A Randomized, Placebo-controlled, Parallel-group, Investigator- and Participant-blinded Phase 2a Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Elevated hsCRP
Phase: PHASE2
Conditions: Coronary Heart Disease
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development 
Clinical Trial Protocol Title: 
A randomized, placebo-controlled, parallel-group, 
investigator- and participant-blinded Phase 2a study to 
investigate the efficacy, safety, and tolerability of DFV890 
for inflammatory marker reduction in adult participants 
with coronary heart disease and elevated hsCRP 
Clinical Trial Protocol Number: CDFV890F12201 / NCT06031844
Version Number: v01 (Clean) 
Compound: DFV890 
Brief Title: A study to investigate the efficacy, safety, and tolerability of DFV890 for 
inflammatory marker reduction in adult participants with coronary heart disease and 
elevated High-sensitivity C-reactive protein (hsCRP) 
Study Phase: IIa 
Sponsor Name: Novartis 
Regulatory Agency Identifier Number(s): IND 166,371 
Approval Date: 18-Jun-2024 (content final) 
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 5.0 dated 14-Jan-2022 

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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 6 
Amendment 01 (June 2024) ................................................................................................ 7 
1 
Protocol summary .............................................................................................................. 10 
1.1 
Summary ................................................................................................................ 10 
1.2 
Schema ................................................................................................................... 13 
1.3 
Schedule of activities (SoA) .................................................................................. 13 
2 
Introduction ....................................................................................................................... 18 
2.1 
Study rationale ....................................................................................................... 18 
2.2 
Background ............................................................................................................ 18 
2.3 
Benefit/Risk assessment ........................................................................................ 19 
2.3.1 
Compound risks .................................................................................... 20 
2.3.2 
Blood sample volume ............................................................................ 23 
3 
Objectives, endpoints, and estimands ................................................................................ 24 
3.1 
Primary estimands ................................................................................................. 25 
3.2 
Secondary estimands ............................................................................................. 26 
4 
Study design ...................................................................................................................... 26 
4.1 
Overall design ........................................................................................................ 26 
4.2 
Scientific rationale for study design ...................................................................... 27 
4.3 
Justification for dose .............................................................................................. 29 
4.4 
Rationale for choice of control drugs (comparator/placebo) or combination 
drugs ...................................................................................................................... 30 
4.5 
Rationale for public health emergency mitigation procedures .............................. 30 
4.6 
Purpose and timing of interim analyses/design adaptations .................................. 31 
4.7 
End of study definition .......................................................................................... 31 
5 
Study population ................................................................................................................ 31 
5.1 
Inclusion criteria .................................................................................................... 31 
5.2 
Exclusion criteria ................................................................................................... 32 
5.3 
Lifestyle considerations ......................................................................................... 35 
5.3.1 
Meals and dietary restrictions ............................................................... 35 
5.4 
Screen failures ....................................................................................................... 36 
5.4.1 
Replacement policy ............................................................................... 36 
5.4.2 
Participant numbering ........................................................................... 36 
6 
Study treatment(s) and concomitant therapy ..................................................................... 37 
6.1 
Study treatment(s) .................................................................................................. 37 

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6.1.1 
Additional study treatments .................................................................. 37 
6.1.2 
Treatment arms/group ........................................................................... 37 
6.2 
Preparation, handling, storage, and accountability ................................................ 38 
6.2.1 
Handling of study treatment .................................................................. 39 
6.2.2 
Handling of other treatment .................................................................. 39 
6.2.3 
Instruction for prescribing and taking study treatment ......................... 39 
6.3 
Measures to minimize bias: randomization and blinding ...................................... 41 
6.3.1 
Treatment assignment, randomization .................................................. 41 
6.3.2 
Treatment blinding ................................................................................ 41 
6.3.3 
Emergency breaking of assigned treatment code .................................. 43 
6.4 
Study treatment compliance .................................................................................. 43 
6.4.1 
Recommended treatment of adverse events .......................................... 44 
6.5 
Dose modification .................................................................................................. 44 
6.6 
Continued access to study treatment after the end of the study ............................. 44 
6.6.1 
Post-trial access ..................................................................................... 44 
6.7 
Treatment of overdose ........................................................................................... 44 
6.7.1 
Reporting of study treatment errors including misuse/abuse ................ 45 
6.8 
Concomitant and other therapy .............................................................................. 45 
6.8.1 
Concomitant therapy ............................................................................. 45 
6.8.2 
Prohibited medication ........................................................................... 47 
7 
Discontinuation of study treatment and participant discontinuation/withdrawal .............. 49 
7.1 
Discontinuation of study treatment ........................................................................ 49 
7.2 
Participant discontinuation from the study ............................................................ 50 
7.3 
Withdrawal of informed consent and exercise of participants’ data privacy 
rights ...................................................................................................................... 50 
7.4 
Lost to follow-up ................................................................................................... 51 
7.5 
Study stopping rules .............................................................................................. 51 
7.6 
Early study termination by the Sponsor ................................................................. 51 
8 
Study Assessments and Procedures ................................................................................... 52 
8.1 
Screening ............................................................................................................... 52 
8.2 
Participant demographics/other baseline characteristics ....................................... 53 
8.3 
Efficacy assessments ............................................................................................. 53 
8.3.1 
IL-6 and IL-18 Cytokines ...................................................................... 53 
8.3.2 
Appropriateness of efficacy assessments .............................................. 53 
8.4 
Safety/tolerability assessments .............................................................................. 54 
8.4.1 
Physical examinations ........................................................................... 55 

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8.4.2 
Vital signs.............................................................................................. 55 
8.4.3 
Electrocardiograms ............................................................................... 55 
8.4.4 
Clinical safety laboratory tests .............................................................. 56 
8.4.5 
Pregnancy testing .................................................................................. 58 
8.4.6 
Appropriateness of safety measurements .............................................. 59 
8.5 
Additional assessments .......................................................................................... 59 
8.6 
Adverse events (AEs), serious adverse events (SAEs), and other safety 
reporting ................................................................................................................. 59 
8.6.1 
Adverse events ...................................................................................... 59 
8.6.2 
Serious adverse events .......................................................................... 61 
8.6.3 
SAE reporting........................................................................................ 62 
8.6.4 
Pregnancy .............................................................................................. 63 
8.6.5 
Disease-related events and/or disease-related outcomes not 
qualifying as AEs or SAEs .................................................................... 63 
8.7 
Pharmacokinetics ................................................................................................... 63 
8.7.1 
PK blood collection ............................................................................... 64 
8.8 
Biomarkers ............................................................................................................. 64 
8.9 
Immunogenicity assessments ................................................................................. 66 
8.10 
Medical resource utilization and health economics ............................................... 66 
9 
Statistical considerations ................................................................................................... 66 
9.1 
Analysis sets .......................................................................................................... 66 
9.2 
Statistical analyses ................................................................................................. 67 
9.2.1 
General considerations .......................................................................... 67 
9.2.2 
Participant demographics and other baseline characteristics ................ 67 
9.2.3 
Treatments ............................................................................................. 67 
9.3 
Primary endpoint(s)/estimand(s) analysis .............................................................. 67 
9.3.1 
Definition of primary endpoint(s) ......................................................... 67 
9.3.2 
Statistical model, hypothesis, and method of analysis .......................... 67 
9.3.3 
Handling of intercurrent events of primary estimand (if applicable) .... 68 
9.3.4 
Handling of missing values not related to intercurrent event ............... 68 
9.3.5 
Sensitivity analyses ............................................................................... 68 
9.3.6 
Supplementary analysis ......................................................................... 69 
9.4 
Secondary endpoint(s)/estimand(s) analysis .......................................................... 69 
9.4.1 
Safety endpoints .................................................................................... 69 
9.4.2 
Pharmacokinetics .................................................................................. 70 
9.4.3 
PK/PD relationships .............................................................................. 70 
9.5 
Exploratory endpoint(s)/estimand(s) analysis ....................................................... 70 

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9.5.1 
Biomarkers ............................................................................................ 70 
9.5.2 
DNA ...................................................................................................... 70 
9.6 
(Other) Safety analyses .......................................................................................... 70 
9.7 
Other analyses ........................................................................................................ 71 
9.8 
Interim analysis ...................................................................................................... 71 
9.9 
Sample size determination ..................................................................................... 71 
9.9.1 
Primary endpoint(s) ............................................................................... 71 
10 Supporting documentation and operational considerations ............................................... 72 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ................... 72 
10.1.1 
Regulatory and ethical considerations .................................................. 72 
10.1.2 
Informed consent process ...................................................................... 73 
10.1.3 
Data protection ...................................................................................... 74 
10.1.4 
Committees structure ............................................................................ 74 
10.1.5 
Data quality assurance ........................................................................... 75 
10.1.6 
Source documents ................................................................................. 76 
10.1.7 
Publication policy.................................................................................. 76 
10.1.8 
Protocol adherence and protocol amendments ...................................... 77 
10.2 
Appendix 2: Abbreviations and definitions ........................................................... 78 
10.2.1 
List of abbreviations .............................................................................. 78 
10.2.2 
Definitions ............................................................................................. 80 
10.3 
Appendix 3: Clinical laboratory tests .................................................................... 84 
10.4 
Appendix 4: Participant Engagement .................................................................... 85 
10.5 
Appendix 5: Liver safety monitoring .................................................................... 86 
10.5.1 
Liver event and laboratory trigger definitions & follow-up 
requirements .......................................................................................... 87 
10.6 
Appendix 6: Renal safety monitoring .................................................................... 90 
10.6.1 
Specific Renal Alert Criteria and Actions and Event Follow-up .......... 90 
11 References ......................................................................................................................... 92 
List of tables 
Table 1-1 
Objectives and related endpoints .......................................................... 10 
Table 1-2 
Assessment Schedule ............................................................................ 15 
Table 3-1 
Objectives and related endpoints .......................................................... 24 
Table 3-2 
Intercurrent events for the primary estimand ........................................ 25 
Table 4-1 
Rationale for study design ..................................................................... 27 
Table 6-1 
Investigational and control drug ............................................................ 37 
Table 6-2 
Dose and treatment schedule ................................................................. 40 

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Table 6-3 
Blinding and unblinding plan ................................................................ 42 
Table 6-4 
Drugs to be used with caution ............................................................... 46 
Table 6-5 
Prohibited drugs due to DDI (CYP3A and CYP2C9 modulators) ........ 48 
Table 6-6 
Prohibited medication ........................................................................... 48 
Table 8-1 
Safety laboratory evaluations ................................................................ 57 
Table 10-1 
Liver event and laboratory trigger definitions ...................................... 87 
Table 10-2 
Follow up requirements for liver laboratory triggers - ALT, AST, 
TBL - ..................................................................................................... 88 
Table 10-3 
Follow up requirements for liver laboratory triggers - Isolated 
Hyperbilirubinemia ............................................................................... 89 
Table 10-4 
Specific renal alert criteria and actions ................................................. 90 
Table 10-5 
Renal Event Follow Up ......................................................................... 91 
List of figures 
Figure 1-1 
Study Design ......................................................................................... 13 
Figure 6-1 
Treatment arms ...................................................................................... 38 
Figure 8-1 
Recommended order of assessments ..................................................... 56 
 
 
 

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Protocol No. CDFV890F12201 
 
Amendment 01 (June 2024) 
Amendment Rationale 
The main purpose of this amendment is to revise the inclusion/exclusion criteria to allow for 
facilitated recruitment in line with the study rationale and allow better representation of the 
study population to that of the contemporary post-myocardial infarction patient population. In 
summary, the key changes to the inclusion/exclusion criteria include: 1) maximum body mass 
index (BMI) increased to 45 kg/m2 from 40 kg/m2, 2) maximum age increased to 85 from 80 
years of age, 3) exclusionary time post multi-vessel coronary artery bypass graft (CABG) 
procedures decreased from 3 years to 6 months, 4) recommended hemoglobin A1C threshold 
increased to 10% from 9% for the determination of uncontrolled diabetes, and 5) systemic 
autoimmune and  systemic inflammatory disease exclusion was clarified. The updates are not 
expected to increase risk to patient safety or result in a meaningful decrease in study drug 
efficacy in the evaluations of dose and directly measured DFV890 exposure on cytokine 
reduction. 
Second, the amendment includes additional expedited reporting instructions and serious adverse 
event (SAE) classification for a potential Hy’s Law case with elevated liver enzymes. The 
amended reporting instructions are aligned to updated Novartis protocol language and not due 
to any safety concerns specific to DFV890. Potential Hy’s law cases must be reported as a 
serious unexpected adverse event promptly, even before other possible causes of liver injury 
have been excluded or all supplementary data is obtained. Along with the expedited reporting 
of a treatment-related SAE due to potential Hy’s law cases of elevated liver enzymes prior to 
ruling out other causes and obtaining supplemental data, study stopping rules are updated 
accordingly to increase from one to two non-life-threatening treatment-related SAEs. A study 
stopping rule is also now included if a death or one life threatening treatment-related SAE 
occurs. In addition, a study stopping rule remains that Novartis may put the study on hold if the 
number and/or severity of adverse events (AEs), abnormal safety monitoring tests, or abnormal 
laboratory findings justifies putting the study on hold even with one treatment-related SAE.  
Third, additional minor edits to the protocol text are included to enhance clarity, accuracy, and 
understanding of the protocol. 
Changes to the protocol 
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underline.  
• Table 1-2: Assessment Schedule is updated to include the Optional Inflammation Marker 
Pre-Screening Informed Consent Form (ICF) in the assessment schedule and to clarify that 
if the Optional Inflammation Marker Pre-Screening ICF is used at Screening visit 1 to 
allow for the collection of the high-sensitivity C-reactive protein (hsCRP) sample, the 
main study ICF, optional genetics ICF, demography, and medical history can be obtained 
at Screening visit 2. 
• Section 2.3.1.3: Potential risk and recommended treatment of infection is updated to 
reflect that the GLP toxicology study in cynomolgus monkeys has been completed as per 
IB edition v06. 

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• Section 5.1: Inclusion Criteria is updated to increase the maximum allowable BMI to 45 
kg/m2 and the maximum allowable age to 85 years old. 
• Section 5.2:  Exclusion criteria that limited the time window after multi-vessel CABG 
surgery, in which a subject may be enrolled, has been reduced to 6 months. The 
hemoglobin A1C threshold value used as guidance for investigators to assess uncontrolled 
diabetes has been increased to 10%. Systemic inflammatory disease was added as an 
exclusionary medical history. 
• Section 6.2: Preparation, handling, storage, and accountability is updated to clarify that 
Drug Accountability and Returns Management (DARM) is not the only possible drug 
accountability log which can be used. 
• Section 6.2.1: Handling of study treatment section is updated to clarify that Drug 
Accountability and Returns Management (DARM) is not the only possible drug 
accountability log which can be used.  
• Table 6-2: Dose and Treatment schedule is updated to correct typographical error for the 
last day of the dosing periods. 
• Section 6.4: Study treatment compliance reporting instructions are updated to clarify that 
IMP compliance is not reported in the case report form (CRF) completion and that clarify 
that Drug Accountability and Returns Management (DARM) is not the only possible drug 
accountability log which can be used. 
• Table 6-4: Drugs to be used with caution is updated to remove indinavir from this list as it 
is a prohibited medication. 
• Section 7.1: Discontinuation of study treatment is updated to provide additional clarity 
regarding when EOT and EOS visits are to occur in case of study treatment 
discontinuation. 
• Section 7.5: Study stopping rules is updated to increase the number of treatment-related 
SAEs to meet stopping occur and to add a stopping rule for death or life-threatening event. 
• Section 8.3.1: IL-6 and IL-18 Cytokines section is updated to reflect that enzyme-linked 
immunosorbent assay (ELISA) will be the analysis method used for IL-6 and IL-18. 
• Section 8.6.2: Serious adverse events is updated to include reporting language relating to 
Hy’s Law. 
• Section 8.7: Pharmacokinetics section is updated to clarify when an unscheduled 
pharmacokinetic (PK) sample may be needed. 
• Section 8.8: Biomarkers section is updated to clarify the handling of unscheduled samples. 
• Section 9.3.2: Treatments section is updated to clarify that compliance is calculated and 
not reported. 
• Section 10.1.2: Informed consent process is updated to include the Optional Inflammation 
Marker Pre-Screening ICF and describe how it is used with the main study ICF. 
• Section 10.2.1: List of abbreviation is updated to include new abbreviations. 
IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities.  

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The changes described in this amended protocol require IRB/IEC approval prior to 
implementation. 
The changes herein affect the Informed Consent. Sites are required to update and submit for 
approval a revised Informed Consent that takes into account the changes described in this 
protocol amendment.  
 

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1 
Protocol summary 
1.1 
Summary 
Protocol Title: 
A randomized, placebo-controlled, parallel-group, investigator- and participant-blinded 
Phase 2a study to investigate the efficacy, safety, and tolerability of DFV890 for inflammatory 
marker reduction in adult participants with coronary heart disease and elevated hsCRP. 
Brief Title: 
A study to investigate the efficacy, safety, and tolerability of DFV890 for inflammatory marker 
reduction in adult participants with coronary heart disease and elevated High-sensitivity 
C-reactive protein (hsCRP). 
Purpose 
The purpose of this study is to evaluate the efficacy, safety, and tolerability of intra-individual 
dose escalation of oral DFV890 in reducing circulating levels of inflammatory markers in adult 
participants with known coronary heart disease and elevated hsCRP. 
Study Indication /Medical Condition: 
Coronary Heart Disease 
Treatment type 
Drug 
Study type 
Interventional 
Objectives, Endpoints, and Estimands: 
Table 1-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
• 
To evaluate the effect of various dose levels 
of DFV890 versus placebo to reduce 
circulating levels of inflammatory markers in 
participants with coronary heart disease and 
elevated hsCRP 
• 
Serum levels of IL-6 and IL-18 at 3 weeks 
after the start of a dosing period 
Secondary objective(s) 
Endpoint(s) for secondary objective(s) 
• 
To evaluate the safety and tolerability of 
DFV890 in participants with coronary heart 
disease and elevated hsCRP 
• 
Adverse events (AE), and parameters from 
safety assessments, including vital signs, 
electrocardiograms, and laboratory 
assessments (urine and blood) 

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Objective(s) 
Endpoint(s) 
• 
To assess the pharmacokinetics (PK) of 
DFV890 in participants with coronary heart 
disease and elevated hsCRP 
• 
Plasma trough concentrations (Ctrough) of 
DFV890 at steady state 
Trial Design: 
• Parallel-group, placebo-controlled, multi-center Phase 2a study 
• Patients with coronary heart disease and elevated hsCRP 
• Investigator- and participant-blinded; matching placebo 
• Randomization 
The trial will be comprised of: 
• A total study duration of approximately 24 weeks 
• A screening period of up to 60 days 
• A treatment duration of approximately 12 weeks 
• Intra-individual study drug uptitration at approximately 3-week intervals over 4 dosing 
periods 
• The visit frequency will include at least 2 screening visits within the 60-day screening 
period followed by visits at approximately Day 1, 22, 43, 64, 85, 92 and a safety 
follow-up phone call at Day 114 
Brief Summary: Cardiovascular diseases (CVD) remain the leading cause of disease burden 
in the world. Persistent inflammation is common in populations at increased risk of CVD events 
and medications that reduce inflammation have been linked to improved CVD outcomes. 
Inhibition of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome 
may safely and effectively lower the risk of CVD among people with known heart disease and 
markers of elevated inflammation. This Phase 2a clinical trial will evaluate the effectiveness, 
safety, and tolerability of increasing dose strengths of an oral daily medication, DFV890, 
administered for 12 weeks, to reduce key markers of inflammation related to CVD risk, such as 
IL-6 and IL-18, in approximately 24 people with known heart disease and an elevated marker 
of inflammation, hsCRP. 
Primary estimand/analysis: 
The primary estimand will address potential intercurrent events that may influence the primary 
endpoints (IL-6 and IL-18) largely with a hypothetical strategy, which aims to estimate the 
effect of treatment under research-like conditions. The primary analysis for each endpoint is 
based on a dose-response modeling approach that integrates all cytokine measurements under 
increasing NLRP3 inflammasome inhibition resulting from uptitrated doses of DFV890. 
Treatment of interest 
The treatment of interest is oral daily DFV890 at various dose levels (10 milligram (mg), 25 mg, 
50 mg and 100 mg daily) on top of clinically indicated standard-of-care CVD prevention 
medications (eg. statin treatment). 

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Number of Participants: 
The study population is comprised of male and female adults. A total of approximately 
24 participants will be enrolled to study intervention. 
Key Inclusion criteria 
• Male and female participants aged between 18 - 85 years (inclusive) at the start of 
screening will be included. 
• Subjects must have a body mass index (BMI) within the range of 18 - 45 kg/m2. 
BMI = Body weight (kg) / [Height (m)]2 
• Documented spontaneous myocardial infarction (MI) (diagnosed according to the 
universal MI criteria with or without evidence of ST segment elevation) at least 30 days 
before the start of screening (Thygesen et al 2007). 
• Participants must have hsCRP levels ≥ 2 mg/L at two timepoints during screening. 
Screening values must be separated by a minimum of 8 days. The initial hsCRP value 
must be a minimum of 30 days after the qualifying MI or after any percutaneous coronary 
intervention (PCI) performed separately from the qualifying MI. 
• For participants on statin therapy (HMG-CoA reductase inhibitor), as clinically 
indicated, participants must be on a stable regimen (at least 4 weeks before 
randomization), with no planned statin dose changes over the course of the trial treatment 
period. Unplanned statin dose changes during the trial treatment period may occur. 
Key Exclusion criteria 
• Patients receiving concomitant medications that are known to be strong or moderate 
inducers of cytochrome CYP2C9 enzyme and/or strong inducers of CYP3A, strong 
inhibitors of CYP2C9 and/or strong or moderate inhibitors of CYP3A and the treatment 
cannot be discontinued or switched to a different medication within 5 half-lives or 1 week 
(whichever is longer) prior to Day 1 and for the duration of the study. 
• Patients with suspected or proven immunocompromised state at screening 
• History of ongoing, chronic, or major recurrent infectious disease, at the discretion of the 
investigator, at the start of screening. 
• Use of any biologic drugs targeting the immune system within 26 weeks of Day 1 
• Multi-vessel Coronary Artery Bypass Graft (CABG) surgery within the past 6 months 
prior to the start of screening 
• Symptomatic Class IV heart failure (New York Heart Association) at the start of 
screening. 
• Planned coronary revascularization (PCI or CABG) or any other major surgical procedure 
during the study 

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Treatment Groups: 
Active treatment: DFV890 administered orally once daily at various doses (0 mg [matching 
placebo], 10 mg, 25 mg, 50 mg, 100 mg) over four dosing periods of ~3 weeks each, for a total 
of ~12 weeks of treatment. Randomized to one of four treatment sequences comprised of 
various doses of DFV890 and/or placebo. Investigational study treatment dose adjustments 
and/or interruptions are not permitted. 
Data Monitoring/Other Committee: No 
Key words 
Coronary heart disease, elevated hsCRP, inflammatory marker reduction, NLRP3 
inflammasome inhibitor 
1.2 
Schema 
Figure 1-1 
Study Design 
 
1.3 
Schedule of activities (SoA) 
The SoA lists all the assessments when they are performed. All data obtained from these 
assessments must be supported in the participant’s source documentation. The “X” in the table 
denotes the assessments to be recorded in the clinical database or received electronically from 
a vendor. The “S” in the table denotes the assessments that are only in the participant’s source 
documentation and do not need to be recorded in the clinical database. 
Participants should be seen for all visits/assessments as outlined in the SoA or as close to the 
designated day/time as possible. Missed or rescheduled visits should not lead to automatic 
discontinuation. 

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Participants who discontinue from study should be scheduled for a final evaluation visit if they 
agree, as soon as possible, at which time all of the assessments listed for the End Of Study 
(EOS) visit will be performed. At this final visit, all dispensed investigational product should 
be reconciled, and the AEs and concomitant medications not previously reported must be 
recorded on the Case Report/Record Form (CRF). 
Every effort will be made to take PK samples at the protocol-specified time. The preferred 
sequence of assessments and data collection during study visits is: Electrocardiogram (ECG), 
vital signs, blood sampling, and any remaining assessments for that visit. For visits during 
which the participant is scheduled to take the study drug, all assessments will be conducted pre-
dose administration. 
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e., pandemic, epidemic or natural disaster that limits or prevents on-site study visits, alternative 
methods of providing continuing care may be implemented by the Investigator as the situation 
dictates. If allowable by a local health authority, national and local regulations and depending 
on operational capabilities, phone calls, virtual contacts (e.g., tele consultation) or visits by site 
staff/ off-site healthcare professional(s) (OHP) staff to the participant´s home, can replace 
certain protocol assessments, for the duration of the disruption until it is safe for the participant 
to visit the site again. If the Investigator delegates tasks to an OHP, the Investigator must ensure 
the individual(s) is/are qualified and appropriately trained to perform assigned duties. The 
Investigator must oversee their conduct and remain responsible for the evaluation of the data 
collected. 

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Table 1-2 
Assessment Schedule 
Period 
Screening 
Treatment 
Follow-Up 
Visit Name 
Screening 1 
Screening 22 
Day 13 
Day 223 
Day 433 
Day 643 
EOT 
EOS 
Safety Follow Up Call 
Visit Numbers1 
1 
10 
100 
110 
120 
130 
199 
1999 
 
Days 
-60 to -9 
-52 to -1 
1 
22 
±2 
43 
±2 
64 
±2 
85 
±2 
92 
±2 
114 
±5 
Optional Inflammation 
Marker Pre-Screening 
Informed consent 
X 
 
 
 
 
 
 
 
 
Main Study Informed 
consent 
X 
  
  
  
  
  
  
  
Genetic consent 
X 
  
  
  
  
  
  
  
Inclusion / Exclusion criteria 
X 
X 
  
  
  
  
  
  
  
Demography 
X 
  
  
  
  
  
  
  
Medical history/current 
medical conditions 
X 
  
  
  
  
  
  
  
Pregnancy and 
assessments of fertility4 
  
X 
X 
X 
X 
X 
X 
X 
  
Physical Examination 
  
S 
S5 
S5 
S5 
S5 
S5 
S 
  
Body Height 
  
X 
  
  
  
  
  
  
  
Body Weight 
  
X 
  
  
  
  
X 
X 
  
Body Temperature 
  
X 
X 
X 
X 
X 
X 
X 
  
Pulse rate 
  
X 
X 
X 
X 
X 
X 
X 
  
Blood Pressure 
  
X 
X 
X 
X 
X 
X 
X 
  
Electrocardiogram (ECG) 
  
X 
  
  
  
  
X 
X 
  
hsCRP 
X 
X 
X 
X 
X 
X 
X 
X 
  
Clinical Chemistry 
  
X 
X 
X 
X 
X 
X 
X 
  
Hematology 
  
X 
X 
X 
X 
X 
X 
X 
  

Novartis 
Confidential 
Page 16 of 92 
Amended Protocol Version 01 (Clean) 
 
Protocol No. CDFV890F12201 
 
Period 
Screening 
Treatment 
Follow-Up 
Visit Name 
Screening 1 
Screening 22 
Day 13 
Day 223 
Day 433 
Day 643 
EOT 
EOS 
Safety Follow Up Call 
Visit Numbers1 
1 
10 
100 
110 
120 
130 
199 
1999 
 
Days 
-60 to -9 
-52 to -1 
1 
22 
±2 
43 
±2 
64 
±2 
85 
±2 
92 
±2 
114 
±5 
Coagulation Panel 
  
X 
X 
  
  
  
X 
X 
  
Urinalysis 
  
X 
X 
  
  
  
X 
X 
  
Randomization 
  
  
S 
  
  
  
  
  
  
Dose administration 
  
  
X6 
  
  
Dose uptitration 
  
  
  
S 
S 
S 
  
  
  
Drug Accountability7 
  
  
  
X 
X 
X 
X 
  
  
PK blood collection 
  
  
  
X8 
X8 
X8 
X8 
X 
  
IL-6 and IL-18 cytokines 
  
X 
X 
X 
X 
X 
X 
X 
  
Blood collection for soluble 
biomarkers9 
  
  
X 
X 
X 
X 
X 
X 
  
Immunophenotyping10 
  
  
X 
X 
X 
X 
X 
X 
  
Lipid Parameters 
  
  
X 
X 
X 
X 
X 
X 
  
CHIP genotyping (optional) 
  
  
X 
  
  
  
X 
  
  
CYP genotyping 
  
  
X 
  
  
  
  
  
  
Exploratory DNA Sampling 
(optional) 
  
  
X 
  
  
  
  
  
  
Concomitant medications 
X 
  
Adverse Events 
X 
  
Serious Adverse Events 
X 
Study completion 
information 
  
  
  
  
  
  
  
X 
  
Safety Follow up Call 
  
  
  
  
  
  
  
  
S 
 

Novartis 
Confidential 
Page 17 of 92 
Amended Protocol Version 01 (Clean) 
 
Protocol No. CDFV890F12201 
 
X Assessment to be recorded in the clinical database or received electronically from a vendor 
S Assessment to be recorded in the source documentation only 
1 Visit structure given for internal programming purpose only 
2 Screening 2 visit should take place at least 8 days after Screening 1 visit and after hsCRP results were reviewed against eligibility criteria. If Optional 
Inflammation Marker Pre-Screening ICF is used at Screening 1 visit, the main study Consent Form can be signed at Screening 2 visit. Refer to 
Section 10.1.2 for more information.  
3 All assessments should be done pre-dose 
4 Serum pregnancy test 
5 Brief physical exam, including rash assessment.  
6 Last dose administration is on Day 84 at home prior to EOT visit on Day 85 
7 IMP administration in the last 2 days before study visit as well as timing of the last dose before study visit should be confirmed with the patient. 
8 The sample taken on the study visit day must be taken approximately 24h (+/-2h) after the dose from previous day (ex: Day 22 pre-dose sample is 
24 hours +/-2 hours after the timing of the Day 21 dose). 
9 May include but not limited to sASC, hsIL-1b, CXCL9, CXCL10, hsIFNg, vWF, protein profiling etc. 
10 May include but not limited to myeloid/lymphoid cell activation/enumeration, Whole Blood/PBMCs, etc.

Novartis 
Confidential 
Page 18 of 92 
Amended Protocol Version 01 (Clean) 
 
Protocol No. CDFV890F12201 
 
2 
Introduction 
2.1 
Study rationale 
The purpose of this study is to evaluate the efficacy, safety, and tolerability of DFV890 in 
reducing circulating levels of inflammatory markers in adult participants with known coronary 
heart disease and elevated hsCRP. The results of the study will be used to inform future 
development plans for DFV890 in cardiovascular disease event risk reduction. 
2.2 
Background 
Cardiovascular disease remains the leading cause of disease burden in the world. The estimated 
global prevalence of cardiovascular disease doubled from 271 million in 1990 to 523 million in 
2019 (Roth et al 2020). A substantial residual risk for cardiovascular disease events related to 
chronic inflammation remains despite standard of care management of classic risk factors 
(diabetes, hypertension, lipids, etc.). 
Atherosclerotic cardiovascular disease is a condition commonly characterized by an elevated 
inflammatory state. Arterial inflammation and endothelial dysfunction play key roles at all 
stages of the atherothrombotic process. Inflammatory mediators are intimately implicated with 
the cascade of events leading to atherosclerotic plaque initiation, progression, and rupture. 
Vascular endothelial cells express a variety of adhesion molecules that recruit monocytes when 
chronically exposed to noxious stimuli or pathological conditions. Adverse conditions such as 
hyperlipidemia are associated with enrichment of a pro-inflammatory subset of monocytes. 
These monocytes apparently enter the intima under the influence of chemotactic stimuli and 
engulf modified low-density lipoprotein (LDL) and cholesterol crystals (Duewell et al 2010). 
The material internalized by phagocytes induces phagolysosomal damage and subsequent 
leakage of contents into cytosol to activate inflammasomes and caspase 1, and consequently the 
generation of interleukin-1β (IL-1β) from pro-interleukin-1β. 
Interleukins are key mediators in the chronic vascular inflammatory response in cardiovascular 
disease and have been demonstrated in animal models and in humans to be potent modulators 
of pro-inflammatory processes. The fact that these cytokines and their receptors are highly 
expressed and are functional in almost all cell types implicated in the pathogenesis of 
atherosclerosis including smooth muscle cells, certain subset of macrophages and T cells, as 
well as endothelium, support the role of interleukins in vascular disease. For example, IL-1β is 
a potent smooth muscle cell mitogen, an activator of endothelial cells and increases extra 
cellular matrix and collagen deposition, which plays a role in plaque burden and arterial 
thickening. Furthermore, lack of IL-1β or ablation of IL-1 receptor has been shown to decrease 
severity of atherosclerosis in apoE deficient mice. 
Clinical evidence from the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcome 
Study) clinical trial demonstrated that IL-1β neutralization with canakinumab can reduce 
cardiovascular risk in patients who have had a prior MI and elevated hsCRP.  In CANTOS, 
increased IL-18 levels at baseline correlated with increased cardiovascular risk, corroborating 
other findings suggesting IL-18 plays a role in cardiovascular disease that is not attenuated by 
IL-1β neutralization (Ridker et al 2020). 

Novartis 
Confidential 
Page 19 of 92 
Amended Protocol Version 01 (Clean) 
 
Protocol No. CDFV890F12201 
 
Through the production of IL-1β and IL-18, the NLRP3 inflammasome has been implicated as 
a major driver of inflammation associated with chronic inflammatory diseases. Mechanistically, 
NLRP3 senses a diverse range of danger signals, and reacts by forming an inflammasome 
protein complex that drives an ensuing inflammatory response. Via genetic knockouts 
(Duewell et al 2010) or pharmacological inhibition (Hettwer et al 2022), abrogation of NLRP3 
function is protective in mouse models of atherosclerosis, exerting a beneficial effect on both 
peripheral inflammatory leukocytes and cytokines, and local anti-inflammatory effects in the 
atherosclerotic plaque. DFV890 is a potent, small molecule inhibitor of the NLRP3 
inflammasome pathway. DFV890 blocks IL-1β secretion, IL-18 secretion and pyroptotic cell 
death in response to a wide variety of NLRP3-dependent danger signals in vitro and in 
mechanistic mouse models in vivo, suggesting that NLRP3 inhibition could have improved 
efficacy over canakinumab in diseases where IL-1β and IL-18 both drive pathology. Through 
the inhibition of IL-1β and IL-18, DFV890 has the potential to significantly reduce 
cardiovascular risk in patients. 
2.3 
Benefit/Risk assessment 
It is not known whether there will be a benefit for participants with known coronary heart 
disease and elevated hsCRP with DFV890 and NLRP3 inhibition. The CANTOS trial 
demonstrated reduction in cardiovascular risk in this population with canakinumab and IL-1β 
inhibition. NLRP3 inhibition could have improved efficacy over canakinumab by inhibiting 
both IL-1β and IL-18; however, this has not yet been demonstrated. 
Based on the clinical experience with DFV890 in the CDFV890A02101 Phase 1 first in human 
(FIH) study, the CDFV890D12201 Phase 2 study in patients with COVID-19, relevant 
nonclinical findings, the biological understanding of the pathways and their relevance to CVD, 
the overall risk-benefit of DFV890 is, to date, considered favorable. The available clinical, 
safety and laboratory assessments from the FIH study and the COVID-19 study show that 
DFV890 is generally well tolerated and has a manageable safety profile. Potential compound 
risks are described in more detail in the following sections. In summary, based on the available 
non-clinical and clinical data the potential risks to be considered for DFV890 include: 1) self-
limiting skin rash/pruritis, 2) changes in hematologic parameters, 3) management of 
concomitant infections, 4) co-administration of live vaccinations, 5) renal abnormalities in 
preclinical models, 6) changes in female reproductive tissues, which were observed in the rat, 
7) considerations for women of child-bearing potential (WOCBP), 8) metabolism by CYP2C9 
and CYP3A4 enzymes, and 9) general considerations related to hypersensitivity to any 
component of the drug product. In addition to the risks noted above, there may be risks to 
DFV890 that are unforeseen and serious. 
The risk to participants in this trial may be minimized by adherence to the eligibility criteria, 
study procedures, stopping rules, and close clinical monitoring. Appropriate eligibility criteria, 
and specific dose-limiting toxicity definitions, as well as specific stopping rules, are included 
in this protocol. Please refer to the Investigator's Brochure (IB) for additional information. 

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Novartis 
Confidential 
Page 24 of 92 
Amended Protocol Version 01 (Clean) 
 
Protocol No. CDFV890F12201 
 
3 
Objectives, endpoints, and estimands 
Table 3-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
• 
To evaluate the effect of various dose levels of 
DFV890 versus placebo to reduce circulating 
levels of inflammatory markers in participants 
with coronary heart disease and elevated 
hsCRP 
• 
Serum levels of IL-6 and IL-18 at 
3 weeks after the start of a dosing period 
Secondary objective(s) 
Endpoint(s) for secondary objective(s) 
• 
To evaluate the safety and tolerability of 
DFV890 in participants with coronary heart 
disease and elevated hsCRP 
• 
Adverse events, and parameters from 
safety assessments, including vital signs, 
electrocardiograms, and laboratory 
assessments (urine and blood) 
• 
To assess the pharmacokinetics of DFV890 in 
participants with coronary heart disease and 
elevated hsCRP 
• 
Plasma trough concentrations (Ctrough) 
of DFV890 at steady state 
Exploratory objective(s) 
Endpoint(s) for exploratory objective(s) 
• 
To explore whether individual variation in genes 
related to drug metabolism confer differential 
pharmacokinetic response to DFV890 
• 
Plasma Ctrough of DFV890 and its 
metabolite, IBW042, by CYP2C9 
genotype 
• 
To assess pharmacokinetics of IBW042, 
metabolite of DFV890 in plasma 
• 
Plasma Ctrough of IBW042 at various 
doses of DFV890 
• 
To assess the effect of DFV890 on 
pharmacodynamic (PD), inflammation-related, 
and cardiovascular disease-related biomarkers 
(including pharmacokinetic/pharmacodynamic 
relationships) 
• 
Pharmacodynamic and inflammation-
related markers may include but are not 
limited to hsCRP, soluble ASC, IL-1β, 
CXCL9, CXCL10, hsIFNg, von-
Willebrand-Factor (vWF), 
myeloid/lymphoid cell 
activation/enumeration by flow cytometry 
(whole blood/PBMC) 
• 
Cardiovascular disease-related 
biomarkers may include but are not 
limited to lipid parameters (e.g., LDL, 
Lp(a), apolipoproteins) 
• 
To explore genetic and proteomic drug-related 
response mechanisms, understand the disease 
and/or the safety and efficacy of DFV890 
 
• 
Exploratory genetic and proteomic 
endpoints may include but are not limited 
to: 
• 
Presence of genetic polymorphisms 
• 
Presence of somatic mutations 
(Clonal Hematopoeisis of 
Indeterminate Potential (CHIP)) and 
their change from baseline) 
• 
Serum or plasma proteins and their 
change from baseline 

Novartis 
Confidential 
Page 25 of 92 
Amended Protocol Version 01 (Clean) 
 
Protocol No. CDFV890F12201 
 
3.1 
Primary estimands 
The primary clinical question of interest is: What is the effect of DFV890 in addition to standard 
of care cardiovascular disease prevention medication in patients with known coronary heart 
disease and elevated hsCRP on the inflammatory markers IL-6 and IL-18, assuming patients 
continue treatment with reasonable adherence and there are no new major cardiovascular 
events, initiations of prohibited medication, or febrile infections, but without regard to changes 
in standard of care cardiovascular disease prevention medication? 
The justification for the estimand is that it will capture the effect of the investigational treatment 
versus placebo under research-like conditions, where participants adhere to their assigned 
treatment regimen and there is no impact of other intercurrent events on the primary endpoints 
(aside from potential changes in standard of care cardiovascular disease prevention medication). 
The estimand is defined by the following attributes: 
1. Population: patients with known coronary heart disease, elevated hsCRP, and background 
cardiovascular disease prevention medication. 
2. Endpoints: Serum IL-6 and IL-18 levels at 3 weeks after the start of a dosing period. 
3. Treatment of interest: DFV890 once daily (QD) or placebo QD. 
4. Handling of intercurrent events: see Table 3-2. 
5. Summary measure: the model-based difference in variable means between treatments. 
Table 3-2 
Intercurrent events for the primary estimand 
Intercurrent event 
Details (if necessary) 
Handling of event 
Permanent discontinuation of 
study treatment 
N/A 
Data collected after this 
intercurrent event will not be 
used for this estimand 
Incidence of a new major 
cardiovascular disease event 
(e.g., MI, stroke, etc.) 
N/A 
Data collected after this 
intercurrent event will not be 
used for this estimand 
Change in standard of 
care CVD prevention 
medication 
N/A 
All data collected after this 
intercurrent event will be used 
for this estimand 
Initiation of a prohibited 
medication for a comorbid 
condition 
Unforeseen use of any 
medication expected to have a 
sustained effect on the primary 
endpoints (i.e., any systemic 
corticosteroids) 
Data collected after this 
intercurrent event will not be 
used for this estimand 
Unforeseen use of medication 
expected to have a limited 
effect on the primary endpoints 
(i.e., any other prohibited 
medications) 
Only the assessment 
immediately following the event 
will be excluded for the 
purpose of this estimand 
New-onset febrile infection 
Febrile infection around time of 
assessment (details to be 
provided in the statistical 
analysis plan (SAP)) 
Only the assessment 
immediately following the event 
will be excluded for the 
purpose of this estimand 

Novartis 
Confidential 
Page 26 of 92 
Amended Protocol Version 01 (Clean) 
 
Protocol No. CDFV890F12201 
 
Intercurrent event 
Details (if necessary) 
Handling of event 
Nonadherence to study 
treatment 
Greater than 20% of missed 
daily doses within 3 weeks 
prior to an assessment 
Only the assessment 
immediately following the event 
will be excluded for the 
purpose of this estimand 
Any missed dose within the 
2 days prior to an assessment 
Only the assessment 
immediately following the event 
will be excluded for the 
purpose of this estimand 
The handling of each intercurrent event specified in Table 3-2, with the exception of changes 
in standard of care cardiovascular disease prevention medication, reflects what is referred to as 
the hypothetical strategy, which aims to mimic a scenario in which the intercurrent event did 
not actually occur and all participants had adhered to the randomized treatment throughout the 
course of the study. To enable this strategy, data from various assessments taking place after 
the event will be excluded from the primary analysis, as described in the table. The exception 
to this is changes to standard of care cardiovascular disease prevention medication, which will 
be handled by a treatment policy strategy, in which any occurrence of the event is ignored, and 
the subsequent data are included in the analysis. 
Additional information on the handling of the intercurrent events in the primary analysis is 
described in Section 9.3.3. 
3.2 
Secondary estimands 
Not applicable. 
4 
Study design 
4.1 
Overall design 
This is a multi-center, randomized, placebo-controlled, participant- and investigator-blinded 
study to evaluate the efficacy, safety, and tolerability of intra-individual dose escalation of 
DFV890 for inflammatory marker reduction in participants with coronary heart disease and 
elevated hsCRP. The study consists of a screening period of up to 60 days, a treatment period 
of approximately 12 weeks, an end of treatment (EOT) visit on Day 85, which is one day after 
the last dose on Day 84, a follow-up period of approximately 1 week and a standard safety-
follow-up call approximately 30 days following the last dose. The overall study duration is 
approximately 24 weeks and approximately 24 participants will be enrolled into the trial. 
The screening period includes 2 visits. During Screening 1, hsCRP levels will be measured. If 
hsCRP levels at Screening 1 meet the eligibility criteria, participants will complete Screening 2 
(at least 8 days after Screening 1), where other eligibility assessments will be performed. 
Participants who don't meet hsCRP levels at Screening 1 visit will be considered screen failures. 
Participants meeting all eligibility criteria will be randomized in a 5:5:1:1 ratio to one of four 
treatment sequences (three DFV890 treatment sequences or a placebo-only sequence). Within 
each DFV890 sequence, participants will start on either oral placebo or DFV890 10 mg QD. 
On Day 1, participants will receive the first oral dose of DFV890 or placebo. After initial 

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Novartis 
Confidential 
Page 28 of 92 
Amended Protocol Version 01 (Clean) 
 
Protocol No. CDFV890F12201 
 
Study Design Aspect 
Rationale 
evidence supports a causal role, no pharmacologic intervention 
trials have yet demonstrated that IL-18 inhibition reduced 
CVD risk. 
Analysis of primary endpoints 
Each participant will contribute data on levels of IL-6 and IL-18 
after 3 weeks of oral daily treatment with DFV890 at up to 
3 different dose levels and/or placebo, depending on treatment 
sequence assignment. A dose-response modeling approach, 
which integrates the IL-6 or IL-18 levels across all dose levels 
to fit a dose-response relationship, will be utilized to quantify 
placebo-adjusted reductions at the highest tested dose level, 
100 mg. The rationale for analyzing all of the IL-6 and IL-18 
data from the end of each 3-week dosing period together in a 
dose-response model is to take advantage of the efficiencies 
introduced by the up titration design. The model treats each 
dosing period as independent of the prior period, which is 
justified because cytokine levels are expected to reach a 
maximum reduction within 7-14 days, and therefore the 3-week 
timepoint is expected to be at steady state reduction. The fact 
that dosing occurs in a monotonically increasing manner 
ensures that no washout between doses is required, as the 
effect is only expected to be greater with higher doses. It is 
possible that subsequent dose levels may reach steady state 
cytokine reduction sooner than if drug had not already been on 
board, but this will not impact the analysis as only the 3-week 
measurement is collected and used in the analysis. 
Treatment Sequences 
In Treatment Sequence 1 and Treatment Sequence 2, 
participants begin with placebo treatment and are followed with 
increasing doses of DFV890. Treatment Sequence 3 and 
Treatment Sequence 4 were primarily included to maintain the 
blind in each dosing period so that there is both active and 
placebo within each dosing period. Treatment Sequence 4, in 
addition, will generate more placebo data, which is useful for 
the primary analysis. More participants are allocated to 
Treatment Sequence 1 and Treatment Sequence 2 as they will 
contribute intra-individual placebo data, thereby making 
analyses more efficient. 
Randomization 
Participants will be randomized in a 5:5:1:1 ratio to the 
4 treatment sequences. Randomization is used to limit 
selection bias and decrease the chance of an imbalance in 
participant characteristics between sequences, thereby 
facilitating an unbiased assessment of the effect of treatment. 
However, with a modest sample size and 4 treatment 
sequences, baseline clinical characteristic imbalances may 
occur across the sequences. This has limited consequence in 
this study design as most of the participants serve as their own 
placebo controls with intra-individual dose-response modeling 
rather than comparison between two equal active and placebo 
treatment arms. 
Blinding 
Blinding of participants and investigators during the study 
allows for an unbiased assessment of study endpoints. 

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4.6 
Purpose and timing of interim analyses/design adaptations 
No interim analysis is planned for this study, but ad-hoc interim analyses may be conducted to 
support decision making concerning the current clinical study, the sponsor's clinical 
development projects in general, or in case of any safety concerns. 
4.7 
End of study definition 
The end of the study is defined as the date of the last visit of the last participant in the study. 
Study completion is defined as when the last participant finishes their last study visit and any 
repeat assessments associated with this visit have been documented and followed-up 
appropriately by the Investigator. 
All randomized and/or treated participants should have a safety follow-up phone call conducted 
at least 30 days after last administration of study treatment. The information collected is kept 
as source documentation. Serious Adverse Event (SAE) reporting continues during this time 
period as described in Section 8.6.3. Documentation of attempts to contact the participant are 
required to be recorded in the source documentation. 
5 
Study population 
The study population is adults with known coronary heart disease and elevated hsCRP. In this 
study, approximately 24 participants will be enrolled. 
5.1 
Inclusion criteria 
Participants eligible for inclusion in this study must meet all of the following criteria: 
1. Written informed consent must be obtained before any assessment is performed. 
2. Able to communicate well with the investigator, to understand and comply with the 
requirements of the study. 
3. Male and female participants aged between 18 - 85 years (inclusive) at the start of 
screening will be included. 
4. Subjects must have a body mass index (BMI) within the range of 18 - 45 kg/m2 at the start 
of screening. BMI = Body weight (kg) / [Height (m)]2 
5. Documented spontaneous myocardial infarction (MI) (diagnosed according to the 
universal MI criteria with or without evidence of ST segment elevation) at least 30 days 
before the start of screening (Thygesen et al 2007). 
Diagnosis of the qualifying MI should be based on medical history of clinical symptoms 
consistent with myocardial ischemia associated with elevation of cardiac biomarkers 
above the 99th percentile of the upper reference limit (preferably troponin) OR 
development of new pathological Q waves regardless of symptoms. For details, refer to 
the Universal Definition of MI (Thygesen et al 2007). 

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Documentation in the medical history to support evidence of prior MI may include: 
• Evidence of an acute MI in hospitalization or medical records: 
• requires documentation of a rise and/or fall of cardiac biomarkers (preferably 
troponin) with at least one value above the 99th percentile of the upper reference 
limit or above criteria diagnostic for MI  
AND 
• Evidence of myocardial ischemia as demonstrated by at least one of the following: 
• Symptoms of ischemia 
• ECG changes indicative of new ischemia (new ST-T changes or new LBBB) 
• Development of pathologic Q waves 
• Imaging evidence of new loss of viable myocardium or new regional wall motion 
abnormality 
If no documented evidence of an acute MI in the medical record, then evidence of a prior 
MI may include: 
• Development of pathological Q waves with or without symptoms 
• Imaging evidence of a region of loss of viable myocardium that is thinned and fails to 
contract in the absence of a non-ischemic cause 
• Pathologic findings of a healed or healing MI  
6. Participants must have hsCRP levels ≥ 2 mg/L at two timepoints during screening. 
Screening values must be separated by a minimum of 8 days. The initial hsCRP value 
must be a minimum of 30 days after the qualifying MI or after any percutaneous coronary 
intervention (PCI) performed separately from the qualifying MI. 
7. For participants on statin therapy (HMG-CoA reductase inhibitor) as clinically indicated, 
participants must be on a stable regimen (at least 4 weeks before randomization), with no 
planned statin dose changes over the course of the trial treatment period. Unplanned statin 
dose changes during the trial treatment period may occur but must be documented as 
described in Section 6.2.2 
5.2 
Exclusion criteria 
Participants meeting any of the following criteria are not eligible for inclusion in this study. 
1. Patients receiving concomitant medications (see list of prohibited drugs: Section 6.8.2) 
that are known to be: 
• strong or moderate inducers of cytochrome CYP2C9 enzyme, or 
• strong inducers of CYP3A, or 
• strong inhibitors of CYP2C9, or 
• strong or moderate inhibitors of CYP3A   
• and the treatment cannot be discontinued or switched to a different medication within 
5 half-lives or 1 week (whichever is longer) prior to Day 1 and for the duration of the 
study. 
2. Use of other investigational drugs within 5 half-lives of Day 1, or until the expected 
pharmacodynamic effect has returned to baseline, whichever is longer. 

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3. History of hypersensitivity to any of the study treatments or excipients or to drugs of 
similar chemical classes. 
4. History of drug abuse or unhealthy alcohol use within the 12 months prior to the start of 
screening, per investigator judgement. 
Unhealthy alcohol use may be considered with a history of, or current, alcohol 
misuse/abuse or “Five or more drinks on the same occasion on each of 5 or more days in 
the past 30 days." However unhealthy alcohol use may be considered at lower level per 
investigator judgement based on the participant's history. 
5. Pregnant or nursing (lactating) women. 
6. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using highly effective methods of contraception for at 
least 3 months prior to first dose administration (Day 1), during dosing and for 7 days after 
stopping of investigational drug. Highly effective contraception methods include: 
• Total abstinence from heterosexual intercourse (when this is in line with the preferred 
and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, post-ovulation methods) and withdrawal are not acceptable methods 
of contraception. 
• Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking 
investigational drug. In case of oophorectomy alone, only when the reproductive 
status of the woman has been confirmed by follow up hormone level assessment. 
• Male sterilization (at least 6 months prior to screening). For female subjects on the 
study the vasectomized male partner should be the sole partner for that subject. 
• Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of 
contraception or placement of an intrauterine device or intrauterine system or other 
forms of hormonal contraception that have comparable efficacy (failure rate <1%), for 
example hormone vaginal ring or transdermal hormone contraception. Based on an 
in vitro induction of CYP3A4, there is a slight potential risk for a DDI of DFV890 
with hormonal contraception at high exposures, therefore oral hormonal contraception 
must be supplemented with a barrier method, preferable a male condom. 
In case of use of oral contraception women should have been stable on the same pill for a 
minimum of 3 months before taking study treatment. Women are considered post-
menopausal and not of childbearing potential if they have had 12 months of natural 
(spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, 
history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or 
without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the 
case of oophorectomy alone, only when the reproductive status of the woman has been 
confirmed by follow up hormone level assessment is she considered not of child-bearing 
potential. Refer to (Section 8.4.5 Pregnancy Testing). If local regulations deviate from the 
contraception methods listed above and require more extensive measures to prevent 
pregnancy, local regulations apply and will be described in the Informed Consent Form 
(ICF). 

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7. Sexually active males unwilling to use a condom during intercourse while taking study 
treatment and for 7 days after stopping study treatment. A condom is required for all 
sexually active male participants to prevent them from fathering a child AND to prevent 
delivery of study treatment via seminal fluid to their partner. In addition, male participants 
must not donate sperm for the time period specified above. 
8. History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system within the past 5 years of the start of screening (except for basal cell 
carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the 
past 3 months, or carcinoma in situ of the cervix or non-invasive malignant colon polyps 
that have been removed). 
9. Any diagnosed psychiatric condition that includes, but is not limited to, a history of mania, 
bipolar disorder, psychotic disorder, schizophrenia, or schizoaffective disorder, depression 
or anxiety, which may jeopardize patient safety or compliance with study procedures, as 
judged by the investigator. 
10. History of ongoing, chronic, or major recurrent infectious disease, at the discretion of the 
investigator, at the start of screening. 
11. Live vaccinations within 1 month prior to Day 1 or live vaccinations planned during the 
trial. 
12. Patients with suspected or proven immunocompromised state at screening, including: 
a. known clinical diagnosis of Human Immunodeficiency Virus (HIV) infection. 
Patients on systemic anti-retroviral therapy are also excluded from the trial; 
b. those with any other medical condition which in the opinion of the investigator places 
the patient at unacceptable risk for participation in immunomodulatory therapy; 
c. absolute neutrophil count ≤ 1000/mm3; 
d. those requiring systemic or local treatment with any immune modulating agent in 
doses with systemic effects e.g., high dose oral or intravenous (i.v.) steroids (> 20 mg 
prednisone orally daily for > 14 days, > 5 mg prednisone orally daily or equivalent 
dose of i.v. steroid) or high dose methotrexate (> 15 mg weekly). 
Topical, inhaled, local steroid use in doses that are not considered to cause systemic 
effects are permitted. 
13. Use of any biologic drugs targeting the immune system (for example, but not limited to): 
TNF blockers, anakinra, rituximab, abatacept, tocilizumab, or canakinumab) within 
26 weeks of Day 1. Refer to Section 6.8.2 of the protocol. 
14. Known diagnosis of a systemic auto-immune or systemic inflammatory disease (eg. 
systemic lupus erythematosus, etc.). 
15. Current use or within 5 half-lives of colchicine at the start of screening. 
16. Participants with a MI resulting from PCI or CABG procedures. 
17. Major non-cardiac surgical or major endoscopic procedure within the past 6 months prior 
to the start of screening. 
18. Multi-vessel CABG surgery within the past 6 months prior to the start of screening. 
19. Planned coronary revascularization (PCI or CABG) or any other major surgical procedure 
during the study (until EOS). 

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20. Symptomatic Class IV heart failure (New York Heart Association) at the start of 
screening. 
21. History or current diagnosis of ECG abnormalities indicating significant risk of safety for 
participants participating in the study such as: 
• Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular 
tachycardia, and clinically significant second or third degree AV block without a 
pacemaker 
• History of familial long QT syndrome or known family history of Torsades de Pointe 
22. Uncontrolled hypertension (defined as systolic blood pressure (SBP) >160 mmHg or 
diastolic blood pressure (DBP) >100 mmHg) at screening. 
23. Uncontrolled diabetes, as defined by the investigator, at screening. The following should 
be considered by the investigator in guiding the determination as part of the overall 
assessment, but should not be considered in isolation: 
• Clinical and laboratory evidence of uncontrolled diabetes may include but are not 
limited to hemoglobin A1C >10%, recurrent fasting glucose >200mg/dL, frequent 
urination/thirst not explained by other causes, etc. 
24. Known nephrotic syndrome diagnosis, or eGFR < 30 mL/min calculated using the 
CKD-EPI formula (https://www.kidney.org/professionals/KDOQI/gfr_calculator), or 
≥ 2+ protein on urine dipstick testing at screening 
25. History of clinically significant liver disease or liver injury at screening as indicated by 
abnormal liver enzymes or function tests (as defined below) including but not limited to 
Alanine Aminotransferase (ALT), Aspartate Transaminase (AST), Serum Glutamic 
Oxaloacetic Transaminase (SGOT), Serum Glutamic Pyruvic Transaminase (SGPT), 
alkaline phosphatase (ALP), serum bilirubin, albumin, and prothrombin time (PT). The 
Investigator should be guided by the following criteria: 
• Any single parameter may not exceed 2 x upper limit of normal (ULN). 
26. Uncontrolled asthma at the start of screening, as defined by the investigator, with high 
likelihood of requiring systemic corticosteroids during treatment period. 
5.3 
Lifestyle considerations 
For the duration of the study, participants should be informed and reminded of the restrictions 
outlined in this section. 
5.3.1 
Meals and dietary restrictions 
Participants are to take DFV890 or placebo once daily at approximately the same time each 
day. 
No grapefruit or grapefruit juice is to be consumed from first day of dosing until 7 days 
following the last dose. 
No St. John’s wort (Hypericum perforatum) is to be consumed 14 days before start of treatment 
until 7 days following the last dose. 

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5.4 
Screen failures 
Participants who sign an ICF and are subsequently found to be ineligible prior to randomization 
will be considered as screen failures. The reason for screen failure should be recorded on the 
appropriate Case Report Form. The demographic information, informed consent, and 
Inclusion/Exclusion pages must also be completed for screen failure participants. No other data 
will be entered into the clinical database for participants who are screen failures, unless the 
participant experienced a SAE during the screening period (see Section 8.6.3 for reporting 
details). If the participant fails to be randomized, the Interactive Response Technology (IRT) 
must be notified within 2 days of the screen fail that the participant was not randomized. Data 
and samples collected from participants prior to screen failure may still be analyzed. 
Participants who are randomized and fail to start treatment, e.g., participants randomized in 
error, will be considered an early terminator. The reason should be recorded on the appropriate 
Case Report Form. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once. Each case of re-screening must be discussed and agreed with Novartis on a 
case-by-case basis. 
Participants who failed their initial screening due to elevated blood pressure (BP) may be re-
screened if anti-hypertensive therapy has been started or increased as a result of initial screening 
BP above these limits. 
Genotyping will not need to be repeated in case of re-screening. 
Participants who are re-screened will be assigned a new participant number and will be 
reconsented. 
5.4.1 
Replacement policy 
The proposed sample size accounts for dropouts at rates depending on the dose level of DFV890 
or placebo (as described in Section 9.9.1), therefore discontinued patients will not be replaced. 
5.4.2 
Participant numbering 
Each participant is identified in the study by a Participant Number (Participant No.), that is 
assigned when the participant is enrolled for screening and is retained for the participant 
throughout his/her participation in the trial. A new Participant No. will be assigned at every 
subsequent enrollment if the participant is rescreened. The Participant No. consists of the Site 
Number (Site No.) (as assigned by Novartis to the investigative site) with a sequential 
participant number suffixed to it, so that each participant’s participation is numbered uniquely 
across the entire database. Upon signing the ICF, the participant is assigned to the next 
sequential Participant No. available. 
A new ICF will need to be signed if the Investigator chooses to rescreen the participant after a 
participant has screen failed, and the participant will be assigned a new Participant No. 

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6 
Study treatment(s) and concomitant therapy 
6.1 
Study treatment(s) 
The investigational drug, DFV890, will be prepared by the sponsor as indicated in Table 6-1. 
DFV890 will be administered orally with food once a day (QD). 
Table 6-1 
Investigational and control drug 
Investigational/ 
Control Drug 
(Name and 
Strength) 
Treatment Form 
or 
Pharmaceutical 
Dosage Form 
Route of 
Administration 
Presentation 
Sponsor (global 
or local) 
DFV890 10 mg 
Tablet 
Oral use 
Blinded Supplies 
in HDPE Bottle of 
35 tablets 
Sponsor (global) 
DFV890 25 mg 
Tablet 
Oral use 
Blinded Supplies 
in HDPE Bottle of 
35 tablets 
Sponsor (global) 
DFV890 10 mg 
Placebo 
Tablet 
Oral use 
Blinded Supplies 
in HDPE Bottle of 
35 tablets 
Sponsor (global) 
DFV890 25 mg 
Placebo 
Tablet 
Oral use 
Blinded Supplies 
in HDPE Bottle of 
35 tablets 
Sponsor (global) 
6.1.1 
Additional study treatments 
No other treatment beyond investigational drug and control drug are included in this trial. 
As this is a population with known coronary heart disease, participants would be expected to 
be on standard of care therapies to reduce risk of recurrence of cardiovascular disease events 
(eg. lipid lowering therapy, anti-hypertensives, etc.), if clinically indicated. 
6.1.2 
Treatment arms/group 
Participants will be assigned at Day 1 to one of the following 4 treatment arms/groups in a ratio 
of 5:5:1:1 

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Figure 6-1 
Treatment arms 
 
6.2 
Preparation, handling, storage, and accountability 
Each study site will be supplied with study treatment in packaging as described 
under Table 6-1 Investigational and control drugs. 
A unique medication number is printed on the study medication label of each bottle. 
Investigator staff will identify the study medication bottle(s) to dispense to the participant by 
contacting the IRT system and obtaining the medication number(s). Drug accountability and 
reconciliation data is recorded in a drug accountability log (e.g. the Drug Accountability and 
Returns Management functionality in the IRT system) 
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, delivery 
of Investigational Medicinal Product (IMP) directly to a participant's home may be permitted 
(if allowed by local or regional health authorities and ethics committees, as appropriate) in the 
event the Investigator has decided that an on-site visit by the participant is no longer appropriate 
or possible, and that it is in the interest of the participant's health to administer the study 
treatment even without performing an on-site visit. The dispatch of IMP from the site to the 
participant’s home remains under the accountability of the Investigator. Each 
shipment/provisioning will be for a maximum of 1-month supply. In this case, regular phone 
calls or virtual contacts (every 2 weeks or more frequently if needed) will occur between the 
site and the participant for instructional purposes, safety monitoring, investigation of any AEs, 
ensuring participants continue to benefit from treatment, and discussion of the participant's 
health status until the participants can resume visits at the study site. 
In order to reduce waste, the study medication will be sent to a site when the first patient enters 
Screening 2 visit. Sites should allow for approximately seven days between screening and 

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randomization visit/first study treatment dose (choose which is applicable for the study) of their 
first participant for the first study medication shipment. For the precise timeframe or to 
accommodate exceptional circumstances, sites should discuss with their Field Monitor. 
6.2.1 
Handling of study treatment 
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secured location to which only the Investigator and designated 
site personnel have access. Upon receipt, all study treatment must be stored according to the 
instructions specified on the labels. 
Clinical supplies are to be dispensed only in accordance with the protocol. Technical complaints 
are to be reported to the respective Novartis Country Organization (CO) Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of each 
country. They will include storage conditions for the study treatment but no information about 
the participant except for the medication number. 
The Investigator or designated site staff (blinded or unblinded, as applicable) must maintain an 
accurate record of the shipment and dispensing of study treatment in a drug accountability log 
(e.g. the Drug Accountability and Returns Management functionality in the IRT system). All 
bottles of study treatment assigned by the IRT will be recorded in the IRT system. Monitoring 
of drug accountability will be performed by field monitors during site or remote monitoring 
visits, and at the completion of the trial.  
As study treatment is administered at home, e.g., oral medication, participants will be asked to 
return all unused study treatment and packaging at each visit or at the time of discontinuation 
of study treatment. 
The site may destroy and document destruction of unused study treatment, drug labels and 
packaging, as appropriate in compliance with site processes, monitoring processes, and per local 
regulation/guidelines. Otherwise, the Investigator will return all unused study treatment, 
packaging, drug labels, and a copy of the completed drug accountability log to 
the Novartis monitor or to the Novartis address provided in the Investigator folder at each site. 
6.2.2 
Handling of other treatment 
The following non-study treatment must be monitored specifically: 
• Statin (HMG-CoA reductase inhibitor) therapy. Any changes in statin dose should be 
recorded on the appropriate Case Report Forms. 
6.2.3 
Instruction for prescribing and taking study treatment 
Participants will be randomized to one of four treatment sequences. Based on the treatment 
sequence assignment, patients will start on either placebo or DFV890 at Day 1 and then receive 
up titrating doses of DFV890 or further placebo at the corresponding study visits. 
Participants will be dispensed with double-blind HDPE bottle packs for each 3-week dosing 
period to ensure the appropriate dosage is being taken while maintaining the blind. 

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Table 6-2 
Dose and treatment schedule 
Dosing Period 
Dose/Strength 
Investigational / Control Drug (Name 
and Strength) + Number of Tablets 
Frequency 
and/or Regimen 
Dosing Period 1 
(Day 1 to 21) 
10 mg 
1 tablet of DFV890 10 mg 
Once daily with 
food for 3 weeks 
0 mg 
1 tablet of 10 mg matching placebo 
Dosing Period 2 
(Day 22 to 42) 
25 mg 
1 tablet of DFV890 25 mg + 1 tablet of 
10 mg matching placebo 
Once daily with 
food for 3 weeks 
10 mg 
1 tablet of DFV890 10 mg + 1 tablet of 
25 mg matching placebo 
0 mg 
1 tablet of 25 mg matching placebo + 
1 tablet of 10 mg matching placebo 
Dosing Period 3 
(Day 43 to 63) 
50 mg 
2 tablets of DFV890 25 mg 
Once daily with 
food for 3 weeks 
25 mg 
1 tablet of DFV890 25 mg + 1 tablet of 
25 mg matching placebo 
0 mg 
2 tablets of 25 mg matching placebo 
Dosing Period 4 
(Day 64 to 84) 
100 mg 
4 tablets of DFV890 25 mg 
Once daily with 
food for 3 weeks 
0 mg 
4 tablets of 25 mg matching placebo 
Up titration will occur at the study visits during the Treatment Period as indicated in Section 1.3, 
Schedule of Activities. 
Each 3-week dosing period (i.e., Day 1-21, Day 22-42, Day 43-63, and Day 64-84) is 
approximately 21 days in duration but must be at least 17 days in duration. The following/next 
visit should be scheduled the day after the last dose of that current dosing period. In the event 
that an up titration visit cannot be scheduled within the allowed visit windows, the participants 
should continue to take their dose up to a maximum of 35 days (maximum number of tablets 
dispensed for a given dosing period) and every effort should be made to schedule the visit before 
the participant's supply of tablets for the given period runs out. 
If participants run out of tablets before the next up titration visit can be scheduled, a visit should 
be scheduled as soon as possible to only perform safety assessments described 
in Section 8.4 (Safety/Tolerability Assessments). Other non-safety assessments described 
in Section 8.3 (Efficacy assessments) must not be performed. Participants will then start the 
next dosing period as applicable. 
The last dose will be taken on Day 84 prior to the EOT visit on Day 85. Allowable visit windows 
are listed in Section 1.3, Schedule of Activities. To achieve the target doses for each time 
period, please refer to Table 6-2. Participants are to take DFV890 or placebo once daily at 
approximately the same time each day. On days of study visits with dose administration, the 
participants should not take their daily dose until they are on-site and instructed to do so by the 
site staff. On days that pre-dose PK samples are obtained, the participant should take DFV890 
or placebo after the pre-dose PK samples, as instructed by site staff. In the event that the 
participants have taken their daily dose on the visit day prior to arriving for their on-site visit, 
the visit and associated assessments should be rescheduled as soon as possible (e.g., next day 
or after the weekend). Participants should take DFV890 or placebo at home with food or no 
later than 5 minutes after completion of the meal with a glass of water or any non-alcoholic 
beverage (see Section 5.3.1 for dietary restrictions). Participants should be instructed to 

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swallow whole tablets and not to chew or break them. On days of study visits with dose 
administration, DFV890 or placebo does not need to be taken with food. 
If vomiting occurs during the course of treatment, participants should not take the study 
treatment (DFV890 or placebo) again before the next scheduled dose. Participants should be 
instructed not to make up missed doses. A missed dose is defined as a case when the full dose 
is not taken within 12h after the approximate time of the usual daily dosing. That day's dose 
should be omitted, and the participant should continue treatment with the next scheduled dose. 
6.3 
Measures to minimize bias: randomization and blinding 
6.3.1 
Treatment assignment, randomization 
At Day 1, all eligible participants will be randomized via IRT to one of the treatment arms. The 
Investigator or his/her delegate will contact the IRT after confirming that the participant fulfills 
all the inclusion/exclusion criteria. The IRT will assign a randomization number to the 
participant, which will be used to link the participant to a treatment arm and will specify a 
unique medication number for the first bottle of study treatment to be dispensed to the 
participant. 
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from participants and Investigator staff. A 
participant randomization list will be produced by the IRT provider using a validated system 
that automates the random assignment of participant numbers to randomization numbers. These 
randomization numbers are linked to the different treatment arms, which in turn are linked to 
medication numbers. A separate medication list will be produced by or under the responsibility 
of Novartis Global Clinical Supply (GCS) using a validated system that automates the random 
assignment of medication numbers to packs containing the study treatment. 
The randomization scheme for participants will be reviewed and approved by a member of the 
Randomization Office. 
6.3.2 
Treatment blinding 
This is a participant- and investigator-blinded study. Participants and investigators will remain 
blinded to study treatment throughout the study, except where indicated below. 
The identity of treatments will be concealed by the use of study drugs that are all identical in 
packaging, labeling, schedule of administration, appearance, and odor. 
Site staff 
All site staff (including study investigator, study nurse) will be blinded to study treatment 
throughout the study. 
Unblinding a single participant at site for safety reasons (necessary for participant management) 
will occur via an emergency system in place at the site. 
Sponsor staff or delegate 
Unblinded sample analysts are required for this study. The sample analysts will receive a copy 
of the randomization schedule (via request to the Randomization Office) to facilitate analysis 

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of the samples. The sample analysts will provide the sample data to the study team under 
blinded conditions unless otherwise allowed. 
The study statistician will be able to access the randomization list at any time throughout the 
study and is allowed to share unblinded information with the rest of the clinical team as 
appropriate for internal decision purposes, as outlined in Table 6-3. For example, unblinded 
summaries and unblinded individual data can be shared with the team for interim analyses. 
Study programmers and other personnel involved in study data analyses (e.g., biomarker expert, 
pharmacometrician, and potentially others) are also allowed to access treatment assignment 
information at any time throughout the study for the purpose of conducting data analyses. 
The Clinical Trial Team (CTT) is allowed to share unblinded results with other sponsor staff 
(e.g., decision boards) as required for internal decision making on the study or the project at the 
time of interim analyses while the study is ongoing. 
All unblinded personnel will otherwise keep randomization lists and data or information that 
could unblind other study team members confidential and secure except as described above. 
Following final database lock, all roles may be considered unblinded. 
Table 6-3 
Blinding and unblinding plan 
Role 
Time or Event 
Randomization 
list generated 
Treatment 
allocation & 
dosing 
Safety event 
(single 
subject 
unblinded) 
Interim 
Analysis/ dose 
escalation/ 
safety review 
Participants 
B 
B 
UI 
B 
Site Staff 
B 
B 
UI 
B 
Global Clinical Supply 
UI 
UI 
UI 
UI 
Randomization Office 
UI 
UI 
UI 
UI 
Statistician/statistical 
programmer/ data analysts 
(e.g. biomarker, PK) 
B 
UI 
UI 
UI 
Unblinded Sponsor staff, e.g. 
for study treatment re-supply, 
unblinded monitor(s), sample 
analyst(s) 
B 
UI 
UI 
UI 
Sponsor CTT 
B 
B 
UI 
UI 
All other Sponsor staff not 
identified above (i.e. project 
team, management & decision 
boards, support functions) 
B 
B 
UI 
UI 
B Complete blinded 
UI Unblinded to individual participant treatment codes 

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6.3.3 
Emergency breaking of assigned treatment code 
Emergency code breaks must only be undertaken when it is required in order to treat the 
participant safely. 
Most often, discontinuation from study treatment and knowledge of the possible treatment 
assignments are sufficient to treat a study participant who presents with an emergency 
condition. Emergency treatment code breaks are performed using the IRT. When the 
Investigator contacts the system to break a treatment code for a participant, he/she must provide 
the requested participant identifying information and confirm the necessity to break the 
treatment code for the participant. The Investigator will then receive details of the 
investigational drug treatment for the specified participant and a fax or email confirming this 
information. The system will automatically inform the Novartis monitor for the site and the 
study team that the code has been broken. 
It is the Investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT/code break cards at any time in case of emergency. The Investigator 
will provide: 
• protocol number 
• participant number 
In addition, oral and written information to the participant must be provided on how to contact 
his/her backup in cases of emergency, or when he/she is unavailable, to ensure that un-blinding 
can be performed at any time. 
6.4 
Study treatment compliance 
The Investigator must promote compliance by instructing the participant to take the study 
treatment exactly as prescribed and by stating that compliance is necessary for the participant’s 
safety and the validity of the study. The participant must also be instructed to contact the 
Investigator if he/she is unable for any reason to take the study treatment as prescribed. 
Compliance will be assessed by the Investigator and/or site study personnel at each visit using 
pill counts and information provided by the participant. This information should be captured in 
the source document at each visit. CRF documented compliance measures, as reported by the 
participant, include: 1) any missed doses within the 2 days prior to the study visit, and 2) 
confirmation that the time the participant took the last dose on the day prior to the study visit 
was 24h ± 2h from the PK sample collection. Assessments of compliance at study visits are 
reflected in Section 1.3, Schedule of Activities. 
All study treatment dispensed and returned must be recorded in a drug accountability log (e.g. 
the Drug Accountability and Returns Management functionality in the IRT system). 

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6.4.1 
Recommended treatment of adverse events 
The following recommendation for managing potential suspected DFV890-related skin rashes 
are provided. 
• Depending on severity, investigators can consider, as per medical judgment, early 
treatment of mild rashes (maculopapular rash covering <10% body surface area with or 
without symptoms, e.g., pruritis, burning) with symptomatic treatment (e.g., topical 
steroids) and close monitoring of the participant's response. 
• For skin rashes covering >10% body surface area (corresponding to a Common 
Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher), investigators 
should discontinue DFV890 and closely monitor participants to ensure resolution of the 
rash. In the case of participants with systemic or cutaneous signs or symptoms suggesting 
a severe cutaneous reaction, a short course of systemic corticosteroids (e.g., prednisone 1 
to 2 mg/kg per day for 5 to 7 days) may be considered. 
At present, there is insufficient information to provide specific recommendations regarding 
treatment of other potential AEs in this participant population. 
Medication used to treat AEs must be recorded on the appropriate CRF. 
6.5 
Dose modification 
Investigational or other study treatment dose adjustments and/or interruptions are not permitted. 
6.6 
Continued access to study treatment after the end of the study 
Investigational drug will not be provided to participants following the end of the study. 
6.6.1 
Post-trial access 
Not applicable. 
6.7 
Treatment of overdose 
In the event of an overdose, the investigator/treating physician should: 
• Contact the medical monitor immediately. 
• Evaluate the participant to determine, in consultation with the medical monitor, whether 
study treatment should be interrupted or whether the dose should be reduced. 
• Closely monitor the participant for any AE/SAE and laboratory abnormalities until 
DFV890 can no longer be detected systemically (at least 7 days). 
• Obtain a plasma sample for PK analysis within 7-10 days from the date of the last dose of 
study treatment if requested by the medical monitor (determined on a case-by-case basis). 
• Document the quantity of the excess dose as well as the duration of the overdose. 

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ulipristal, vardenafil, venetoclax, vicriviroc, 
vilaprisan, voclosporin, zanubrutinib 
Moderate inhibitor of CYP2C9 
amiodarone, ataciguat, azapropazone, 
benzbromarone, bucolome, milk thistle (silymarin, 
silibinin)1, nitisinone, oxandrolone, 
phenylbutazone, piperine2, tienilic acid 
1 Herbal product 
2 Food product 
Investigators at their discretion may administer concomitant medications known to be 
metabolized by CYP3A. All participants receiving such medications may however require 
higher doses of the concomitant drug as efficacy might be compromised by DFV890. 
Particularly, caution is advised when DFV890 is co-administered with drugs that are sensitive 
substrates of CYP3A and/or have a narrow therapeutic index. 
If it cannot be replaced by other medications, investigators may, at their discretion, 
co‑administer known moderate inhibitors of CYP2C9. Their duration, however, should be kept 
as short as possible, and participants must be closely monitored. 
The participant and the investigator should be aware of potential signs of DDIs of the 
concomitant medication and in the event of suspected toxicity; administration of concomitant 
medication should be discontinued according to investigator judgment and an unscheduled PK 
sample should be taken to evaluate systemic exposure to DFV890. 
6.8.2 
Prohibited medication 
Strong or moderate inhibitors of CYP3A and/or strong inhibitors of CYP2C9 are prohibited. 
Strong or moderate inducers of CYP2C9 and/or strong inducers of CYP3A or strong or 
moderate dual inhibitors of CYP2C9 / CYP3A are also prohibited (for detailed list 
see Table 6-5 below (please note that this list may not be comprehensive)). 
Considering the DDI potential for DFV890, should a participant have an incidental and limited 
need for a prohibited medication to be taken within the restricted timeframe, investigators 
should discuss the case with the sponsor. The administration of any prohibited concomitant 
medication may require the participant to be withdrawn or DFV890 treatment to be put on hold. 
Use of the treatments displayed in the below table is prohibited approximately 5 half-lives or 
1 week (whichever is longer) prior to Day 1 until end of study as described in Table 6-6. 

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Table 6-5 
Prohibited drugs due to DDI (CYP3A and CYP2C9 modulators) 
Category of 
interaction 
Drug Names 
Strong inhibitors 
of CYP3A 
boceprevir, ceritinib, clarithromycin, cobicistat, conivaptan, 
danoprevir/ritonavir3, elvitegravir/ritonavir3, grapefruit juice2, idelalisib, 
indinavir, indinavir/ritonavir3, itraconazole, josamycin, ketoconazole, 
lopinavir/ritonavir3, mibefradil, mifepristone, nefazodone, 
nelfinavir, ombitasvir/paritaprevir/dasabuvir/ritonavir (Viekira Pak)3, 
posaconazole, ribociclib, ritonavir, saquinavir, saquinavir/ritonavir3, telaprevir, 
telithromycin, tipranavir/ritonavir3, troleandomycin, tucatinib, voriconazole 
Moderate 
inhibitors of 
CYP3A 
aprepitant, amprenavir, atazanavir, atazanavir/ritonavir3, 
casopitant, cimetidine, ciprofloxacin, crizotinib, darunavir, darunavir/ritonavir3, 
diltiazem, dronedarone, duvelisib, erythromycin, faldaprevir, fedratinib, 
fluconazole, grapefruit juice, imatinib, isavuconazole, istradefylline, lefamulin, 
letermovir, Magnolia vine (Schisandra sphenanthera)1, netupitant, nilotinib, 
ravuconazole, tofisopam, verapamil, voxelotor 
Strong inhibitors 
of CYP2C9 
miconazole, sulfaphenazole, tasisulam 
Strong inducers of 
CYP2C9 
None reported to date 
Moderate inducers 
of CYP2C9 
enzalutamide, rifampicin 
Strong inducers of 
CYP3A 
apalutamide, avasimibe, carbamazepine, enzalutamide, ivosidenib, 
lumacaftor, mitotane, phenobarbital, phenytoin, rifampicin, rifapentine, 
St. John’s wort (Hypericum perforatum)1 
1 Herbal product 
2 The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and 
preparation-dependent. Studies have shown that it can be classified as a “strong CYP3A inhibitor” 
when a certain preparation was used (e.g., high dose, double strength) or as a “moderate CYP3A 
inhibitor” when another preparation was used (e.g., low dose, single strength). 
3 combination therapy 
Table 6-6 
Prohibited medication 
Medication 
Prohibition period 
Action taken 
Inhibitors and inducers of CYP3A or 
CYP2C9 according to Table 6-5 
5 half-lives or 1 week (whichever is 
longer) prior to Day 1 through EOS 
Discontinue study 
treatment 
Other investigational drugs 
Within 5 half-lives of Day 1 through 
EOS 
Discontinue study 
treatment 
Systemic or local treatment with any 
immune modulating agent in doses 
with systemic effects 
4 weeks prior to Day 1 through EOS 
Discontinue study 
treatment 
Biologic drugs targeting the immune 
system 
26 weeks prior to Day 1 until EOS 
Discontinue study 
treatment 
Colchicine 
Within 5 half-lives of the time of 
screening through EOS 
Discontinue study 
treatment 
Live vaccinations 
4 weeks prior to Day 1 through EOS 
Discontinue study 
treatment 

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7 
Discontinuation of study treatment and participant 
discontinuation/withdrawal 
7.1 
Discontinuation of study treatment 
Discontinuation of study treatment for a participant occurs when study treatment is permanently 
stopped for any reason (prior to the planned completion of study treatment administration, if 
any) and can be initiated by either the participant or the Investigator. 
The Investigator must discontinue study treatment for a given participant if he/she believes that 
continuation would negatively impact the participant's well-being. 
Discontinuation from study treatment is required under the following circumstances: 
• Participant decision 
• Pregnancy 
• Use of prohibited treatment as per recommendations in the prohibited treatment section 
• Any situation in which continued study participation might result in a safety risk to the 
participant 
• Following emergency unblinding 
• Emergence of at least one of the following AEs: 
• An AE of severe intensity (corresponding to CTCAE Grade 3 or higher) or life-
threatening SAE, considered to be related to DFV890 treatment 
• Skin rashes greater than mild (covering >10% of the body surface area, corresponding 
to CTCAE Grade 2 or higher) and considered to be related to DFV890 treatment 
• Any laboratory abnormalities, that in the judgment of the investigator, taking into 
consideration of the participant's overall status, prevents the participant from 
continuing participation in the study. 
• Any situation, in the judgment of the investigator, in which study participation might 
result in a safety risk to the patient 
• Severe hypersensitivity reaction occurs, including any of the following: anaphylaxis, 
fever, chills, urticaria, dyspnea, headache, myalgia, hypotension. 
If a liver or renal event occurs, follow guidelines outlined in Section 10.5 and 
Section 10.6 regarding discontinuation of study treatment. 
If discontinuation from study treatment occurs, the Investigator should make a reasonable effort 
to understand the primary reason for the participant’s discontinuation from study treatment and 
record this information. 
Participants who discontinue from study treatment agree to return for the end of treatment (EOT 
visit) and follow-up visits (EOS and Safety Follow-Up Call) indicated in Section 1.3 Schedule 
of Activities. If EOT visit cannot be performed the day after the last dose is taken, only EOS 
visit should be performed. 
If the participant cannot or is unwilling to attend any visit(s), the site staff should maintain 
regular telephone contact with the participant, or with a person pre-designated by the 

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participant. This telephone contact should preferably be done according to the study visit 
schedule. 
After discontinuation from study treatment, at a minimum, in abbreviated visits, the following 
data should be collected at clinic visits or via telephone/email contact: 
• New / concomitant treatments 
• AEs / SAEs 
The Investigator must also contact the IRT to register the participant’s discontinuation from 
study treatment. 
7.2 
Participant discontinuation from the study 
Discontinuation from study is when the participant permanently stops receiving the study 
treatment, and further protocol-required assessments or follow-up, for any reason. 
If the participant agrees, a final evaluation at the time of the participant’s study discontinuation 
should be made as detailed in Section 1.3 Schedule of Activities. 
7.3 
Withdrawal of informed consent and exercise of participants’ 
data privacy rights 
Withdrawal of consent/opposition to use of data and/or biological samples occurs in countries 
where the legal justification to collect and process the data is consent and when a participant: 
• Explicitly requests to stop use of their data 
and 
• No longer wishes to receive study treatment 
and 
• Does not want any further visits or assessments (including further study-related contacts) 
This request should be as per local regulations (e.g. in writing) and recorded in the source 
documentation. 
Withdrawal of consent impacts the ability to further contact the participant, collect follow-up 
data (e.g. to respond to data queries) and potentially other country-specific restrictions. It is 
therefore very important to ensure accurate recording of withdrawal vs. discontinuation based 
on the protocol definitions of these terms. 
In this situation, the Investigator should make a reasonable effort (e.g. telephone, e-mail, letter) 
to understand the primary reason for the participant’s decision to withdraw their 
consent/exercise data privacy rights and record this information. The Investigator shall clearly 
document if the participant has withdrawn his/her consent for the use of data in addition to a 
study discontinuation. 
Study treatment must be discontinued, and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up. 

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If the participant agrees, a final evaluation at the time of the participant’s withdrawal of 
consent/exercise data privacy rights should be made as detailed in Section 1.3 Schedule of 
Activities. 
Further details on withdrawal of consent or the exercise of participants' data privacy rights are 
included in the corresponding ICF. 
7.4 
Lost to follow-up 
For participants whose status is unclear because they fail to appear for study visits or fail to 
respond to any site attempts to contact them without stating an intention to discontinue from 
study treatment or discontinue from study or withdraw consent (or exercise other participants’ 
data privacy rights), the Investigator must show "due diligence" by documenting in the source 
documents steps taken to contact the participant, e.g. dates of telephone calls, registered letters, 
etc. A participant should not be considered as lost to follow-up until the planned end of the 
study would have occurred. 
7.5 
Study stopping rules 
The study will be stopped, and no further dosing will occur pending a full safety review, if 
any/all of the following criteria are met: 
• Any death or life-threatening event occur that is considered to be related to DFV890 
treatment; 
• Two or more SAEs of a similar type (other than death or life-threatening) occur that are 
considered to be related to DFV890 treatment; 
• Two or more participants experience hypersensitivity reactions of moderate to severe 
intensity that are considered to be related to DFV890 treatment; 
• Two or more participants experience a similar AE which was assessed as severe in 
intensity and are considered to be related to DFV890 treatment; 
• Novartis considers that the number and/or severity of AEs, abnormal safety monitoring 
tests, or abnormal laboratory findings justifies putting the study on hold. 
Dependent on regional guidance, any restart following a temporary hold due to stopping rules 
being met will require prior submission and approval of a substantial CTA amendment to the 
competent authorities. 
7.6 
Early study termination by the Sponsor 
The study can be terminated by Novartis at any time. 
Reasons for early termination (but not limited to): 
• Unexpected, significant, or unacceptable safety risk to participants enrolled in the study 
• Decision based on recommendations from applicable board(s) after review of safety and 
efficacy data 
• Discontinuation of study treatment development for cardiovascular disease event risk 
reduction. 

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In taking the decision to terminate, Novartis will always consider participant welfare and safety. 
Should early termination be necessary, instructions will be communicated at the time of 
notification. The Investigator may be informed of additional procedures to be followed in order 
to ensure that adequate consideration is given to the protection of the participant’s interests. The 
Investigator or Novartis depending on local regulation will be responsible for informing 
Institutional Review Board/Independent Ethics Committee (IRBs/IECs) of the early 
termination of the trial. 
8 
Study Assessments and Procedures 
Study procedures and their timing are summarized in Section 1.3 Schedule of Activities. 
Adherence to the study design requirements, including those specified in Section 1.3 Schedule 
of Activities, is essential and required for study conduct. Protocol waivers or exemptions are 
not allowed. 
Immediate safety concerns should be discussed with Novartis upon occurrence or awareness to 
determine if the participant should continue or discontinue study treatment. 
Laboratory results that could unblind the study will not be reported to investigative sites or other 
blinded personnel until the study has been unblinded. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. 
8.1 
Screening 
The screening assessments should be completed as per Section 1.3, Schedule of Activities, 
starting with informed consents. The assessments should be performed in order from the least 
invasive/burdensome to the more invasive/burdensome for the participant. Screening 
assessments (including safety laboratory assessments and hsCRP) may be repeated once (twice 
for vitals – see Section 8.4.2) at the discretion of the Investigator if there are questionable results 
or if abnormalities are felt to be due to inherent variability of the test procedure. If the repeat 
value remains outside the specified range, the participant will be considered a screen failure 
(See Section 5.4 for more details about screen failures). During screening, the investigator 
should detect any active infections that would disqualify the participant from this study 
(exclusion criterion). 
The decision to locally test the participant for active SARS-CoV-2 infection in order to evaluate 
the exclusion criterion is at the investigator's discretion and should be in adherence to local 
policies or regulations. However, it is highly recommended that PCR or antigen testing for 
COVID-19 be completed within 1 week prior to first dosing. If testing is performed, negative 
test results are required prior to enrollment into the study. PCR or antigen test against 
COVID-19 is mandatory where required by the local Health Authority and/or by local 
regulations. COVID-19 testing should be completed via nasal or throat swabs. If testing is not 
performed, the investigator must document their discussion with the participant regarding 
testing, and the rationale for not testing, in the source documentation. This requirement may be 
ignored if the pandemic is declared ended by the country where the site is located and resumed 
if the pandemic recurs. 

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8.2 
Participant demographics/other baseline characteristics 
Country-specific regulations should be considered for the collection of demographic and 
baseline characteristics in alignment with eCRF. 
Participant demographics: age, sex, race/predominant ethnicity (if permitted) and relevant 
medical history/current medical conditions (until date of signature of informed consent), and 
date of prior MI will be recorded in the eCRF. Participant race/ethnicity data are collected and 
analyzed to identify any differences in the safety and/or efficacy profile of the treatment due to 
these characteristics. In addition, these data are necessary to assess the diversity of the study 
population as required by health authorities. 
All prescription medications, over-the-counter drugs, and significant non-drug therapies prior 
to the start of the study must be documented. See the protocol Section 6.8.1 Concomitant 
Therapy for further details on what information must be recorded on the appropriate page of the 
eCRF. 
8.3 
Efficacy assessments 
The efficacy assessments described in this section will be evaluated in all participants. Samples 
will be collected as defined in Section 1.3, Schedule of Activities. 
8.3.1 
IL-6 and IL-18 Cytokines 
The circulating serum levels of the cytokines IL-6 and IL-18 will be measured by an enzyme-
linked immunosorbent assay (ELISA) at a qualified vendor. Detailed descriptions of the assays 
will be included in the bioanalytical data reports and assay validation reports. 
Planned time points for all assessments are provided in Section 1.3 Schedule of Activities. 
8.3.2 
Appropriateness of efficacy assessments 
The result of the NLRP3 inflammasome formation is the production of IL-1β from pro-IL-1β. 
Similarly, pro-IL-18 is cleaved into its active form, IL-18. These cytokines are released to 
activate a variety of inflammatory cells and produce IL-6, which stimulates the production of 
CRP from the liver and amplifies the inflammatory cascade within the vessel wall. 
Abrogation of NLRP3 inflammasome function is protective in mouse models of atherosclerosis, 
exerting a beneficial effect on both peripheral inflammatory leukocytes and cytokines, and local 
anti-inflammatory effects in the atherosclerotic plaque. Measures of local anti-inflammatory 
effects in the atherosclerotic plaque are not well-established surrogate outcomes of 
cardiovascular disease risk reduction and are challenging to measure in clinical trials (usually 
done with non-invasive imaging with or without specific tracers), especially in relatively small 
samples sizes over short treatment periods. Therefore, the reduction in circulating cytokines 
will be examined as primary efficacy markers in this early exploratory Phase 2a trial. For 
example, reductions in IL-6 with IL-1β neutralization with canakinumab in Phase 2 trials 
preceded the demonstration of cardiovascular disease risk benefit in the CANTOS trial. 
Through the production of IL-1β and IL-18, the NLRP3 inflammasome has been implicated as 
a major driver of inflammation associated with chronic inflammatory diseases. As the 
magnitude of IL-1β reduction is not clearly benchmarked to cardiovascular disease reduction 

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monitoring and discussion of the participant´s health status until it is safe for the participant to 
visit the site again. 
8.4.1 
Physical examinations 
A complete physical examination will include the examination of general appearance, skin 
(including rash assessment), neck (including thyroid), eyes, ears, nose, throat, lungs, heart, 
abdomen, back, lymph nodes, extremities, vascular, and neurological. Information for all 
physical examinations must be included in the source documentation at the study site. Clinically 
relevant findings that are present prior to signing informed consent must be recorded on the 
appropriate CRF that captures medical history. Significant findings made after signing informed 
consent, which meet the definition of an AE must be recorded as an AE. 
A brief physical exam will include the examination of general appearance, a skin assessment 
for rash, a brief cardiorespiratory assessment, and vital signs (oral body temperature, BP [SBP 
and DBP] and pulse rate). 
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram (kg) in indoor clothing, 
but without shoes) will be measured at the time points specified in Section 1.3, Schedule of 
Activities. Body weight will be measured on a calibrated scale and under similar conditions 
(e.g., in similar indoor clothing and at a similar time of day). 
8.4.2 
Vital signs 
Vital signs will include the collection of oral body temperature (recorded in °C), BP and pulse 
rate measurements. 
After the participant has been sitting for 3 minutes, with back supported and both feet placed 
on the floor, systolic and diastolic BP will be measured using an automated validated device, 
e.g., OMRON with an appropriately sized arm cuff. In case the arm cuff sizes available are not 
large enough for the participant's arm circumference, a sphygmomanometer with an 
appropriately sized cuff may be used. 
If vital signs are out-of-range at screening (see Exclusion Criteria Section 5.2 of the protocol 
for details), two additional readings can be obtained, so that up to three consecutive assessments 
are made, with the participant seated quietly for approximately five minutes preceding each 
repeat assessment. The last reading must be within the ranges provided in the eligibility criteria 
in order for the participant to qualify. 
In case of repeated vital assessments, the eCRF should contain the qualifying results. 
8.4.3 
Electrocardiograms 
ECGs must be recorded after 10 minutes rest in the supine position to ensure a stable baseline. 
In the case of a series of assessments, ECG should be the first assessment obtained while the 
participant is at rest. 

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Figure 8-1 
Recommended order of assessments  
 
The Fridericia QT interval corrected by Fridericia’s formula (QTcF) must be used for clinical 
decisions. The Investigator must calculate QTcF if it is not auto-calculated by the ECG machine. 
Single local 12 lead ECGs are collected. ECGs will be locally collected and evaluated. 
Interpretation of the tracing must be made by a qualified physician and documented on the 
appropriate CRF. Each ECG tracing should be labeled with the study number, participant 
initials (where regulations permit), participant number, date, and kept in the source documents 
at the study site. Clinically significant abnormalities present at screening should be reported on 
the appropriate CRF. Clinically significant findings must be discussed with Novartis prior to 
enrolling the participant in the study. New or worsened clinically significant findings occurring 
after informed consent must be recorded as AEs. 
The original ECGs on non-heat-sensitive paper, appropriately signed, must be archived at the 
study site. 
Additional, unscheduled, safety ECGs may be repeated at the discretion of the Investigator at 
any time during the study as clinically indicated. For any ECGs with participant safety concerns, 
two additional ECGs must be performed to confirm the safety finding. ECG safety monitoring, 
or a review process, should be in place for clinically significant ECG findings at baseline before 
administration of study treatment and during the study. 
Clinically significant abnormalities must be recorded on the CRF as either medical 
history/current medical conditions or AEs as appropriate. 
8.4.4 
Clinical safety laboratory tests 
Clinically significant abnormalities must be recorded as either medical history/current medical 
conditions or AEs as appropriate. 
In the case where a laboratory range is not specified by the protocol, but a value is outside the 
reference range for the laboratory at screening and/or initial baseline, a decision regarding 
whether the result is of clinical significance or not shall be made by the Investigator (in 
consultation with Novartis, as needed) and shall be based, in part, upon the nature and degree 
of the observed abnormality. The assessment may be repeated once prior to randomization. 
In all cases, the Investigator must document in the source documents, the clinical considerations 
(i.e., result was/was not clinically significant and/or medically relevant) in allowing or 
disallowing the participant to continue in the study. 
A central laboratory will be used for analysis of all safety specimens collected. Details on the 
collection, shipment of samples and reporting of results by the central laboratory are provided 
to Investigators in the central laboratory manual. 
As per Section 4.5, during a public health emergency as declared by local or regional 
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visits, if participants cannot visit the site for protocol-specified safety lab assessments, an 
alternative lab (local) collection site may be used. 
All abnormal lab results must be evaluated for criteria defining an AE and reported as such if 
the criteria are met. For those lab AEs, repeated evaluations are mandatory until normalization 
of the result(s) or until the result is no longer considered to be clinically significant. 
Table 8-1 
Safety laboratory evaluations 
Test Category 
Test Name 
Hematology 
Hematocrit, Hemoglobin, Platelets, Red blood 
cells (RBC), White blood cells (WBC) and 
Differential (Basophils, Eosinophils, 
Lymphocytes, Monocytes, Neutrophils, Bands) 
Clinical Chemistry 
Albumin, Alkaline phosphatase (ALP), Alanine 
transferase (ALT), Aspartate aminotransferase 
(AST), Gamma-glutamyl-transferase (GGT), 
Lactate dehydrogenase (LDH), Bicarbonate, 
Calcium, Chloride, Magnesium, Phosphate, 
Potassium, Sodium, Creatine kinase, Creatinine, 
Total Bilirubin, Direct Bilirubin, Indirect Bilirubin, 
LDL Cholesterol (non-fasting), Urea Nitrogen or 
Urea, Urate, Amylase, Lipase, Glucose (non-
fasting), eGFR 
Urinalysis 
Macroscopic Panel (Dipstick) (Color, Bilirubin, 
Occult Blood, Macroscopic Blood, Glucose, 
Ketones, Leukocytes esterase, Nitrite, pH, 
Protein, Specific Gravity, 
If macroscopic panel comes back with abnormal 
values: Microscopic Panel (Erythrocytes, 
Leukocytes, Casts, Crystals, Bacteria and yeast 
cells, Epithelial cells) 
Coagulation Panel 
Prothrombin time (PT)*, International normalized 
ratio [INR]), Partial Thromboplastin Time (PTT)*, 
Activated partial thromboplastin time (APTT) 
*(PT and PTT only at screening) 
Liver Event Testing and Liver Follow-Up Testing 
Alanine transferase (ALT), alkaline phosphatase 
(ALP), aspartate aminotransferase (AST), 
gamma-glutamyl transferase (GGT), total 
bilirubin (TBIL), international normalized ratio 
(INR), albumin, creatinine kinase (CK), 
glutamate dehydrogenase (if available), 
prothrombin time (PT) 
To evaluate for hemolysis: reticulocytes, 
haptoglobin, unconjugated (indirect) bilirubin 
These tests are in addition to routine testing, to 
be performed only in follow-up to safety events 
when indicated in Section 10.5 Liver safety 
monitoring 
Renal follow-up Testing 
Serum: albumin, total protein, creatinine, 
cystatin C, blood urea nitrogen (BUN), 
electrolytes (sodium, potassium, phosphate, 

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Test Category 
Test Name 
calcium), bicarbonate and uric acid 
Urine: protein, creatinine, albumin, dipstick 
(specific gravity, pH, heme, protein, glucose, 
leukocyte esterase and nitrite) and sediment 
microscopy (crystals, casts, RBCs, WBCs, 
epithelial cells)  
Calculate urine albumin-to-creatinine ratio (may 
be done on a spot urine), urine protein-to-
creatinine ratio (may be done on a spot urine) 
These tests are in addition to routine testing, to 
be performed only in follow-up to safety events 
when indicated in Section 10.6, Renal safety 
monitoring 
Pregnancy Test 
Serum pregnancy test 
Inclusion/Exclusion 
For inclusion or exclusion criteria testing not 
already included above, please refer 
to Section 5.1 and Section 5.2. 
Urinalysis: A midstream urine sample (approx. 30 mL) will be obtained, in order to avoid 
contamination with epithelial cells and sediments and allow proper assessments. 
8.4.5 
Pregnancy testing 
A condom is required for all sexually active male participants to prevent them from fathering a 
child AND to prevent delivery of study treatment via seminal fluid to their partner during study 
treatment and for at least 7 days following completion of treatment. In addition, male 
participants should not donate sperm while taking study treatment, and for 7 days after stopping 
study treatment. 
All pre-menopausal women who are not surgically sterile will have pregnancy testing. 
Additional pregnancy testing might be performed if requested by local requirements. 
Serum pregnancy testing is required at all time points as indicated in Section 1.3, Schedule of 
Activities. 
As per Section 4.5, during a public health emergency as declared by local or regional 
authorities' i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site study 
visits, if participants cannot visit the site to have serum pregnancy tests, urine pregnancy test 
kits may be used. Relevant participants can perform the urine pregnancy test at home and report 
the result to the site. It is important that participants are instructed to perform the urine 
pregnancy test first and only if the test result is negative proceed with the administration of the 
study treatment. A communication process should be established with the participant so that the 
site is informed and can verify the pregnancy test results (e.g., following country specific 
measures). 
Assessments of fertility 
A woman is considered of childbearing potential from menarche and until becoming post-
menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, 

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bilateral salpingectomy, and bilateral oophorectomy. Medical documentation of oophorectomy, 
hysterectomy, or tubal ligation must be retained as source documents. 
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause and an appropriate clinical profile. 
In absence of the medical documentation confirming permanent sterilization, or if the post-
menopausal status is not clear, the investigator should use his medical judgment to appropriately 
evaluate the fertility state of the woman and document it in the source document. 
8.4.6 
Appropriateness of safety measurements 
The safety assessments selected are standard for this indication/participant population. 
8.5 
Additional assessments 
No additional tests will be performed on participants entered into this study. 
8.6 
Adverse events (AEs), serious adverse events (SAEs), and other 
safety reporting 
The definitions of AEs and serious AEs can be found in Section 8.6. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up of all AEs. 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 8.6.3. 
8.6.1 
Adverse events 
An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign 
[including abnormal laboratory findings], symptom or disease) in a clinical investigation 
participant after providing written informed consent for participation in the study. Therefore, 
an AE may or may not be temporally or causally associated with the use of a medicinal 
(investigational) product. 
The Investigator has the responsibility for managing the safety of individual participants and 
identifying AEs. 
Novartis qualified medical personnel will be readily available to advise on trial-related medical 
questions or problems. 
The occurrence of AEs must be sought by non-directive questioning of the participant at each 
visit during the study. AEs also may be detected when they are volunteered by the participant 
during or between visits or through physical examination findings, laboratory test findings, or 
other assessments. 

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AEs must be recorded under the signs, symptoms, or diagnosis associated with them, 
accompanied by the following information (as far as possible) (if the event is serious refer 
to Section 8.6.2): 
1. The severity grade. 
• mild: usually transient in nature and generally not interfering with normal activities 
• moderate: sufficiently discomforting to interfere with normal activities 
• severe: prevents normal activities 
2. Its relationship to the study treatment. If the event is due to lack of efficacy or progression 
of underlying illness (i.e. progression of the study indication) the assessment of causality 
will usually be ‘Not suspected.’ The rationale for this guidance is that the symptoms of a 
lack of efficacy or progression of underlying illness are not caused by the trial drug, they 
happen in spite of its administration and/or both lack of efficacy and progression of 
underlying disease can only be evaluated meaningfully by an analysis of cohorts, not on a 
single participant 
3. Its duration (start and end dates or ongoing) and the outcome must be reported 
4. Whether it constitutes a SAE (see Section 8.6.2 for definition of SAE) and which 
seriousness criteria have been met 
5. Action taken regarding study treatment. 
All AEs must be treated appropriately. Treatment may include one or more of the 
following: 
• Dose not changed 
• Dose Reduced/increased 
• Drug interrupted/permanently discontinued 
6. Its outcome 
• not recovered/not resolved; 
• recovered/resolved 
• recovered/resolved with sequelae 
• fatal; or unknown 
Conditions that were already present at the time of informed consent should be recorded in 
medical history of the participant. 
AEs (including lab abnormalities that constitute AEs) should be described using a diagnosis 
whenever possible, rather than individual underlying signs and symptoms. 
AE monitoring should be continued for at least 30 days following the last dose of study 
treatment. 
Once an AE is detected, it must be followed until its resolution or until it is judged to be not 
recovered/not resolved (e.g., continuing at the end of the study), and assessment must be made 
at each visit (or more frequently, if necessary) of any changes in severity, the suspected 
relationship to the interventions required to treat it, and the outcome. 
Information about adverse drug reactions for the investigational drug can be found in the IB. 

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Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria: 
• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges or significant changes from 
baseline or the previous visit. 
8.6.2 
Serious adverse events 
An SAE is defined as any AE [appearance of (or worsening of any pre-existing)] undesirable 
sign(s), symptom(s), or medical conditions(s) which meets any one of the following criteria: 
• fatal 
• life-threatening 
Life-threatening in the context of a SAE refers to a reaction in which the participant was at 
risk of death at the time of the reaction; it does not refer to a reaction that hypothetically 
might have caused death if it were more severe (please refer to the ICH-E2D Guidelines). 
• results in persistent or significant disability/incapacity 
• constitutes a congenital anomaly/birth defect, fetal death or a congenital abnormality or 
birth defect 
• requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
• elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 
• social reasons and respite care in the absence of any deterioration in the participant’s 
general condition 
• treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 
• is medically significant, e.g., defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life-threatening or result in death or hospitalization but might jeopardize the participant or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant.” Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that 
do not result in hospitalization or development of dependency or abuse (please refer to the 
ICH-E2D Guidelines). 

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All new malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 
All reports of intentional misuse and abuse of the product are also considered serious AEs 
irrespective of whether a clinical event has occurred. 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
Treatment-emergent elevations in AST or ALT (>2x baseline AND 3x ULN) in combination 
with total bilirubin >2x ULN or jaundice in the absence of cholestasis (defined as ALP < 2 
ULN) or other causes of hyperbilirubinemia can be an indicator of severe drug induced liver 
injury (Hy’s Law). For this reason, a potential Hy’s Law case requires expedited reporting, and 
will be handled as a serious unexpected adverse event (assessing it as medically significant in 
the absence of any other seriousness criteria). It must be reported as an SAE to the sponsor 
promptly (i.e., even before all other possible causes of liver injury have been excluded). 
Reporting should include all available information, especially that needed for evaluating the 
diagnosis, severity and likelihood that the study treatment caused the reaction. For patient 
monitoring and to better understand potential etiologies, the investigator must initiate a close 
follow-up until complete resolution of the problem and completion of all attempts to obtain 
supplementary data. 
8.6.3 
SAE reporting 
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
has provided informed consent and until 30 days following the last administration of study 
treatment must be reported to Novartis safety immediately, without undue delay, but under no 
circumstances later than within 24h of obtaining knowledge of the events (Note: If more 
stringent, local regulations regarding reporting timelines prevail). Detailed instructions 
regarding the submission process and requirements are to be found in the Investigator folder 
provided to each site. Information about all SAEs is collected and recorded on the Serious 
Adverse Event Report Form; all applicable sections of the form must be completed in order to 
provide a clinically thorough report. 
Screen Failures 
SAEs occurring after the participant has provided informed consent until the time the participant 
is deemed a Screen Failure must be reported to Novartis. 
Randomized OR Treated Participants: 
SAEs collected between time participant signs ICF until 30 days after the participant has 
discontinued from study treatment. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
immediately, without undue delay, but under no circumstances later than within 24h of the 
Investigator receiving the follow-up information (Note: If more stringent, local regulations 
regarding reporting timelines prevail). An SAE occurring at a different time interval or 

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otherwise considered completely unrelated to a previously reported one must be reported 
separately as a new event. 
If the SAE is not previously documented in the IB or Package Insert (new occurrence) and is 
thought to be related to the study treatment, a CMO & PS Department associate may urgently 
require further information from the Investigator for health authority reporting. Novartis may 
need to issue an Investigator Notification (IN) to inform all Investigators involved in any study 
with the same study treatment that this SAE has been reported. 
Suspected Unexpected Serious Adverse Reactions will be collected and reported to the 
competent authorities and relevant ethics committees in accordance with national regulatory 
requirements in participating countries. 
Any SAEs experienced after the 30-day period following the last administration of study 
treatment should only be reported to Novartis Safety if the Investigator suspects a causal 
relationship to study treatment, unless otherwise specified by local law/regulations. 
8.6.4 
Pregnancy 
If a female trial participant becomes pregnant, the study treatment should be stopped, and the 
pregnancy consent form should be presented to the trial participant. The participant must be 
given adequate time to read, review and sign the pregnancy consent form. This consent form is 
necessary to allow the Investigator to collect and report information regarding the pregnancy. 
To ensure participant safety, each pregnancy occurring after signing the informed consent must 
be reported to Novartis within 24h of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications. 
Pregnancy should be recorded and reported by the Investigator to the Novartis Chief Medical 
Office and Patient Safety. Pregnancy follow-up should be recorded on the same form and should 
include an assessment of the possible relationship to the study treatment and any pregnancy 
outcome. Any SAE experienced during pregnancy must be reported. 
If a female partner of a male trial participant who took study treatment in this study becomes 
pregnant, pregnancy outcomes should be collected. Consent to report information regarding 
these pregnancy outcomes should be obtained from the mother. 
After consent is provided, the pregnancy reporting will occur up to one year after the estimated 
date of delivery. 
8.6.5 
Disease-related events and/or disease-related outcomes not qualifying 
as AEs or SAEs 
Not applicable.  All AEs and SAEs will be reviewed. 
8.7 
Pharmacokinetics 
PK plasma samples will be collected at the visits defined in Section 1.3 Schedule of Activities. 
Follow instructions outlined in the laboratory manual regarding sample collection, numbering, 
processing, and shipment. See the potential use of residual samples for more information 

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(Section 8.8). In case needed (e.g., due to suspected toxicity-related AEs), an unscheduled 
sample should be collected as near as possible to the event in order to assess a potential PK 
relationship. 
PK samples will be obtained from all participants, but samples will be analyzed in participants 
at all DFV890 dose levels except the placebo group. 
DFV890 and IBW042 will be determined by a validated LC-MS/MS method; the anticipated 
Lower Limit of Quantification (LLOQ) is 1 ng/mL. 
Concentrations will be expressed in mass per volume units. Concentrations below the LLOQ 
will be reported as “zero” and missing data will be labeled as such in the Bioanalytical Data 
Report. 
Due to sparse sampling only plasma trough concentrations (Ctrough) will be available. 
8.7.1 
PK blood collection 
For details on PK blood collection and processing, labeling, and shipment instructions, see 
laboratory manual. 
The exact clock time of dosing, as well as actual sample collection date and time will be entered 
on the PK blood collection summary page of the CRF. Sampling problems will be noted in the 
relevant field of the CRF. 
8.8 
Biomarkers 
The primary endpoint cytokines, IL-6 and IL-18, are addressed in Section 8.3. The current 
section describes the exploratory biomarker strategy. 
The exploratory biomarker analyses will be used to further investigate the effect of DFV890 at 
the molecular and cellular level, for example the composition of various immune cells that can 
be affected by NLRP3 inhibition.   Additional biomarkers will be utilized to investigate changes 
that may relate to pathway inhibition or mechanism of action. In addition, cardiovascular 
markers, for example lipid parameters, will be measured to understand disease-related 
effect.  Further potential predictive biomarkers of efficacy will be explored, including but not 
limited to markers present in known downstream process of the inhibited pathway or other 
inflammatory mechanisms (e.g., hsCRP). 
While the goal of the biomarker assessments is to provide supportive data for the clinical study, 
there may be circumstances when a decision is made to stop a collection, or not perform or 
discontinue an analysis due to either practical or strategic reasons (e.g., inadequate sample 
number, issues related to the quality of the sample or issues related to the assay that preclude 
analysis, impossibility to perform correlative analyses, etc.). Therefore, depending on the 
results obtained during the study, sample analysis may be omitted at the discretion of Novartis.  
In an event of unscheduled biomarker sampling, Novartis may analyze samples or discard them. 
Samples will be collected from all participants in this study as specified in Section 1.3 Schedule 
of Activities.  The exploratory biomarker strategy may include, but is not limited to, biomarkers 
that will inform on: 
• PD and inflammation-related markers: 

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• Soluble Biomarkers: hsCRP, sASC, hsIL-1b, CXCL9, CXCL10, hsIFNg, vWF 
• Immunophenotyping: myeloid / lymphoid cell activation/enumeration by flow 
cytometry (whole blood/PBMC) 
• Cardiovascular disease-related biomarkers: 
• Lipid parameters: Total cholesterol, HDL, LDL, triglycerides, Lp(a), apolipoproteins 
• Further exploratory biomarkers may be investigated based on study outcomes. 
These markers may include but are not limited to MPO and free elastase, MMPs, 
fibrinogen, fibrosis (Biomarker plasma/serum) 
• Stratification markers (i.e., hsCRP) 
• Genetic markers that may impact primary and exploratory readouts or PK (to be done as 
part of the end of study analysis and will not be used for eligibility purposes):  
• CHIP mutations 
• CYP2C9 polymorphism assessment 
Profiling in serum and plasma 
Samples collected in serum and plasma may be investigated in multiplex hypotheses-free 
platforms where relevant to better understand the disease profile, or for markers that may be 
associated with treatment response or predict response to treatment. 
Residual Samples 
Samples and data may be used for another protocol specified endpoint or may be used for 
exploratory analyses related to the NLRP3 pathway, inflammation, cardiovascular disease, 
and/or PK. This may include, but is not limited to, additional analysis for bioanalytical purposes, 
protein binding, metabolite profiling or quantification, indicators of enzymatic activity, 
assessment of impact on clinical outcome, and the identification of potential biomarkers that 
may be predictive of benefit from treatment with DFV890. Given the exploratory nature of the 
work, the method used for the analyses may not be validated, and as such, the results from this 
exploratory analysis may not be included in the Clinical study report (CSR). 
Optional Biomarker Samples 
Optional Genetics 
The study includes an optional genetic research component which requires a separate informed 
consent signature if the participant agrees to participate. As permitted by local governing 
regulations and by IRB/EC, it is required as part of this protocol that the Investigator present 
these options to the participant. 
The purpose of genetic research may be to better understand the safety and efficacy of DFV890, 
or to learn more about human diseases, or to help develop ways to detect, monitor and treat 
diseases. 
As technology changes over time, the most appropriate technology will be used at the time the 
exploratory genetic research is performed. This may include the study of the entire genome. 

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Laboratory manuals will be provided with detailed information on sample collection, handling, 
and shipment. 
DNA samples 
The use of DNA to search for biomarkers of disease and drug action is exploratory. Any results 
from this DNA study will not be placed in the participant’s medical records. As an additional 
confidentiality measure, sample information is stored in one secured database while genetic 
data is stored in an independent secured database. 
Optional Additional Research 
If the participant agrees, by signing the optional consent for Additional Research, biological 
samples and data that remain after analysis is completed may be used for additional research to 
help better understand how the study treatment works, learn more about the disease, improve 
the way clinical studies are conducted, or to help develop ways to detect, monitor or treat human 
diseases. A decision to perform such exploratory research studies would be based on outcome 
data from this study or from new scientific findings related to the drug class or disease, as well 
as assay availability. 
8.9 
Immunogenicity assessments 
Immunogenicity is not evaluated in this study. 
8.10 
Medical resource utilization and health economics 
Medical resource utilization (RU) and health economics parameters are not evaluated in this 
study. 
9 
Statistical considerations 
9.1 
Analysis sets 
For all analyses, unless specified otherwise, treatment will be defined as a dose level of DFV890 
or placebo (placebo, DFV890 10 mg, DFV890 25 mg, DFV890 50 mg, or DFV890 100 mg). 
Participants will be analyzed according to either the treatment(s) received or to the assigned 
treatment sequence, depending on the analysis. 
The safety analysis set will include all participants that received any study treatment. 
The PK analysis set will include all participants with at least one available valid (i.e., not flagged 
for exclusion) PK concentration measurement, who received any study treatment and with no 
protocol deviations that impact on PK data. 
The PD analysis set will include all participants that received study treatment and had no 
protocol deviations with relevant impact on PD data. 

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9.2 
Statistical analyses 
9.2.1 
General considerations 
Unless stated otherwise, baseline for all calculations will be the last measurement recorded prior 
to dosing on Day 1. 
9.2.2 
Participant demographics and other baseline characteristics 
Demographic and other baseline data including disease characteristics will be listed by 
treatment sequence for the safety analysis set. Relevant medical histories and current medical 
conditions at baseline will be listed by system organ class and preferred term by treatment 
sequence. 
9.2.3 
Treatments 
Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be listed according to the Anatomical Therapeutic Chemical classification 
system by treatment sequence for the safety analysis set. 
Compliance will be calculated as the percentage of participants who took a predefined 
percentage of the number of prescribed doses of study treatment. 
9.3 
Primary endpoint(s)/estimand(s) analysis 
9.3.1 
Definition of primary endpoint(s) 
The primary endpoints are the serum levels of IL-6 and IL-18 at 3 weeks after the start of a 
dosing period. 
The definition of the primary estimand is provided is Section 3.1. 
9.3.2 
Statistical model, hypothesis, and method of analysis 
The primary analysis will assess the effect of DFV890 on the change in IL-6 and IL-18 
compared to placebo in a dose-response model, separately for the two biomarkers. 
An Emax model will be fit to the post-baseline values of each biomarker, with a random effect 
(reflecting between-participant variability) on the placebo response E0 and on ED50 (the dose 
that produces half the maximal effect), a covariate on E0 for the baseline value of the biomarker, 
and a covariate on ED50 for baseline body weight. All biomarker measurements will be 
logarithm-transformed prior to the analysis. 
An additional random effect reflecting between-participant variability on Emax may be 
incorporated if the data allows. 
Additional details of the model will be specified in the SAP. 
From each model, the predicted response at each treatment and associated 80% confidence 
interval (CI) will be extracted, along with the difference to placebo for each DFV890 dose level, 
the corresponding 2-sided 80% CI, and the p-value. The estimated response and the difference 
to placebo will be back-transformed and reported on the ratio scale. 

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In case of convergence issues, a linear mixed effects model will be fit in place of the Emax model 
(to be referred to as 'traditional model'). The model will include treatment as a fixed effect, a 
random intercept effect for participant, and the baseline value of the biomarker and baseline 
body weight as covariates. All biomarker measurements will be logarithm-transformed prior to 
the analysis. The least-square mean and associated 80% CI for each treatment, and the estimated 
mean difference to placebo for each DFV890 dose level, the p-value, and 2-sided 80% CI will 
be extracted from the model and back-transformed to the ratio scale for reporting. 
From the model-based quantities, the following efficacy criteria will be evaluated at the median 
baseline value of the biomarker and the median baseline body weight: 
1. At least one of the following is observed in relation to placebo at the 100 mg dose: 
• IL-6 reduction ≥ 25%, or  
• IL-6 reduction ≥ 20% + IL-18 reduction ≥ 10%, or 
• IL-6 reduction ≥ 15% + IL-18 reduction ≥ 20%. 
2. For any of the above criteria that are achieved, the one-sided p-value for the comparison 
of DFV890 vs. placebo for the associated biomarker(s) is less than 0.1. 
9.3.3 
Handling of intercurrent events of primary estimand (if applicable) 
As described in Section 3.1, the intercurrent events will be handled according to a hypothetical 
strategy, reflecting a scenario in which a given participant with an event had not actually 
experienced the event, with the exception of a change to standard of care cardiovascular disease 
prevention medication. To enable this strategy, depending on the type of event, either (1) the 
biomarker assessment at the visit immediately following the event will be set to missing for the 
primary analysis or (2) all subsequent biomarker assessments will be set to missing for the 
primary analysis, as described in that section. 
The data from these assessments will be implicitly imputed in the primary analysis under the 
assumption that the outcome in the affected participant would be no different than in the 
population of participants assigned to the same treatment but that did not experience the event. 
Although measurements collected after the events handled by this strategy are not used for the 
analysis, the planned assessments will take place for possible evaluation of supportive 
estimands. If no measurements are collected after the intercurrent event is experienced, these 
missing measurements will not be imputed. 
9.3.4 
Handling of missing values not related to intercurrent event 
Missing data not related to intercurrent events are expected to be intermittent and will be 
assumed to be missing at random. These data will not be explicitly imputed. 
9.3.5 
Sensitivity analyses 
As a sensitivity analysis to the Emax model described in Section 9.3.2, a Hill coefficient other 
than 1 may be explored. 
If the Emax model converges on either of the two primary endpoints, the traditional model 
described in Section 9.3.2 will be performed as a sensitivity analysis on that endpoint. 

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9.3.6 
Supplementary analysis 
As a supplementary analysis, the primary analysis may be performed as described, except that 
some or all biomarker measurements collected after any change in standard of care 
cardiovascular disease prevention medication may be excluded from the analysis. 
9.4 
Secondary endpoint(s)/estimand(s) analysis 
Not applicable. 
9.4.1 
Safety endpoints 
The safety set will be used for all safety analyses. 
Adverse events 
The number (and percentage) of participants with treatment emergent AEs will be summarized 
by treatment, primary system organ class, and preferred term. An additional summary by 
treatment, primary system organ class, preferred term, and maximum severity may be reported 
if deemed necessary. 
A separate summary by treatment sequence, primary system organ class, and preferred term 
will also be provided. 
Treatment-emergent AEs are those with an onset after the start of a specific dosing period, or 
which were present prior to the start of the dosing period but increased in severity, changed 
from being not suspected to being suspected of study treatment relationship, or developed into 
SAEs after the start of the dosing period. 
For the purposes of these summaries, a dosing period is defined as an approximate 3-week 
interval between scheduled visits as given in the study design figure (Figure 1-1). For example, 
the first dosing period will begin at Day 1 (randomization) and end on the Day 22 visit, at which 
point the next treatment will be administered according to the specific treatment sequence. 
A participant with multiple AEs within a primary system organ class is only counted once 
towards the total of the primary system organ class. 
Vital signs 
All vital signs data will be summarized by treatment and visit/time. 
12-lead ECG 
All ECG data will be summarized by treatment and visit/time. 
Clinical laboratory evaluations 
All laboratory data will be summarized by treatment and visit/time. 

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9.4.2 
Pharmacokinetics 
Summary statistics of DFV890 plasma concentration data will be provided by treatment and 
visit/sampling time point, including the frequency of concentrations below the LLOQ and 
reported as zero. 
Drug concentrations below LLOQ will be treated as missing for the calculation of the geometric 
means and geometric coefficient of variation (CV%), and as zero for all other calculations. 
Summary statistics will include mean (arithmetic and geometric), standard deviation (SD), and 
CV (arithmetic and geometric), median, minimum, and maximum concentration. 
9.4.3 
PK/PD relationships 
Refer to Section 9.7. 
9.5 
Exploratory endpoint(s)/estimand(s) analysis 
9.5.1 
Biomarkers 
The following inflammation-related exploratory biomarkers (hsCRP, soluble ASC, CXCL9, 
CXCL10, hsIFNg, Interleukin-1b (IL-1b), and neutrophil activation/frequency in whole blood) 
and disease-related biomarkers (LDL and Lp(a)) will be analyzed using a linear mixed effects 
model of the same form as the traditional model specified for the primary endpoints 
in Section 9.3.2. 
Biomarker values above the Upper Limit of Quantification (ULOQ) will be imputed as ULOQ 
and values below the LLOQ will be imputed as LLOQ/2 for these analyses. 
9.5.2 
DNA 
Exploratory DNA analyses might include presence of genetic polymorphisms in the 
inflammasome pathway, presence and change from baseline of somatic mutations (clonal 
hematopoieisis). Other exploratory DNA studies are designed to investigate the association 
between genetic factors (genotypes) and clinical assessments (phenotypes) which are collected 
during the clinical trial. Without prior evidence of a strong association, a number of possible 
associations are evaluated with exploratory analyses. A range of statistical tests are used for the 
analyses. Additional data, from other clinical trials, are often needed to confirm associations. 
Alternatively, if the number of participants enrolled in the study is too small to complete proper 
statistical analyses, the data may be combined, as appropriate, with those from other studies to 
enlarge the dataset for analysis. 
Data generated on hypothesis-free platforms will be reported separately (e.g. CSR addendum). 
9.6 
(Other) Safety analyses 
Not applicable. 

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10 
Supporting documentation and operational considerations 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1 
Regulatory and ethical considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
international ethical guidelines 
• Applicable ICH Good Clinical Practice (GCP) guidelines 
• Applicable laws and regulations 
The protocol, protocol amendments, ICF, IB, [IDFU], and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the Investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
Protocols and any substantial amendments/modifications to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an immediate 
hazard to study participants. 
The Investigator will be responsible for the following: 
Signing a protocol signature page confirming his/her agreement to conduct the study in 
accordance with these documents and all of the instructions and procedures found in this 
protocol and to give access to all relevant data and records to Novartis monitors, 
auditors, Novartis Quality 
Assurance 
representatives, 
designated 
agents 
of Novartis, 
IRBs/IECs, and regulatory authorities as required 
Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/IEC 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures 
Providing oversight of the conduct of the study at the site and adherence to requirements of 
21 CFR (Code of Federal Regulations), ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device Regulation 2017/745 for 
clinical device research (if applicable), and all other applicable local regulations 
Inform Novartis immediately if an inspection of the clinical site is requested by a regulatory 
authority 

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10.1.2 
Informed consent process 
The Investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the participant and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representatives will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and data protection 
requirements, where applicable, and the IRB/IEC or study center. 
Informed consent must be obtained before conducting any study-specific procedures (e.g. all of 
the procedures described in the protocol). The process of obtaining informed consent must be 
documented in the participant source documents. 
The medical record must include a statement that written informed consent was obtained before 
the participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
A copy of the ICF(s) must be provided to the participant. 
Participants who are rescreened are required to sign a new ICF. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples 
for optional additional research. The Investigator or authorized designee will explain to each 
participant the objectives of the additional research. Participants will be told that they are free 
to refuse to participate and may withdraw their consent at any time and for any reason during 
the storage period. A separate signature will be required to document a participant’s agreement 
to allow any remaining specimens to be used for additional research. Participants who decline 
to participate in this optional additional research will document this. 
Eligible participants may only be included in the study after providing (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent. 
Information about common side effects already known about the investigational treatment can 
be found in the IB. This information will be included in the participant informed consent and 
should be discussed with the participant upon obtaining consent and during the study as needed. 
Any new information regarding the safety profile of the investigational drug that is identified 
between IB updates will be communicated as appropriate, for example, via an IN or an 
aggregate safety finding. New information might require an update to the informed consent and 
then must be discussed with the participant. 
The following informed consents are included in this study: 
• Optional Inflammation Marker Pre-Screening ICF, which can only be used for Screening 
Visit 1. 
• Main study ICF, which can be used at Screening 1 visit if the optional Inflammation 
Marker Pre-Screening ICF is not used. The main study ICF can be used at Screening 2 
visit if the optional Inflammation Marker Pre-Screening ICF was used at Screening 1 visit. 
The main study ICF includes: 
• A subsection that requires a separate signature for the ‘Optional Consent for 
Additional Research’ to allow future research on data/samples collected during this 
study 

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• Optional consent for activities that may be done outside of the study site 
• As applicable, Pregnancy Outcomes Reporting Consent for female participants or the 
female partners of any male participants who took study treatment 
• Patient information sheet for female partners of any male participants who took study 
treatment 
• Optional Genetics Consent to provide a sample for exploratory DNA studies 
The study includes an optional DNA component which requires a separate signature if the 
participant agrees to participate. It is required as part of this protocol that the Investigator 
presents this option to the participants, as permitted by local governing regulations. The process 
for obtaining consent should be exactly the same as described above for the main informed 
consent. 
Declining to participate in these optional assessments (DNA) will in no way affect the 
participant’s ability to join the main research study. 
A copy of the approved version of all consent forms must be provided to Novartis after IRB/IEC 
approval. 
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e. pandemic, epidemic or natural disaster, that may challenge the ability to obtain a standard 
written informed consent due to limits that prevent an on-site visit, Investigator may conduct 
the informed consent discussion remotely (e.g. telephone, videoconference) if allowable by a 
local health authority. 
Guidance issued by local regulatory bodies on this aspect prevail and must be implemented and 
appropriately documented (e.g., the presence of an impartial witness, sign/dating separate ICFs 
by trial participant and person obtaining informed consent, etc.). 
10.1.3 
Data protection 
Participants will be assigned a unique identifier by Novartis. Any participant records or datasets 
that are transferred to Novartis will contain the identifier only; participant names or any 
information which would make the participant identifiable will not be transferred. 
The participant must be informed that his/her personal study-related data will be used 
by Novartis in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by Novartis, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
Novartis has appropriate processes and policies in place to handle personal data breaches 
according to applicable privacy laws. 
10.1.4 
Committees structure 
Not applicable. 

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10.1.5 
Data quality assurance 
Monitoring details describing strategy, including definition of study critical data items and 
processes (e.g., risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of Novartis. No records may be transferred to 
another location or party without written notification to Novartis. 
10.1.5.1 Data collection 
All data captured for this study will have an external originating source (either written or 
electronic) with the CRF not being considered as source. 
Designated Investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (eCRF). The eCRFs have been built using fully validated secure web-
enabled software that conforms to 21 CFR Part 11 requirements, Investigator site staff will not 
be given access to the Electronic Data Capture (EDC) system until they have been trained. 
Automatic validation programs check for data discrepancies in the eCRFs, allow modification 
and/or verification of the entered data by the Investigator staff. 
The Investigator/designee is responsible for assuring that the data (recorded on CRFs) (entered 
into eCRF) is complete, accurate, and that entry and updates are performed in a timely manner. 
The Investigator must certify that the data entered are complete and accurate. 
After final database lock, the Investigator will receive copies of the participant data for 
archiving at the investigational site. 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
10.1.5.2 Database management and quality control 
Novartis personnel (or designated Contract Research Organization (CRO)) will review the data 
entered by investigational staff for completeness and accuracy. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the investigational site via the EDC system. Designated Investigator 
site staff are required to respond promptly to queries and to make any necessary changes to the 
data. 
Concomitant treatments and prior medications entered into the database will be coded using the 
World Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system. Medical history/current medical conditions and 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
terminology. 

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Dates of screenings, randomizations, screen failures and treatment completion, as well as 
randomization codes and data about all study treatment (s) dispensed to the participant and all 
dosage changes will be tracked using an IRT. The system will be supplied by a vendor, who 
will also manage the database. The data will be sent electronically to Novartis (or a designated 
CRO) at specific timelines. 
Each occurrence of a code break via IRT will be reported to the clinical team and monitor. The 
code break functionality will remain available until study shut down or upon request 
of Novartis. 
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked, and the treatment codes will be unblinded and made 
available for data analysis/moved to restricted area to be accessed by independent programmer 
and statistician. Any changes to the database after that time can only be made after written 
agreement by Novartis development management. 
10.1.6 
Source documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site. 
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
Investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available. 
The Investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. The Investigator must also keep the original 
ICF signed by the participant (a signed copy is given to the participant). 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. Study monitors will perform ongoing source data verification 
to confirm that data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently approved 
protocol and any other study agreements, ICH GCP, and all applicable regulatory requirements. 
Key study personnel must be available to assist the field monitor during these visits. Continuous 
remote monitoring of each site’s data may be performed by a centralized Novartis /Clinical 
Research Associate organization. Additionally, a central analytics organization may analyze 
data & identify risks & trends for site operational parameters and provide reports 
to Novartis clinical teams to assist with trial oversight. 
10.1.7 
Publication policy 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov. In 
addition, after study completion (defined as last participant last visit (LPLV)) and finalization 
of the study report the results of this trial will be submitted for publication and posted in a 
publicly accessible database of clinical trial results, such as the Novartis clinical trial results 
website and all required health authority websites (e.g., Clinicaltrials.gov, etc.). 

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For details on the Novartis publication policy including authorship criteria, please refer to 
the Novartis publication policy training materials that were provided to you at the trial 
Investigator meetings. 
Any data analysis carried out independently by the Investigator should be submitted 
to Novartis before publication or presentation. 
Summary results of primary and secondary endpoints will be disclosed based upon the global 
LPLV date, since multinational studies are locked and reported based upon the global LPLV. 
10.1.8 
Protocol adherence and protocol amendments 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure the safety of participants should 
be administered as deemed necessary on a case-by-case basis. Under no circumstances 
including incidental collection is an Investigator allowed to collect additional data or conduct 
any additional procedures for any purpose involving any investigational drugs under the 
protocol, other than the purpose of the study. If despite this interdiction prohibition, data, 
information, observation would be incidentally collected, the Investigator shall immediately 
disclose it to Novartis and not use it for any purpose other than the study, except for the 
appropriate monitoring on study participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
Investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by 
Novartis and approved by the IRB/IEC and health authorities, where required, it cannot be 
implemented. 
10.1.8.1 Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. 
Only amendments that are required for participant safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the Investigator is 
expected to take any immediate action required for the safety of any participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis should 
be notified of this action and the IRB/IEC at the study site should be informed according to 
local regulations. 

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10.2 
Appendix 2: Abbreviations and definitions 
10.2.1 
List of abbreviations 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
AST 
Aspartate Aminotransferase 
BID 
bis in die/twice a day 
BMI 
Body Mass Index 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
CABG 
Coronary Artery Bypass Graft 
CANTOS 
Canakinumab Anti-Inflammatory Thrombosis Outcome Study 
CFR 
Code of Federal Regulations 
CHIP 
Clonal Hematopoeisis of Indeterminate Potential 
CK 
Creatine Kinase 
CO 
Country Organization 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
Through concentration 
CTT 
Clinical Trial Team 
CV 
Coefficient of Variation 
CVD 
Cardiovascular Disease Prevention 
DARM  
Drug Accountability and Returns Management 
DBP 
Diastolic Blood Pressure 
DDI 
Drug-Drug Interaction 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
ELISA 
Enzyme-linked immunosorbent assay 
EOS 
End Of Study 
eSource 
Electronic Source 
FIH 
First in Human 
GCP 
Good Clinical Practice 
GCS 
Global Clinical Supply 
GGT 
Gamma-Glutamyl Transferase 
h 
Hour 
HIV 
Human Immunodeficiency Virus 
hsCRP 
High-sensitivity C-Reactive Protein 
i.v. 
intravenous 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 

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ICH 
International Council for Harmonization of Technical Requirements for Pharmaceuticals 
for Human Use 
IEC 
Independent Ethics Committee 
IL-1b 
Interleukin-1b 
IMP 
Investigational Medicinal Product 
IN 
Investigator Notification 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
LDH 
Lactate Dehydrogenase 
LDL 
Low density lipoprotein 
LFT 
Liver function test 
LLOQ 
Lower Limit of Quantification 
LPLV 
Last Participant Last Visit 
MedDRA 
Medical dictionary for regulatory activities 
mg 
milligram(s) 
MI 
Myocardial Infarction 
mL 
milliliter(s) 
NLRP3 
NOD-, LRR- and pyrin domain-containing protein 3 
OHP 
Off-site Healthcare Professional 
PCI 
Percutaneous coronary intervention 
PD 
Pharmacodynamic(s) 
PK 
Pharmacokinetic(s) 
PoC 
Proof of Concept 
PT 
Prothrombin Time 
QD 
Once a day 
QTcF 
QT interval corrected by Fridericia’s formula 
RBC 
Red Blood Cell(s) 
RU 
Resource Utilization 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic Blood Pressure 
SD 
Standard Deviation 
SoA 
Schedule of Activities 
ULN 
Upper Limit of Normal 
ULOQ 
Upper Limit of Quantification 
vWF 
von-Willebrand-Faktor 
WBC 
White Blood Cell(s) 
WHO 
World Health Organization 

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10.2.2 
Definitions 
Additional 
treatment 
Medicinal products that may be used during the clinical trial as described in 
the protocol, but not as an IMP (e.g., any background therapy) 
Assessment 
A procedure used to generate data required by the study 
Auxiliary medicinal 
product 
Medicinal product used for the needs of a clinical trial as described in the 
protocol, but not as an IMP (e.g., rescue medication, challenge agents, 
background treatment or medicinal products used to assess endpoints in the 
clinical trial). 
Concomitant therapy is not considered as AMP. 
Biologic Samples 
A biological specimen including, for example, blood (plasma, serum), saliva, 
tissue, urine, stool, etc. taken from a study participant 
CE marking 
A marking by which a manufacturer indicates that a device is in conformity 
with the applicable requirements set out in European Union legislation 
providing for its affixing. 
CE marking of medical devices is required prior to lawfully placing them on 
the European Union market. 
Clinical Outcome 
Assessment (COA) 
A measure that describes or reflects how a participant feels, functions, or 
survives 
Clinical Trial Team 
A group of people responsible for the planning, execution and reporting of all 
clinical trial activities. Examples of team members include the Study Lead, 
Medical Monitor, Trial Statistician etc. 
Coded Data 
Personal Data which has been de-identified by the investigative center team 
by replacing personal identifiers with a code. 
Cohort 
A group of individuals who share a common exposure, experience or 
characteristic, or a group of individuals followed-up or traced over time 
Control drug 
A study intervention (active or placebo) used as a comparator to reduce 
assessment bias, preserve blinding of investigational drug, assess internal 
study validity, and/or evaluate comparative effects of the investigational drug 
Cycles 
Number and timing or recommended repetitions of therapy are usually 
expressed as number of days (e.g., q28 days) 
Discontinuation 
from study 
Point/time when the participant permanently stops receiving the study 
treatment and further protocol required assessments or follow-up, for any 
reason. No specific request is made to stop the use of their samples or data. 
Discontinuation 
from study 
treatment 
Point/time when the participant permanently stops receiving the study 
treatment for any reason (prior to the planned completion of study intervention 
administration, if any). Participant agrees to the other protocol required 
assessments including follow-up. No specific request is made to stop the use 
of their samples or data. 
Dosage 
Dose of the study treatment given to the participant in a time unit (e.g., 100 
mg QD, 75 mg BID) 
Electronic Data 
Capture (EDC) 
EDC is the electronic acquisition of clinical study data using data collection 
systems, such as Web-based applications, interactive voice response 
systems and clinical laboratory interfaces. EDC includes the use of Electronic 
Case Report Forms (eCRFs) which are used to capture data transcribed from 
source data/documents used at the point of care 
End of the clinical 
trial 
The end of the clinical trial is defined as the last visit of the last participant. 
Enrollment 
Point/time of participant entry into the study at which informed consent must 
be obtained. The action of enrolling one or more participants 

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eSource (DDE) 
eSource Direct Data Entry (DDE) refers to the capture of clinical study data 
electronically, at the point of care. eSource Platform/Applications combines 
source documents and case report forms (eCRFs) into one application, 
allowing for the real time collection of clinical trial information to Novartis and 
other oversight authorities, as appropriate 
Estimand 
As defined in the ICH E9(R1) addendum, estimand is a precise description of 
the treatment effect reflecting the clinical question posed by the trial objective. 
It summarizes at a population-level what the outcomes would be in the same 
participants under different treatment conditions being compared. Attributes of 
an estimand include the population, variable (or endpoint) and treatment of 
interest, as well as the specification of how the remaining intercurrent events 
are addressed and a population-level summary for the variable. 
Healthy volunteer 
A person with no known significant health problems who volunteers to be a 
study participant  
Intercurrent events 
Events occurring after treatment initiation that affect either the interpretation 
or the existence of the measurements associated with the clinical question of 
interest. 
Investigational 
drug/ treatment 
The drug whose properties are being tested in the study 
Investigational 
Medical Device 
Medical Device being assessed for safety or performance in a clinical 
investigation. This includes devices already on the market and being 
evaluated for new intended uses, new populations, new materials, or design 
changes 
Medication number 
A unique identifier on the label of medication kits 
Mis-randomized 
participants 
Mis-randomized participants are those who were not qualified for 
randomization and who did not take study treatment, but have been 
inadvertently randomized into the study or the participant allocated to an 
invalid stratification factor 
Off-site 
Describes trial activities that are performed at remote location by an OHP 
professional, such as procedures performed at the participant's home. 
Off-site healthcare 
Professional (OHP) 
A qualified healthcare professional, who performs certain protocol procedures 
for the participant in an off-site location such as a participant's home. 
Other treatment 
Treatment that may be needed/allowed during the conduct of the study (i.e., 
concomitant or rescue therapy) 
Part 
A sub-division of a study used to evaluate specific objectives or contain 
different populations. For example, one study could contain a single dose part 
and a multiple dose part, or a part in participants with established disease and 
in those with newly-diagnosed disease 
Participant 
A trial participant (can be a healthy volunteer or a patient). "Participant" 
terminology is used in the protocol whereas term "Subject" is used in data 
collection 
Participant number 
A unique number assigned to each participant upon signing the informed 
consent. This number is the definitive, unique identifier for the participant and 
should be used to identify the participant throughout the study for all data 
collected, sample labels, etc. 
Patient-Reported 
Outcome (PRO) 
A measurement based on a report that comes directly from the participant 
about the status of a participant's health condition without amendment or 
interpretation of the participant's report by a clinician or anyone else 

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Period 
The subdivisions of the trial design (e.g., Screening, Treatment, Follow-up) 
which are described in the Protocol. Periods define the study phases and will 
be used in clinical trial database setup and eventually in analysis 
Perpetrator drug 
A drug which affects the pharmacokinetics of the other drug 
Personal data 
Participant information collected by the Investigator that is coded and 
transferred to Novartis for the purpose of the clinical trial. This data includes 
participant identifier information, study information and biological samples. 
Randomization 
The process of assigning trial participants to investigational drug or 
control/comparator drug using an element of chance to determine the 
assignments in order to reduce bias. 
Randomization 
number 
A unique identifier assigned to each randomized participant 
Remote 
Describes any trial activities performed at a location that is not the 
investigative site. 
Rescreening 
If a participant fails the initial screening and is considered as a Screen Failure, 
he/she can be invited once for a new Screening visit after medical judgment 
and as specified by the protocol 
Run-in Failure 
A participant who is screened but not randomized/treated after the run-in 
period (where run-in period requires adjustment to participant's intervention or 
other treatment) 
Screen Failure 
A participant who did not meet one or more criteria that were required for 
participation in the study 
Source 
Data/Document 
Source data refers to the initial record, document, or primary location from 
where data comes. The data source can be a database, a dataset, a 
spreadsheet or even hard-coded data, such as paper or eSource 
Stage in cancer 
The extent of a cancer in the body. Staging is usually based on the size of the 
tumor, whether lymph nodes contain cancer, and whether the cancer has 
spread from the original site to other parts of the body 
Start of the clinical 
trial 
The start of the clinical trial is defined as the signature of the informed 
consent by the first participant 
Study device 
Study device is a medical device (marketed or investigational) that is used in 
a circumstance that makes it part of the investigation. 
Study treatment 
Any drug or combination of drugs or intervention administered to the study 
participants as part of the required study procedures; includes investigational 
drug(s), control(s) or background therapy 
Tele-visit 
Procedures or communications conducted using technology such as 
telephone or videoconference, whereby the participant is not at the 
investigative site where the Investigator will conduct the trial. 
Treatment 
arm/group 
A treatment arm/group defines the dose and regimen or the combination and 
may consist of 1 or more cohorts. 
Treatment of 
interest 
The treatment of interest and, as appropriate, the alternative treatment to 
which comparison will be made. These might be individual interventions, 
combinations of interventions administered concurrently, e.g., as add-on to 
standard of care, or might consist of an overall regimen involving a complex 
sequence of interventions. This is the treatment of interest used in describing 
the related clinical question of interest, which might or might not be the same 
as the study treatment. 

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Variable (or 
endpoint) 
The variable (or endpoint) to be obtained for each participant that is required 
to address the clinical question. The specification of the variable might include 
whether the participant experiences an intercurrent event. 
Withdrawal of 
consent 
Withdrawal of consent from the study occurs when the participant explicitly 
requests to stop use of their data and/or biological samples AND no longer 
wishes to receive study treatment AND does not agree to further protocol 
required assessments. This request should be in writing (depending on local 
regulations) and recorded in the source documentation. 
This request should be distinguished from a request to discontinue the study. 
Other study participant's privacy rights are described in the corresponding 
ICF. 

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10.3 
Appendix 3: Clinical laboratory tests 
Not applicable 

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10.4 
Appendix 4: Participant Engagement 
The following participant engagement initiatives are included in this study and will be provided, 
as available, for distribution to study participants at the time points indicated. If compliance is 
impacted by cultural norms or local laws and regulations, sites may discuss modifications to 
these requirements with Novartis. 
• Thank You letter 
• Plain language trial summary - after CSR publication 

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10.5 
Appendix 5: Liver safety monitoring 
To ensure participant safety and enhance reliability in determining the hepatotoxic potential of 
an investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed. 
Please refer to Table 10-1 in Section 10.5 for complete definitions of liver laboratory triggers. 
Once a participant is exposed to study treatment, every liver event defined in Table 10-1 should 
be followed up by the Investigator or designated personnel at the trial site, as summarized 
below. Additional details on actions required in case of liver events are outlined in Table 10-2. 
Repeat liver chemistry tests (i.e., ALT, AST, TBL, PT/INR, ALP and G-GT) to confirm 
elevation. 
These liver chemistry repeats will be performed using the central laboratory. If results will not 
be available from the central laboratory, then the repeats can also be performed at a local 
laboratory to monitor the safety of the participant. If a liver event is subsequently reported, any 
local liver chemistry tests previously conducted that are associated with this event should have 
results recorded on the appropriate CRF. 
• If the initial elevation is confirmed, close observation of the participant will be initiated, 
including consideration of treatment interruption if deemed appropriate. 
• Discontinuation of the investigational drug (refer to the Discontinuation of study treatment 
section), if appropriate 
• Hospitalization of the participant if appropriate 
• Causality assessment of the liver event 
• Thorough follow-up of the liver event should include 
• These investigations can include based on Investigator’s discretion: serology tests, 
imaging, and pathology assessments, hepatologist’s consultancy; obtaining more 
detailed history of symptoms and prior or concurrent diseases, history of concomitant 
drug use, exclusion of underlying liver disease 
All follow-up information and procedures performed must be recorded as appropriate in the 
CRF. 

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10.5.1 
Liver event and laboratory trigger definitions & follow-up requirements 
Table 10-1 
Liver event and laboratory trigger definitions 
 
Definition/ threshold 
Liver laboratory triggers 
If ALT, AST and total bilirubin 
normal at baseline: 
• 
ALT or AST > 5 × ULN 
• 
Total bilirubin > 3 × ULN (in the absence of known Gilbert 
syndrome) 
• 
ALT or AST > 3 × ULN and INR > 1.5 
• 
Potential Hy’s Law cases (defined as ALT or AST > 3 × 
ULN and Total bilirubin > 2 × ULN [mainly conjugated 
fraction] without notable increase in ALP to > 2 × ULN) 
• 
Any clinical event of jaundice (or equivalent term) 
• 
ALT or AST > 3 × ULN accompanied by (general) 
malaise, fatigue, abdominal pain, nausea, or vomiting, or 
rash with eosinophilia 
• 
Any adverse event potentially indicative of a liver toxicity 
If ALT or AST abnormal at 
baseline: 
• 
ALT or AST > 3x baseline or > 300 U/L (whichever occurs 
first) 

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Table 10-2 
Follow up requirements for liver laboratory triggers - ALT, AST, TBL - 
ALT 
TBL 
Liver Symptoms 
Action 
ALT increase without bilirubin increase: 
 
If normal at baseline: 
ALT > 3 x ULN 
Normal 
For participants with 
Gilbert’s syndrome: No 
change in baseline 
TBL 
None 
• 
No Action 
If elevated at 
baseline: 
ALT > 2 x baseline 
or > 300 U/L 
(whichever occurs 
ﬁrst) 
If normal at baseline: 
ALT > 5 x ULN for 
more than two weeks 
Normal 
For participants with 
Gilbert’s syndrome: No 
change in baseline 
TBL 
None 
• 
Interrupt study 
treatment 
• 
Measure ALT, 
AST, ALP, GGT, 
TBIL, INR, 
albumin, and CKin 
48-72h. 
• 
Follow-up for 
symptoms. 
• 
Initiate close 
monitoring and 
workup for 
competing 
etiologies. 
• 
Study treatment 
can be restarted if 
liver enzymes 
return to baseline. 
If elevated at 
baseline: 
ALT > 3 x baseline 
 AND >5x ULN for 
more than two weeks 
or 
ALT ≥ 5x baseline 
AND ≥ 8x ULN 
If normal at baseline: 
ALT > 8 x ULN 
Normal 
None 
ALT increase with bilirubin increase: 
If normal at baseline: 
ALT > 3 x ULN 
TBL > 2 x ULN (or 
INR > 1.5) 
For participants with 
Gilbert’s syndrome: 
Doubling of direct 
bilirubin 
None 
If elevated at 
baseline: 
ALT > 2 x baseline 
AND >3x ULN 
If normal at baseline: 
ALT > 3 x ULN 
Normal or elevated* 
Severe fatigue, 
nausea, vomiting, right 
upper quadrant pain* 
If elevated at 
baseline: 
ALT > 2 x baseline 
AND >3x ULN 
* This situation suggests liver injury based on (i) elevation of ALT, and (ii) the presence of symptoms of 
liver injury. Even if bilirubin is normal, the presence of liver symptoms indicates potentially severe liver 
injury. 

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Table 10-3 
Follow up requirements for liver laboratory triggers - Isolated 
Hyperbilirubinemia 
Criteria 
Actions required 
Follow-up monitoring 
Total Biliruin 
(isolated) 
 
 
>1.5 – 3.0 ULN 
• 
Maintain treatment 
• 
Repeat Liver function test (LFTs) 
within 48-72h 
Monitor LFTs weekly until 
resolution to ≤ Grade 1 or to 
baseline 
> 3 - 10 × ULN (in 
the absence of 
known Gilbert 
syndrome) 
• 
Interrupt treatment 
• 
Repeat LFT within 48-72h 
• 
Hospitalize if clinically appropriate 
• 
Establish causality 
• 
Record the AE and contributing 
factors (e.g., conmeds, med hx, lab) 
in the appropriate CRF 
Monitor LFTs weekly until 
resolution to ≤ Grade 1 or to 
baseline (ALT, AST, total bilirubin, 
Alb, PT/INR, ALP and GGT) 
Test for hemolysis (e.g., 
reticulocytes, haptoglobin, 
unconjugated [indirect] bilirubin) 
> 10 x ULN 
• 
Discontinue the study treatment 
immediately 
• 
Hospitalize the participant 
• 
Establish causality 
• 
Record the AE and contributing 
factors (e.g., conmeds, med hx, lab) 
in the appropriate CRF 
ALT, AST, total bilirubin, Alb, 
PT/INR, ALP and GGT until 
resolution (frequency at 
Investigator discretion) 
Any AE potentially 
indicative of a 
liver toxicity 
• 
Consider study treatment 
interruption or discontinuation 
• 
Hospitalization if clinically 
appropriate 
• 
Establish causality 
• 
Record the AE and contributing 
factors (e.g., conmeds, med hx, lab) 
in the appropriate CRF 
Investigator discretion 
Based on Investigator’s discretion investigation(s) for contributing factors for the liver event 
can include: Serology tests, imaging and pathology assessments, hepatologist’s consultancy; 
obtaining more detailed history of symptoms and prior or concurrent diseases, history of 
concomitant drug use, exclusion of underlying liver disease. 

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10.6 
Appendix 6: Renal safety monitoring 
Once a participant is exposed to study treatment, the following two categories of abnormal renal 
laboratory alert values should be assessed during the study period: 
• Serum creatinine increase ≥ 25% compared to baseline during normal hydration status 
• Any one of the following: 
• Urine protein-creatinine ratio (PCR) ≥1g/g or ≥100 mg/mmol, OR 
• New onset dipstick proteinuria ≥ 3+, OR 
• New onset dipstick hematuria ≥ 3+ (after excluding menstruation, UTI, extreme 
exercise, or trauma) 
Abnormal renal event findings must be confirmed within 24-48h after the first assessment. 
Once a participant is exposed to study treatment, renal laboratory alerts or renal safety events 
should be monitored and followed up by the Investigator or designated trial staff as summarized 
in Table 10-5. 
10.6.1 
Specific Renal Alert Criteria and Actions and Event Follow-up 
Table 10-4 
Specific renal alert criteria and actions 
Renal Event 
Actions 
eGFR decrease 25 – 49% 
• 
Consider causes and possible interventions 
• 
Repeat laboratory values within 48 hrs of 
receipt of abnormal test results. Assess 
patient for signs and symptoms of illness, 
AKI, etc. 
eGFR decrease ≥ 50 % * OR if <18 years old, 
eGFR < 35 mL/min/1.73 m2 
• 
Consider causes and possible interventions 
• 
Repeat assessment within 24-48h if possible 
• 
Repeat laboratory values within 48 hrs of 
receipt of abnormal test results. Assess 
patient for signs and symptoms of illness, 
AKI, etc. 
• 
Consider drug interruption or discontinuation 
unless other causes are diagnosed and 
corrected 
• 
Consider referral to nephrologist for 
diagnosis and management 
• 
Consider patient hospitalization and 
specialized treatment 
New onset dipstick proteinuria ≥ 3+ OR Protein-
creatinine ratio (PCR) ≥ 1g/g Cr 
• 
Confirm presence of true proteinuria by 
quantification: protein-creatinine on first 
morning void 
• 
Consider causes and possible interventions 
• 
Assess serum albumin & serum total protein 
• 
Repeat assessment to confirm 

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Renal Event 
Actions 
• 
Consider drug interruption or discontinuation 
unless other causes are diagnosed and 
corrected 
• 
Consider referral to a nephrologist 
New onset hematuria ≥ 3+ on urine dipstick 
• 
Obtain urine microscopy to distinguish 
hemoglobinuria or myoglobinuria from 
hematuria 
• 
Assess sCr 
• 
Exclude infection, trauma, calculi, bleeding 
from the distal urinary tract/bladder, 
menstruation 
• 
Consider bleeding disorder 
* Corresponds to KDIGO criteria for Acute Kidney Injury 
Table 10-5 
Renal Event Follow Up 
FOLLOW-UP OF RENAL EVENTS 
Monitor patient regularly (frequency dependent on clinical course and consultant advisement) until - 
• 
Event resolution: sCr within 10% of baseline or PCR < 1 g/g Cr, or ACR <300 mg/g Cr, or 
• 
Event stabilization: sCr level with ±10% variability over last 6 months or PCR stabilization at a 
new level with ±50% variability over last 6 months. 
• 
Analysis of urine renal markers in samples collected over the course of the DIN event 

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11 
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