Effect of Evolocumab on Coronary Plaque Characteristics: a Multimodality Imaging Study
Phase: PHASE4
Conditions: Coronary Artery Disease
Sponsor: Annapoorna Kini

Effect of Evolocumab on Coronary Plaque Characteristics: 
a Multimodality Imaging Study
YELLOW III 
PI: Annapoorna Kini, MD, MRCP, FACC
NCT04710368
Document Date: 06-24-2021

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Effect of Evolocumab on Coronary Plaque Characteristics:  
a Multimodality Imaging Study 
YELLOW III  
 
STUDY PROTOCOL 
Version: 1.2 
Date: 06-24-2021 
 
 
 
Principal Investigator:  
Annapoorna Kini, MD, MRCP, FACC 
Professor of Medicine, Cardiology 
Director, Cardiac Catheterization Lab 
Director, Interventional Cardiology Fellowship Program  
The Zena and Michael A. Wiener Cardiovascular Institute 
The Icahn School of Medicine at Mount Sinai 
One Gustave L. Levy Place, Box 1030 
New York, NY 10029-6574 
 
 
 
 
 

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BACKGROUND INFORMATION AND RATIONALE 
 
Coronary artery disease (CAD) remains a leading cause of death in most countries 
despite modern therapy including intensive statin treatment, prompt coronary 
revascularization, and dual antiplatelet therapy. Reducing levels of low-density lipoprotein 
(LDL) cholesterol is a cornerstone of the prevention of cardiovascular disease (1). Statins 
are highly efficacious in lowering LDL cholesterol. However, many patients, especially 
those with very high initial LDL cholesterol levels and those who have unacceptable side 
effects with high-dose statins, do not reach recommended target levels of LDL cholesterol 
(2,3). The risk of recurrent cardiovascular events after acute coronary syndrome (ACS) 
or in chronic coronary heart disease remains related to LDL-C levels among statin-treated 
patients (4-6). These observations suggest that there is a considerable unmet medical 
need for additional, more effective therapeutic options with acceptable side-effect profiles.  
Proprotein convertase subtilisin kexin type 9 (PCSK9) impairs LDL receptor recycling to 
the hepatic surface which leads to reduced removal of LDL particles from the circulation 
(7). Monoclonal antibodies against PCSK9 lower LDL-C levels when administered alone 
or in combination with statins and have shown potential as an alternative therapy for 
patients who experience intolerable adverse effects during statin therapy (8-10). Inhibition 
of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol 
levels by 59% from baseline level to 30 mg per deciliter and reduced the risk of 
cardiovascular events in a large randomized FOURIER trial including patients with 
atherosclerotic cardiovascular disease on statin therapy (11). In the GLAGOV trial, 

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addition of evolocumab in patients treated with moderate or high intensity statin therapy 
resulted in greater decrease in percent atheroma volume (PAV) assessed by 
intravascular ultrasound (IVUS) during 18 month of therapy (12), while there was no 
plaque regression observed in patients treated with statins alone. Reduction in the 
atherosclerotic disease burden, atheroma (PAV) was observed in 67% of the evolocumab 
and 47% of the placebo group regardless of baseline LDL-C levels. 
One-third of the patients treated with evolocumab and almost half of statin-treated 
patients from the GLAGOV trial did not demonstrate plaque volume reduction despite the 
significant lipid reduction suggesting that different mechanisms might be responsible for 
lesion regression in a subgroup of patients, and these patients might require different 
treatment approach. Another possibility is that beneficial changes in lesion morphology 
were not captured in the study due to inherent limitations of IVUS. Optical coherence 
tomography (OCT) provides high-resolution (10-20 µm) in vivo images of plaque 
morphology and is the only currently available intravascular imaging modality capable of 
the assessment of the fibrous cap thickness in vivo (13,14). The presence of a thin fibrous 
cap overlying a large necrotic core is the hallmark of high-risk vulnerable plaques (14,15). 
While intravascular ultrasound (IVUS) lacks the spatial resolution to accurately access 
the changes in fibrous cap thickness (FCT), OCT’s superior image resolution allows the 
accurate detection of thin cap fibroatheroma (TCFA) and estimate the effect of various 
lipid-lowering therapies on FCT (16-18). The aim of the ongoing HUYGENS study is to 
evaluate the effect of evolocumab combined with maximally tolerated statin therapy on 

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OCT defined FCT in subjects with non-ST-elevation acute coronary syndrome (NSTE-
ACS). 
Near-infrared spectroscopy (NIRS) detects the lipid (cholesterol) content of 
atherosclerotic plaques by generating lesion “chemogram” and calculating  lipid core 
burden index (LCBI) characterizing the amount of lipid on a 0 to 1000 scale. Large lipid-
core plaques (LCP) detected by NIRS have been shown to be a signature of plaques 
causing STEMI and are associated with a high risk of periprocedural MI (19,20). 
Results of YELLOW I and II. In a series of YELLOW trials, we investigated the effect of 
statins on high-risk lipid-rich coronary plaques using intravascular imaging in patients with 
stable CAD. The aim of our first YELLOW (Reduction in Coronary Yellow Plaque, Lipids 
and Vascular Inflammation by Aggressive Lipid Lowering) trial was to explore whether 
these benefits are attributable to reduction in plaque lipid content in obstructive coronary 
lesions (21). In the study, we randomized 87 patients with multivessel CAD to intensive 
(rosuvastatin 40 mg daily) or standard-of-care lipid-lowering therapy. Patients underwent 
PCI for the culprit lesion at the baseline, while obstructive nontarget lesion (NTL) was 
treated at the staged procedure, follow-up. The inclusion criterion for the trial was FFR 
less or equal 0.8. NTLs were evaluated at baseline and after 7 weeks of therapy with 
NIRS and IVUS. The primary endpoint was the change in lipid-core burden index at the 
4-mm maximal segment (maxLCBI4mm). Upon follow-up, median reduction in 
maxLCBI4mm was significantly greater in the intensive versus standard group suggesting 
that short-term intensive statin therapy may reduce lipid content in obstructive lesions.  

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In our subsequent YELLOW II study, all patients with obstructive NTL received high-dose 
statin therapy for 8-12 weeks (22). The aim of the study was to characterize the 
relationship between the changes in plaque morphology assessed by NIRS/IVUS and 
OCT, HDL functionality and gene expression in peripheral blood mononuclear cells 
(PBMC) using microarray analysis. At the follow-up, we observed a significant increase 
in fibrous cap thickness (FCT) in the study lesion, enhancement of cholesterol efflux 
capacity (CEC) and significant perturbations of PBMC transcriptome in patients with 
stable coronary artery disease (CAD) treated with 40 mg rosuvastatin for 8-12 weeks. As 
a result, the prevalence of TCFA reduced from 20 to 7% (P=0.003) and there was a 
significant independent association between the thickening of the fibrous cap and 
improved CEC independent of lipid lowering and CRP reduction. In addition, we observed 
significant transcriptomic perturbations in genes related to cholesterol synthesis, 
regulation of fatty acid unsaturation, cellular cholesterol uptake, efflux and inflammation 
suggesting that several independent molecular mechanisms might be responsible for the 
beneficial effects of statin on plaque morphology. The unique translational combination 
of multi-modality intravascular imaging with clinically relevant cellular biology and 
comprehensive transcriptomics represents a powerful approach to assessing the effects 
and mechanisms of the efficacy of different lipid-lowering therapies for stabilizing 
atherosclerotic plaques.  
With OCT imaging, we observed an increase in FCT after intensive statin therapy only in 
a subset of the study patients. Traditionally, response to statins is measured by the 
changes in serum lipids, however, these changes do not predict the beneficial changes 

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in FCT, therefore, it is important to distinguish statin responders from non-responders 
using non-invasive methods. In our recent analysis, YELLOW II transcriptomic data was 
used to predict whether a patient’s FCT increased in response to statin therapy using 
machine learning models (23). One of the model used 18 genes and was able identify 
statin responders with an accuracy of 95.7%, sensitivity of 94.3% and specificity of 97.1%.  
Hypothesis. In the YELLOW III study, we hypothesize that LDL-C lowering with 
evolocumab 140 mg every 2 weeks will result in a significant increase in OCT-defined 
minimal FCT and reduction of plaque lipid content assessed by NIRS compared to 
baseline in patients with CAD undergoing percutaneous coronary intervention (PCI). In 
addition, we hypothesize that there is an association between the changes in patient’s 
plaque characteristics and PBMC gene expression and lipid metabolites at the baseline, 
which would allow us to develop a predictive model for detecting subjects that 
demonstrate the greatest response regarding plaque morphology to PCSK9 inhibition 
therapy. YELLOW III will provide an additional contribution to the ongoing HYUGENS 
study due to its unique design combining intravascular imaging and transcriptomic based 
machine learning approach, which will allow to uncover molecular mechanisms 
responsible for the beneficial changes in atherosclerotic lesions of patients treated with 
evolocumab.  

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STUDY OBJECTIVES 
The aim of the study is to assess the effect of evolocumab on coronary plaque 
morphology using intravascular imaging, NIRS/IVUS and OCT, and PBMC gene 
expression analysis in patients with stable CAD on maximally tolerated statin therapy.  
Primary endpoints. The primary end-points are the changes from baseline to follow-up 
(follow-up value minus baseline value) in (1) the minimal FCT assessed by OCT and (2) 
NIRS maxLCBI4mm after 26 weeks of evolocumab. 
Secondary endpoints. The secondary endpoints are the changes in (1) the maximal lipid 
arc, lipid length, lipid volume index, macrophage accumulation and calcification by OCT; 
(2) PAV and TAV defined by IVUS and (3) PBMC gene expression.  In recognition of the 
role of lipids in CAD and atherosclerosis, we will perform lipidomics to analyze lipid 
metabolites and lipid derivatives in blood plasma and serum in order to identify CAD 
biomarkers. Measuring lipid metabolites (and their effectors) might directly lead to the 
identification pathways of lipid action or lipid metabolism in patients receiving treatment. 
We will also perform Mass Cytometry (CyTOF) of PBMC to characterize the immune 
profile and responses in patients receiving a combination of evolocumab plus statin with 
an eye on identifying biomarkers for detecting and/or predicting favorable changes in 
plaque morphology as a result of PCSK9 inhibition therapy. Other parameters including 
the levels of CRP, resistin, adiponectin, perilipin and Lp(a) will also be measured for the 
same purpose.  

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Exploratory endpoints. Major Adverse Cardiac Events (MACE) will be defined as a 
combined clinical endpoint of death, MI (Q wave or non Q-wave with CK-MB >3 times 
above the upper normal limit (48 U/L), urgent revascularization or stroke at 30 days and 
1 year.  
 
STUDY PROCEDURES 
This is a single center single arm study, which will be performed in the Cardiac 
Catheterization laboratory of the Mount Sinai Hospital, New York, NY. After informed 
consent, patients undergoing clinically indicated elective PCI with a non-obstructive lesion 
and optimal background statin therapy will be eligible for screening (Figure 1). Non-
obstructive lesions (30-50% stenosis) identified by angiography in a non-culprit vessel 
with lipid-rich plaque will be studied. Subjects will receive evolocumab 140 mg 
subcutaneously every 2 weeks for 26 weeks. Serial NIRS/IVUS and OCT imaging will be 
performed in the non- obstructive lesions, first during PCI and subsequently after 26 
weeks.  
1. Screening. Written informed consent must be obtained from all subjects before any 
study-specific procedures are performed. We will screen patients scheduled for 
elective coronary angiography and/or coronary artery stenting, who are receiving 
statin therapy for at least 4 weeks or with history of statin intolerance (should not 
exceed 20% of the total cohort) with acceptable LDL-C levels. Patients with non-
obstructive lesion (30-50% stenosis) by angiography and lipid-rich plaque with lipid 
arc >90° and minimal fibrous cap thickness ≤ 120 µm detected by OCT will comprise 

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the final study population. Women of childbearing potential will undergo urine 
pregnancy testing. If necessary, we may request serum pregnancy testing to confirm 
equivocal urine-based results.   
2. PCI and baseline imaging. Culprit vessel PCI will be performed according to best 
current practice. During the same angiographic procedure baseline OCT and 
NIRS/IVUS imaging of the non-obstructive study lesion will be performed after 
administration of intra-coronary NTG. A total of 25ml of blood will be drawn from the 
sheath during angiography for transcriptomic profiling of PBMC (mRNA and miRNA), 
lipidomics and cytokine analyses. Patients will undergo assessment of lipid levels, 
CK-MB, Troponin I, liver function, CBC, and hsCRP. 
3. Study drug allocation. All patients will receive subcutaneously administered 
evolocumab 140 mg every 2 weeks for 26 weeks in addition to statins. Evolocumab 
will be administered on day 1 (the day of the first treatment) and through week 26 
with a personal injector or prefilled auto injector/pens.  
4. Clinical visits. Study visits will occur during screening (day 1), weeks 12 and 26 
(time of follow-up procedure). Subjects must fast overnight when fasting lipid 
samples are to be obtained. 
5. Follow up Procedure. The follow-up procedure will be scheduled 26 weeks after 
the baseline PCI and should occur within ±2 weeks of their specified date. First, 
routine angiography to check the previous stent will be performed, then, repeat 
NIRS/IVUS and OCT of the non-obstructive study lesion will be performed after 
administration of intra-coronary nitroglycerin. A total of 25ml of blood will be drawn 

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from the sheath during angiography for transcriptomic profiling of PBMC (mRNA and 
miRNA), lipidomics and cytokine analyses.. All study patients will undergo repeat 
assessment of lipid levels, CK-MB, Troponin I, liver function, CBC, and hsCRP. 
Bivalirudin or Heparin will be used as anticoagulation as per standard PCI protocol. 
All patients will have repeat CK-MB and Tnl levels measured at 6-8 hours and if in 
hospital, 16-24 hours post PCI, and thereafter if levels continue to rise  
6. Post Follow-up. After the follow up procedure patients will be referred back to their 
primary care physician as is our usual practice. All further adjustment of lipid 
lowering and other medications will be at the discretion of the primary care physician. 
The treatment received after 26 weeks of evolocumab will be documented, and  
clinical telephone follow up will be performed at 30 days, 6 months and 1 year after 
the follow-up procedure 
7. Data analysis. Off-line image analysis will be performed by the Mount Sinai Intravascular 
Imaging core laboratory, which will have no knowledge of patient clinical presentation and 
treatment.. Statistical and bioinformatics analyses will be performed by an independent 
biostatistician unaware of clinical data.  
For predictive model construction, each patient will be identified as an evolocumab 
responder or non-responder depending on whether FCT increased or decreased after the 
treatment. Similar to our YELLOW II transcriptomic sub study (23), an elastic net 
regularized generalized linear model and K top scoring pair (KTSP) classifier model will be 
built using clinical variables and PBMC transcriptomic, lipidomics and cytokine analyses 
data to predict changes in FCT to ascertain whether a patient's FCT will increase in 
response to treatment. The transcriptomic data will be pre-processed to identify the 

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mechanism of missing data, and data imputations will be performed for non-ignorable 
missing data. The accuracy, sensitivity and specificity of both algorithms will be evaluated 
in order to select the highest performing model. We believe that the predictive model might 
allow patients to have their FCT response approximated without undergoing intravascular 
imaging.  
8. Safety reporting. Subjects will be carefully monitored during the study for possible 
Adverse Events (AEs) from the time of enrollment to the completion of their 
participation in the study. All adverse events will be fully investigated by the Principal 
Investigator, classified according to the current definitions of the International 
Organization for Standardization (ISO) and reported to the Mount Sinai Hospital IRB 
and Amgen Safety. Timeframes for submission of safety data and aggregate reports 
to Amgen are described in Tables 1 and 2.  
In addition, an independent data and safety monitoring board (DSMB), comprising 
3 cardiologists  with extensive clinical research experience will oversee this study. 
The DSMB will be informed within 24 hours of all major adverse events (MACE) 
defined as a combined clinical endpoint of death, MI (Q wave or non Q-wave with 
CK-MB >3 times above the upper normal limit (48 U/L), urgent revascularization or 
stroke at 30 days and 1 year. All minor adverse events will be reported to the 
DSMB within 5 working days of knowledge of the event. The DSMB will convene 
after 30, 70 and 110 patients have completed the final procedure and at study 
closure. The DSMB will have complete discretion to adjudicate all events (major 
and minor), and, after fair deliberation and at any stage of the trial, to recommend 
the termination of the study, for whatever reason as they see fit insofar as it may 
pertain to adverse event occurrence(s). If the DSMB is to recommend termination 
of the study, the investigators will be given a single opportunity to respond to any 
concerns the DSMB may raise. After final consideration, if the DSMB again 
recommends termination of the study, then the study will be terminated. The 
DSMB may only terminate the study on the basis of MACE and adverse events. 
 

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9. Institutional Review Board (IRB). Prior to study initiation and when amended, the 
study protocol and will be submitted for review and approval to the Icahn School of 
Medicine at Mount Sinai IRB. Site personnel must provide reports of the progress, 
or completion, termination or discontinuation of the study to the institutional IRB at 
appropriate intervals.  The primary investigator will verify that each subject has 
consented, in writing, to direct access to his/her original medical records for trial-
related monitoring, audit, IRB/IEC review, and regulatory inspection 
 
Inclusion criteria: 
 Men or women aged  18 years or older at screening who signed written Informed 
Consent 
 Patients with coronary artery disease undergoing cardiac catheterization and PCI 
for a culprit lesion, who also have a non-obstructive study lesion (30-50% stenosis) 
identified by angiography in a non-culprit vessel. 
 Patients with non-obstructive coronary artery disease and a 30-50% lesion 
identified by angiography 
 Patients who are not candidates for PCI or CABG over the next 12 months, in the 
opinion of the investigator  
 Patients treated with statins for at least 4 weeks with LDL-C level ≥ 80 mg/dL for 
low- or moderate -intensity statin use and ≥ 60 mg/dL for high-dose statin at 
screening (Table 3). Patients with history of statin intolerance and LDL-C ≥ 100 
mg/dL. 

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 Angiographic criteria: 30-50% reduction of lumen diameter in addition to the target 
study lesion. The study segment should not have a history of percutaneous 
coronary intervention (PCI) or coronary artery bypass grafting (CABG), and may 
not be a bypass graft. 
 OCT criteria:  study lesion should have a lipid-rich plaque with lipid arc >90° and 
fibrous cap thickness ≤120 µm.  
 Women of childbearing potential must agree to be on an acceptable method of 
birth control/contraceptive 
 
Exclusion criteria: 
 Patients who have acute myocardial infarction (Q wave or non-Q wave with CK-
MB > 5 times above the upper normal (31.5 ng/ml) within 72 hours) 
 Patients who are in cardiogenic shock 
 Patients with left main disease or patients requiring coronary artery bypass graft 
surgery 
 Patients with elevated CK-MB (>6.3 ng/ml) or Tnl (>0.5 ng/ml) 
 Patients with platelet count < 100,000 cell/mm3 
 Patients who have co-morbidity which reduces life expectancy to one year 
 Patients who are currently participating in another investigational drug/device 
study 
 Patients with liver disease 
 Patient with creatinine > 2.0 mg/dL 
 Pregnant women and women of childbearing potential who intend to have 
children during the duration of the trial 
 Patients having undergone heart transplantation, or those that may undergo 
heart transplantation during the study period 
 Patients with active autoimmune disease    
 
 

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Table 1. Timeframes for submission of safety data and aggregate reports to 
Amgen 
Safety Data 
Timeframe for submission to 
Amgen 
Send to 
Suspected Unexpected Serious 
Adverse Reaction (SUSARs) 
At time of regulatory submission 
Amgen Safety 
Pregnancy/Lactation exposure 
and any associated 
reports/outcomes (i.e. 
unexpected pregnancy, 
pregnancy of partner, 
spontaneous abortion, 
congenital anomaly etc.) 
Within 1 business day of Sponsor 
awareness, for reports meeting serious 
criteria 
Not to exceed 15 calendar days of 
Sponsor awareness, for non-serious 
reports 
Amgen Safety 
Listing for Safety data 
reconciliationaa 
Once per year and at the end of the 
study 
NASCR Manager 
Annual Safety Report 
(US IND Annual Report) 
 
Annually 
 
NASCR Manager 
Other aggregate analyses 
(any report containing Safety 
data generated during the 
course of the study) 
At the time of Sponsor submission to 
any body governing research conduct 
(eg. RA, IRB etc.) 
NASCR Manager 
Final (End of Study Report, 
including): 
 
Unblinding data for blinded 
studies 
 
Reports of unauthorized use 
of a marketed product 
 
At the time of Sponsor submission to 
any body governing research conduct 
(eg. RA, IRB etc.) but no later than 1 
calendar year of study completion 
 
NASCR Manager 
a Listing for reconciliation should include all ICSRs submitted to Amgen Safety per contract  
 
 
 

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Table 2. Timeframes for submission of safety data and aggregate reports to Amgen 
- Device related adverse events for studies using Amgen devicesa and Product 
complaints 
Safety Data 
Timeframe for submission to 
Amgen 
Send to 
Serious Adverse Device 
Effectb (SADE)  
Within 1 business day of Sponsor 
awareness  
Amgen Safety 
Adverse Device Effect 
(ADE)  
Not to exceed 15 calendar days of 
Sponsor awareness 
Amgen Safety 
Product Complaintc 
Immediately, not to exceed 1 
business day of Sponsor awareness 
Amgen Quality 
a Refer to local Safety representative (LSO) to clarify reporting requirements for the Amgen device per 
regulations in the country where the study is being conducted. 
b Adverse device effect is: any adverse event related to the use of a medical device. Adverse device effects 
include adverse events resulting from insufficient or inadequate instructions for use, adverse events 
resulting from any malfunction of the device, or adverse events resulting from use error or from intentional 
misuse of the device. 
c Product Complaint is: Any written, electronic or oral communication that alleges deficiencies related to the 
identity, quality, durability, reliability, safety, effectiveness, or performance of a drug, combination product, 
or device after it is released for distribution to market or clinic by either: (1) Amgen or (2) distributors or 
partners for whom Amgen manufactures the material.  This includes all components distributed with the 
drug, such as packaging, drug containers, delivery system, labelling, and inserts. Examples include: 
• 
Device that is damaged or broken 
• 
Bent or blunt needles 
• 
Missing or illegible labeling 
• 
Inability of customer to administer the product 
• 
Product with an unexpected color, appearance, or particles 
• 
User error (i.e, an act or omission of an act that results in a different combination product or medical 
device response than intended by the manufacturer or expected by the user, where the user attempted to 
use the combination product or medical device in good faith and experienced difficulty or deficiency 
administering the product). 

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Reports of misuse of a combination product or medical device (i.e, the intentional and improper use of a 
combination product or medical device not in accordance with the authorized product information) are not 
considered Product Complaints. 
 
 
 
Table 3. High-, Moderate-, and Low-Intensity Statin Therapy* 
 
High-Intensity Statin Therapy 
Moderate- and low- intensity statin therapy 
Atorvastatin ≥40 mg 
Rosuvastatin ≥20 mg 
Atorvastatin <40 mg 
Rosuvastatin <20 mg 
Simvastatin < 80 mg 
Pravastatin ≤ 80 mg 
Lovastatin ≤ 40 mg 
Fluvastatin ≤ 80 mg 
Pitavastatin ≤ 4 mg 
 
Stone et al. 2014 2013 ACC/AHA Blood Cholesterol Guideline on the Treatment of Blood Cholesterol to 
Reduce Atherosclerotic Cardiovascular Risk in Adults. JACC Vol. 63, No. 25, 63(25 Pt B):2889-934. 
 
 
 
 
 
 
 

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ACS – acute coronary syndrome; LCBI – lipid core burden index; OCT – optical coherence tomography; 
PAV=percent atheroma volume; SC – subcutaneously; TAV=total atheroma volume; FCT – fibrous cap thickness; 
PBMC - peripheral blood mononuclear cell 
 
 
Patient population (n = 130): 
 Patients with stable CAD undergoing PCI who also have a 
suitable for imaging non-obstructive lesion (30-50% stenosis) 
identified by angiography in a non-culprit vessel  
Evolocumab 140 mg every 2 weeks in 
addition to statins for 26 weeks 
Baseline procedure: 
After culprit vessel PCI, non-target study lesion undergoes 
OCT. If lipid-rich plaque is detected (maximal lipid arc >90° and 
minimal fibrous cap thickness ≤ 120 µm), patient is enrolled 
and NIRS/IVUS is performed 
Follow-up procedure: 
Repeat angiogram followed by OCT and 
NIRS/IVUS of the study lesion 
Primary endpoints: change in minimal 
fibrous cap thickness (∆FCT) and 4 mm 
maximal LCBI (∆maxLCBI4mm) 
Secondary endpoints: 
 
Maximal lipid arc, lipid length, lipid 
volume index, macrophage 
accumulation and  calcification by OCT 
 
PAV and TAV defined by IVUS 
 
PBMC gene expression and lipidomics 
Figure 1. YELLOW III study flow chart 
Blood sample 
for PBMC 
transcriptomic 
analysis  
Blood sample 
for PBMC 
transcriptomic 
analysis  

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reproduced, used or disclosed without written permission from the Principal Investigator.                  Version: 1.2 
 
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