the estimates, auxiliary variables are considered in 
the imputation model. Auxiliary variables are variables that may be correlated with the missing data or be good 
predictors of missingness. These variables will also serve to strengthen the missing at random assumption. In 
addition to the primary covariates, four auxiliary variables will be considered for the multiple imputation model:  
age (≤ 65 years / > 65 years), time between onset of MI and PCI (<6h / ≥ 6h),  PCI- Index MI-related artery 
(LAD / no LAD), and infarct mass (Yes / No). These variables have been associated with MI-related reduced 
LVEF.  
Auxiliary variables are included in the imputation model if 1) they have no missing values in the primary analysis 
population and 2) if they are correlated with the observed Day 84 values or if they are predictors of missingness. 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 17/31 
TMPL-SOP-STAT-001a 
 
For continuous variables, the correlation between the observed Day 84 values and the potential auxiliary 
variables is computed using PROC CORR. If the correlation coefficient is more than 0.1 and the resulting p-
value is less than 10%, then the variable is included in the imputation model. Should no correlation be found, 
a t-test is computed to compare the means of the continuous variable between subjects with different study 
completion statuses (i.e., subjects who prematurely discontinued the study and subjects who completed the 
study). If the conditions of normality and homoscedasticity are not verified, then a non-parametric Wilcoxon 
test is done instead. If the means differ at the level of 10%, then the variable is added to the imputation model.  
For categorical variables, a t-test (or Wilcoxon test) is used to compare the means of observed Day 84 values 
amongst the different categories. Alternatively, a chi-square test can be done to test the association between 
the categorical variable and study completion status. If the p-value is less than 10%, then the variable will be 
included in the imputation model. 
The primary analysis and the sensitivity analyses presented here above are repeated on the ITT and PP 
populations. 
Below is a sample program to conduct the multiple imputation sensitivity analyses: 
/* Imputation step */ 
proc mi data=<dataset_SA> nimpute = PCTMISSING seed=30185 out=<out_mi>; 
/* use a version of the dataset where Day84 is missing */ 
  class <trt> <country> <categorial auxiliary variable(s)>; 
  /* order of imputation - from most complete to least complete*/ 
  var <trt> <baseline> <country> <auxiliary variable1> <auxiliary variable2>         
<auxiliary variable3> <auxiliary variable4> <Day84> ;  
  monotone reg; 
run; 
/* Compute change from baseline with imputed data */ 
data <anal_mi>; 
  set <out_mi>; 
  <change> = <Day84> - <baseline> ; 
run; 
/* Analysis step */ 
ods output lsmeans=lsmeans type3=type3 estimates=diffs; 
proc mixed data = anal_mi method=type3; 
/* repeat the analysis for each imputed dataset */ 
  by _imputation_; 
  class <country> <trt>(ref=last); 
  model <change> = <baseline> <country> <trt>; 
  LSMEANS <trt> /CL diff=all; 
 
  estimate "High Dose(B) vs Reference(C)" <trt> 0 1 -1  /CL e; 
  estimate "Low Dose(A) vs Reference(C)"  <trt>  1 0 -1 /CL e; 
  estimate "High Dose(B) vs Low dose(A)"  <trt> -1 1 0  /CL e; 
run; 
/* Pooling step of adjusted means and mean differences */ 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 18/31 
TMPL-SOP-STAT-001a 
 
/* Sort by a grouping variable i.e. trt for lsmeans or label for diffs*/ 
proc sort data = <output table>; 
by <group variable> _imputation_; 
run; 
 
proc mianalyze data = <sorted output table>; by <group variable>; 
modeleffects estimate; 
stderr stderr; 
ods output parameterestimates = <pooled_estimatename>; 
run; 
Exploratory Subgroup analysis of the primary efficacy endpoint: 
The analysis of absolute values and changes from baseline in LVEF and the ANCOVA primary model (including 
the covariate of interest and the treatment-by-covariate interaction) are repeated on mITT for subgroups 
defined in Section 6.6. For subjects who prematurely discontinue the study, measurements made at the time 
of study withdrawal are considered in the analysis. 
Forest plots for mean differences to ramipril and for mean differences between higher dose and lower dose of 
firibastat are created by corresponding subgroup if applicable. 
Exploratory analysis of the primary efficacy endpoint: 
The analysis of absolute values and changes from baseline in LVEF and the ANCOVA primary model (including 
the covariate of interest and the treatment-by-covariate interaction) are repeated on mITT with combining 
higher dose and lower dose of firibastat compared to ramipril. For subjects who prematurely discontinue the 
study, measurements made at the time of study withdrawal are considered in the analysis. 
7.5.2 Secondary efficacy endpoint 
As for the primary efficacy endpoint, a hierarchical step-down testing procedure is applied for each of the 
secondary efficacy endpoints in order to control the overall type I error due to multiplicity of treatment 
comparisons. 
Change from baseline in left-ventricular end-diastolic and end-systolic volumes: 
The absolute values and changes from baseline in left-ventricular end-diastolic and end-systolic volumes 
assessed by CMRI are listed by subject and summarized with descriptive statistics and analyzed using an 
ANCOVA as for the primary efficacy endpoint, i.e., considering the treatment group as factor, baseline value 
and country as covariates. 
Change from baseline in average peak of longitudinal and circumferential strain: 
The absolute values and changes from baseline in the average peak of longitudinal and circumferential strain 
in the infarcted segments assessed by CMRI are listed by subject and summarized with descriptive statistics 
and analyzed using an ANCOVA as for the primary efficacy endpoint, considering the treatment group as factor 
and baseline value and country as covariates. 
Infarct mass: 
The infarct mass assessed by CMRI at the end of the treatment is listed by subject and analyzed using an 
ANCOVA. The ANCOVA includes treatment group as factor and country as covariate. 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 19/31 
TMPL-SOP-STAT-001a 
 
MACE: 
The MACE which occurred during the course of the study are adjudicated by an independent committee. The 
number of committee-confirmed events per subject are described per category (listed and summarized by PT). 
The time to first confirmed MACE is derived as the number of days elapsed from the first administration of study 
treatment to the first confirmed MACE onset. Descriptive statistics (mean, SD, median, Q1 and Q3, minimum 
and maximum) of this time is presented by treatment group on the safety population 
If the number of subjects with confirmed MACE is sufficient (at least 5 subjects in at least one group), the time 
to first confirmed MACE is tested using censored data analysis. For the subjects without MACE, the subject is 
censored and the time to first confirmed MACE is the number of days elapsed from the first administration of 
study treatment to EOT Visit (Day 84) or Early Termination Visit, whichever occurs first. Median or Q1 time with 
95% CI is estimated using the Kaplan-Meier method. Number and percentage of subjects who had an event or 
were censored are reported. A Kaplan-Meier survival curve is generated by treatment group. 
Changes from Baseline in NT-proBNP, PIIINP, and CRP: 
The absolute values and changes from baseline in NT-proBNP, PIIINP, and CRP are listed by subject and 
summarized with descriptive statistics, and analyzed using an ANCOVA as for the primary efficacy endpoint, 
considering the treatment group as factor and baseline value and country as covariates. 
Slope of decrease in copeptin: 
Copeptin is assessed at each visit. The change from baseline in copeptin are listed by subject and summarized 
with descriptive statistics; Copeptin is analyzed using a mixed model for repeated measures (MMRM) where 
intercept and slope considered as random. The model includes treatment group as a fixed factor, baseline value 
and country as covariates, and time, treatment group by time interaction, and baseline by time interaction. 
Time is calculated in days as date of copeptin assessment - date of first study treatment intake. The restricted 
maximum likelihood (REML) estimation approach is used, and the default covariance structure is unstructured. 
Estimate of slope is presented by treatment group. Difference in slopes between the treatment groups and 
associated 95% CI are also presented. Comparison of slopes between the treatment groups is performed using 
the hierarchical step-down testing procedure. 
The decrease of copeptin is graphically illustrated. The mean at each time point used for the figure is estimated 
from the model. 
7.6 
ANALYSES OF SAFETY 
7.6.1 Adverse events 
An AE is defined as treatment-emergent if the first onset or worsening is after the first administration of IP 
(firibastat and/or ramipril) and not more than 30 days after the last administration of IP. 
Adverse events are coded using MedDRA dictionary version 21.1 or higher.   
The number (%) of subjects reporting each treatment emergent AE (TEAE) are summarized by SOC and PT 
where subjects with more than one TEAE within a particular SOC and PT are counted only once for that SOC 
and PT. Percentages are based on the number of subjects actually receiving a given treatment (based on the 
safety population) within each treatment group. Separate summaries are given for all TEAEs, treatment-related 
AEs, Serious AEs (SAEs), and AEs leading to discontinuation of study treatment. 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 20/31 
TMPL-SOP-STAT-001a 
 
TEAEs are considered as related to the study treatment if for the question “Relationship to Study Drug?” the 
answer is “potentially related”, “probably related” or “definitely related” or missing. 
 
The following AEs of clinical and special interest are summarized separately: 
• Skin reactions reviewed by the dermatologists 
• Diabetes insipidus 
For skin reaction, the number (%) of subjects are summarized by final diagnosis and relationship to IP according 
to dermatologist 
Individual subject data listings of AEs including outcome, action taken, severity, relationship to IP, and 
seriousness are performed for overall AEs, SAEs, and drug-related SAEs. 
7.6.2 Clinical examination findings 
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual values and changes from 
baseline in weight are presented at each visit and by treatment group. Individual values of clinical examination 
findings are listed. 
7.6.3 Vital signs 
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual values and changes from 
baseline are presented at each visit and by treatment group for SBP, DBP, and HR. 
For SBP the frequencies of values <100 mmHg are tabulated at each visit and by treatment group. 
7.6.4 Clinical laboratory evaluations 
All laboratory data are converted to standard units.  
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual (absolute) values and changes 
from baseline values are presented for clinical laboratory values for each treatment group at each time point. 
The number of subjects with clinical laboratory values categorized as below, within, or above normal ranges, 
are tabulated showing the change from baseline (shift tables) for each clinical laboratory analyte by treatment 
group and by study visit. 
Laboratory values that are outside the normal range are also flagged in the data listings and presented with 
the corresponding normal ranges. Any out-of-range values that are identified by the investigator as being 
clinically significant are also shown in a data listing. 
If laboratory values equal to «<x» or «>x», then the value x will be retained for the analysis. 
The laboratory data are listed with suitable flags indicating abnormal values (L=Lower than reference range, 
H=Higher than reference range, NV = Normal value, CS = Clinically significant, NCS = Not clinically significant). 
7.6.5 Twelve-lead electrocardiogram 
The number and percentage of subjects with normal and abnormal ECG findings (rhythm, QRS duration) is 
summarized for each treatment group at each time point. 
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual (absolute) values and changes 
from baseline values are presented for QT duration for each treatment group at each time point. 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 21/31 
TMPL-SOP-STAT-001a 
 
7.7 
INTERIM ANALYSES 
The futility IA will not be performed (see Section 1). 
7.8 
DETERMINATION OF SAMPLE SIZE 
The sample size determination is based on the primary efficacy endpoint (i.e., the change from baseline in LVEF 
assessed by CMRI on Day 84), on an equal randomization, using a 2-sided 5% nominal level of significance. 
The SD of the primary efficacy variable is estimated to 10%. 
Based on an estimated difference of 5% between the treatment groups on the primary efficacy variable, around 
88 evaluable subjects per group are needed to achieve 90% power (accounting for the futility IA at 50% of the 
maximum information). Assuming of a dropout/non-evaluable rate of about 10%, 98 subjects per group are 
expected to be randomized, namely a total of 294 subjects. 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 22/31 
TMPL-SOP-STAT-001a 
 
8. LIST OF TABLES, FIGURES AND LISTINGS 
The table hereunder presents preliminary list of content of tables, figures and listings which will be integrated 
in study report. The structure and numbering are proposed according the ICH guidelines - E3: Structure and 
Content of CSRs. 
8.1 
Section 10 of CSR (STUDY SUBJECTS) 
Output Number  
Title 
Analysis 
population 
 
Section 10.1 
Disposition of subjects 
 
Table 
10.1.1 
Disposition of subjects 
ITT 
Table 
10.1.2 
Reasons for discontinuation of study  
ITT 
Listing 
10.1.1 
Other reasons for discontinuation of study 
ITT 
Table 
10.1.3 
Subjects randomized by country 
ITT 
Table 
10.1.4 
Overview of analysis populations 
All screened 
subjects 
Table 
10.1.5 
Major protocol deviations 
ITT 
 
Section 10.2 
Demographics and baseline characteristics 
 
Table 
10.2.1 
Demographics and clinical examination findings at Baseline mITT 
Table 
10.2.2 
Acute MI details and troponin peak test 
mITT 
Table 
10.2.3 
Results of the coronary angiography, TIMI flow after PCI – 
Central reading 
mITT 
Table 
10.2.4 
Medical History 
mITT 
Table 
10.2.5 
Prior medications 
mITT 
Table 
10.2.6 
Concomitant medications 
mITT 
 
Section 10.3 
Treatment exposure and compliance 
 
Table 
10.3.1 
Treatment exposure and compliance 
mITT 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 23/31 
TMPL-SOP-STAT-001a 
 
8.3 
Section 11 of CSR (EFFICACY EVALUATION) 
Output Number  
Title 
Analysis 
population 
Section 11.1 
Primary efficacy endpoints 
 
Table 
11.1.1 
Summary statistics of LVEF 
mITT 
Table 
11.1.2 
Сhanges from baseline in LVEF 
mITT 
Table 
11.1.3 
Primary efficacy model, treatment effects on changes from 
baseline in LVEF 
mITT 
Table 
11.1.4 
Sensitivity analysis on completed subjects: Primary efficacy model, 
treatment effects on changes from baseline in LVEF 
mITT 
Table 
11.1.5 
Sensitivity analysis, missing data imputed: Primary efficacy model, 
treatment effects on changes from baseline in LVEF 
mITT 
Table 
11.1.6 
Primary efficacy model, treatment effects on changes from 
baseline in LVEF, investigation of ‘Treatment by Baseline’ 
interaction 
mITT 
Table 
11.1.7 
Primary efficacy model, treatment effects on changes from 
baseline in LVEF, investigation of ‘Treatment by country’ 
interaction 
mITT 
Table 
11.1.8 
Summary statistics of LVEF 
ITT 
Table 
11.1.9 
Сhanges from baseline in LVEF 
ITT 
Table 
11.1.10 
Primary efficacy model, treatment effects on changes from 
baseline in LVEF 
ITT 
Table 
11.1.11 
Sensitivity analysis on completed subjects: Primary efficacy model, 
treatment effects on changes from baseline in LVEF 
ITT 
Table 
11.1.12 
Sensitivity analysis, missing data imputed: Primary efficacy model, 
treatment effects on changes from baseline in LVEF 
ITT 
Table 
11.1.13 
Summary statistics of LVEF 
PP 
Table 
11.1.14 
Сhanges from baseline in LVEF 
PP 
Table 
11.1.15 
Primary efficacy model, treatment effects on changes from 
baseline in LVEF 
PP 
Table 
11.1.16 
Sensitivity analysis on completed subjects: Primary efficacy model, 
treatment effects on changes from baseline in LVEF 
PP 
Table 
11.1.17 
Sensitivity analysis, missing data imputed: Primary efficacy model, 
treatment effects on changes from baseline in LVEF 
PP 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 24/31 
TMPL-SOP-STAT-001a 
 
Output Number  
Title 
Analysis 
population 
Section 11.2 
Primary efficacy endpoint – subgroup analyses 
 
Table 
11.2.X 
Summary statistics of LVEF by <subgroup name> 
mITT 
Table 
11.2.X 
Сhanges from baseline in LVEF by <subgroup name>  
mITT 
Table 
11.2.X 
Primary efficacy model, treatment effects on changes from 
baseline in LVEF by <subgroup name>  
mITT 
Figure 
11.2.1 
Forest plot for the mean differences, firibastat higher dose vs 
ramipril  
mITT 
Figure 
11.2.2 
Forest plot for the mean differences, firibastat lower dose vs 
ramipril  
mITT 
Figure 
11.2.3 
Forest plot for the mean differences, firibastat higher dose vs 
firibastat lower dose 
mITT 
Section 11.3 
Primary efficacy endpoint – subgroup analyses 
 
Table 
11.3.X 
Summary statistics of LVEF in two groups 
mITT 
Table 
11.3.X 
Сhanges from baseline in LVEF in two groups 
mITT 
Table 
11.3.X 
Primary efficacy model, treatment effects on changes from 
baseline in LVEF in two groups 
mITT 
Section 11.4 
Secondary efficacy endpoints 
 
Table 
11.4.1 
Summary statistics of left-ventricular end-diastolic volume 
mITT 
Table 
11.4.2 
Сhanges from baseline in left-ventricular end-diastolic volume 
mITT 
Table 
11.4.3 
Treatment effects on changes from baseline in left-ventricular 
end-diastolic volume 
mITT 
Table 
11.4.4 
Summary statistics of left-ventricular end-systolic volume 
mITT 
Table 
11.4.5 
Сhanges from baseline in left-ventricular end-systolic volume 
mITT 
Table 
11.4.6 
Treatment effects on changes from baseline in left-ventricular 
end-systolic volume 
mITT 
Table 
11.4.7 
Summary statistics of average peak of longitudinal strain 
mITT 
Table 
11.4.8 
Сhanges from baseline in average peak of longitudinal strain 
mITT 
Table 
11.4.9 
Treatment effects on changes from baseline in average peak of 
longitudinal strain 
mITT 
Table 
11.4.10 
Summary statistics of average peak of circumferential strain 
mITT 
Table 
11.4.11 
Сhanges from baseline in average peak of circumferential strain 
mITT 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 25/31 
TMPL-SOP-STAT-001a 
 
Output Number  
Title 
Analysis 
population 
Table 
11.3.12 
Treatment effects on changes from baseline in average peak of 
circumferential strain 
mITT 
Table 
11.4.13 
Summary statistics of infarct mass 
mITT 
Table 
11.4.14 
Treatment effects on infarct mass 
mITT 
Table 
11.4.15 
Summary of MACEs adjudicated by treatment group, category and 
PT 
Safety 
Table 
11.4.16 
Summary of time to the first confirmed MACE adjudicated (days) 
Safety 
Table 
11.4.17 
Estimated median time to the first confirmed MACE adjudicated 
(days) 
Safety 
Figure 
11.4.1 
Kaplan-Meier curve of time to the first confirmed MACE 
adjudicated (days) 
Safety 
Table 
11.4.18 
Summary statistics of NT-proBNP 
mITT 
Table 
11.4.19 
Сhanges from baseline in NT-proBNP 
mITT 
Table 
11.4.20 
Treatment effects on changes from baseline in NT-proBNP 
mITT 
Table 
11.4.21 
Summary statistics of PIIINP 
mITT 
Table 
11.4.22 
Сhanges from baseline in PIIINP 
mITT 
Table 
11.4.23 
Treatment effects on changes from baseline in PIIINP 
mITT 
Table 
11.4.24 
Summary statistics of CRP 
mITT 
Table 
11.4.25 
Сhanges from baseline in CRP 
mITT 
Table 
11.4.26 
Treatment effects on changes from baseline in CRP 
mITT 
Table 
11.4.27 
Summary statistics of copeptin 
mITT 
Table 
11.4.28 
Сhanges from baseline in copeptin 
mITT 
Table 
11.4.29 
Treatment effects on copeptin 
mITT 
Figure 
11.4.2 
Decrease of copeptin 
mITT 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 26/31 
TMPL-SOP-STAT-001a 
 
8.4 
Section 12 of CSR (SAFETY EVALUATION) 
Output Number  
Title 
Analysis 
population 
 
Section 12.1 
Adverse events 
 
Table 
12.1.1 
Summary of all treatment-emergent adverse events by 
treatment group, primary SOC, and PT within primary SOC 
Safety 
Table 
12.1.2 
Summary of treatment-emergent adverse events related to 
study treatment by treatment group, primary SOC, and PT 
within primary SOC 
Safety 
Table 
12.1.3 
Summary of serious treatment-emergent adverse events 
by treatment group, primary SOC, and PT within primary 
SOC 
Safety 
Table 
12.1.4 
Summary of serious adverse events by treatment group, 
primary SOC, and PT within primary SOC 
Safety 
Table 
12.1.5 
Summary of treatment-emergent adverse events leading to 
discontinuation of study treatment by treatment group, 
primary SOC, and PT within primary SOC 
Safety 
Table 
12.1.6 
Summary of treatment-emergent skin reactions reviewed 
by the dermatologists by treatment group, final diagnosis 
and relationship to treatment according dermalotolist 
Safety 
Table 
12.1.7 
Summary of treatment-emergent diabetes insipidus by 
treatment group, primary SOC, and PT within primary SOC 
Safety 
Section 12.2 
Other safety endpoints 
 
Table 
12.2.1 
Body weight: Summary statistics 
Safety 
Table 
12.2.1 
Body weight: Changes from baseline 
Safety 
Table 
12.2.X 
Vital signs, <SBP, DBP, HR>: Summary statistics 
Safety 
Table 
12.2.X 
Vital signs, <SBP, DBP, HR>: Changes from baseline 
Safety 
Table 
12.2.X 
Vital signs, SBP < 100 mmHg 
Safety 
Table 
12.2.X 
Laboratory evaluations, <parameter>: Summary statistics Safety 
Table 
12.2.X 
Laboratory evaluations, <parameter>: Changes from 
baseline 
Safety 
Table 
12.2.X 
Laboratory evaluations, <parameter>: Frequencies of 
abnormal values 
Safety 
Table 
12.2.X 
Laboratory evaluations, <parameter>: Shift table of 
change from baseline by visit 
Safety 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 27/31 
TMPL-SOP-STAT-001a 
 
Output Number  
Title 
Analysis 
population 
Table 
12.2.X 
12-lead ECG evaluations, Rhythm 
Safety 
Table 
12.2.X 
12-lead ECG evaluations, QRS duration 
Safety 
Table 
12.2.X 
12-lead ECG evaluations, QT duration: Summary statistics Safety 
Table 
12.2.X 
12-lead ECG evaluations, QT duration: Changes from 
baseline 
Safety 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 28/31 
TMPL-SOP-STAT-001a 
 
8.5 
Appendix 16.2 of CSR (SUBJECT DATA LISTINGS) 
 
All subjects included in clinical DB are listed (if not specified otherwise). 
 
Listing Number  Title 
 
Section 16.2.1 
 
Disposition and discontinued subjects 
16.2.1.1 
Informed consent details 
16.2.1.2 
Populations 
16.2.1.3 
Study visits 
16.2.1.4 
Screening failures and withdrawals (prior or after to randomization) 
 
Section 16.2.2 
 
Protocol deviations 
16.2.2.1 
Protocol deviations  
 
Section 16.2.3 
 
Subjects excluded from population 
16.2.3.1 
Subjects excluded from Safety, ITT, m-ITT and PP sets 
Section 16.2.4 
 
Demographic data and baseline characteristics 
16.2.4.1 
Demographic and clinical examinations at baseline 
16.2.4.2 
Acute myocardial infarction details 
16.2.4.3 
TIMI flow after PCI – Central reading 
16.2.4.4 
Troponin peak test details 
16.2.4.5 
Medical history 
16.2.4.6 
Previous and concomitant medications 
 
Section 16.2.5 
 
Study treatment compliance and exposure 
16.2.5.1 
Study treatment administration 
16.2.5.2 
Dose titration details 
16.2.5.3 
Study treatment exposure and compliance 
 
Section 16.2.6 
 
Individual efficacy response data 
16.2.6.1 
CMRI: LVEF, absolute values and changes from baseline 
16.2.6.2 
CMRI: Left-ventricular end-diastolic and end-systolic volumes, absolute values and 
changes from baseline 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 29/31 
TMPL-SOP-STAT-001a 
 
Listing Number  Title 
16.2.6.3 
CMRI: Average peak of longitudinal and circumferential strain, and infarct mass, 
absolute values and changes from baseline 
16.2.6.4 
MACEs 
16.2.6.5 
Biomarkers: NT-proBNP, PIIINP and CRP, absolute values and changes from baseline 
16.2.6.6 
Biomarkers: Copeptin, absolute values and changes from baseline 
 
Section 16.2.7 
 
Adverse events listings 
16.2.7.1 
Listing of all adverse events by subject 
16.2.7.2 
Adverse events – MedDRA coding details 
 
Section 16.2.8 
 
Other safety endpoints 
16.2.8.1 
Clinical examination data 
16.2.8.2 
Vital signs 
16.2.8.3 
Laboratory evaluations 
16.2.8.4 
12-lead ECG evaluations 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 30/31 
TMPL-SOP-STAT-001a 
 
REFERENCES 
[1] ICH guidelines - E9: Statistical Principles for Clinical Trials, Adopted in EU by CPMP, March 1998, issued 
as CPMP/ICH/363/96  
[2] ICH guidelines - E3: Structure and Content of Clinical Study Reports, Adopted in EU by CPMP, December 
95, issued as CPMP/ICH/137/95  
[3] Chen, Z. W., Yu, Z. Q., Yang, H. B., Chen, Y. H., Qian, J. Y., Shu, X. H., & Ge, J. B. (2016). Rapid predictors 
for the occurrence of reduced left ventricular ejection fraction between LAD and non-LAD related ST-
elevation myocardial infarction. BMC cardiovascular disorders, 16(1), 1-8. 
 
 
 
 


 
STATISTICAL ANALYSIS PLAN 
 
SPONSOR    
Quantum Genomics 
STUDY NAME 
QUORUM 
 
 
 
Confidential 
Page 31/31 
TMPL-SOP-STAT-001a 
 
DOCUMENT HISTORY 
 
Version 
Date 
Description of change 
Performed by 
Draft 0.1 03-APR-2020 
First version of the document created. 
Mariya Antonova 
Draft 0.2 21-JUL-2020 
SAP updated according to sponsor’s comments 
Mariya Antonova 
Draft 0.3 25-JAN-2021 
SAP updated according to sponsor’s comments 
Isabelle Josse 
Final 
04-MAR-2021 SAP updated according to sponsor’s comments 
Isabelle Josse 
Final 2 
20-JUL2021 
Clarification on the sensitivity analysis with multiple imputations 
Addition of decision rules for baseline medical history (smoking, 
diabetes, hypertension, dyslipidemia) 
Addition of the definition of TEAE 
Addition of groupings for the relationships of AEs with the treatment of 
the study (Not related / Related) 
Completion of the definition of the mITT (baseline: before or within 8 
hours of taking the first IP) 
Isabelle Josse