A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)
Phase: PHASE1
Conditions: Cardiovascular Disease
Sponsor: Amgen

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 1 of 106 
CONFIDENTIAL 
Title:  A Phase 1, Randomized, Double-blind, Placebo-controlled, Single 
Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a) 
Amgen Protocol number (AMG 890):  20170544 
IND number BB-IND 136605 
NCT Number:  NCT03626662 
Clinical Study Sponsor: 
Amgen Inc. 
One Amgen Center Drive 
Thousand Oaks, CA 91320-1799 
Tel:  1 805 447-1000 
Key Sponsor Contact(s): 
, MD 
Medical Sciences Medical Director 
Tel:  
Email:  
Global Early Clinical Development Manager 
Tel:  
Email: 
Date 
Amendment 1 Date 
Amendment 2 Date 
Amendment 3 Date 
Amendment 4 Date 
Amendment 5 Date 
Amendment 6 Date 
Superseding Amendment 6 Date 
Amendment 7 Date 
04 May 2018 
20 September 2018 
07 February 2019 
02 May 2019 
17 May 2019 
13 December 2019 
21 December 2020 
25 March 2021 
07 December 2021 
Confidentiality Notice 
This document contains confidential information of Amgen Inc. 
This document must not be disclosed to anyone other than the site study staff and 
members of the institutional review board/independent ethics committee/institutional 
scientific review board or equivalent. 
The information in this document cannot be used for any purpose other than the 
evaluation or conduct of the clinical investigation without the prior written consent of 
Amgen Inc. 
If you have questions regarding how this document may be used or shared, call the 
Amgen Medical Information number:  US sites, 1- 800-77-AMGEN; Australia sites, 
1-800-803-638; Amgen’s general number in the US (1-805-447-1000).

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 2 of 106 
CONFIDENTIAL 
 
 
Investigator’s Agreement 
I have read the attached protocol entitled, A Phase 1, Randomized, Double-blind, 
Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics and Pharmacodynamics of AMG 890 in Subjects With Elevated 
Plasma Lipoprotein(a), dated 07 December 2021, and agree to abide by all provisions 
set forth therein.   
I agree to comply with the International Council for Harmonisation (ICH) Tripartite 
Guideline on Good Clinical Practice (GCP) and applicable national or regional 
regulations/guidelines.  
I agree to ensure that Financial Disclosure Statements will be completed by: 
 
me (including, if applicable, my spouse [or legal partner] and dependent children) 
 
my subinvestigators (including, if applicable, their spouses [or legal partners] and 
dependent children) 
at the start of the study and for up to 1 year after the study is completed, if there are 
changes that affect my financial disclosure status. 
I agree to ensure that the confidential information contained in this document will not be 
used for any purpose other than the evaluation or conduct of the clinical investigation 
without the prior written consent of Amgen Inc.  
 
 
 
Signature 
 
 
Name of Investigator 
 
Date (DD Month YYYY) 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 3 of 106 
CONFIDENTIAL 
 
 
1. 
Protocol Synopsis 
Title:  A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study 
to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 890 in 
Subjects With Elevated Plasma Lipoprotein(a) 
Study Phase:  1  
Indication:  Treatment of adults with atherosclerotic cardiovascular disease to reduce the risk of 
cardiovascular events 
Primary Objective:  To assess the safety and tolerability of AMG 890 when administered 
subcutaneously (SC) as a single dose to subjects with elevated plasma Lp(a). 
Secondary Objectives:  
 
To characterize the pharmacokinetics (PK) of AMG 890 when administered SC as a 
single dose to subjects with elevated plasma Lp(a) 
 
To characterize the pharmacodynamics (PD) effects of AMG 890 on plasma Lp(a) 
 
To assess the safety, tolerability, and PD effects of AMG 890 when administered in 
combination with statins  
Exploratory Objectives:  
 
To assess the effects of AMG 890 on total cholesterol and cholesterol fractions (very-low 
density lipoprotein cholesterol [VLDL-C], low-density lipoprotein cholesterol [LDL-C], and 
high-density lipoprotein cholesterol [HDL-C]), triglycerides, apolipoprotein A1 (ApoA1) 
and total apolipoprotein B (ApoB)  
 
To qualitatively assess AMG 890 urinary excretion following a single SC dose 
administration 
Hypotheses: 
 
AMG 890 will be safe and well tolerated when administered SC as a single dose in 
subjects with elevated plasma Lp(a) 
 
AMG 890 PK and/or PD data from this study will support the selection of dose and 
frequency of AMG 890 administration for future multi-dose trials 
Primary Endpoints: 
 
Subject incidence of treatment-emergent adverse events 
 
Safety laboratory analytes, vital signs, and electrocardiograms (ECGs) 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 4 of 106 
CONFIDENTIAL 
 
 
Secondary Endpoints:   
 
AMG 890 PK parameters including, but not limited to, maximum observed concentration 
(Cmax), the time of maximum observed concentration (tmax), and area under the 
concentration-time curve (AUC) 
 
Pharmacodynamic parameters: 
o 
Change and percent change in plasma Lp(a) levels at each scheduled visit up to 
the end of treatment visit 
Study Design:   
This is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) study in 
subjects with elevated plasma Lp(a), which will be conducted at 3 to 10 sites in the United States 
and Australia.  Additional sites and countries may be added. 
Approximately 
 subjects will enroll in 9 SAD cohorts. As described in Table 1 below, for each 
cohort, subjects will be randomized to receive AMG 890 or placebo SC in a  
3:1 ratio.  As of Amendment 6, enrollment in cohorts 1 to 8 is closed.  There were no safety 
concerns noted that would preclude enrollment into the higher dose cohorts 8 and 9. 
Table 1.  Planned Treatment by Cohort 
Cohort 
Number of Subjects 
Investigational Product 
(SC administration) 
1 a 
6 
AMG 890 3 mg 
2 
Placebo 
2 a 
6 
AMG 890 9 mg 
2 
Placebo 
3 a 
6 
AMG 890 30 mg 
2 
Placebo 
4 a 
6 
AMG 890 75 mg 
2 
Placebo 
5 a 
6 
AMG 890 225 mg 
2 
Placebo 
6 b,s 
9 
AMG 890 9 mg 
3 
Placebo 
7 b,s 
9 
AMG 890 75 mg 
3 
Placebo 
8 b,s 
6 
AMG 890 225 mg 
2 
Placebo 
9 b,s 
6 
AMG 890 675 mg 
2 
Placebo 
a  subjects with screening plasma Lp(a)  70 nmol/L and  199 nmol/L  
b  subjects with screening plasma Lp(a)  200 nmol/L  
s  at least 6 subjects must be on a stable dose of a statin for at least 6 weeks in each of cohorts 6 to 9 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 5 of 106 
CONFIDENTIAL 
 
 
As described in the Eligibility Criteria, cohorts 1 to 5 will enroll subjects with plasma Lp(a) 
between 70 nmol/L and 199 nmol/L, inclusive.  Cohorts 6 to 9 will enroll subjects with plasma 
Lp(a) equal to or greater than 200 nmol/L.  At least 6 subjects in each of cohorts 6 to 9 will be on 
a stable dose of statin for at least 6 weeks.  
For cohorts 1 to 5, the first 2 enrolled subjects will be randomized in a 1:1 ratio (sentinel pair) and 
will be dosed on the same day at the same study site, as will cohort 9. Within the pair and while 
maintaining treatment blind, 1 subject will receive AMG 890 and the other subject will receive 
placebo. If deemed safe by the investigator, and no less than 24 hours after sentinel pair dosing, 
the same dose will be administered to the remaining cohort subjects.  
Enrollment into cohorts 1 to 5 will be staggered. Subsequent cohorts will be dosed after the dose 
regimen in the preceding cohort has been found by the Dose Level Review Team (DLRT) to be 
safe and reasonably tolerated based on available safety data through study day 15 for all 
subjects. Enrollment into cohorts 5 to 7 will be initiated after the dose regimen in cohort 4 has 
been found by the DLRT to be safe and reasonably tolerated based on available safety data 
through study day 15.  
Enrollment into cohort 8 is closed. Enrollment into cohort 9 can be initiated after the dose regimen 
in cohort 5 has been found by the DLRT (“DLRM 5” in study schema) to be safe and reasonably 
tolerated based on available safety data through at least study day 15 for all subjects. 
The planned dose escalation schedule may be modified based on treatment-emergent data 
(safety and/or PD).  Dose adjustments (if any) will be made by Amgen on a treatment cohort and 
not on an individual basis. As of Amendment 6, enrollment in Cohorts 1 to 8 is closed. There were 
no safety concerns noted that would preclude enrollment into the higher dose cohorts, 8 and 9. 
Sample Size:   
The sample size is based on practical considerations.  Approximately 
 subjects will be 
enrolled.  With at least 6 subjects receiving AMG 890 in each cohort, there is at least a 74 
chance of detecting an adverse event (AE) with a true incidence of 20 within each cohort.  With 
at least 10 subjects receiving both AMG 890 and statin, there is at least an 89 chance of 
detecting an adverse event with a true AE incidence rate of 20.  With 
 subjects receiving 
AMG 890 there is a 95 chance of detecting an adverse event with a true incidence of 5. 
Summary of Subject Eligibility Criteria:   
Eligibility criteria include: 
Across all study cohorts, women of non-reproductive potential and men, both with age between 
18 and 60 years, inclusive, for cohorts 1 to 5; with age between 18 and 65 years, inclusive, for 
cohorts 6 to 8; and with age between 18 and 70 years, inclusive, for cohort 9.  Subjects 
without any clinically significant abnormality in medical history at the time of randomization. 
For cohorts 1 to 5, plasma Lp(a)  70 nmol/L and  199 nmol/L, at screening  
For cohorts 6 to 9, plasma Lp(a)  200 nmol/L, at screening; for cohorts 6 to 9, at least 6 subjects 
in each cohort must be on a stable dose of statin for at least 6 weeks at the time of enrollment 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 6 of 106 
CONFIDENTIAL 
 
 
Investigational Product: 
Amgen Investigational Product Dosage and Administration:   
A total of 
 subjects will be randomized to receive AMG 890 or equal volume of placebo by SC 
injection as a single dose.  The planned doses for AMG 890 are as follows:  single SC doses of 
3 mg, 9 mg, 30 mg, 75 mg, 225 mg, and 675 mg.  
The planned dose escalation schedule may be modified based on treatment-emergent data 
(safety and/or PD).  Dose adjustments (if any) will be made by Amgen on a treatment cohort and 
not on an individual basis.  Each of cohorts 1 to 5 may be expanded up to 
 subjects, while 
applying the same eligibility criteria and the 3:1 AMG 890 to placebo randomization ratio.  
Control Group:  The control group will be those subjects who will be administered placebo.  
Within each cohort, 2 subjects (or 3 subjects if a cohort consists of 
 subjects) will receive an 
equal volume of placebo.  
Procedures:   
Screening 
After written informed consent has been obtained, all screening procedures and tests that 
establish study eligibility will be performed within 28 days prior to day 1 visit.  Study procedures 
are summarized in the Schedule of Assessments.   
Serious Adverse Events will be collected from the time the Informed Consent Form (ICF) is 
signed. 
Day -3 to Day -1  
Subjects in cohorts 1 to 5 will be considered enrolled once the subject is deemed eligible by the 
investigator based on screening and day -1 assessments. Subjects enrolled will be admitted to 
the research facility at day -1. 
Subjects in cohorts 6 to 9 will be considered enrolled once the subject is deemed eligible by the 
investigator based on screening and the day -3 to -1 assessments. The first 2 subjects enrolled in 
cohort 9 (sentinel pair) will be admitted to the research facility on day -1. Subjects enrolled in 
cohorts 6 to 8 and cohort 9 (other than the sentinel pair) will return to the clinic at day 1.   
Treatment  
After completion of all pre-dose procedures on day 1, subjects will receive their dose of 
AMG 890 or placebo.   
For cohorts 1 to 5, subjects will stay in the research facility for a residency period from day -
1 through day 4.  For cohort 9, sentinel pair subjects will stay in the research facility for a 
residency period from day -1 through day 2.  After completion of day 4 procedures for cohorts 1 to 
5 or completion of day 2 procedures for the cohort 9 sentinel pair, subjects will be discharged and 
will return to the research facility at specified time points as per the schedule of assessments for 
additional collection of blood and urine samples for laboratory assessments, PK and PD 
measurements, and completion of safety assessments through the end of the study.  
For cohorts 6 to 8 and cohort 9 (other than the sentinel pair), subjects will not have a required 
residency period, but will report to the research facility on day 1 for completion of the day 
1 scheduled procedures according to the Schedule of Assessments (Table 4 to Table 9). 
All adverse events (including serious adverse events) and use of concomitant medication will be 
collected throughout the study. 
End of Treatment 
Subjects will return to the research facility for an end of treatment visit according to the schedule 
below. If the subject is required to have a follow-up period due to plasma Lp(a) level, the end of 
study (EOS) visit for the subject will be as described under Follow-up, below. 
 Cohorts 1 and 2 on day 113  
 Cohorts 3 to 7 on day 225 
 Cohorts 8 and 9 on day 365 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 7 of 106 
CONFIDENTIAL 
 
 
The end of treatment visit will complete the subject’s participation in this study unless a follow-up 
is required.  The end of treatment visit for cohorts 8 and 9 will be the same as the end of study 
visit (day 365). 
If there is a clinically significant clinical or laboratory abnormality that requires monitoring, 
subjects will be followed until resolution of the abnormality or until it is considered stable.  
Follow-up  
If at the day 113 visit for cohorts 1 and 2 and the day 225 visit for cohorts 3 to 7, the plasma Lp(a) 
level has not returned to  80 of baseline (mean of screening and day 1 predose), subjects will 
return to the clinical study site for follow-up. Cohorts 1 and 2 will return for safety and exploratory 
PD monitoring visits every 2 weeks until Lp(a) level returns to  80 of baseline.  When the 
protocol amendment 2 is implemented, the follow-up visits will continue approximately monthly, 
as needed, and will include only Lp(a) monitoring as described below for cohorts 3 to 7. 
For cohorts 3 to 7, subjects will return to the clinical study site for Lp(a) monitoring approximately 
monthly starting from when the site has been notified of the Lp(a) follow-up requirement until the 
Lp(a) level returns to  80 of baseline. 
For cohorts 8 and 9, all subjects, regardless of the on-study Lp(a) level, will participate in the 
study through the EOS (day 365). 
For a full list of study procedures, including the timing of each procedure, please refer to 
Section 10 and the Schedule of Assessments (Table 4 to Table 9). 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 8 of 106 
CONFIDENTIAL 
 
 
Statistical Considerations: 
Descriptive statistics will be provided for selected demographics, safety, PK, and PD data. Data 
for subjects receiving placebo will be combined across all cohorts. Descriptive statistics on 
continuous measurements will include means, medians, standard deviations, and ranges, while 
categorical data will be summarized using frequency counts and percentages.  Data will be 
summarized by treatment group and at each time point when samples are collected. 
The number and percent of subjects reporting any treatment-emergent adverse events will be 
tabulated by system organ class and preferred term and will be further classified by relationship 
to treatment.   
For a full description of statistical analysis methods, please refer to Section 13. 
Sponsor:  Amgen Inc. 
 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 9 of 106 
CONFIDENTIAL 
 
 
2. 
Study Design and Treatment Schema 
 
 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 10 of 106 
CONFIDENTIAL 
 
 
3. 
Study Glossary 
Abbreviation or Term Definition/Explanation 
ADA 
anti-drug antibody 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
Apo(a) 
Apolipoprotein(a) 
ApoA1 
apolipoprotein A1 
ApoB 
apolipoprotein B 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUClast 
area under the concentration-time curve from time zero to the last 
quantifiable concentration 
BMI 
body mass index 
BP 
blood pressure 
Cmax 
maximum serum concentration 
CRF 
case report form 
DILI 
drug-induced liver injury 
DLRM 
Dose Level Review Meeting 
DLRT 
Dose Level Review Team 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate  
Enrolled  
Defined as when the subject has fulfilled all conditions to be randomized 
and to receive study drug.  
End of Study for 
Individual Subject 
Defined as the last day that protocol-specified procedures are conducted 
for an individual subject. 
EOS 
end of study - Defined as when the last subject is assessed or receives 
an intervention for evaluation in the study; if the study includes multiple 
parts (eg, safety follow-up or survival assessment), the end of study 
would include these additional parts 
EOT 
end of treatment - defined as the last assessment for the protocol 
specified treatment phase of the study for an individual subject 
FDA 
Food and Drug Administration 
FIH 
first-in-human 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice(s) 
Heart rate 
number of cardiac cycles per unit of time 
HepCAb 
hepatitis C virus antibody 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 11 of 106 
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Abbreviation or Term Definition/Explanation 
HIV 
human immunodeficiency virus 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
INR 
international normalized ratio 
IPIM 
Investigational Product Instruction Manual 
IRB 
institutional review board 
IUD 
intrauterine device 
Lp(a) 
Lipoprotein(a) 
MRSD 
maximum recommended starting dose 
PD 
pharmacodynamic(s) 
PEF 
peak expiratory flow 
PK 
pharmacokinetic(s) 
PR interval 
PR interval is measured from the beginning of the P wave to the 
beginning of the QRS complex in the heart's electrical cycle as 
measured by ECG 
Primary Completion 
Date 
Defined as when the last subject is assessed or receives an intervention 
for the purposes of final collection of data for the primary endpoint(s). 
QRS interval 
QRS interval the interval between the Q wave and the S wave in the 
heart's electrical cycle as measured by ECG; represents the time it takes 
for the depolarization of the ventricles 
QT interval 
QT interval is a measure of the time between the start of the Q wave and 
the end of the T wave in the heart's electrical cycle as measured by 
ECG. 
QTc interval 
QT interval corrected for heart rate  
SAER 
serious adverse event report 
SCR 
Screening 
SiRNA 
small interfering RNA 
SOA 
Schedule of assessments 
Source Data 
Information from an original record or certified copy of the original record 
containing information for use in clinical research.  The information may 
include, but is not limited to, clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation 
of the trial.  Source data are contained in source documents (original 
records or certified copies).  (ICH Guideline [E6]).  Examples of source 
data include Subject identification, Randomization identification, and 
Stratification Value. 
study day 1 
defined as the first day that protocol specified investigational 
product(s)/protocol-required therapies is/are administered to the subject 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 12 of 106 
CONFIDENTIAL 
 
 
Abbreviation or Term Definition/Explanation 
Tmax, tmax 
Time to maximum serum concentration 
TBIL 
total bilirubin 
ULN 
upper limit of normal 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 13 of 106 
CONFIDENTIAL 
 
 
TABLE OF CONTENTS 
1. 
Protocol Synopsis ................................................................................................ 3 
2. 
Study Design and Treatment Schema ................................................................. 9 
3. 
Study Glossary ................................................................................................... 10 
4. 
OBJECTIVES ....................................................................................................... 17 
4.1 
Primary ..................................................................................................... 17 
4.2 
Secondary ................................................................................................. 17 
4.3 
Exploratory ................................................................................................ 17 
5. 
BACKGROUND AND RATIONALE ...................................................................... 17 
5.1 
Disease ..................................................................................................... 17 
5.2 
Amgen Investigational Product Background .............................................. 20 
5.2.1 
Pharmacology ........................................................................... 21 
5.2.2 
Pharmacokinetics ...................................................................... 22 
5.2.3 
Toxicology ................................................................................. 22 
5.3 
Risk Assessment ....................................................................................... 23 
5.4 
Non-Amgen Non-investigational Medicinal Product ................................... 25 
5.5 
Rationale ................................................................................................... 25 
5.5.1 
Dose Rationale .......................................................................... 26 
5.6 
Clinical Hypotheses ................................................................................... 28 
6. 
EXPERIMENTAL PLAN ........................................................................................ 28 
6.1 
Study Design ............................................................................................. 28 
6.2 
Number of Sites ........................................................................................ 30 
6.3 
Number of Subjects ................................................................................... 30 
6.4 
Replacement of Subjects .......................................................................... 30 
6.5 
Estimated Study Duration .......................................................................... 30 
6.5.1 
Study Duration for Subjects ....................................................... 30 
7. 
SUBJECT ELIGIBILITY ........................................................................................ 32 
7.1 
Inclusion Criteria ....................................................................................... 32 
7.2 
Exclusion Criteria ...................................................................................... 33 
8. 
SUBJECT ENROLLMENT .................................................................................... 37 
8.1 
Randomization/Treatment Assignment ...................................................... 38 
8.2 
Site Personnel Access to Individual Treatment Assignments .................... 39 
9. 
TREATMENT PROCEDURES .............................................................................. 39 
9.1 
Classification of Product(s), Medical Device(s), and/or 
Combination Product(s) ............................................................................. 39 
9.2 
Investigational Product .............................................................................. 40 
9.2.1 
Amgen Investigational Product .................................................. 40 
9.2.2 
Dosage, Administration, and Schedule ...................................... 40 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 14 of 106 
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9.2.3 
Dosing Error .............................................................................. 41 
9.2.4 
Dose-cohort Study Escalation and Stopping Rules .................... 41 
9.2.4.1 
Dose Level Review Meetings .................................. 41 
9.2.4.2 
Dose Stopping Rules ............................................... 43 
9.3 
Other Protocol-required Therapies ............................................................ 47 
9.4 
Hepatotoxicity Stopping and Rechallenge Rules ....................................... 47 
9.4.1 
Criteria for Permanent Withholding of Amgen 
Investigational Product and Other Protocol-required 
Therapies due to Potential Hepatotoxicity ................................. 47 
9.5 
Concomitant Therapy ................................................................................ 48 
9.6 
Alcohol and Tobacco Restrictions ............................................................. 48 
9.7 
Exercise .................................................................................................... 49 
9.8 
Product Complaints ................................................................................... 49 
9.9 
Excluded Treatments, Medical Device Use, and/or Procedures 
During Study Period .................................................................................. 49 
10. 
STUDY PROCEDURES ....................................................................................... 51 
10.1 
Schedule of Assessments ......................................................................... 51 
10.2 
General Study Procedures ........................................................................ 60 
10.2.1 
Screening .................................................................................. 61 
10.3 
Description of Study Procedures ............................................................... 63 
10.4 
Pharmacokinetic and Pharmacodynamic Analysis .................................... 70 
10.6 
Biomarker Development ............................................................................ 71 
10.7 
Pharmacogenetic Studies ......................................................................... 71 
10.8 
Sample Storage and Destruction ............................................................... 72 
11. 
WITHDRAWAL FROM TREATMENT, PROCEDURES, AND STUDY .................. 73 
11.1 
Subjects’ Decision to Withdraw ................................................................. 73 
11.2 
Investigator or Sponsor Decision to Withdraw or Terminate 
Subjects’ Participation Prior to Study Completion ...................................... 74 
11.3 
Reasons for Removal From Treatment, or Study ...................................... 74 
11.3.1 
Reasons for Removal From Treatment ...................................... 74 
11.3.2 
Reasons for Removal From Study ............................................. 74 
12. 
SAFETY DATA COLLECTION, RECORDING, AND REPORTING ....................... 74 
12.1 
Definition of Safety Events ........................................................................ 74 
12.1.1 
Adverse Events ......................................................................... 74 
12.1.2 
Serious Adverse Events ............................................................ 75 
12.2 
Safety Event Reporting Procedures .......................................................... 76 
12.2.1 
Adverse Events ......................................................................... 76 
12.2.1.1 
Reporting Procedures for Adverse Events 
That do not Meet Serious Criteria ............................ 76 
12.2.1.2 
Reporting Procedures for Serious Adverse 
Events ..................................................................... 77 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 15 of 106 
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12.2.1.3 
Serious Adverse Events after the Protocol-
required Reporting Period ....................................... 78 
12.2.1.4 
Method of Detecting Adverse Events and 
Serious Adverse Events .......................................... 79 
12.3 
Pregnancy and Lactation Reporting .......................................................... 79 
13. 
STATISTICAL CONSIDERATIONS ...................................................................... 80 
13.1 
Study Endpoints, Analysis Sets, and Covariates ....................................... 80 
13.1.1 
Study Endpoints ........................................................................ 80 
13.1.1.1 
Primary Endpoints ................................................... 80 
13.1.1.2 
Secondary Endpoints .............................................. 80 
13.1.1.3 
Exploratory Endpoints ............................................. 80 
13.1.2 
Analysis Sets ............................................................................. 80 
13.1.2.1 
Safety Analysis Set ................................................. 80 
13.1.2.2 
Pharmacokinetic (PK) Analysis Set ......................... 81 
13.1.2.3 
Pharmacodynamics (PD) Analysis Set .................... 81 
13.1.2.4 
Covariates and Subgroups ...................................... 81 
13.1.3 
Handling of Missing and Incomplete Data .................................. 81 
13.2 
Sample Size Considerations ..................................................................... 81 
13.3 
Access to Individual Subject Treatment Assignments by Amgen 
or Designees ............................................................................................. 81 
13.4 
Planned Analyses ..................................................................................... 82 
13.4.1 
Data Monitoring Committee (DMC), Data Review 
Team (DRT) or Dose Level Review Team (DLRT) .................... 82 
13.4.2 
Primary Analysis ........................................................................ 82 
13.4.3 
Final Analysis ............................................................................ 82 
13.5 
Planned Methods of Analysis .................................................................... 82 
13.5.1 
General Considerations ............................................................. 82 
13.5.2 
Primary Endpoint(s) ................................................................... 83 
13.5.2.1 
Safety Endpoint(s) ................................................... 83 
13.5.3 
Secondary Endpoint(s) .............................................................. 84 
13.5.3.1 
Pharmacokinetics (PK) Analysis .............................. 84 
13.5.3.2 
Pharmacodynamic (PD) Analysis ............................ 84 
13.5.4 
Exploratory Endpoints ............................................................... 84 
13.5.4.1 
Total Cholesterol, Cholesterol Fractions, 
and Apolipoproteins................................................. 84 
13.5.4.2 
Qualitative Assessment of AMG 890 in 
Urine ....................................................................... 85 
14. 
REGULATORY OBLIGATIONS ............................................................................ 85 
14.1 
Informed Consent ...................................................................................... 85 
14.2 
Institutional Review Board/Independent Ethics Committee ........................ 86 
14.3 
Subject Confidentiality ............................................................................... 86 
14.4 
Investigator Signatory Obligations ............................................................. 87 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 16 of 106 
CONFIDENTIAL 
 
 
15. 
ADMINISTRATIVE AND LEGAL OBLIGATIONS .................................................. 87 
15.1 
Protocol Amendments and Study Termination .......................................... 87 
15.2 
Study Documentation and Archive ............................................................ 88 
15.3 
Study Monitoring and Data Collection ....................................................... 88 
15.4 
Investigator Responsibilities for Data Collection ........................................ 89 
15.5 
Language .................................................................................................. 90 
15.6 
Publication Policy ...................................................................................... 90 
15.7 
Compensation ........................................................................................... 91 
16. 
REFERENCES ..................................................................................................... 92 
17. 
APPENDICES ...................................................................................................... 98 
List of Tables 
Table 1.  Planned Treatment by Cohort ........................................................................... 4 
Table 2.  Predicted AMG 890 Human Exposures After Single Dose 
Administration at the Proposed Clinical Doses and Margins 
Relative to Repeat-Dose Cynomolgus Monkey Exposures at 
the NOAEL ............................................................................................. 27 
Table 3.  Cohort Dose Stopping Rules........................................................................... 46 
Table 4.  Schedule of Assessments – Dosing Period for Cohorts 1 to 5 ........................ 52 
Table 5.  Schedule of Assessments – Post-Dosing for Cohorts 1 to 5 ........................... 53 
Table 6.  Schedule of Assessments – Dosing Period for Cohorts 6 and 7 ..................... 55 
Table 7.  Schedule of Assessments – Post-Dosing for Cohorts 6 and 7 ........................ 56 
Table 8.  Schedule of Assessments – Dosing Period for Cohorts 8 and 9 ..................... 57 
Table 9.  Schedule of Assessments – Post-Dosing for Cohorts 8 and 9 ........................ 58 
Table 10.  Serious Adverse Event Reporting via Paper CRF ......................................... 78 
 
List of Appendices 
Appendix A.  Additional Safety Assessment Information ................................................ 98 
Appendix B.  Serious Adverse Event Report Form ...................................................... 100 
Appendix C.  Pregnancy Notification Form .................................................................. 105 
Appendix D.  Lactation Notification Form ..................................................................... 106 
 

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4. 
OBJECTIVES 
4.1 
Primary 
The primary objective of the study is to assess the safety and tolerability of 
AMG 890 when administered subcutaneously (SC) as a single dose to subjects with 
elevated plasma Lipoprotein(a) (Lp[a]). 
4.2 
Secondary 
The secondary objectives are:  
 
To characterize the pharmacokinetics (PK) of AMG 890 when administered 
SC as a single dose to subjects with elevated plasma Lp(a) 
 
To characterize the pharmacodynamics (PD) effects of AMG 890 on  
plasma Lp(a) 
 
To assess the safety, tolerability, and PD effects of AMG 890 when 
administered in combination with statins  
4.3 
Exploratory 
The exploratory objectives are:  
 
To assess the effects of AMG 890 on total cholesterol and cholesterol 
fractions (very-low density lipoprotein cholesterol [VLDL-C], low-density 
lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol  
[HDL-C]), triglycerides, apolipoprotein A1 (ApoA1) and total apolipoprotein B 
(ApoB)  
 
To qualitatively assess AMG 890 urinary excretion following a single SC dose 
administration 
5. 
BACKGROUND AND RATIONALE 
5.1 
Disease 
According to the World Health Organisation (WHO), cardiovascular disease is the 
leading cause of death and disability, accounting for approximately 31 of all deaths 
and 46 of deaths from noncommunicable diseases worldwide (WHO, 2014).  Of the 
deaths related to cardiovascular disease (CVD), approximately 80 are from myocardial 
infarction or stroke (WHO, 2014).  In the United States (US), more than 1 in 3 individuals 
have some form of CVD (Roger et al, 2012), and CVD is the leading cause of death  
(Xu et al, 2016).  The morbidity associated with myocardial infarction and stroke 
continues to be serious and multifaceted, and reducing this morbidity is an important 

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treatment goal.  Each year, it is estimated that 935,000 Americans have a myocardial 
infarction or coronary death, 155,000 have a silent first myocardial infarction, 
610,000 have a new stroke (ischemic or hemorrhagic), and 185,000 have a recurrent 
stroke (Mozaffarian et al, 2015).  After a cardiovascular (CV) event, patients may 
struggle to regain their independence and suffer from both acute and long term 
reductions in health-related quality of life, including diminished mobility and functionality, 
as well as increased anxiety, depression, fatigue, and sexual dysfunction  
(Mendes de Leon et al, 1998; Simpson and Pilote, 2003; Brink et al, 2005;  
Schweikert et al, 2009; Bach et al, 2011). 
The advances in identifying modifiable risk factors for cardiovascular disease (CVD), 
including smoking, hypertension, diabetes mellitus, obesity and dyslipidemias have 
allowed the development of evidence-based guidelines and therapeutic measures that 
significantly contributed to reduction of CVD burden and mortality (Egan et al, 2016).  
Notwithstanding, for more than 30 of all deaths occurring in the USA, CVD is still listed 
as the underlying cause.  
While lipid lowering therapy research has historically focused on lowering LDL-C to 
reduce CV risk (Robinson et al, 2005), compelling evidence from epidemiologic studies 
characterizes elevated plasma lipoprotein(a) (Lp(a)) as a strong independent risk factor 
for atherosclerotic CVD (Danik et al, 2006; Bennet et al, 2008; Kamstrup et al, 2008; 
Emerging Risk Factors Collaboration, 2009; Dubé et al, 2012; Jacobson, 2013; 
Kamstrup et al, 2013; Willeit et al, 2014; Kassner et al, 2015). Further, Mendelian 
randomization studies (Ohro-Melander, 2015; Nordestgaard and Langsted, 2016) and an 
expert working group (Averna et al, 2017) suggest a causal link between elevated 
plasma Lp(a) levels and CVD.  
Lp(a) has been strongly associated with the prevalence of coronary heart disease (CHD) 
(Hopewell et al, 2011) independently of ethnicity (Virani et al, 2012), LDL-C level 
(Gurdasani et al, 2012) and other traditional CV risk factors such as age, sex, smoking 
status, blood pressure, body mass index, total plasma cholesterol and history of 
diabetes (Erqou et al, 2009).  Plasma Lp(a) levels have also been positively associated 
with CHD severity, as measured by the number of occluded coronary vessels  
(Habib et al, 2009), or the Global Registry of Acute Coronary Events (GRACE) risk score  
(Guler et al, 2013).  Furthermore, Lp(a) apheresis was shown to stabilize coronary 
lesions, thus resulting in coronary atherosclerosis regression in chronic coronary disease 
patients (Safarova et al, 2013).  In terms of clinical outcomes, Lp(a) concentrations at 

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1 year can predict the risk for future cardiovascular heart disease (CHD) and CV events 
in patients with stable CHD as shown in the Long-Term Intervention with Pravastatin in 
Ischaemic Disease (LIPID) study (Nestel et al, 2013).  Additionally, elevated Lp(a) 
concentrations were associated with worse prognosis (ie, cardiac death and non-fatal 
MI) in CHD patients followed-up for a period of an average of 4 years (Kwon et al, 2015).  
An independent positive relationship of Lp(a) with sudden cardiac death has been found 
(Kunutsor et al, 2016) with a further trend towards an inverse association between Lp(a) 
and total mortality being also reported (Onat et al, 2016).  In this context, elevated Lp(a) 
levels were associated with an increased risk for HF in the general population as seen in 
the Copenhagen City Heart Study and the Copenhagen General Population Study  
(Katsiki et al, 2016; Kamstrup and Nordestgaard, 2016).  Despite some conflicting 
results reporting the association of Lp(a) on stroke prevalence (Unal et al, 2013), 
previous studies and meta-analyses reported that higher Lp(a) concentrations were 
related to the presence and severity of ischemic stroke (Smolders et al, 2007; 
Nave et al, 2015); these associations were greater in men compared with women 
(Li et al, 2014), more pronounced in blacks (Boden-Albala et al, 2010), and events tend 
to be more severe in younger patients (ie,  55 years) compared with older ones 
(Nave et al, 2015).  Hyperliporoteinemia (a) has been also linked to ischemic strokes in 
children and adolescents (Sultan et al, 2014; Akshintala et al, 2015).  Finally, Lp(a) has 
been implicated in the development and progression of carotid artery disease 
(Ronald et al, 2011; Gardener et al, 2009), with the prevalence and severity of peripheral 
artery disease, and with the prevalence and progression of abdominal aortic aneurysm 
(Schillinger et al, 2002; Takagi et al, 2009; Stather et al, 2014; Poller et al, 2015;  
Kotani et al, 2017). 
Studies show that either statins (Tziomalos et al, 2009; Nordestgaard et al, 2010; 
Khera et al, 2014; Kei et al, 2013) or ezetimibe (Moutzouri et al, 2013) have little impact 
on plasma Lp(a).  On the other hand, nicotinic acid (niacin), besides exerting positive 
effects on cholesterol and triglycerides reduces Lp(a), with high doses (2-4 g) reducing it 
significantly (Carlson et al, 1989; Goldberg et al, 2000).  Whether this holds true for 
individuals with high levels of Lp(a) has not been shown as yet.  A meta-analysis of the 
beneficial effects of nicotinic acid on cardiovascular events (Bruckert et al, 2010) did not 
discriminate whether lowering plasma Lp(a) might have contributed to the positive 
results or not.  More recently, proprotein convertase subtilisin/kexin type 9 (PCSK9) 
inhibitors have been able to demonstrate reductions greater than 25 in plasma Lp(a) 

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concomitant with intensive LDL-C reductions (Desai et al, 2013; Raal et al, 2014; 
Gaudet et al, 2017; Sabatine et al, 2015).  Interestingly, in patients with LDL-receptor 
negative homozygous familial hypercholesterolemia, evolocumab was, as expected, 
ineffective in reducing LDL-C, but Lp(a) was lowered by 20 (Raal et al, 2015).  While 
the role of the LDL receptor in Lp(a) clearance is unclear, the upregulation of other 
receptors potentially involved in Lp(a) clearance may explain these findings, eg, the 
VLDL-receptor that mediates the uptake of Lp(a) into macrophages, an increased 
catabolic fraction rate or, a reduced synthesis (Desai et al, 2013).  Another therapeutic 
approach to patients with very high plasma Lp(a) levels has been lipoprotein apheresis.  
Apheresis has been in clinical use for decades (Abel et al, 1914; Vogt, 2017) and 
reduces apoB100 containing lipoproteins (namely LDL-C and Lp[a]).  A single treatment 
reduces both by about 60–70, followed by a rapid return to baseline, making weekly 
treatment sessions necessary (Thompson et al, 2010).  Retrospective evaluations of 
clinical data and analyses of the German Lipoprotein Apheresis Registry (GLAR) show 
that cardiovascular events were reduced significantly after establishing a regular 
apheresis schedule (von Dryander et al, 2013; Rosada et al, 2014; Schettler et al, 2015).  
A non-randomised prospective observational multicenter study in high-risk patients, 
showed a reduction of major adverse cardiac events and of major adverse non-cardiac 
events after 2 (Leebmann et al, 2013) as well as after 5 years (Roesler et al, 2016) of 
lipid apheresis therapy. 
Although significant advances have been made in the understanding of the molecular, 
metabolic, epidemiological, pathobiological, clinical and analytic aspects of Lp(a), there 
is no definitive evidence that reduction in Lp(a) will impact cardiovascular risk  
(Ellis et al, 2017).  Intensive pharmacologic lowering of high Lp(a) concentrations via 
alternative approaches must be investigated in order to demonstrate protection against 
cardiovascular disease (Witztum and Ginsberg, 2016). 
5.2 
Amgen Investigational Product Background  
Small interfering (also called short interfering) RNA (siRNA) molecules are synthetic 
RNA duplexes that disrupt the expression of specific genes with complementary 
nucleotide sequences by degrading messenger RNA (mRNA) after transcription, 
preventing translation (Agrawal et al, 2003). 
Once inside a cell, the antisense (guiding) strand of the siRNA double strand is loaded 
into an RNA-induced silencing complex (RISC), while the other 1 is degraded.  The 
loaded RISC is then directed to an mRNA which has a perfectly complementary 

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sequence of the guide strand.  Argonaute proteins present in RISC cleave the target 
mRNA, which is then further degraded by exonucleases.  Dissociation of the target 
mRNA strand from RISC after the cleavage allow more mRNA to be silenced, enabling 
continual degradation of target mRNA and leading to efficient and potent gene silencing 
(Agrawal et al, 2003). 
AMG 890 is an siRNA designed to target the mRNA transcribed from the LPA gene, 
which encodes apo(a) protein in liver cells.  Thus, AMG 890 is able to specifically knock 
down hepatic Lp(a) production.  
The siRNA molecule is formed by the hybridization of 2 partially complementary 
single-strands of ribonucleic acid (RNA) with 21 consecutive complementary base pairs.  
Nucleotide and sugar-phosphate backbone chemical modifications, such as 2-Fluro 
bases or phosphorodiester linkages, reduce off-target effects, and enhance metabolic 
stability and potency for SC administration.  The sense strand sequence contains a  
tri-N-acetylgalactosamine (NAG) moiety conjugated to its 5’ end, which directs trafficking 
of AMG 890 to hepatocytes.  The triantennary NAG binds the asialoglycoprotein receptor 
(ASGPR) with high affinity (Tanowitz et al, 2017).  ASGPR is an endocytic scavenger 
receptor which clears asialoglycoproteins from the circulation and it is almost exclusively 
expressed on liver cells (Grewal, 2010). 
Refer to the specific section of the AMG 890 Investigator Brochure (IB) for additional 
information related to the physical, chemical, and pharmaceutical properties and 
formulation(s). 
5.2.1 
Pharmacology 
AMG 890 is a synthetic, siRNA NAG-conjugated, liver-targeted therapy that inhibits 
apo(a) translation and Lp(a) production. 
Amgen’s nonclinical program showed that AMG 890 can achieve a sustained  80 
reduction in plasma Lp(a) and is suitable for monthly SC administration. The studies 
supporting this conclusion included efficacy data collected from transgenic mice and 
cynomolgus monkeys demonstrating that Lp(a) levels can be specifically targeted with 
AMG 890 to inhibit apo(a) translation. 
A summary of the AMG 890 nonclinical pharmacology studies is as follows: 
 
In double transgenic mice expressing the human apo(a) transgene and 
human ApoB, AMG 890 reduced Lp(a) and apo(a) levels by  80 for 
36 days following administration of a single subcutaneous dose of 1 mg/kg. 
Levels of Lp(a) remained below pre-dose values at day 36. 

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 
In lean cynomolgus monkeys, a single 2 mg/kg dose of AMG 890 significantly 
reduced Lp(a) and apo(a) levels by  80 for up to 6 weeks. A recovery was 
observed thereafter with serum Lp(a) levels starting to rise after day 60 but 
they remained lower than pre-dose values up until day 100 of the study.  
 
A dose ranging study in lean cynomolgus monkeys showed a 
dose-dependent reduction in serum Lp(a) levels after treatment with 
AMG 890 at 0.1, 1, 3 or 10 mg/kg for 80 days although serum Lp(a) did not 
significantly differ between the 3 mg/kg and 10 mg/kg dose groups.  Plasma 
AMG 890 PK levels were rapidly cleared within a range of 2 to 29 days after 
dosing, while suppression of Lp(a) levels persisted for up to 80 to 140 days.  
The effect of AMG 890 on the reduction of serum Lp(a) levels after a second 
dose was also evaluated and indicated similar Lp(a) reductions as observed 
after the first dose. 
5.2.2 
Pharmacokinetics 
AMG 890 was administered subcutaneously to non-human primates at a single dose of 
0.1, 1, 3 and 10 mg/kg. AMG 890 pharmacokinetics was linear over the dose range of 
0.1 to 10 mg/kg SC; the dose normalized AUClast and Cmax were within 3-fold.  Mean 
terminal half-life (t1/2) values after SC administration ranged from 3.13 to 5.09 hours.   
5.2.3 
Toxicology 
The Sprague-Dawley rat and cynomolgus monkey were selected as the toxicology 
species for AMG 890.  The subcutaneous (SC) route of administration was chosen 
based on the intended clinical route of administration.  The monkey is a pharmacologic 
relevant animal model, but the rat does not make apo(a) so is not. 
In in vitro secondary pharmacodynamic studies, AMG 890 did not cause complement 
activation in human serum or cytokine stimulation or platelet activation in human whole 
blood. 
In monkey safety pharmacology assessments, there were no AMG 890-related 
qualitative or quantitative electrocardiographic (ECG) changes or changes in blood 
pressure, heart rate, body temperature, respiratory rate or neurological function at up to 
150 mg/kg, the highest dose level tested. 
AMG 890 was well tolerated in the rat and monkey toxicology studies.  All dose levels in 
the monkey toxicology studies reduced serum Lp(a) by  90.  In the GLP rat and 
monkey 57-day toxicology studies, AMG 890 was administered at 10, 30 and 150 mg/kg 
every 4 weeks on days 1, 29 and 57 (necropsy on day 58).  At 10 mg/kg, there were no 
AMG 890-related changes in the rat.  In the monkey at 10 mg/kg, the only 
AMG 890-related changes were vacuolation of Kupffer cells of the liver and vacuolation 
of macrophages in the subcutis at the injection site and in the lymph nodes; these 

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phagocytic cells contained basophilic material consistent with test article uptake 
(Frazier, 2014; Henry et al, 2008).  Other AMG 890-related changes that occurred either 
at higher dose levels or a more frequent dosing regimen (eg, weekly in the exploratory 
studies) included transient, minimal increases in serum alanine aminotransferase (ALT), 
and minimal to mild increases in serum alkaline phosphatase (ALP) and bilirubin.  
Additional AMG 890-related changes occurring at doses greater than 10 mg/kg or with 
increased frequency of dosing, included the presence of basophilic granules in the 
proximal tubular cells of the kidney, and liver changes consisting of hepatocellular 
vacuolation, increased single cell necrosis and increased mitoses of hepatocytes in the 
rat and hepatocellular hypertrophy with cytoplasmic rarefaction in the monkey.  The only 
AMG 890-related finding considered secondary to silencing of LPA gene expression was 
reduction in serum Lp(a) in monkeys.  None of the AMG 890-related changes were 
considered adverse due to their low severity and absence of light microscopic evidence 
of tissue injury.  All the AMG 890-related changes are anticipated to be reversible 
(recovery phases of the GLP rat and monkey studies were ongoing at the time of 
IND/CTA filing).  In both the rat and monkey, the no adverse effect level (NOAEL) for the 
GLP toxicology studies was determined to be 150 mg/kg, the highest dose evaluated. 
5.3 
Risk Assessment 
This is the first study in human subjects with AMG 890. The assessment of potential side 
effects is based on the pre-clinical studies conducted to date (Section 5.2.3) and the 
literature.  Overall, safety data from the nonclinical studies support the proposed doses 
and dosing schedule in this FIH study. 
Earlier therapeutic antisense oligonucleotide molecules relied on numerous 
phosphorothioate backbone modifications to increase metabolic stability and increase 
gene silencing effectiveness (Chi et al, 2017).  However, such modifications have also 
been shown to elicit strong platelet activation, aggregation and thrombus formation 
(Flieri, 2015). The affinity of the phosphorothioate backbone for various cellular proteins 
also affects certain pathways, such as inhibition of the intrinsic coagulation pathway and 
activation of the alternative pathway of complement (Farman and Kornbrust, 2003; 
Henry et al, 2002).  The most concerning proinflammatory changes seen in animal 
models include glomerulonephritis and vasculitis.  These effects seem to relate to high 
doses and plasma exposures (Engelhardt et al, 2015).  AMG 890 is a double strand 
siRNA of a novel generation, which contains a majority of phosphodiester backbone 
linkages and 2’-fluoro and 2’-metoxy nucleotide chemical modifications.  In general, 

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these modifications provide enhanced resistance to degradation, lower toxicity and 
increased hybridization affinity (Judge et al, 2006; Wu et al, 2014; Crooke et al, 2016). 
Furthermore, the tri-N-acetylgalactosamine (NAG) moiety conjugated to 1 of the siRNA 
strands directs trafficking of AMG 890 to hepatocytes and mediates its internalization via 
the high affinity ASGPR, which may allow the use of lower effective doses and lower 
exposures (Chen et al, 2018).  Therefore, the risks associated with earlier antisense 
oligonucleotides such as platelet and complement activation, and proinflammatory 
changes are considered low for AMG 890.  In addition, organ toxicity related to 
intracellular accumulation and off-target effects of the siRNA are not expected at the 
doses administered. (Chi et al, 2017; Janas et al, 2018).  Injection site reactions, 
hypersensitivity reactions, including anaphylaxis, and development of anti-drug 
antibodies (ADAs) are considered potential risks.   
To minimize risk, a sentinel dosing strategy will be adopted for cohorts 1 to 5, and safety 
data will be reviewed in an accumulative manner during dose level review meetings 
(DLRM) prior to progressing to the next dose level in the study. Specific cohort dose 
stopping rules are specified in this protocol (Section 9.2.4). All study subjects will be 
closely monitored and frequently assessed for adverse events throughout the study.  
The laboratory safety monitoring includes evaluation of routine chemistry (including 
bicarbonate/CO2 and liver function tests), hematology, and coagulation assessments.  
Lactate will be measured reflexively in the presence of an anion gap metabolic acidosis.  
Potential anaphylactic reactions will be assessed by Sampson criteria (Sampson et al, 
2006).  If Sampson criteria are positive, the potential anaphylactic reaction will be 
confirmed by measuring tryptase in blood plasma within 30 minutes of symptoms, if 
feasible.  Bioanalytical testing for anti-AMG 890 antibodies will be conducted only if there 
are unexpected PD findings or a safety signal in this study or future studies that warrants 
further investigation. Additional blood samples may be obtained to rule out anti-
AMG 890 antibodies during the study. 
New onset or worsening neuropathy were reported during the clinical development 
program of an siRNA for the treatment of hereditary transthyretin amyloidosis.  
Neuropathy events have not been described in other recent human studies of 
antisense-based therapies (Chi et al, 2017), and safety pharmacology non-human 
primate studies did not disclose any evidence of neurologic effect of AMG 890 at all 
tested doses up to 150 mg/kg, the highest tested dose.  However, clinical neurologic 
assessments are part of the safety evaluations throughout this study.  If treatment 

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emergent neuropathy is suspected, dosing will be suspended and subjects will be 
directed to a specialist for further evaluation. 
Low levels of Lp(a) have been associated with increased prevalence of type 2 diabetes 
mellitus (reviewed in Paige et al, 2017).  There is uncertainty about the strength of this 
association, and available evidence does not suggest a causal link (Ye et al, 2014).  
Some evidence suggests that the hyperinsulinemia present in type 2 diabetes may lead 
to lower Lp(a) levels (Purnell et al, 1995; Neele et al, 1999).  Fasting blood glucose will 
be monitored throughout the study.  
The proposed risk assessment for the study is in accordance with the requirements of 
regulatory guidelines and strategies to identify and mitigate risks for FIH clinical trials 
with investigational medicinal products.  
Refer to the AMG 890 IB, Section 10, for additional information. 
5.4 
Non-Amgen Non-investigational Medicinal Product  
For cohorts 6 to 9, at least 6 subjects in each cohort are required to be on a stable dose 
of statin for at least 6 weeks prior to enrollment as defined in subject eligibility 
(Section 7.1).  Specific product, dose and dosage schema should be defined by the 
subject’s medical background and follow subject’s health care provider instructions.  
For additional information, refer to the manufacturer package insert. 
Statins are not provided or reimbursed by Amgen (except if required by local regulation).  
5.5 
Rationale 
A substantial body of evidence demonstrates the clear association between higher 
plasma Lp(a) levels and increased risk for cardiovascular atherosclerotic disease 
development.  Furthermore, Mendelian randomization studies, experimental data and 
results from apheresis cohorts suggest a causal role for Lp(a) and vascular disease.  
Nevertheless, there is yet a lack of evidence demonstrating that reduction in plasma 
Lp(a) is able to cause a significant reduction in cardiovascular risk.  Currently available 
lipid-reducing medications, such as statins or PCSK9 inhibitors, are able to promote 
limited lowering of Lp(a).  Therefore, the demonstration of effective and safe lowering of 
high Lp(a) concentrations by the inhibition of apo(a) translation through siRNA 
technology may provide a novel tool serving patients against cardiovascular 
atherosclerotic disease. 

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5.5.1 
Dose Rationale 
The starting dose and safety margins for this study were calculated based on the no 
observed adverse effect levels (NOAELs) determined in the 57-day GLP repeat-dose rat 
and cynomolgus monkey (NHP) toxicology studies [Q4W(x3) dosing, Section 5.2.3] and 
the predicted Lp(a) changes in humans, based on K-PD modeling analysis using single 
and multiple-dose PK and Lp(a) data in cynomolgus monkeys administered 
AMG 890 SC (Section 5.2.2).  The NOAEL in the repeat-dose rat and NHP studies were 
both 150 mg/kg.  The maximum recommended starting dose (MRSD), using the 
methodology described by the Food and Drug Administration Guidance for Starting Dose 
Estimation, “Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for 
Therapeutics in Adult Healthy Volunteers” (US FDA, 2005) for calculating the human 
equivalent dose on a body surface area basis, was calculated to be 145 mg using a 
default safety factor of 10 and the rat NOAEL, as this was the lower value between the 
2 species (290 mg based on cynomolgus NOAEL).  Therefore, the proposed starting 
dose of 3 mg is 486-fold lower than the MRSD based on scaling using body surface area 
and assuming a human body weight of 60 kg.   
Similarly, based on the rat and cynomolgus NOAEL of 150 mg/kg, the proposed starting 
dose of 3 mg is 3000-fold lower than the MRSD on a dose (mg/kg)-basis, assuming a 
human body weight of 60 kg.  These calculated margins are conservative as only a 
single starting dose will be given, and the NOAEL was determined from Q4W (x3) 
repeat-dose studies over a 57-day period.   
The selection of the doses being evaluated in this study are also supported by the 
calculated exposure safety margins derived from the 57-day GLP rat and monkey 
toxicology studies and the model-predicted human AMG 890 PK and Lp(a) profiles.  
Results from the population PK model indicate that the predicted mean human PK Cmax 
and AUC values in the highest dose cohort (675 mg) are 2260 ng/mL and 
43800 hr*ng/mL, respectively.  These predicted human exposures are at least 11-fold 
and 21-fold lower than those observed at the NOAEL in the 57-day GLP rat and NHP 
toxicology studies, respectively (Table 2).  In addition, the predicted human exposures at 
the proposed starting dose of 3 mg in humans are anticipated to be at least 2850-fold 
and 4660-fold lower than the NOAEL exposures in rat and NHPs, respectively.  
Therefore, the 3 mg starting dose was selected based on the conservative safety 
margins, as well as the low anticipated biological effect on Lp(a) suppression to support 

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evaluation of the AMG 890 dose-response relationship in subjects with elevated Lp(a) 
levels.  
Table 2.  Predicted AMG 890 Human Exposures After Single Dose 
Administration at the Proposed Clinical Doses and Margins Relative to 
Repeat-Dose Cynomolgus Monkey Exposures at the NOAEL 
Dose 
(mg) 
Predicted Exposure 
Exposure Margins 
Cmaxa 
AUClasta 
Cmax 
(ng/mL) 
AUClast  
 (ng*hr/mL) 
Rat 
Cyno 
Monkey 
Rat 
Cyno  
Monkey 
3 
10.0 
163 
4420 
4660 
2850 
5620 
9 
30.1 
527 
1470 
1550 
880 
1730 
30 
100 
1890 
442 
466 
245 
483 
75 
251 
4820 
176 
186 
96.3 
190 
225 
753 
14600 
58.7 
62.0 
31.8 
62.5 
675 
2260 
43800 
19.6 
21.0 
10.6 
20.8 
AUClast – area under the concentration-time curve from time zero to the last quantifiable concentration;   
Cmax – maximum observed concentration 
a Rat day 29 exposure at 150 mg/kg: Cmax  44200 ng/mL, AUC  464000 ng*hr/mL; 
Monkey day 29 exposure at 150 mg/kg: Cmax  46600 ng/mL, AUC  913000 ng*hr/mL  
Given the hepatic site target and rapid elimination of AMG 890 from systemic circulation, 
there is limited clinical relevance in correlating transient AMG 890 levels with the 
long-acting effects of Lp(a) reduction.  Therefore, a K-PD model was also developed to 
predict Lp(a) levels in humans based on NHP efficacy data, and were simulated at the 
proposed clinical doses.  Assuming similar potency in Lp(a) lowering effect between 
NHP and humans, the results from the K-PD model analysis indicate that for the 
proposed single starting dose of 3 mg, the maximum Lp(a) reduction from baseline is 
predicted to be 39.  In addition, a single dose of 75 mg is predicted to achieve Lp(a) 
reduction levels  80 from baseline.  These simulation results support the dose range 
to be evaluated in this study. 
Subjects will be assessed across the proposed range of dose levels to evaluate the 
magnitude and durability of Lp(a) reduction, to determine if AMG 890 PK and PD 
translates from animal to humans, and to assess the safety and tolerability of the drug. 

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The proposed dose range for cohorts 1 to 9 (3, 9, 30, 75, 225, and 675 mg) allows for 
reasonable step increases in the dose escalation between the proposed starting dose 
and the highest dose.  The doses were selected to allow for round mL injection volumes 
to circumvent any potential dosing errors due to extra dilution steps, as well as to 
evaluate specific dose levels (eg, 30 mg, 75 mg) that are anticipated to approach or 
achieve target Lp(a) reduction levels ( 80 decrease from baseline) in the majority of 
subjects based on the K-PD Lp(a) simulation results.   
In cohorts 1 to 7 of this study, considerable variability has been observed in PK and 
Lp(a) response between low and high baseline Lp(a) subjects. Given this variability, the 
225 mg and 675 mg cohorts in high baseline Lp(a) subjects (cohorts 8 and 9) will allow 
for more intensive and robust PK and Lp(a) data evaluation to support broader options 
for AMG 890 Ph 3 dose and regimen selection. The 675 mg dose (cohort 9) is also 
anticipated to provide a wide range of exposures with minimal overlap in exposure 
distributions across subjects with high baseline Lp(a) (9 fold increase from 9 mg in 
cohort 6 to 675 mg in cohort 9), and to provide additional safety information at a higher 
dose and with longer durations of Lp(a) suppression.  
Finally, for cohorts 1 to 5 and cohort 9, a sentinel dosing strategy ensures that only 
1 subject will receive active drug at the start of each dose level and after being deemed 
safe by the investigator, the same dose will be administered to the remaining cohort 
subjects.   
5.6 
Clinical Hypotheses 
AMG 890 will be safe and well tolerated when administered subcutaneously as a single 
dose to subjects with elevated plasma Lp(a). 
The PK and/or PD data from this study will support the selection of dose and frequency 
of AMG 890 administration for future multi-dose trials.  
6. 
EXPERIMENTAL PLAN 
6.1 
Study Design 
This is a FIH randomized, double-blind, placebo-controlled, single ascending dose 
(SAD) study in subjects with elevated plasma Lp(a).  AMG 890 will be evaluated as SC 
injections in adult subjects.  Approximately 
 subjects will enroll in 9 SAD cohorts. As 
described in Table 1, for each cohort, subjects will be randomized to receive 
AMG 890 or placebo SC in a 3:1 ratio.  As of Amendment 6, enrollment in cohorts 1 to 8 

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is closed.  There were no safety concerns noted that would preclude enrollment into the 
higher dose cohorts, 8 and 9. 
As described in the Eligibility Criteria (Section 7), cohorts 1 to 5 will enroll subjects with 
plasma Lp(a) between 70 nmol/L and 199 nmol/L, inclusive.  Cohorts 6 to 9 will enroll 
subjects with plasma Lp(a) equal to or greater than 200 nmol/L.  In cohorts 6 to 9, at 
least 6 subjects in each cohort will be on a stable dose of statin. 
For cohorts 1 to 5, and cohort 9, the first 2 enrolled subjects will be randomized in a 
1:1 ratio (sentinel pair) and will be dosed on the same day at the same study site.  Within 
the pair and while maintaining treatment blind, 1 subject will receive AMG 890 and the 
other subject will receive placebo. If deemed safe by the investigator after review of 
available safety data at least 24 hours after the sentinel pair is dosed, the same dose will 
be administered to the remaining subjects of the cohort. 
Enrollment into cohorts 1 to 5 will be staggered. Escalation to the next cohort will occur 
after the assessment of the safety and tolerability of each dose level.  The 
recommendation to dose escalate will be based on the blinded review of safety data 
(including but not limited to vital signs, ECGs, treatment emergent adverse events, and 
clinical laboratory results) during the DLRM.  Within each cohort, the safety data will be 
assessed after all 8 subjects have been enrolled and have been followed for 15 days.  
Emerging PD data may be reviewed in a blinded fashion at the DLRM as the data 
become available. The Dose Level Review Team (DLRT) will be responsible for dosing 
recommendations, which may include escalation to the next planned dose, adding 
additional cohorts, escalation to an intermediate dose (a dose lower than the next 
planned dose), de-escalation to a lower dose; continuation, delay, or termination of 
dosing; or repetition or expansion of a cohort.   
Enrollment into cohorts 5 to 7 can be initiated after the dose regimen in cohorts 1 to 
4 has been found by the DLRT to be safe and reasonably tolerated based on available 
safety data through study day 15 of cohort 4.  Enrollment in cohort 8 is closed.  
As of Amendment 6, enrollment in Cohorts 1 to 8 is closed.  There were no safety 
concerns noted that would preclude enrollment into the higher dose cohorts, 8 and 9. 
For cohort 9, the same randomization ratio (3:1) of AMG 890 to placebo will apply. 
In consideration of the DLRT recommendations and review of emerging safety and/or 
PD data, dose adjustments (if any) will be made by Amgen on a treatment cohort basis 
and not on an individual basis.   

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The study endpoints are defined in Section 13.1 
6.2 
Number of Sites 
This study will be conducted at 3 to 10 sites in the US and Australia.  Additional sites in 
the same or in other countries may be added as necessary to complete enrollment. 
Sites that do not enroll subjects within 1 month of site activation for enrollment may be 
closed. 
6.3 
Number of Subjects 
Participants in this clinical investigation are referred to as “subjects.” 
The sample size is based on practical considerations.  Sample size is discussed in 
Section 13.2.  It is anticipated that an approximate total of 
 subjects in a total of 
9 cohorts will be enrolled in this study.  
6.4 
Replacement of Subjects 
In the event subjects are enrolled, but are withdrawn prior to IP administration, a 
replacement subject may be enrolled in the subject’s place.  
Additionally, subjects who are withdrawn from the study (Section 11) may be replaced at 
the discretion of the Amgen Medical Monitor in consultation with the investigator or 
designee.  The replacement subject will be assigned to receive the identical treatment as 
the replaced subject, but will be assigned a replacement number associated with this 
new record.  All data from the replaced subjects will be captured, identified, and kept in 
the clinical trial database. 
6.5 
Estimated Study Duration 
6.5.1 
Study Duration for Subjects 
Subject participation will vary according to enrollment scheme. The duration of the 
follow-up period for each cohort was defined based on the simulation results from the 
population K-PD model describing the Lp(a) response to AMG 890 administration 
developed based on 57-day GLP repeat-dose cynomolgus monkey toxicology and 
PK/PD studies (Section 5.2.1).  Data suggest that the lengths of study participation 
proposed will allow plasma Lp(a) levels to return at least to 80 of the baseline levels for 
each subject after administration across the proposed AMG 890 clinical doses. 
For cohorts 1 and 2, planned subject participation will last up to 141 days, including a 
28-day screening period prior to investigational product (IP) administration and on-study 
period (through the end of treatment visit) lasting 113 days.  

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For cohorts 3 to 7, planned subject participation will last up to 253 days, including a 
28-day screening period prior to IP administration and on-study period (through the end 
of treatment visit) lasting 225 days.  
For cohorts 8 and 9, planned subject participation will last up to 393 days, including a 
28-day screening period prior to IP administration and on-study period (through the end 
of study visit) lasting 365 days.  
For cohorts 1 to 7, the end of treatment visit will complete the subject’s participation in 
this study unless a follow-up period is required.  If there is a clinically significant clinical 
or laboratory abnormality that requires monitoring, subjects will be followed until 
resolution of the abnormality or until it is considered stable.   
For cohorts 1 to 9, if at the end of treatment visit, the plasma Lp(a) level has not returned 
to  80 of baseline (mean of screening and day 1 predose), the follow-up period will be 
required.  
The end of treatment visit for cohorts 8 and 9 will be the same as the end of study visit 
(day 365). 
Subjects in cohorts 1 and 2 will return to the clinical study site approximately every 
2 weeks until the Lp(a) level returns to  80 of baseline.  Assessments during the 
follow-up period will include physical examination; vital signs; and collection of blood 
samples for chemistry, hematology, lipid, Lp(a), and biomarker development.  When the 
protocol amendment 2 is implemented, the follow-up visits will continue approximately 
monthly, as needed, and will include only Lp(a) monitoring as described below for 
cohorts 3 to 7. 
Subjects in cohorts 3 to 7 will return to the clinical study site for Lp(a) monitoring 
approximately monthly starting from when the site has been notified of the Lp(a) 
follow-up requirement until the Lp(a) level returns to  80 of baseline. 
Lp(a) assessments in the follow-up period will be performed by Medpace.  
Primary Completion:  The primary completion date is defined as the date when the last 
subject is assessed or receives an intervention for the final collection of data for the 
primary endpoint(s), for the purposes of conducting the primary analysis, whether the 
study concluded as planned in the protocol or was terminated early.   
The primary completion date is the date when the last subject has completed the 
assessments for day 365 of cohort 9. 

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If the study concludes prior to the primary completion date originally planned in the 
protocol (ie, early termination of the study), then the primary completion date will be the 
date when the last subject is assessed or receives an intervention for evaluation in the 
study (ie, last subject last visit). 
End of Study:  The end of study date is defined as the date when the last subject is 
assessed or receives an intervention for evaluation in the study (ie, last subject last 
visit), following any additional parts in the study (eg, follow-up period; long-term 
follow-up), as applicable.  
7. 
SUBJECT ELIGIBILITY 
Investigators are expected to maintain a screening log of all potential study candidates.  
Before any study-specific activities/procedure, the appropriate written informed consent 
must be obtained (see Section 14.1).  
7.1 
Inclusion Criteria 
A subject that has provided written informed consent may be eligible for inclusion in this 
study only if the following criteria are met:  
101 
Men and women with ages between 18 and 60 years old, inclusive, for cohorts 
1 to 5; and with ages between 18 and 65 years old, inclusive, for cohorts 6 to 8; 
and with ages 18 and 70 years old, inclusive, for cohort 9. 
102 
Plasma Lp(a): 
 
 70 nmol/L and  199 nmol/L for cohorts 1 to 5  
 
 200 nmol/L for cohorts 6 to 9 
103 
For cohorts 6 to 9, subjects who are on statin must be on a stable dose of the 
same statin for at least 6 weeks prior to enrollment, and plan to remain on a 
stable dose (ie, no change in medication or dosage) for the duration of the study 
104 
Body mass index (BMI)  18 and  32 kg/m2, at screening, for cohorts 1 to 8; 
BMI  18 and  40 kg/m2, at screening, for cohort 9. 

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105 
Women must be of non-reproductive potential: 
 
Postmenopausal defined as: 
 
Age  55 years with cessation of menses for 12 months or more, OR 
 
Age  55 years and no spontaneous menses for at least 12 months, 
AND with a follicle-stimulating hormone level  40 IU/L or according to 
the definition of “postmenopausal range” for the laboratory involved, 
OR 
 
History of hysterectomy, OR 
 
History of bilateral oophorectomy 
106 
Men must agree to practice an acceptable method of effective birth control while 
on study or for 90 days after receiving investigational product (for subjects who 
withdraw prior to end of study).  Acceptable methods of effective birth control 
include sexual abstinence; vasectomy; or a condom with spermicide (men) in 
combination with barrier methods (diaphragm, cervical cap or cervical sponge), 
hormonal birth control or IUD (female partner of male participant) 
107 
Men must be willing to abstain from sperm donation while on study or for 90 days 
after receiving investigational product (for subjects who withdraw prior to end of 
study) 
7.2 
Exclusion Criteria 
A subject will not be eligible for inclusion in this study if any of the following criteria apply: 
201 
Currently receiving treatment in another investigational device or drug study, or 
less than 30 days or 5 half-lives (whichever is longer), since ending treatment on 
another investigational device or drug study(s) prior to receiving the first dose of 
investigational product 
202 
Women who are lactating/breastfeeding or who plan to breastfeed while on 
study or through 90 days after receiving investigational product (for subjects 
who withdraw prior to end of study) 
203 
Men with partners who are pregnant or planning to become pregnant while the 
subject is on study or through 90 days after receiving investigational product. 
204 
Positive pregnancy test at screening or at any pre-dose time point. 
205 
History or evidence of a clinically significant disorder, condition or disease  
(eg, symptomatic heart failure, documented previous myocardial infarction in the 
previous 12 months, active infection requiring antimicrobial therapy that will not 
be completed prior to randomization, or major surgery in the previous 3 months 
of screening) that, in the opinion of the investigator or Amgen Medical Monitor, if 
consulted, would pose a risk to subject safety or interfere with the study 
evaluation, procedures or completion.  Exceptions include: 

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 
Subjects with controlled and stable arterial hypertension, with a 
systolic blood pressure [SBP]  150 mmHg or diastolic blood pressure 
[DBP]  90 mmHg at screening and day -1 for cohorts 1 to 5 or 
day -3 to -1 for cohorts 6 to 9, with no change in medication and 
dosage for at least 6 weeks prior to enrollment, and expected to 
remain on this dose and medication for the entire duration of the 
study.  Subjects not on medication are excluded from the study if 
systolic blood pressure [SBP]  150 mmHg or diastolic blood pressure 
[DBP]  90 mmHg at screening or day -1 for cohorts 1 to 5 or day -
3 to -1 for cohorts 6 to 9.  If the initial BP is elevated, the reading may 
be repeated again at least 15 minutes later and the lower of the 
2 readings may be used. 
 
For cohorts 6 to 9, at least 6 subjects in each cohort with diagnosis of 
hyperlipidemia on treatment with a stable dose of the same statin 
(with or without concomitant ezetimibe) for at least 6 weeks prior to 
enrollment, and expected to remain on this dose and medication for 
the entire duration of the study 
 
For cohort 9, diagnosis of diabetes is not excluded provided 
diabetes is well-controlled according to treating physician’s 
assessment and discretion, and the subject is on stable doses of 
diabetes medications for at least 6 weeks prior to enrollment 
206 
Planned elective surgery to occur at any time from screening visit through the 
end of treatment visit for cohorts 1 to 7, and through the end of study visit for 
cohorts 8 and 9 
207 
Estimated glomerular filtration rate (eGFR)  60 mL/min/1.73 m2, as defined by 
the local laboratory, at screening  
208 
Triglycerides  5.65 mmol/L (ie, 500 mg/dL) at screening  
209 
History or clinical evidence of liver disfunction, including total bilirubin  upper 
limit of normal (ULN) or ALT or AST  1.1 ULN of the laboratory’s reference at 
screening or at day -1 for cohorts 1 to 5, or day -3 to -1 for subjects not on statin 
in cohorts 6 to 9.  For subjects on stable dose of statin in cohorts 6 to 9, ALT or 
AST  1.5 ULN of the laboratory’s reference at screening or at day -3 to -1.  
210 
History or clinical evidence of bleeding diathesis or any coagulation disorder, 
including prothrombin time (PT), activated partial thromboplastin time (aPTT), 
thrombin time (TT), or platelet count outside of the laboratory’s normal reference 
range at screening  
211 
For cohorts 1 to 8, history or clinical evidence of diabetes mellitus, including a 
fasting glucose  125 mg/dL (6.9 mmol/L) at screening 
212 
History or clinical evidence of peripheral neuropathy 
213 
History of malignancy of any type, other than in situ cervical cancer or surgically 
excised non-melanomatous skin cancers occurring more than 5 years prior to 
randomization 
214 
Positive results for human immunodeficiency virus (HIV) antibodies, hepatitis B 
surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus 

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ribonucleic acid (RNA).  For hepatitis C, hepatitis C antibody (HepCAb) testing is 
done at screening, followed by hepatitis C virus RNA by polymerase chain 
reaction (PCR) if hepatitis C antibody is positive. 
215 
Subject was previously enrolled in this study or has been previously exposed to 
AMG 890 
216 
Use of any herbal medicines, vitamins or supplements known to affect lipid 
metabolism (eg, fish oils  4000 mg/day, red yeast rice extract), within 30 days 
prior to dosing on day 1  
217 
All herbal supplements and nutritional supplements (with the exception of those 
known to affect lipid metabolism, which are excluded as above) taken within 
30 days prior to dosing on day 1 and continued use, if appropriate, must be 
reviewed and approved by the investigator and Amgen Medical Monitor.  Written 
documentation of this review and Amgen acknowledgement is required for 
subject participation. 
218 
Use of any over-the-counter medications within 14 days or prior to dosing on 
day 1.  Exceptions are listed below: 
 
Acetaminophen (paracetamol), up to 2 grams per day for analgesia 
 
For cohorts 6 to 9, use of low-dose acetylsalycilic acid (up to 162.5 mg 
daily) is allowed, provided it is stable for at least 6 weeks prior to 
enrollment and is planned to be the same dose for the duration of the 
study 
219 
Use of any prescription medications within 14 days or 5 half-lives (whichever is 
longer), prior to dosing on day 1.  Exceptions are listed below: 
 
Hormone replacement therapy (eg, estrogen, thyroid) provided subject is 
stable on replacement therapy 
 
Medication for the management of arterial hypertension, including but not 
limited to angiotensin-converting enzyme inhibitors, angiotensin-receptor 
blockers, calcium channel blockers, beta blockers, or low-dose thiazides, 
provided it is stable (ie, no change in drug or dose) for at least 6 weeks 
prior to enrollment 
 
For cohorts 6 to 9, use of antiplatelet therapy (low-dose acetylsalicylic 
acid, clopidogrel or ticagrelor) is allowed, provided subjects have been on 
a stable dose for at least 6 weeks prior to enrollment and plan to be on 
the same dose for the duration of the study 
 
For cohorts 6 to 9, at least 6 subjects in each cohort must be on a stable 
dose of statin (ie, no change in drug or dose) for at least 6 weeks prior to 
enrollment and plan to be on the same dose for the duration of the study 
 
For cohorts 6 to 9, use of ezetimibe is allowed, provided subjects have 
been on a stable dose for at least 6 weeks prior to enrollment and plan to 
be on the same dose for the duration of the study 
 
For cohorts 6 to 9, medication used to manage chronic conditions not 
excluded by other exclusion criteria, provided subjects have been on a 
stable dose for at least 6 weeks prior to enrollment and plan to be on the 
same dose for the duration of the study. Medication must be reviewed 

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and approved by the investigator, and acknowledged by the Amgen 
Medical Monitor.  Written documentation of this review and Amgen 
acknowledgement is required for subject participation. 
 
For cohort 9, medication used to manage diabetes not excluded by 
other exclusion criteria, provided subjects have been on a stable 
dose for at least 6 weeks prior to enrollment and plan to be on the 
same dose for the duration of the study.  Medication must be 
reviewed and approved by the investigator, and acknowledged by 
the Amgen Medical Monitor.  Written documentation of this review 
and Amgen acknowledgement is required for subject participation. 
220 
Currently receiving apheresis as lipid reducing therapy 
221 
Subject has known sensitivity to any of the products or components to be 
administered during dosing 
222 
Has donated or lost  500 mL of blood or plasma within 60 days of day 1 
223 
A corrected QT interval (QTc) at screening of  450 msec in men or  470 msec 
in women or history of long QT syndrome 
224 
History of substance abuse within 12 months before screening 
225 
Positive test for drugs of abuse at screening or on day -1 for cohorts 1 to 5 or 
day -3 to -1 for cohorts 6 to 9 
226 
Use of nicotine or tobacco containing products (including but not limited to: 
snuff, chewing tobacco, cigars, cigarettes, electronic cigarettes, pipes, or 
nicotine patches) during the 6 months before screening  
227 
Unwilling or unable to abstain from nicotine or tobacco containing products 
(including but not limited to: snuff, chewing tobacco, cigars, cigarettes, electronic 
cigarettes, pipes, or nicotine patches) throughout the course of the study  
228 
Subject is unwilling or unable to limit alcohol consumption throughout the course 
of the study: 
 
Alcohol is prohibited 48 hours prior to admission to the research facility  
(day -1 for cohorts 1 to 5 and the sentinel pair of cohort 9; day 1 for 
cohorts 6 to 9 (other than the sentinel pair) and during the residency 
periods, and 
 
Alcohol consumption is limited to no more than 1 drink per day for 
females and 2 drinks per day for males for the duration of the study 
(1 drink is equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt 
liquor, 5 ounces of wine or 1.5 ounces of 80 proof distilled spirits) 
229 
Subject will not be available for protocol-required study visits or procedures 
(including the research facility residency period), to the best of the subject’s and 
investigator’s knowledge 
230 
Any other condition that might reduce the chance of obtaining data required by 
the protocol (eg, known poor compliance) or that might compromise the ability to 
give informed consent 

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8. 
SUBJECT ENROLLMENT 
Before subjects begin participation in any study-specific activities and procedures, 
Amgen requires a copy of the site’s written institutional review board or independent 
ethics committee (IRB/IEC) approval of the protocol, informed consent form, and all 
other subject information and/or recruitment material, if applicable (see Section 14.2).  
All subjects and/or legally acceptable representatives must personally sign and date the 
informed consent form before commencement of study-specific activities/procedures.  A 
subject is considered enrolled when study entry criteria are met.  The investigator (or 
designee) will document the enrollment decision and date in the screening log, subject’s 
medical record and in the enrollment case report form (CRF). 
Each subject who enters into the screening period for the study (defined as the time at 
which the subject signs the informed consent) receives a unique subject identification 
number before any study procedures are performed.  The subject identification number 
will be assigned manually. The subject identification number must remain constant 
throughout the entire clinical study; it must not be changed after initial assignment.   
The unique subject identification number will consist of 11 digits.  The first 3 digits will 
represent the last 3 digits of the protocol number (ie, 544).  The next 5 digits will 
represent the country code and site number (eg, 66001) and will be identical for all 
subjects at the site.  The next 3 digits will be assigned in sequential order as subjects 
are screened (eg, 001, 002, 003).  To illustrate, the first subject to enter screening at site 
66001 will receive the number 54466001001.  This number will be used to identify the 
subject throughout the clinical study and must be used on all study documentation 
related to that subject.   
Subjects who do not meet the eligibility criteria within the 28-day screening period will 
not be eligible for enrollment.  Subjects may be re-screened up to 3 times upon 
discussion with and approval by the Amgen Medical Monitor.  The subject must be 
re-consented if a re-screen occurs outside the 28-day screening period.  Re-screen 
subjects will repeat all screening procedures.   
Subjects not meeting study entry criteria will be documented as screen failures.  
Subjects may be eligible to begin treatment once all screening tests and procedures are 
completed and results indicate that all eligibility criteria are met.  A site representative 
will complete and send the enrollment eligibility worksheet to the sponsor or designee.  

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The Amgen representative will acknowledge receipt and send confirmation of cohort, 
dose level assignment, and randomization number. 
8.1 
Randomization/Treatment Assignment 
An Amgen representative will notify the site(s) in writing when a cohort is open to screen 
new subjects. As of Amendment 6, enrollment in Cohorts 1 to 8 is closed. There were no 
safety concerns noted that would preclude enrollment into the higher dose cohorts, 8 
and 9. 
On day -1 for cohorts 1 to 5 or day -3 to -1 for cohorts 6 to 9 (or up to day 1), eligible and 
enrolled subjects will be randomized to a treatment assignment in a double-blind 
fashion.  Within each cohort, subjects will be randomly assigned in a 3:1 ratio to receive 
either AMG 890 or placebo.  They will be assigned a randomization number based in 
sequential order in which they qualified to be randomized.  Subjects will be considered 
randomized once a unique subject randomization number has been assigned.  For 
cohorts 1 to 5, dosing should occur within 24 hours of randomization; for cohorts 6 to 9, 
dosing should occur within 3 days ( 72 hrs) of randomization.  If dosing cannot occur 
within the window for randomization, the Medical Monitor may be contacted to approve 
dosing outside the window (up to an additional 24 hours after randomization).  The 
randomization date is to be documented in the subject’s medical record and enrollment 
eCRF. 
For cohorts 1 to 5, and cohort 9, the first 2 subjects (sentinel pair) will be randomized.  
One subject will receive AMG 890 and 1 subject will receive placebo.  Subjects will be 
monitored for at least 24 hours before the remaining subjects in the cohort are dosed.  
Remaining subjects may be subsequently dosed provided there are no safety or 
tolerability concerns as assessed by the Principal Investigator. 
For cohorts 6 to 9, at least 6 subjects in each cohort will be on a stable statin for 6 weeks 
prior to enrollment.  Randomization in cohorts 6 to 8 will not use a sentinel dosing 
strategy.  For cohorts 6 and 7, once 6 subjects not on a stable dose of statin are enrolled 
into cohort 6, then 6 subjects not on a stable dose of statin may be enrolled into 
cohort 7.  Similarly, once 6 subjects on a stable dose of a statin are enrolled into 
cohort 6, then 6 subjects on a stable dose of a statin may be enrolled into cohort 7.   
Enrollment in cohort 8 is closed, supported by the approval to dose escalate to the 
225 mg dose of cohort 5 after the DLRT found that the previous dose regimen in cohorts 

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1 to 4 was safe and reasonably tolerated.  In addition, the dose in cohort 5 was well 
tolerated with no safety signals observed in low Lp(a) level subjects. 
Cohort 9 may be enrolled concurrently with cohort 8 or after cohort 8 has completed 
enrollment.  If cohort 9 and cohort 8 are fully enrolled and there are additional subjects 
who have passed screening visit procedures, these subjects may be allowed to be 
enrolled and randomized in cohort 9 with approval of Amgen. 
Amgen will provide a randomization schedule to the unblinded pharmacist at the site.  
The unblinded pharmacist will prepare all treatments accordingly.  Subjects 
randomization will occur in accordance with the randomization schedule.  
8.2 
Site Personnel Access to Individual Treatment Assignments 
The subjects and the investigative site staff, except for the unblinded pharmacist, will be 
blinded to treatment assignment.  
A subject’s treatment assignment should only be unblinded when knowledge of the 
treatment is essential for the further management of the subject which may potentially 
impact the safety of subjects currently enrolled or subjects in subsequent cohorts.  
Unblinding at the study site for any other reason will be considered a protocol deviation.  
The investigator is strongly encouraged to contact the Amgen Study Manager before 
unblinding any subject’s treatment assignment, but must do so, in writing, within 
1 working day after the event.   
Treatment assignments will be unblinded after final database lock.  After final database 
lock and receipt of written authorization from Amgen to unblind, the unblinded 
pharmacist will release the specified unblinded pharmacy records to site staff designated 
to enter the subject treatment into each subject’s Unblinded Investigational Product 
Administration CRF. 
9. 
TREATMENT PROCEDURES 
9.1 
Classification of Product(s), Medical Device(s), and/or 
Combination Product(s) 
The Amgen Investigational Product(s) used in this study include: AMG 890 and placebo.   
The Investigational Product Instruction Manual (IPIM), a document external to this 
protocol, contains detailed information regarding the storage, preparation, destruction, 
and administration of AMG 890 and placebo.  

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9.2 
Investigational Product 
All investigational product(s) will be administered at the research facility by the 
investigator or designate.  
A physician must be immediately available at the time of administration of Investigational 
Product in case of complication(s).  
9.2.1 
Amgen Investigational Product 
AMG 890 will be distributed using Amgen clinical study drug distribution procedures.  For 
cohorts 1 to 7, AMG 890 will be provided in a 6 mL sterile vial filled with 1 mL deliverable 
volume of 150 mg/mL AMG 890.  For cohorts 8 and 9, AMG 890 will be provided in a 
2 mL sterile vial filled with 1 mL deliverable volume of 75 mg/mL AMG 890. 
For cohorts 1 to 7, placebo will be presented in 5 mL sterile vials filled with 1 mL 
deliverable volume; for cohorts 8 and 9, placebo will be provided in 2 mL sterile vials 
filled with 1 mL deliverable volume. Placebo will be stored under the same conditions as 
AMG 890. 
9.2.2 
Dosage, Administration, and Schedule 
Subjects will receive AMG 890 or volume-matched placebo, respectively, via blinded SC 
injection in the abdomen according to the Schedule of Assessments (SOA) (Table 4, 
Table 5, Table 6, Table 7, Table 8, and Table 9).  AMG 890 administration time should 
be chosen carefully to avoid any interference or inconvenience with time point of safety 
assessments or PK/PD measurements.  
For cohorts 1 to 5, and the sentinel pair of cohort 9, subjects will be admitted to the 
clinical site on day –1.  Subject residency is approximately 5 days for cohorts 1 to 5, and 
is approximately 3 days for the sentinel pair of cohort 9.  Cohorts 6 to 9 (other than the 
sentinel pair) will report to the clinical site on day 1 and will not have a required 
residency period.  At the Investigator’s discretion, subjects may stay at the clinic 
overnight from the check-in visit and/or day 1 for subject’s convenience.  Subjects will be 
randomized in a 3:1 ratio to receive AMG 890 or placebo, respectively, via SC injection, 
according to the Schedule of Assessments (Table 4 to Table 9). 
A single dose will be administered on day 1 following all required pre-dose procedures 
and confirmation of enrollment eligibility.  For cohorts 1 to 5, and cohort 9, subjects will 
be dosed in a staggered fashion where 2 subjects will be dosed initially (randomized to 
AMG 890 or placebo in a 1:1 ratio), followed by the remaining subjects after a minimum 
of 24 hours and provided there are no safety or tolerability concerns as assessed by the 

Product:  AMG 890 
Protocol Number:  20170544 
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Page 41 of 106 
CONFIDENTIAL 
 
 
principal investigator.  For cohorts 6 to 8, subjects may be dosed concurrently (see 
Section 8.1 for details). 
The planned dose levels are, in milligrams (mg): 3, 9, 30, 75, 225 and 675. 
Across all cohorts, the date, time, package lot number, and quantity administered are to 
be recorded on the individual subject’s Investigational Product Administration eCRF prior 
to database lock. 
The Investigator or study physician must be available when the subject receives the 
initial dose of AMG 890 for immediate intervention in case of complication(s).  The 
subject’s residency may be extended at the discretion of the investigator.  During the 
residency periods, an immediately accessible emergency room with resuscitation 
equipment must be available.  
Prior to discharge, clinical assessments per SOA (Table 4 to Table 9) will be completed. 
9.2.3 
Dosing Error  
The effects of overdose/underdose of this product are not known.  In case of dosing 
error, consultation with the Amgen medical monitor as soon as possible is recommended 
to discuss subject management and prompt reporting of clinically apparent or laboratory 
adverse events possibly related to the dosing error.  Subjects should be monitored 
closely until symptom resolution.  Adverse events should be reported and documented 
according to instructions available in Section 12.  
9.2.4 
Dose-cohort Study Escalation and Stopping Rules 
The planned doses of AMG 890 are shown in Table 1.  
The dosing schedule is described by the Schema in the Protocol Synopsis. 
9.2.4.1 
Dose Level Review Meetings 
Dose level review meetings will be held to review subject data and monitor safety before 
escalation to the next higher dose cohort.  The DLRT members will be composed of the 
investigators actively enrolling subjects at the time of the meeting (ie, have subjects in 
screening or already enrolled), the unblinded Amgen Medical Monitor, Amgen Global 
Safety Officer (GSO) or designated safety scientist, Clinical Study Manager, and 
Biostatistics representative.  Additional members may be added as needed (eg, clinical 
pharmacologist).  The DLRT voting members will include the investigator(s), Amgen 
Medical Monitor and Amgen GSO or designees.  The DLRT is responsible for dosing 
recommendations, which may include escalation to the next planned dose, escalation to 

Product:  AMG 890 
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Date:  07 December 2021 
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an intermediate dose (a dose lower than the next planned dose), de-escalation to a 
lower dose; continuation, delay, or termination of dosing; or repetition or expansion of a 
cohort.  Clear stopping rules will be followed, and ad hoc DLRMs will be held if 
necessary.  All available study data, including demographics, medical history, 
concomitant medications, adverse events, electrocardiograms (if applicable), vital signs, 
and clinical laboratory test results will be reviewed.  If available, emerging PK and PD 
data may also be reviewed in a manner that does not unblind individual treatment 
assignments.   
Except for the unblinded Amgen Medical Monitor who will review data on an ongoing 
basis throughout the duration of study in an unblinded manner, data will be reviewed 
blinded (ie, treatment assignment will not be revealed) unless unblinding is deemed 
necessary for the review team to make dosing decisions.  If deemed necessary, 
unblinding will be performed to assist dose change recommendations. 
Investigators who are not actively enrolling subjects at the time of the DLRM will not 
participate in the DLRM. They will be informed of the decisions of the DLRT. 
For cohorts 1 to 5, and cohort 9, escalation to a higher dose cohort will only proceed 
when the previous dose regimen has been found to be safe and reasonably tolerated 
based on available safety data through study day 15 for all subjects and upon 
unanimous recommendation of the DLRT.  Available data from previous cohorts will also 
be considered.  The next cohort will be open for enrollment immediately following the 
DLRT recommendation and Amgen decision.   
Enrollment into cohorts 6 to 8 will be initiated after cohort 4 dose level has been found by 
the DLRT to be safe and reasonably tolerated based on available safety data through 
study day 15.  Cohorts 5, 6 and 7 may be enrolled in parallel.  For cohorts 6 and 7, 
eligible subjects will be first enrolled into cohort 6 and then into cohort 7.  Cohort 8 will 
be enrolled after implementation of this protocol amendment.  Enrollment into cohort 
9 can be initiated after the preceding dose regimen has been found by the DLRT to be 
safe and reasonably tolerated based on available safety data through at least study day 
15 of cohort 5. See Section 8.1 for details.  
The planned dose escalation schedule may be modified based on treatment-emergent 
data (safety and/or PD).  Dose adjustments, if any, will be made by Amgen on a 
treatment cohort and not on an individual basis. 

Product:  AMG 890 
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The review of available safety data and dosing change decisions will be documented in 
meeting minutes.  Amgen will issue a written notification of a dose change decision to 
investigators. 
9.2.4.2 
Dose Stopping Rules 
Determination of the severity of adverse events will be as follows: mild (aware of sign or 
symptom, but easily tolerated), moderate (discomfort enough to cause interference with 
usual activity), and severe (incapacitating with inability to work or do usual activity). 
Recommendations will be made by the DLRT to stop or modify dosing if suspected 
adverse drug reactions and/or changes in safety data (including but not limited to vital 
signs, electrocardiogram (ECG), or clinical laboratory results) are observed and these 
changes pose a significant health risk.  The unblinded Amgen Medical Monitor will 
review data in an unblinded manner on an ongoing basis, and may suspend dosing and 
convene a DLRM at any time based on emerging safety data.  In addition, dose 
escalation will be stopped or modified as shown in Table 3. 
Clinically or medically significant suspected adverse drug reactions, and serious adverse 
events considered to be related to study procedures will be followed until resolved or 
considered stable.  
Administration of any drug by any route can cause anaphylaxis.  Anaphylaxis is a 
life-threatening medical emergency in which prompt intervention is critical.  Therefore, in 
the case of a suspected event, monitoring, preferably continuous hemodynamic 
monitoring, is essential. Monitoring should include blood pressure, continuous pulse 
rate, pulse oximetry, and electrocardiographic monitoring.  Intravenous access should be 
obtained as soon as possible. These measures should be used to monitor response to 
therapy and direct subsequent interventions.  The decision to initiate specific treatment 
for anaphylaxis, which may include the prompt administration of parenteral epinephrine, 
requires clinical judgment, should not be delayed by other procedures, and should follow 
the World Allergy Organization Anaphylaxis Guidelines (Ronna et al, 2014) or the local 
institutional practices.   
Any subject with suspected anaphylactic reaction should be evaluated using the clinical 
criteria for diagnosis of anaphylaxis below (Sampson et al, 2006).  If the criteria for 
anaphylaxis is met, a blood tryptase test must be collected as soon as the effective 
treatment has been rendered.  Treatment administration for a suspected anaphylaxis 
event should not be delayed by any clinical or laboratory test collection. The event and 

Product:  AMG 890 
Protocol Number:  20170544 
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CONFIDENTIAL 
 
 
test results should be documented in the subject’s medical record and reported as an 
adverse event as appropriate (Section 12). 

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Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosa, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula), and at 
least 1 of the following 
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced 
peak expiratory flow [PEF], hypoxemia) 
b. Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction 
(eg, hypotonia [collapse], syncope, incontinence) 
 
2. Two or more of the following that occur rapidly after exposure to a likely allergen 
(minutes to several hours): 
c. Involvement of the skin or mucosa (eg, generalized hives, itch, swollen  
lips-tongue-uvula) 
d. Respiratory compromise (eg, dyspnea, bronchospasm, stridor, reduced PEF, 
hypoxemia) 
e. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, 
incontinence) 
f. 
Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 
 
3. Reduced BP after exposure to an allergen (minutes to several hours): 
g. Systolic BP  90 mmHg or greater than 30 decrease from that person’s baseline 
 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
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Table 3.  Cohort Dose Stopping Rules 
Scenario 
Action 
Any occurrence of a 
suspected adverse 
drug reaction classified 
as moderate in 2 or 
more subjects in the 
same cohort 
 
Stop dosing additional subjects and convene DLRM (if event 
occurs outside of the regularly scheduled DLRM) 
 
Review adverse event and all relevant safety data for evidence 
of relationship to treatment and clinical or medical significance 
 
Consider unblinding as appropriate1 
 
Upon unanimous decision by the DLRT members, 1 of the 
following recommendations may be made: 
o 
stop enrollment of the cohort (if applicable)  
o 
resume enrollment of the cohort as planned  
o 
resume enrollment of the cohort at a lower dose  
o 
expand the cohort at the same dose  
o 
add a lower dose cohort to the study  
o 
escalate to an intermediate dose (a dose lower than the 
next planned dose)  
o 
escalate to the next planned dose 
Any occurrence of a 
suspected adverse 
drug reaction classified 
as severe  
 
Stop dosing additional subjects and convene DLRM (if event 
occurs outside of the regularly scheduled DLRM) 
 
Review adverse event and all relevant safety data for evidence 
of relationship to treatment and clinical or medical significance 
 
Consider unblinding as appropriate1 
 
If the adverse event is determined by unanimous decision of the 
DLRT members to be related to study drug (after breaking of the 
study blind) and clinically or medically significant, no further 
doses should be administered at this dose and no dose 
escalation should proceed.  Enrollment of the study may 
continue at a lower dose or a lower dose cohort may be added 
to the study. 
 
Otherwise (ie, if considered not related to study drug or not 
clinically relevant), upon unanimous decision of the DLRT 
members, 1 of the following recommendations may be made: 
o 
resume enrollment of the cohort as planned 
o 
resume enrollment of the cohort at a lower dose 
o 
expand the cohort at the same dose 
o 
add a lower dose cohort to the study 
o 
escalate to an intermediate dose (a dose lower than the 
next planned dose) 
o 
escalate to the next planned dose 
1 A subject’s treatment assignment should only be unblinded when knowledge of the treatment is essential 
for the further management of the subject, or may impact the safety of subjects currently enrolled, or 
subjects in subsequent cohorts. 
The Amgen Medical Monitor will be unblinded to treatment assignment throughout the duration of the study. 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 47 of 106 
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9.3 
Other Protocol-required Therapies 
For cohorts 6 to 9, at least 6 subjects in each cohort are required to be on a stable dose 
of the same statin through EOS as defined in subject eligibility (Section 7). 
Specific product, dose and dosage regimen should be defined by subject’s health care 
provider, based on the individual medical background.  Subject must be on stable dose 
of the same drug for 6 weeks prior to enrollment.  
For additional information, refer to the manufacturer package insert. 
Information about therapy name, indication, dose, unit, frequency, route, start date, and 
stop date should be collected in the concomitant medication eCRF. 
Protocol required therapies that are commercially available are not provided or 
reimbursed by Amgen (except if required by local regulation).  The investigator will be 
responsible for obtaining supplies of these protocol-required therapies.  
9.4 
Hepatotoxicity Stopping and Rechallenge Rules 
Subjects with abnormal hepatic laboratory values (ie, ALP, AST, ALT, TBIL) and/or 
international normalized ratio (INR) and/or signs/symptoms of hepatitis (as described 
below) may meet the criteria for withholding or permanent discontinuation of Amgen IP 
or other protocol-required therapies (as specified in the FDA Guidance for Industry 
Drug-induced Liver Injury:  Premarketing Clinical Evaluation, July 2009). 
9.4.1 
Criteria for Permanent Withholding of Amgen Investigational 
Product and Other Protocol-required Therapies due to Potential 
Hepatotoxicity 
Investigational product and other protocol-required therapies, as appropriate, should be 
discontinued permanently and the subject should be followed according to the 
recommendation in the Appendix A (Additional Safety Assessment Information) for 
possible drug-induced liver injury (DILI), if ALL the criteria below are met: 
 
TBIL  2x upper limit of normal (ULN) or INR  1.5 
 
AND increased AST or ALT from the relevant baseline value as specified below:  
Baseline AST or ALT value 
AST or ALT elevation 
 ULN 
 3x ULN 

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 
AND no other cause for the combination of the above laboratory abnormalities is 
immediately apparent; important alternative causes for elevated AST/ALT and/or 
TBIL values include, but are not limited to: 
o Hepatobiliary tract disease 
o Viral hepatitis (eg, Hepatitis A/B/C/D/E, Epstein-Barr Virus, cytomegalovirus, 
herpes simplex virus, varicella, toxoplasmosis, and Parvovirus) 
o Right sided heart failure, hypotension or any cause of hypoxia to the liver 
causing ischemia.   
o Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and 
dietary supplements, plants and mushrooms 
o Heritable disorders causing impaired glucuronidation (eg, Gilbert’s Syndrome, 
Crigler-Najjar syndrome) and drugs that inhibit bilirubin glucuronidation  
(eg, indinavir, atazanavir) 
o Alpha-1 antitrypsin deficiency 
o Alcoholic hepatitis 
o Autoimmune hepatitis  
o Wilson’s disease and hemochromatosis 
o Nonalcoholic Fatty Liver Disease including Steatohepatitis (NASH)  
o Non-hepatic causes (eg, rhabdomylosis, hemolysis) 
9.5 
Concomitant Therapy 
Throughout the study, Investigators may prescribe any concomitant medications or 
treatments deemed necessary to provide adequate supportive care except for those 
listed in Section 12. 
Concomitant therapies are to be collected from informed consent through the end of 
treatment visit for cohorts 1 to 7, and through the EOS for cohorts 8 and 9.  Collect 
therapy name, indication, dose, unit, frequency, route, start date, and stop date.  
Concomitant medications will not be collected after the end of treatment visit for any 
subjects with additional safety follow-up in cohorts 1 to 7. 
9.6 
Alcohol and Tobacco Restrictions 
Subjects must limit alcohol consumption throughout the course of study participation 
(refer to Exclusion Criteria, Section 7.2).  Alcohol is prohibited for approximately 
48 hours prior to admission to the research facility (day -1 for cohorts 1 to 5 and the 
sentinel pair of cohort 9; day -3 to -1 for cohorts 6 to 9 [other than the sentinel pair]), and 
throughout the residency period.  Alcohol consumption is limited to no more than 
2 drinks per day for males and 1 drink per day for females for the duration of the study 
(1 drink is equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces 
of wine or 1.5 ounces of 80 proof distilled spirits).  

Product:  AMG 890 
Protocol Number:  20170544 
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Only non-nicotine or non-tobacco using subjects should be enrolled.  Subjects should 
not have used any nicotine or tobacco containing products within the last 6 months prior 
to screening.  Subjects must abstain from nicotine or tobacco containing products 
(including but not limited to:  snuff, chewing tobacco, cigars, cigarettes, electronic 
cigarettes, pipes, or nicotine gum or nicotine patches) throughout the screening period 
and for the duration of the study. 
9.7 
Exercise 
Subjects should abstain from strenuous exercise for 72 hours before each blood 
collection for clinical laboratory tests.  Subjects may participate in light recreational 
activities during study. 
9.8 
Product Complaints 
A 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(s) or device(s) after it is released for distribution to market or 
clinic by either Amgen or by distributors and partners for whom Amgen manufactures the 
material.   
This includes any drug(s), device(s), or combination product(s) provisioned and/or 
repackaged or modified by Amgen.  Drug(s) or device(s) includes investigational 
product, AMG 890 or placebo.   
Any product complaint(s) associated with the investigational product supplied by Amgen 
are to be reported according to the instructions provided in the IPIM. 
9.9 
Excluded Treatments, Medical Device Use, and/or Procedures 
During Study Period  
Use of any over-the-counter or prescription medications within 14 days or 5 half-lives 
(whichever is longer), prior to dosing on day 1 and during the study is not permitted, 
unless to treat an adverse event.  Additionally, use of any herbal medicines, vitamins or 
supplements known to affect lipid metabolism (eg, fish oils  4000 mg/day, red yeast rice 
extract), within 30 days prior to dosing on day 1 and for the duration of the study is not 
permitted.   
Accepted exceptions are: 
 
Acetaminophen (or paracetamol) up to 2 grams per day for analgesia 
 
Hormone replacement therapy (eg, estrogen, thyroid) provided subject is 
stable on replacement therapy 

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CONFIDENTIAL 
 
 
 
Medication for the management of arterial hypertension, including but not 
limited to angiotensin-converting enzyme inhibitors, angiotensin-receptor 
blockers, calcium channel blockers, beta blockers, or low-dose thiazides, 
provided it is stable (ie, no change in drug or dose) for at least 6 weeks 
prior to enrollment, as defined in Exclusion Criterion 219 (Section 7.2) 
 
For cohorts 6 to 9, at least 6 subjects in each cohort must be on a stable 
dose of the same statin for at least 6 weeks prior to enrollment, and plan 
to remain on a stable dose (ie, no change in medication or dosage) for 
the duration of the study, as defined in Inclusion Criterion 103  
(Section 7.1) 
 
For cohorts 6 to 9, ezetimibe is permitted as long as subjects have been 
on a stable dose for at least 6 weeks prior to enrollment, and plan to 
remain on the same dose for the duration of the study, as defined in 
Exclusion Criterion 219 (Section 7.2) 
 
For cohorts 6 to 9, antiplatelet therapy (low-dose acetylsalycilic acid, 
clopidogrel or ticagrelor) is permitted as long as subjects have been on a 
stable dose for at least 6 weeks prior to enrollment, and plan to remain on 
the same dose for the duration of the study, as defined in Exclusion 
Criterion 219 (Section 7.2) 
 
For cohorts 6 to 9, medication used to manage chronic conditions not 
excluded by exclusion criteria, provided subjects have been on a stable 
dose for at least 6 weeks prior to enrollment and plan to be on the same 
dose for the duration of the study. Medication must be reviewed and 
approved by the investigator, and acknowledged by the Amgen Medical 
Monitor.  Written documentation of this review and Amgen 
acknowledgement is required for subject participation, as defined in 
Exclusion 219 (Section 7.2) 
 
For cohort 9, medication used to manage diabetes not excluded by 
other exclusion criteria, provided subjects have been on a stable 
dose for at least 6 weeks prior to enrollment and plan to be on the 
same dose for the duration of the study.  Medication must be 
reviewed and approved by the investigator, and acknowledged by 
the Amgen Medical Monitor.  Written documentation of this review 
and Amgen acknowledgement is required for subject participation, 
as defined in Exclusion 219 (Section 7.2). 
All herbal supplements and nutritional supplements (with the exception of those known 
to affect lipid metabolism, excluded above) should not be taken within 30 days prior to 
dosing on day 1 and should not be used during the study, unless reviewed and approved 
by the investigator and Amgen Medical Monitor.  Written documentation of this review 
and Amgen acknowledgement is required for subject participation.   
Any changes regarding concomitant medications should be recorded on the subject’s 
source documents and the CRF along with the reason for the change. 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
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10. 
STUDY PROCEDURES 
10.1 
Schedule of Assessments 

Product:  AMG 890  
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Table 4.  Schedule of Assessments – Dosing Period for Cohorts 1 to 5 
Activity 
Screening 
Check-in 
Treatment Period 
Study Day 
-28 to -2 
-1 
1 
2 
3 
4 
Study Time (Hours) 
 
 
Predose 
0 
1 
2 
3 
6 
9 
12 
24 
36 
48 
72 
Study Time (Minutes) 
 
 
 
0 
10 
30 
60 
120 
180 
360 
540 
720 
 
 
 
 
General and Safety Assessments 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to residency 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Residency 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Discharge from residency 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinatione 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Weight 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs (BP, HR, RR, TEMP) 
X 
X 
X 
 
 
 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
ECGd 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigational Product Administration 
IP administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory assessments 
Chemistry and hematology panels 
Xa 
Xa 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
eGFR 
Xa 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation panel 
Xa 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Urinalysis 
Xa 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Urine pregnancy test 
Xa 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (postmenopausal females only) 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, HepCAb, HBsAg, HBcAb 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug and cotinine screen 
Xa 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmacodynamic Assessments 
Lp(a)g 
X 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Lipid panelf 
Xa,b 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmacogenomic sample (optional) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Pharmacokinetic Assessments 
AMG 890 serum PK collection 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AMG 890 pooled urine PK collectionc 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Footnotes defined after Table 5 

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Protocol Number:  20170544 
Date:  07 December 2021 
Page 53 of 106 
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Table 5.  Schedule of Assessments – Post-Dosing for Cohorts 1 to 5 
Activity 
 
 
 
 
 
 
 
 
 
Cohorts 1 and 2 
Cohorts 3 to 5 
 
 
 
 
 
 
 
 
 
 
End of 
Treatment 
Follow-up 
 
 
 
End of 
Treatment 
Follow-
up 
Study Day 
7 
15 
18 
22 
29 
43 
57 
71 
85 
113 
Every 2 
weeks 
113 
155 
183 
225 
Monthly 
Study Time (Hours) 
144 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
General and Safety Assessments 
 
 
Informed Consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinatione 
X 
X 
 
 
X 
 
X 
 
X 
X 
 
X 
 
 
X 
 
Weight 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
Height 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs (BP, HR, RR, TEMP) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
ECGd 
X 
X 
 
 
X 
 
X 
 
 
X 
 
X 
 
 
X 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
X 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
Serious Adverse Eventsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X 
X 
X 
X 
X 
Investigational Product Administration 
 
 
IP administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory assessments 
 
 
Chemistry and hematology panels 
X 
X 
 
X 
X 
 
X 
 
X 
X 
 
X 
X 
X 
X 
 
eGFR 
X 
 
 
 
X 
 
X 
 
X 
X 
 
X 
 
 
X 
 
Coagulation panel 
X 
X 
 
X 
X 
 
X 
 
X 
X 
 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
 
X 
 
X 
 
X 
X 
 
X 
 
 
X 
 
Urine pregnancy test 
 
 
 
 
 
 
 
 
 
Xa 
 
 
 
 
Xa 
 
FSH (postmenopausal females only) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, HepCAb, HBsAg, HBcAb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug and cotinine screen 
 
 
 
 
 
 
 
 
 
Xa 
 
 
 
 
Xa 
 
Pharmacodynamic Assessments 
 
 
Lp(a)g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lipid panelf 
X 
X 
 
 
X 
 
X 
 
X 
X 
 
 
 
 
X 
 
Pharmacokinetic Assessments 
 
 
AMG 890 serum PK collection 
X 
X 
 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
AMG 890 pooled urine PK 
collectionc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Laboratory tests to be performed at the local laboratory. For eligibility determination on day -1, only ALT, AST, and TBIL in the chemistry panel will be performed at 
the local laboratory. 
b For screening purposes, lipid panel will measure triglycerides only. 
c Urine will be pooled for PK analysis as 12-hour samples from the time of dosing to day 4 (72 hours post-dose) for cohorts 3 to 5. Urine will be pooled for PK analysis 
as 24-hour samples for cohorts 1 and 2. 

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CONFIDENTIAL 
 
 
d ECG will be single trace for screening purposes. Baseline ECGs on day -1 will be composed of 3 triplicate tracings. On-study ECGs will be single triplicate tracings.  
e Physical examination to include neurologic examination as specified in protocol Section 10.3. 
f On-study lipid panel includes apolipoprotein A1 and apolipoprotein B. 
g Plasma Lp(a) to be analyzed by Medpace.  
h When the current protocol amendment is implemented, the follow-up visits will continue approximately monthly.  

Product:  AMG 890  
Protocol Number:  20170544 
Date:  07 December 2021 
Page 55 of 106 
CONFIDENTIAL 
 
 
Table 6.  Schedule of Assessments – Dosing Period for Cohorts 6 and 7 
Activity 
Screening 
Dosing 
Precheck 
Treatment Period 
Study Day 
-28 to -4 
-3 to -1 
1 
2 
4 
Study Time (Hours) 
 
 
Predose 
0 
 
2 
3 
6 
9 
24 
30 
72 
Study Time (Minutes) 
 
 
 
0 
30 
60 
120 
180 
360 
540 
 
 
 
General and Safety Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationd 
X 
X 
 
 
 
 
 
 
 
 
X 
 
X 
Weight 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs (BP, HR, RR, TEMP) 
X 
X 
X 
 
 
X 
X 
 
X 
 
X 
 
X 
ECGc 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigational Product Administration 
IP administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Laboratory Assessments 
Chemistry and hematology panels 
Xa 
Xa 
 
 
 
 
 
 
 
 
X 
 
X 
eGFR 
Xa 
X 
 
 
 
 
 
 
 
 
 
 
 
Coagulation panel 
Xa 
X 
 
 
 
 
 
 
 
 
X 
 
X 
Urinalysis 
Xa 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
Xa 
Xa 
 
 
 
 
 
 
 
 
 
 
 
FSH (postmenopausal females only) 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, HepCAb, HBsAg, HBcAb 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
Drug and cotinine screen 
Xa 
Xa 
 
 
 
 
 
 
 
 
 
 
 
Pharmacodynamic Assessments 
Lp(a)f 
X 
 
X 
 
 
 
 
 
 
 
X 
 
X 
Lipid panele 
Xa, b 
 
X 
 
 
 
 
 
 
 
 
 
 
Pharmacogenomic sample (optional) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Pharmacokinetic Assessments 
AMG 890 serum PK collection 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Footnotes defined after Table 7 

Product:  AMG 890  
Protocol Number:  20170544 
Date:  07 December 2021 
Page 56 of 106 
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Table 7.  Schedule of Assessments – Post-Dosing for Cohorts 6 and 7 
Activity 
 
 
 
 
 
 
 
 
 
End of 
Treatment 
Follow-
up 
Study Day 
7 
15 
29 
43 
57 
85 
113 
155 
183 
225 
Monthly 
Study Time (Hours) 
144 
 
 
 
 
 
 
 
 
 
 
General and Safety Assessments 
Informed Consent 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationd 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
Weight 
 
 
 
 
 
 
 
 
 
X 
 
Height 
 
 
 
 
 
 
 
 
 
 
 
Vital signs (BP, HR, RR, TEMP) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
ECGc 
X 
 
X 
 
X 
 
 
X 
 
X 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Serious Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigational Product Administration 
IP administration 
 
 
 
 
 
 
 
 
 
 
 
Laboratory Assessments 
Chemistry and hematology panels 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
eGFR 
 
 
 
 
 
 
 
 
 
X 
 
Coagulation panel 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
X 
 
Urine pregnancy test 
 
 
 
 
 
 
 
 
 
Xa 
 
FSH (postmenopausal females only) 
 
 
 
 
 
 
 
 
 
 
 
HIV, HepCAb, HBsAg, HBcAb 
 
 
 
 
 
 
 
 
 
 
 
Drug and cotinine screen 
 
 
 
 
 
 
 
 
 
Xa 
 
Pharmacodynamic Assessments 
Lp(a)f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lipid panele 
 
 
X 
 
X 
X 
 
X 
 
X 
 
Pharmacokinetic Assessments 
AMG 890 serum PK collection 
X 
X 
 
 
 
 
 
 
 
 
 
a Laboratory tests to be performed at the local laboratory. For eligibility determination on day -3 to -1, only ALT, AST, and TBIL in the chemistry panel will be performed 
at the local laboratory.  
b For screening purposes, lipid panel will measure triglycerides only. 
c ECG will be single trace for the study for cohorts 6 and 7. 
d Physical examination to include neurologic examination as specified in protocol Section 10.3. 
e On-study lipid panel assessments includes apolipoprotein A1 and apolipoprotein B. 
f  Plasma Lp(a) to be analyzed by Medpace. 

Product:  AMG 890  
Protocol Number:  20170544 
Date:  07 December 2021 
Page 57 of 106 
CONFIDENTIAL 
 
 
Table 8.  Schedule of Assessments – Dosing Period for Cohorts 8 and 9 
Activity 
Screening 
Dosing 
Precheck 
Treatment Period 
Study Day 
-28 to -4 
-3 to -1 
1 
2 
4 
Study Time (Hours) 
 
 
Predose 
0 
 
2 
3 
6 
9 
24 
30 
72 
Study Time (Minutes) 
 
 
 
0 
30 
60 
120 
180 
360 
540 
 
 
 
General and Safety Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to residency 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationd 
X 
X 
 
 
 
 
 
 
 
 
X 
 
X 
Weight 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs (BP, HR, RR, TEMP) 
X 
X 
X 
 
 
X 
X 
 
X 
 
X 
 
X 
ECGc 
X 
X 
 
 
 
 
X 
X 
X 
X 
X 
 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigational Product Administration 
IP administration 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Laboratory Assessments 
Chemistry and hematology panels 
Xa 
Xa 
 
 
 
 
 
 
 
 
X 
 
X 
eGFR 
Xa 
X 
 
 
 
 
 
 
 
 
 
 
 
Coagulation panel 
Xa 
X 
 
 
 
 
 
 
 
 
X 
 
X 
Urinalysis 
Xa 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
Xa 
Xa 
 
 
 
 
 
 
 
 
 
 
 
FSH (postmenopausal females only) 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, HepCAb, HBsAg, HBcAb 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
Drug and cotinine screen 
Xa 
Xa 
 
 
 
 
 
 
 
 
 
 
 
Pharmacodynamic Assessments 
Lp(a)f 
X 
 
X 
 
 
 
 
 
 
 
X 
 
X 
Lipid panele 
Xa, b 
 
X 
 
 
 
 
 
 
 
 
 
 
Pharmacogenomic sample (optional) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Pharmacokinetic Assessments 
AMG 890 serum PK collection 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Footnotes defined after Table 9 

Product:  AMG 890  
Protocol Number:  20170544 
Date:  07 December 2021 
Page 58 of 106 
CONFIDENTIAL 
 
 
Table 9.  Schedule of Assessments – Post-Dosing for Cohorts 8 and 9 
Activity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
End of 
Study 
(End of 
Treatment) 
Study Day 
7 
15 
29 
43 
57 
85 
113 
155 
183 
225 
253 
281 
309 
337 
365 
Study Time (Hours) 
144 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
General and Safety Assessments 
Informed Consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationd 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
 
 
 
X 
Weight 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Height 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs (BP, HR, RR, TEMP) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
X 
ECGc 
X 
 
X 
 
X 
 
 
X 
 
X 
 
 
 
 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigational Product Administration 
IP administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory Assessments 
Chemistry and hematology panels 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
X 
eGFR 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
Coagulation panel 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
 
 
 
X 
Urinalysis 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
Urine pregnancy test 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xa 
FSH (postmenopausal females only) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, HepCAb, HBsAg, HBcAb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug and cotinine screen 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xa 
Pharmacodynamic Assessments 
Lp(a)f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lipid panele 
 
 
X 
 
X 
X 
 
X 
 
X 
 
 
 
 
X 
Pharmacokinetic Assessments 
AMG 890 serum PK collection 
X 
X 
X 
 
X 
X 
X 
Xg 
 
 
 
 
 
 
 
a Laboratory tests to be performed at the local laboratory. For eligibility determination on day -3 to -1 Precheck visit, only ALT, AST, and TBIL in the chemistry panel will 
be performed at the local laboratory.  
b For screening purposes, lipid panel will measure triglycerides only. 
c ECG will be single trace for screening purposes. Baseline ECGs on day -3 to -1 Precheck visit, will be composed of 3 triplicate tracings for a total of 9 ECGs  
(3 sets of triplicates). For 2, 3, 6, 9, 24, and 72 hours post-dose, ECGs will be performed in a standardized method, in triplicate. After the 72 hour post-dose ECG time 
point, ECG will be single trace. See Section 10.3 for details on ECGs.  
d Physical examination to include neurologic examination as specified in protocol Section 10.3. 

Product:  AMG 890  
Protocol Number:  20170544 
Date:  07 December 2021 
Page 59 of 106 
CONFIDENTIAL 
 
 
e On-study lipid panel assessments includes apolipoprotein A1 and apolipoprotein B. 
f Plasma Lp(a) to be analyzed by Medpace.  
g PK sample collection on day 155 is required for cohort 9 subjects only. 
h Only the sentinel pair in cohort 9 is required to be admitted for a residency period (from day -1 to completion of day 2 procedures). 
 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 60 of 106 
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10.2 
General Study Procedures 
A signed and dated IRB/IEC approved ICF must be obtained prior to performing any 
study-specific procedures including discontinuing standard therapy for purposes of this 
study.  
During the study, every effort should be made to perform the study procedures as 
indicated on the SOA (Table 4 to Table 9).  Every effort should be taken to collect all 
biomarker and PK samples as described in the SOA.  If sample processing/shipment on 
a weekend/holiday is not logistically feasible for a site, this needs to be documented and 
will not be considered a protocol deviation.  
Subjects will be seen in the clinic for study evaluations.  When electrocardiograms 
(ECGs), vital signs, blood sample collections, and biomarker sample collection occur at 
the same visit, ECGs and vital signs should be collected before blood samples.  The 
time of blood sample collection must be recorded with the exact time of collection (do not 
use the time that samples were frozen or any other time point).  The study specific 
manuals provide additional details regarding the requirements for these procedures.   
Acceptable deviation windows applicable to visits and sample collections follow: 
 
 5 minutes on the first hour PK assessments on day 1,  10 minutes for the 
subsequent PK assessments on the same day (dosing day) 
 
 1 hour on days 2 to 4 for PK samples 
 
 1 day on days 7 through 29 for study visits  
 
 3 days from day 43 through the end of treatment visit for study visits of cohorts 
1 to 7 and through the end study visit for cohorts 8 and 9 
Laboratory samples will be analyzed according to the following: 
 
At screening, hematology, chemistry, triglycerides, coagulation assessments, 
FSH, HIV and hepatitis serology tests, eGFR, urine pregnancy test, and drug & 
cotinine tests will be analyzed at local laboratories. 
 
At day -1 for cohorts 1 to 5 or day -3 to -1 for cohorts 6 to 9, tests that will be 
analyzed at local laboratories for eligibility determination will be: alanine 
aminotransferase (ALT), aspartate aminotransferase (AST); and total bilirubin 
(TBIL) in the chemistry panel; urine pregnancy test; and drug & cotinine tests. 
The day -1 tests for cohorts 1 to 5 or day -3 to -1 tests for cohorts 6 to 9 that will 
be analyzed at a central laboratory will be: hematology, chemistry (including ALT, 
AST, and TBIL for baseline measurements), eGFR, coagulation assessments, 
and urinalysis. 
 
The on-study hematology, chemistry, lipid panel, eGFR, coagulation 
assessments, and urinalysis will be analyzed at a central laboratory. 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 61 of 106 
CONFIDENTIAL 
 
 
 
All Lp(a) assessments, including for screening purposes, will be performed by 
Medpace. 
 
Blood and urine PK, biomarker development, pharmacogenomic, and 
 samples will be sent to Amgen or its designee, for 
analysis (if applicable) and storage. 
 
On-study urine pregnancy tests and the drug and cotinine screen tests will be 
analyzed locally. 
 
Follow-up period chemistry and hematology for cohorts 1 and 2 will be performed 
at the central laboratory. 
Refer to the provided laboratory manual for detailed collection, processing, and shipping 
procedures.  Additional procedures deemed necessary as part of standard of care or as 
required by local laws and regulations may be performed at the Investigator’s discretion. 
10.2.1 
Screening  
After written informed consent is obtained, subjects will be screened in order to assess 
and confirm eligibility for study participation. All screening procedures must be 
performed within 28 days prior to start of investigational product (IP) administration, 
unless otherwise noted.  Subject re-consent is required if subject signature exceeds 
28 days before IP dosing on day 1.   
Subjects who meet the study entry criteria will be eligible for enrollment.  Subjects who 
do not meet the eligibility criteria within the 28-day screening period are not eligible for 
enrollment.  Ineligible subjects will be documented as screen failures.  If a subject is an 
alternate on day -1 for cohorts 1 to 5 or day -3 to -1 for cohorts 6 to 9, and is not enrolled 
in the study because he/she is not needed to fulfill the enrollment requirement, the 
subject would not be considered a screen failure. The subject could be enrolled 
subsequently if the day -1 for cohorts 1 to 5 or day -3 to -1 for cohorts 6 to 9, procedures 
are performed again, the subject meets eligibility criteria, and the subject is within the 
28-day screening period. The latest day -1 for cohorts 1 to 5 or day -3 to -1 for cohorts 
6 to 9, results would be reported.  Subjects outside of the 28-day screening period could 
be considered for re-screening as described in the Re-screening section below. 
Laboratory assessments used to determine subject eligibility may be repeated once for 
confirmation (up to a total of 2 times during the 28-day screening period) if necessary 
before the subject is considered a screen failure.  If any assessments are repeated 
during the screening period, the value that is closest to the enrollment date will apply for 
the determination of eligibility.   

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 62 of 106 
CONFIDENTIAL 
 
 
If the initial blood pressure measurement is elevated, the assessment may be repeated 
again at least 15 minutes later and the lower of the 2 readings may be used for 
screening. 
The following procedures are to be completed during the screening period at the time 
points designated in the Schedules of Assessments (Table 4 to Table 9).  Assessments 
that were performed as standard of care prior to signature of informed consent but within 
28 days prior to start of treatment with AMG 890 can be used as screening assessments 
and do not need to be repeated to confirm subject eligibility.  Hepatitis serology does not 
need to be repeated to determine eligibility if it was performed within 6 weeks prior to 
start of treatment with AMG 890.  
 
Confirmation that the ICF has been signed  
 
Medical history 
 
Physical examination  
 
Demographic data including sex, age, race, and ethnicity will be collected in 
order to study their possible association with subject safety 
 
Weight and height 
 
Vital signs (ie, blood pressure, heart rate, respiratory rate, temperature)   
 
ECG (in single trace, to confirm no medically significant condition, including 
corrected QT interval (QTc) equal to or shorter than 450 msec in men or 
470 msec in women) 
 
Document concomitant medications  
 
Laboratory assessments: hematology, chemistry, and coagulation panel, eGFR, 
urinalysis, urine pregnancy test (females only), FSH (post-menopausal women 
only), triglycerides, HIV and hepatitis serology, and plasma Lp(a) 
 
Drug & cotinine screen  
 
Serious adverse event reporting 
Re-screening: 
A subject may be rescreened up to 3 times in consultation with the Amgen Medical 
Monitor. The subject must be re-consented if a re-screening attempt occurs outside the 
28-day screening period.  
Re-screened subjects must be documented as screen failed in the subject’s medical 
record and subsequently documented as re-screened.  Subjects will retain the same 
subject identification number assigned at the time of initial screening.  Once the subject 
is recorded as re-screened, a new 28-day screening window will begin.  

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 63 of 106 
CONFIDENTIAL 
 
 
10.3 
Description of Study Procedures  
The sections below provide a description of the individual study procedures listed in the 
Schedule of Assessments (Table 4 to Table 9). 
Informed Consent 
A signed ICF must be obtained from each subject prior to any study-mandated 
procedures. 
Subject Residency 
Subjects in cohorts 1 to 5 will check-in at the research facility on day -1 and will stay in 
the research facility for a residency period through day 4.  After completion of day 
4 procedures, subjects will be discharged. The sentinel pair of cohort 9 will stay in the 
research facility from day -1 through day 2. After completion of day 2 procedures, 
subjects will be discharged. 
Demographic Data 
Demographic data collection including sex, age, race, and ethnicity will be collected in 
order to study possible association with subject safety.  Additionally, demographic data 
will be used to study the impact of protocol-required therapy on biomarker variability and 
PK.  
Medical History 
A complete medical history will be obtained at screening by the investigator or 
designated site physician. Medical history will include information on the subject’s 
current health and surgical history. Relevant medical history findings will be recorded in 
the subject’s source and on the appropriate pages of the CRF.  Record all findings on 
the medical history eCRF. 
Concomitant Medications 
Concomitant therapies are to be collected from informed consent through the end of 
treatment visit in the source documents and eCRF for cohorts 1 to 7; for cohorts 8 and 9, 
concomitant therapies are to be collected through the EOS visit (day 365).  If the case, 
statin use and medication for blood pressure control are to be collected as concomitant 
medications.  Collect drug, therapy name, indication, dose, unit, frequency, route, start 
date, and stop date (if applicable). 
Physical Examination  
A complete physical examination (breast, rectal and genital examination are not 
required) will be performed by the investigator or designee at screening and at the time 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 64 of 106 
CONFIDENTIAL 
 
 
points specified in the Schedules of Assessments (Table 4 to Table 9).  The physical 
examination will include general appearance, including examination of the skin, spleen, 
and respiratory, cardiovascular, musculoskeletal, and neurological systems. 
The individual performing the physical examination will characterize their findings as 
either normal or abnormal.  Abnormal physical examination findings found during 
screening should be reported on the Medical History eCRF.  Abnormal physical 
examination findings found during the study, if clinically significant, should be noted in 
the event eCRF. 
A clinical neurologic examination will be performed at every physical examination as 
specified in the SOA.  The clinical neurologic examination will be performed to access 
signs of new onset peripheral neuropathy. The examination should be reported in the 
subject records and must include the following assessments: 
o muscle mass and tone, presence of tremor, fasciculation or paralysis 
o strength in all 4 members, including proximal and distal muscular groups 
o gait, by observation of a short regular walk, heel and toe walk. 
o symmetry of sensitivity to pressure (dull tool), temperature and pain (sharp 
tool) 
o proprioception in upper and lower extremities 
o symmetry of reflexes assessed on the upper extremities (biceps, triceps and 
brachioradial) and lower extremities (patellar and achilles) 
If there is clinical evidence of treatment-emergent neuropathy, dosing will be suspended, 
the subject will be directed to a neurology specialist for a complete neurologic 
assessment, and the unblinded medical monitor will be informed. The identified 
neurologic abnormality is to be reported on the adverse event CRF.  
Height Measurements 
Height in centimeters should be measured without shoes at screening. 
Weight Measurements 
Weight in kilograms should be measured without shoes. 
Body Mass Index (BMI) 
BMI will be calculated at screening using the following formula: 
BMI (kg/m2)  weight (kg)/[height (cm)/100]2 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 65 of 106 
CONFIDENTIAL 
 
 
Vital Signs 
The following measurements must be performed: systolic/diastolic blood pressure, heart 
rate, respiratory rate, and temperature.  Record all measurements on the vital signs 
eCRF. 
The subject must be in a supine position in a rested and calm state for at least 5 minutes 
before blood pressure assessments are conducted.  If the subject is unable to be in the 
supine position, the subject should be in most recumbent position as possible.  The 
position selected for a subject should be the same that is used throughout the study and 
documented on the vital signs eCRF.  If the initial blood pressure measurement is 
elevated, the assessment may be repeated again at least 15 minutes later and the lower 
of the 2 readings may be used. 
The location for temperature measurement selected for a subject should be the same 
that is used throughout the study and documented on the vital signs eCRF. 
Electrocardiograms   
The subject must be in a supine position in a rested and calm state for at least 5 minutes 
before ECG assessment is conducted.  If the subject is unable to be in the supine 
position, the subject should be in most recumbent position as possible. 
The Screening ECG will be performed as a single ECG for screening purposes. 
For cohorts 1 to 5, day -1 pre-dose ECGs will be performed on 3 occasions separated by 
at least 30 minutes all in triplicate for a total of 9 ECGs (3 sets of triplicate). This is the 
baseline ECG.  At all other time points, ECGs will be performed in a standardized 
method, in triplicate, and approximately 30 seconds apart, prior to blood draws or other 
invasive procedures.  Each ECG must include the following measurements: QRS, QT, 
QTc, RR, and PR intervals. 
For cohorts 6 and 7, all ECGs will be performed as a single ECG for all time points, and 
prior to blood draws or other invasive procedures.  The ECG must include the following 
measurements: Heart Rate, QRS, QT, QTc, and PR intervals. 
For cohorts 8 and 9, the screening ECG will be performed as a single trace. The day -
3 to -1 pre-check visit ECG will be the Baseline ECG and will be performed on 
3 occasions separated by at least 30 minutes, all in triplicate for a total of 9 ECGs (3 sets 
of triplicates).  Each set of triplicate ECGs should be run consecutively and completed 
within a total of 5 minutes from the start of the first to the completion of the third.  For 
ECGs at 2, 3, 6, 9, 24, and 72 hours post-dose, ECGs will be performed in a 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 66 of 106 
CONFIDENTIAL 
 
 
standardized method, in triplicate and run consecutively (triplicate ECGs should be 
completed within a total of 5 minutes from the start of the first to the completion of the 
third).  ECGs will be performed prior to blood draws or other invasive procedures.  At all 
other time points after 72 hours post-dose, ECGs will be performed as a single trace and 
prior to blood draws or other invasive procedures.  Each ECG must include the following 
measurements: QRS, QT, QTc, RR, and PR intervals. 
The investigator or designated site physician will review all ECGs.  Once signed, the 
original ECG tracing will be retained with the subject’s source documents.  At the 
request of the sponsor, a copy of the original ECG will be made available to Amgen or 
designee. 
Standard ECG machines provided by the sponsor should be used for all study-related 
ECG procedures. 
Clinical Laboratory Tests 
The tests will be conducted on samples collected and analyzed by standard laboratory 
procedures at the time points specified in the Schedule of Assessments (Table 4 to 
Table 9).  Blood will be collected after fasting at least 10 hours at all clinical laboratory 
time points. The test results are to be recorded on the eCRFs.  All laboratory test results 
must be reviewed and signed by the Principal Investigator or qualified designee.  Missed 
test(s) that are not done must be reported as such on the eCRFs. 
At screening, chemistry, hematology, coagulation assessments, urinalysis, and 
triglycerides will be analyzed by the local laboratory.  At day -1 for cohorts 1 to 5 or 
day -3 to -1 for cohorts 6 to 9, for eligibility determination, the local laboratory will test 
only AST, ALT, and TBIL in the chemistry panel; a central lab will analyze hematology, 
chemistry (including ALT, AST, and TBIL for baseline measurements), eGFR, 
coagulation assessments, and urinalysis.  On-study and follow-up laboratory 
assessments, unless specifically noted to the contrary, will be analyzed by a central 
laboratory. 
Additional procedures deemed necessary as part of standard of care, for safety reasons 
or as required by local laws and regulations may be performed at the investigator’s 
discretion.   
The following laboratory tests will be conducted on samples collected and analyzed by 
standard laboratory procedures: 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 67 of 106 
CONFIDENTIAL 
 
 
Hematology 
The following hematology tests will be performed: 
 
Red blood cell count 
 
Hemoglobin 
 
Hematocrit 
 
Platelet count 
 
White blood cell count with differential count: 
o Total neutrophils 
o Eosinophils 
o Basophils 
o Lymphocytes 
o Monocytes 
Clinical Chemistry 
A fasting (at least 10 hours) blood sample will be assessed at screening and will be 
analyzed at the local laboratory.  
Fasting (at least 10 hours) blood samples will be assessed at all time points indicated as 
on-study in the SOA (Table 4 to Table 9) and analyzed at the central laboratory. The 
clinical chemistry tests listed below will be performed: 
 
Glucose  
 
Sodium 
 
Chloride 
 
Calcium  
 
Phosphorus  
 
Potassium  
 
Magnesium 
 
Bicarbonate or total CO2 
 
Creatinine 
 
Blood urea nitrogen (BUN) 
 
Alanine aminotransferase (ALT) 
 
Aspartate aminotransferase (AST) 
 
Total bilirubin  
 
Direct bilirubin  
 
Alkaline phosphatase (ALP)  
 
Creatine Kinase  
 
Total protein 
 
Albumin  
 
Tryptase (to be performed at the discretion of the 
PI or qualified designee)a  
 
Lactate, (to be performed at discretion of the PI 
or designee)b 
 
Estimated glomerular filtration rate (eGFR)c 
a Tryptase to be collected in the case of a suspected anaphylactic reaction 
b Lactate to be collected if an anion-gap acidosis is identified 
c eGFR for screening will be calculated at the local laboratory, and the formula used should be recorded in 
subject’s source documents for future reference. 

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Coagulation Assessments 
The following coagulation assessments will be performed:  
 
Prothrombin time (PT) in international normalized ratio (INR) 
 
Activated partial thromboplastin time (aPTT) 
 
Thrombin time (TT) 
Urinalysis 
The urinary tests listed below will be performed: 
Bilirubin 
Blood 
Glucose 
Ketones 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic exam (To be performed at the discretion of 
the PI or qualified designee): 
White blood cells 
Red blood cells 
Epithelial cells 
Casts 
Bacteria  
Crystals 
Hepatitis B, Hepatitis C and HIV status 
Hepatitis B surface antigen, HBcAb, HepCAb, and HIV status will be assessed. If the 
results show a positive HepCAb, hepatitis C virus RNA by PCR is necessary.  The test 
must be confirmed negative at screening for the subject to be eligible for this study. 
Pregnancy Test (Females Only) 
A urinary pregnancy test will be performed on all female subjects at screening; day -1 for 
cohorts 1 to 5 or day -3 to day -1 for cohorts 6 to 9; for cohort 1 to 7 the end of treatment 
visit; and for cohorts 8 and 9 at Day 225 and the end of study, as specified in the SOA  
(Table 4 to Table 9).  Pregnancy tests must be confirmed negative for the subject to be 
eligible for this study. 
Serum Follicle Stimulating Hormone Test (Females Only) 
Additional serum may be collected for an FSH test if required to ensure menopause in a 
female subject.  Results must be consistent with postmenopausal status per local 
laboratory ranges for inclusion in this study.  Postmenopausal status will be recorded on 
the medical history eCRF. 
Drug Screen 
A urine screen for drugs with a high potential of abuse (according to the local lab 
standards) will be performed at screening; day -1 for cohorts 1 to 5 or day -3 to 

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day -1 for cohorts 6 to 9; and at the end of treatment visit for cohorts 1 to 7; and for 
cohorts 8 and 9, on day 365.  The following drugs will be tested: 
 
Tetrahydrocannabinol  
 
Benzodiazepines 
 
Cocaine 
 
Opiates 
 
Amphetamines 
 
Barbiturates 
Subjects with a positive result at time points specified in the SOA will be excluded from 
the study at screening.  The intention is to detect drugs of abuse and not those 
prescribed therapeutically.  Subjects with a positive drug test may be retested once at 
the discretion of the Principal Investigator in consultation with the Amgen Medical 
Monitor.  The result will be documented in the source document but will not be recorded 
on the CRF. 
Lipid Panel 
A fasting (at least 10 hours) blood sample triglycerides will be assessed at screening 
and analyzed at the local laboratory.  
Fasting (at least 10 hours) blood samples will be collected at all time points indicated as 
the on-study lipid panel in the SOA (Table 4 to Table 9). The following analytes will be 
assessed:  
 
Total cholesterol 
 
LDL-C (by ultracentrifugation) 
 
HDL-C 
 
VLDL-C 
 
Triglycerides 
 
Apolipoprotein A1 (apoA1) 
 
Apolipoprotein B (apoB) 
The following analytes will be collected per the Schedule of Assessments: 

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10.4 
Pharmacokinetic and Pharmacodynamic Analysis 
Blood samples for determination of AMG 890 serum concentrations and for the 
evaluation of plasma Lp(a) dynamic response will be assessed at time points indicated 
in the Schedule of Assessments (Table 4 to Table 9). Collection time points may be 
added or removed based on affluence of data informing the PK of AMG 890 and its PD 
effects.  
For cohorts 1 to 5, urine PK samples for a qualitative assessment of AMG 890 levels will 
be assessed at the time points indicated in the Schedule of Assessments.  
 
After dosing, all urine passed (including urine passed during bowel 
movements) must be collected including the first voiding of the following day. 
Urine will be collected and pooled in 12-hour interval samples from the time 
of dosing through day 4 (72 hours post-dose) for cohorts 3 to 5, and through 
day 2 as a 24-hour interval sample after dosing for cohorts 1 and 2.  The total 
volume of urine collected (mL) for each collection interval is to be reported.  
 
The start and stop time of each collection interval (to the minute) is to be 
reported. 
 
The entire interval specimen should be collected in a properly labeled urine 
container and refrigerated at 2C to 8C during collection. 
 
The subject should be informed that a normal intake of fluids during the 
collection period is desirable.  
The PK and PD samples must be collected within the following windows: 
 
 5 minutes on the first hour assessments on day 1;  10 minutes for the 
subsequent assessments on the same day (dosing day) 
 
 1 hour on days 2 to 4  
 
 1 day on days 7 through 29 
 
 3 days from day 43 through the end of treatment visit for study visits of cohorts 
1 to 7 and through the end study visit for cohorts 8 and 9 
The precise time of all sample collection should be documented. 
Detailed sample collection, processing, storage and shipping instructions are provided in 
the laboratory manual. 

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10.6 
Biomarker Development 
Biomarkers are objectively measured and evaluated indicators of normal biologic 
processes, pathogenic processes, or pharmacologic responses to a therapeutic 
intervention.  Biomarker development can be useful in developing markers to identify 
disease subtypes, guide therapy, and/or predict disease severity.  
10.7 
Pharmacogenetic Studies 

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10.8 
Sample Storage and Destruction  
Laboratory samples collected can be analyzed for any of the tests outlined in the 
protocol and for any tests necessary to minimize risks to study subjects.  This includes 
testing to ensure analytical methods produce reliable and valid data throughout the 
course of the study.  This can also include, but is not limited to, investigation of 
unexpected results, incurred sample reanalysis, and analyses for method transfer and 
comparability. 
All samples and associated results will be coded prior to being shipped from the site for 
analysis or storage.  Samples will be tracked using a unique identifier that is assigned to 
the samples for the study.  Results are stored in a secure database to ensure 
confidentiality. 
If informed consent is provided by the subject, Amgen can do additional testing on 
remaining samples (ie, residual and back-up) to investigate and better understand 
hyperlipoproteinemia(a), the dose response and/or prediction of response to AMG 890, 
characterize antibody response, and characterize aspects of the molecule  
(eg, mechanism of action/target, metabolites) and additional insights into cardiovascular 
disease.  Results from this analysis are to be documented and maintained, but are not 
necessarily reported as part of this study.  Samples can be retained for up to 20 years. 
Since the evaluations are not expected to benefit the subject directly or to alter the 
treatment course, the results of pharmacogenetic, biomarkers, biomarker development, 
or other exploratory studies are not placed in the subject’s medical record and are not to 
be made available to the subject, members of the family, the personal physician, or other 
third parties, except as specified in the informed consent. 
The subject retains the right to request that the sample material be destroyed by 
contacting the investigator.  Following the request from the subject, the investigator is to 
provide the sponsor with the required study and subject number so that any remaining 
blood, biomarker, PK, and pharmacogenetic samples can be located and destroyed.  
Samples will be destroyed once all protocol-defined procedures are completed.  

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However, information collected from samples prior to the request for destruction, will be 
retained by Amgen. 
The sponsor is the exclusive owner of any data, discoveries, or derivative materials from 
the sample materials and is responsible for the destruction of the sample(s) at the 
request of the subject through the investigator, at the end of the storage period, or as 
appropriate (eg, the scientific rationale for experimentation with a certain sample type no 
longer justifies keeping the sample).  If a commercial product is developed from this 
research project, the sponsor owns the commercial product.  The subject has no 
commercial rights to such product and has no commercial rights to the data, information, 
discoveries, or derivative materials gained or produced from the sample.   
See Section 14.3 for subject confidentiality. 
11. 
WITHDRAWAL FROM TREATMENT, PROCEDURES, AND STUDY 
11.1 
Subjects’ Decision to Withdraw 
Subjects have the right to withdraw from the study at any time and for any reason 
without prejudice to their future medical care by the physician or at the institution. 
Subjects (or a legally acceptable representative) can decline to continue receiving 
investigational product and/or other protocol-required therapies or procedures at any 
time during the study but continue participation in the study.  If this occurs, the 
investigator is to discuss with the subject the appropriate processes for discontinuation 
from investigational product, device or other protocol-required therapies and must 
discuss with the subject the options for continuation of the SOA (Table 4 to Table 9) 
including different options of follow-up (eg, in person, by phone/mail, through 
family/friends, in correspondence/communication with other treating physicians, from the 
review of medical records) and collection of data, including endpoints, and adverse 
events.  Subjects who have discontinued investigational product and/or protocol required 
therapies or procedures should not be automatically removed from the study.  Whenever 
safe and feasible it is imperative that subjects remain on study to ensure safety 
surveillance and/or collection of outcome data.  The investigator must document the 
level of follow-up that is agreed to by the subject. 
Withdrawal of consent for a study means that the subject does not wish to receive 
further protocol-required therapies or procedures, and the subject does not wish to or is 
unable to continue further study participation.  Subject data up to withdrawal of consent 
will be included in the analysis of the study, and where permitted, publicly available data 

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can be included after withdrawal of consent.  The investigator is to discuss with the 
subject appropriate procedures for withdrawal from the study. 
11.2 
Investigator or Sponsor Decision to Withdraw or Terminate 
Subjects’ Participation Prior to Study Completion 
The investigator and/or sponsor can decide to withdraw a subject(s) from investigational 
product, protocol procedures, or the study as a whole at any time prior to study 
completion.   
Subjects may be eligible for continued treatment with Amgen investigational product(s) 
and/or other protocol required therapies by a separate protocol or as provided for by the 
local country’s regulatory mechanism, based on parameters consistent with 
Section 15.1.  
11.3 
Reasons for Removal From Treatment, or Study 
11.3.1 
Reasons for Removal From Treatment 
Reasons for removal from protocol-required investigational product(s) or procedural 
assessments include any of the following: 
 
subject request 
 
safety concern (eg, due to an adverse event, ineligibility determined, protocol 
deviation, non-compliance, or pregnancy) 
 
death 
 
lost to follow-up 
 
decision by sponsor (other than subject request, safety concern, lost to follow-up) 
11.3.2 
Reasons for Removal From Study 
Reasons for removal of a subject from the study are: 
 
decision by sponsor  
 
withdrawal of consent from study 
 
death 
 
lost to follow-up 
12. 
SAFETY DATA COLLECTION, RECORDING, AND REPORTING 
12.1 
Definition of Safety Events 
12.1.1 
Adverse Events 
An adverse event is defined as any untoward medical occurrence in a clinical trial 
subject.  The event does not necessarily have a causal relationship with study treatment.  
The investigator is responsible for ensuring that any adverse events observed by the 
investigator or reported by the subject are recorded in the subject’s medical record.   

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The definition of adverse events includes worsening of a pre-existing medical condition.  
Worsening indicates that the pre-existing medical condition or underlying disease 
(eg, diabetes, migraine headaches, gout) has increased in severity, frequency, and/or 
duration more than would be expected and/or has an association with a significantly 
worse outcome than expected.  A pre-existing condition that has not worsened more 
than anticipated (ie, more than usual fluctuation of disease) during the study, or involves 
an intervention such as elective cosmetic surgery or a medical procedure while on study, 
is not considered an adverse event.  Abnormal laboratory findings without clinical 
significance are usually not considered adverse events.  However, laboratory value 
changes that require treatment or adjustment in current therapy may be considered 
adverse events. 
The investigator’s clinical judgment is used to determine whether a subject is to be 
removed from treatment due to an adverse event.  In the event a subject, or subject’s 
legally acceptable representative requests to withdraw from protocol-required therapies 
or the study due to an adverse event, refer to Section 11.1 for additional instructions on 
the procedures recommended for safe withdrawal from protocol-required therapies or 
the study.   
12.1.2 
Serious Adverse Events 
A serious adverse event is defined as an adverse event that meets at least 1 of the 
following serious criteria:  
 
fatal 
 
life threatening (places the subject at immediate risk of death) 
 
requires in patient hospitalization or prolongation of existing hospitalization 
 
results in persistent or significant disability/incapacity 
 
congenital anomaly/birth defect 
 
other medically important serious event 
An adverse event would meet the criterion of “requires hospitalization,” if the event 
necessitated an admission to a health care facility (eg, overnight stay).   
If an investigator considers an event to be clinically important, but it does not meet any 
of the serious criteria, the event could be classified as a serious adverse event under the 
criterion of “other medically important serious event.”  Examples of such events could 
include allergic bronchospasm, convulsions, blood dyscrasias, drug induced liver injury 
(DILI) (see Appendix A for DILI reporting criteria), or events that necessitate an 
emergency room visit, outpatient surgery, or urgent intervention. 

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12.2 
Safety Event Reporting Procedures 
12.2.1 
Adverse Events 
12.2.1.1 
Reporting Procedures for Adverse Events That do not Meet Serious 
Criteria 
The investigator is responsible for ensuring that all adverse events observed by the 
investigator or reported by the subject that occur after the first dose of investigational 
product through the end of treatment visit are reported using the Event eCRF. 
The investigator must assign the following adverse event attributes: 
 
Adverse event diagnosis or syndrome(s), if known (if not known, signs or symptoms), 
 
Did the event start prior to the first dose of investigational product, 
 
Assessment of seriousness, 
 
Dates of onset and resolution (if resolved), 
 
Severity, 
 
Assessment of relatedness to investigational product, protocol required therapies, 
and/or study mandated procedures 
 
Action taken, and 
 
Outcome of event. 
The adverse event grading scale used will be the Amgen Standard Adverse Event 
Grading Scale: mild (aware of sign or symptom, but easily tolerated), moderate 
(discomfort enough to cause interference with usual activity), and severe (incapacitating 
with inability to work or do usual activity).  The grading scale used in this study is 
described in the Appendix A.   
The investigator must assess whether the adverse event is possibly related to the 
investigational product (AMG 890 or placebo).  Relatedness means that there are facts 
or reasons to support a relationship between investigational product and the event. 
The investigator must assess whether the adverse event is possibly related to any study 
mandated activity (eg, administration of investigational product, protocol-required 
therapies, use of medical device(s) and/or procedure (including any screening 
procedure(s)).   
The investigator is responsible for reviewing laboratory test results and determining 
whether an abnormal value in an individual study subject represents a clinically 
significant change from the subject’s baseline values.  In general, abnormal laboratory 
findings without clinical significance (based on the Investigator's judgment) are not to be 
recorded as adverse events.  However, laboratory value changes that require treatment 

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or adjustment in current therapy are considered adverse events.  Where applicable and 
preferentially, clinical sequelae (not the laboratory abnormality) are to be recorded as the 
adverse event. 
The investigator is expected to follow reported adverse events until stabilization or 
reversibility.  
12.2.1.2 
Reporting Procedures for Serious Adverse Events 
The investigator is responsible for ensuring that all serious adverse events observed by 
the investigator or reported by the subject that occur after signing of the informed 
consent through the end of study visit (last visit where data for primary endpoints are 
collected) are recorded in the subject’s medical record and are submitted to Amgen.  All 
serious adverse events must be submitted to Amgen within 24 hours following the 
investigator’s knowledge of the event via the Event eCRF and using the paper based 
Serious Adverse Event Report (SAER) Form (see Table 10 and Appendix B). 
The investigator must assess whether the serious adverse event is possibly related to 
the investigational product (AMG 890 or placebo).  Relatedness means that there are 
facts or reasons to support a relationship between investigational product and the event.  
The investigator must assess whether the serious adverse event is possibly related to 
any study mandated activity (eg, administration of investigational product,  
protocol-required therapies, use of medical device(s) and/or procedure (including any 
screening procedure(s)).   
The investigator is expected to follow reported serious adverse events until stabilization 
or reversibility. 
New information relating to a previously reported serious adverse event must be 
submitted to Amgen.  All new information for serious adverse events must be sent to 
Amgen within 24 hours following knowledge of the new information.  If specifically 
requested, the investigator may need to provide additional follow-up information, such as 
discharge summaries, medical records, or extracts from the medical records.  
Information provided about the serious adverse event must be consistent with that 
recorded on the Event eCRF. 
If a subject is permanently withdrawn from protocol-required therapies because of a 
serious adverse event, this information must be submitted to Amgen.   

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To comply with worldwide reporting regulations for serious adverse events, the treatment 
assignment of subjects who develop serious, unexpected, and related adverse events 
may be unblinded by Amgen before submission to regulatory authorities.  
Amgen will report serious adverse events and/or suspected unexpected serious adverse 
reactions as required to regulatory authorities, investigators/institutions, and IRBs/IECs 
in compliance with all reporting requirements according to local regulations and good 
clinical practice. 
The investigator is to notify the appropriate IRB/IEC of serious adverse events occurring 
at the site and other adverse event reports received from Amgen, in accordance with 
local regulatory requirements and procedures. 
Table 10.  Serious Adverse Event Reporting via Paper CRF 
Serious Adverse Event Reporting via Paper CRF 
 
Facsimile transmission of the Serious Adverse Event Report Form (see 
Appendix B) is the preferred method to transmit this information. 
 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the Serious Adverse Event Report Form 
sent by overnight mail or courier service. 
 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Serious Adverse Event Report Form within the designated 
reporting time frames. 
 
Once the study has ended, serious adverse event(s) should be reported to Amgen 
(regardless of causality) if the investigator becomes aware of a serious adverse 
event.  The investigator should use the paper-based Serious Adverse Event 
Contingency Report Form to report the event. 
12.2.1.3 
Serious Adverse Events after the Protocol-required Reporting 
Period 
There is no requirement to monitor study subjects for serious adverse events following 
the protocol-required reporting period or after end of study.  However, these serious 
adverse events should be reported to Amgen (regardless of causality) if the investigator 
becomes aware of them.  Per local requirements in some countries (eg, European Union 
[EU] member states), investigators are required to report serious adverse events that 
they become aware of after end of study.  If serious adverse events are reported, the 
investigator is to report them to Amgen within 24 hours following the investigator’s 
knowledge of the event.  

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Serious adverse events reported outside of the protocol-required reporting period will be 
captured within the safety database as clinical trial cases for the purposes of expedited 
reporting.  
If further safety related data is needed to fulfill any regulatory reporting 
requirements for a reportable event, then additional information may need to be 
collected from the subject’s records after the subject ends the study. 
12.2.1.4 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting adverse events and/or serious 
adverse events.  Open-ended and non-leading verbal questioning of the subject is the 
preferred method to inquire about adverse event occurrence. 
12.3 
Pregnancy and Lactation Reporting 
If a female subject becomes pregnant, or a male subject fathers a child following 
exposure to the Amgen investigational product (AMG 890 or placebo) report the 
pregnancy to Amgen Global Patient Safety as specified below. 
Investigators should report pregnancies that occur during the study or through 90 days 
after receiving the Amgen investigational product (AMG 890 or placebo), for subjects 
who withdraw prior to end of study.  
The pregnancy should be reported to Amgen Global Patient Safety within 24 hours of 
the investigator’s knowledge of the pregnancy.  Report a pregnancy on the Pregnancy 
Notification Worksheet (Appendix C).  Amgen Global Patient Safety will follow-up with 
the investigator regarding additional information that may be requested. 
If a female subject becomes pregnant during the study, the investigator should attempt 
to obtain information regarding the birth outcome and health of the infant.   
If the outcome of the pregnancy meets a criterion for immediate classification as a 
Serious Adverse Event (eg, female subject experiences a spontaneous abortion, 
stillbirth, or neonatal death or there is a fetal or neonatal congenital anomaly) the 
investigator will report the event as a Serious Adverse Event. 
If a female breastfeeds following exposure to the Amgen Investigational Product 
(AMG 890 or placebo) report the lactation case to Amgen as specified below. 
In addition to reporting a lactation case during the study, investigators should report 
lactation cases that occur through 90 days after receiving the Amgen Investigational 
Product (AMG 890 or placebo) for subjects who withdraw prior to end of study.  

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Any lactation case should be reported to Amgen Global Patient Safety within 24 hours of 
the Investigator’s knowledge of event.  Report a lactation case on the Lactation 
Notification Worksheet (Appendix C).  Amgen Global Patient Safety will follow-up with 
the investigator regarding additional information that may be requested. 
If a male subject's female partner becomes pregnant, the investigator should discuss 
obtaining information regarding the birth outcome and health of the infant from the 
pregnant partner. 
13. 
STATISTICAL CONSIDERATIONS 
13.1 
Study Endpoints, Analysis Sets, and Covariates 
13.1.1 
Study Endpoints 
13.1.1.1 
Primary Endpoints  
 
Subject incidence of treatment-emergent adverse events 
 
Safety laboratory analytes, vital signs, and electrocardiograms (ECGs) 
13.1.1.2 
Secondary Endpoints 
 
AMG 890 PK parameters including, but not limited to, maximum observed 
concentration (Cmax), the time of maximum observed concentration (tmax), and 
area under the concentration-time curve (AUC) 
 
Pharmacodynamic parameters: 
o Change and percent change in plasma Lp(a) levels at each scheduled visit 
up to the end of treatment visit 
13.1.1.3 
Exploratory Endpoints 
 
Change and percent change in total cholesterol and cholesterol fractions  
(very-low density lipoprotein cholesterol [VLDL-C], low-density lipoprotein 
cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]), 
triglycerides, apolipoprotein A1 (ApoA1) and total apolipoprotein B (ApoB) at 
each scheduled visit 
 
AMG 890 excretion in urine 
13.1.2 
Analysis Sets 
For all analyses, subjects will be analyzed according to the dose and treatment they 
received, not the dose and treatment to which they were randomized.  
13.1.2.1 
Safety Analysis Set 
The safety analysis set will consist of all study subjects who receive at least 1 dose of 
AMG 890 or placebo. 

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Subjects withdrawing prior to AMG 890 or placebo administration due to adverse events 
related to study procedure will not be included in the safety analysis set but those 
adverse events will be listed. 
13.1.2.2 
Pharmacokinetic (PK) Analysis Set 
The PK analysis set will consist of all dosed subjects for whom at least 1 PK parameter 
or endpoint can be reliably estimated. 
13.1.2.3 
Pharmacodynamics (PD) Analysis Set 
The PD analysis set will consist of all dosed subjects for whom at least 1 PD parameter 
has a baseline value and at least 1 post-baseline measurement available.  Baseline 
values for Lp(a) are defined as the mean of screening and day 1 predose.  If for any 
reason only 1 value is available, then that value will be used as baseline. 
13.1.2.4 
Covariates and Subgroups 
Baseline values may be used as a covariate in analyses. For any variable, unless 
otherwise defined, baseline is defined as the last assessment taken prior to the 
first administration of AMG 890 or placebo. 
No subgroup analyses are planned. 
13.1.3 
Handling of Missing and Incomplete Data  
The frequency of missing and incomplete data is expected to be low in this study and 
therefore, missing data will not be imputed. 
13.2 
Sample Size Considerations 
The sample size is based on practical considerations.  Approximately 
subjects will be 
enrolled.  With at least 6 subjects receiving AMG 890 in each cohort, there is at least a 
74 chance of detecting an adverse event (AE) with a true incidence of 20 within each 
cohort.  With at least 10 subjects receiving both AMG 890 and statin, there is at least an 
89 chance of detecting an adverse event with a true AE incidence rate of 20.  With 
 subjects receiving AMG 890 there is a 95 chance of detecting an adverse event 
with a true incidence of 5. 
13.3 
Access to Individual Subject Treatment Assignments by Amgen or 
Designees 
Blinded individuals will not have access to unblinded information until the study is 
formally unblinded. Amgen staff and their designees involved in the study will not be 
blinded, but will only be given treatment assignments when there is a need to use the 
information for analysis, discussion and internal decision making. The Amgen Medical 

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Monitor will be unblinded to treatment assignment throughout the duration of the study. 
Access to treatment assignments and other restricted data are described in Amgen 
standard documents. Unblinded individuals are to ensure unblinding and potentially 
unblinding information should not be distributed to the investigators or subjects prior to 
the study being formally unblinded. 
13.4 
Planned Analyses 
13.4.1 
Data Monitoring Committee (DMC), Data Review Team (DRT) or Dose 
Level Review Team (DLRT) 
The DLRT voting members are responsible for dose level recommendations. The key 
objectives of the DLRT are to review data, monitor safety, and make dose change 
recommendations.  Except for the unblinded Amgen Medical Monitor who will review 
data in an unblinded manner, DLRMs will be conducted in a blinded manner.  Please 
refer to Section 9.2.4.1 for details.  
13.4.2 
Primary Analysis 
The primary analysis will occur after all subjects have completed the end of treatment 
visit. 
13.4.3 
Final Analysis 
The final analysis will occur after all subjects have completed the study. 
13.5 
Planned Methods of Analysis 
13.5.1 
General Considerations 
Descriptive statistics will be provided for selected demographics, adverse events, vital 
signs, ECG, PK, and selected laboratory measurements. Descriptive statistics on 
continuous measurements will include means, medians, standard deviations, and 
ranges, while categorical data will be summarized using frequency counts and 
percentages. Data will be presented and summarized by treatment cohort and at each 
time point. Graphical summaries of the data may also be presented. 
Data for subjects receiving placebo will be combined across cohorts 1 to 5 and 
separately across cohorts 6 to 9.  
When data are summarized by time, the values recorded against the scheduled time 
points listed in the protocol will be used. When assessing minimum/maximum increases 
or decreases over the study, all assessments, including unscheduled assessments will 
be used.  Unless stated otherwise in the statistical analysis plan, the data analysis will 
be conducted using subjects in the safety analysis set. For statistical analyses 

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comparing change from baseline, only subjects with both baseline and at least 1  
post-baseline assessment will be included. 
At the primary analysis, the primary, secondary, and exploratory endpoints (if applicable) 
will be analysed. All data up to each subject’s end of treatment visit will be included in 
the primary analysis. The follow-up time points will be summarized at the final analysis. 
13.5.2 
Primary Endpoint(s) 
13.5.2.1 
Safety Endpoint(s) 
13.5.2.1.1 
Adverse Events 
All subjects who receive a dose of AMG 890 or placebo in the safety analysis set will be 
included in the analysis of the primary endpoints. Subject incidence of all 
treatment-emergent adverse events will be tabulated by system organ class and 
preferred term according to the medical dictionary for regulatory activities (MedDRA) 
terminology. Tables of fatal adverse events, serious adverse events, adverse events 
leading to withdrawal from IP or other protocol-required therapies, and significant 
treatment emergent adverse events will also be provided if observed. The number and 
percentage of subjects reporting adverse events will be evaluated for each dose cohort 
and across dose cohorts. 
13.5.2.1.2 
Vital Signs 
Vital signs will be listed and reviewed for each subject. Summaries of heart rate and 
blood pressure data over time and change from baseline will be provided. The analyses 
of vital signs will include summary statistics over time (for each protocol scheduled study 
visit) by cohort. Depending on the size and scope of changes, summaries of changes 
from baseline over time may be provided.  
13.5.2.1.3 
Electrocardiogram 
For cohorts 1 to 5 and cohorts 8 and 9, summaries over time and/or changes from 
baseline over time will be provided for ECG parameters (eg, RR, PR, QRS, QTc). 
Subjects’ maximum change from baseline in QTc will be categorized and the number 
and percentage of subjects in each group will be summarized. Subjects’ maximum 
post-baseline values will also be categorized and the number and percentage of 
subjects in each group will be summarized. Baseline ECG recording is defined as the 
mean of the 3 sets of triplicate ECG results (a total of 9 assessments) at study day -1 for 
cohorts 1 to 5, and at the day -3 to -1 visit for cohorts 8 and 9. 

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For cohorts 6 and 7, the ECG measurements will be performed as per standard of care 
for routine safety monitoring, rather than for purposes of assessment of potential QTc 
effect.  Since these evaluations may not necessarily be performed under the rigorous 
conditions expected to lead to meaningful evaluation of QTc data; summaries and 
statistical analyses of ECG measurements are not planned, and these data would not be 
expected to be useful for meta-analysis with data from other trials. 
13.5.2.1.4 
Clinical Laboratory 
Analyses of laboratory values will include summary statistics over time (for each protocol 
scheduled visit) by cohort. Additional summaries may include descriptive statistics of 
changes from baseline over time. 
13.5.3 
Secondary Endpoint(s) 
13.5.3.1 
Pharmacokinetics (PK) Analysis  
Serum samples will be analyzed for AMG 890 concentrations using a validated assay. 
Individual concentration-time plots for AMG 890 will be presented for each subject as 
well as mean concentration-time plots for each cohort. Pharmacokinetic parameters 
including but not limited to AUC, Cmax, and tmax will be estimated using 
non-compartmental methods. Actual dosing and sampling times will be used for 
calculation of PK parameters. Summary statistics will be generated for each PK 
parameter for each dose cohort using the PK analysis set. 
13.5.3.2 
Pharmacodynamic (PD) Analysis 
Change and percent change in plasma Lp(a) levels at each scheduled visit up to the end 
of treatment visit. 
13.5.4.1 
Total Cholesterol, Cholesterol Fractions, and Apolipoproteins 
Summary statistics will be provided for total cholesterol, cholesterol fractions (very-low 
density lipoprotein cholesterol [VLDL-C], low-density lipoprotein cholesterol [LDL-C], and 
high-density lipoprotein cholesterol [HDL-C]), triglycerides, apolipoprotein A1 [ApoA1] 
and total apolipoprotein B [ApoB]) at each scheduled visit by cohort.  

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13.5.4.2 
Qualitative Assessment of AMG 890 in Urine 
Urine samples will be collected and AMG 890 in urine will be analyzed so that fractions 
of dose eliminated unchanged in urine may be determined.  Subject-level data and 
cohort summary statistics may be presented as appropriate. 
14. 
REGULATORY OBLIGATIONS 
14.1 
Informed Consent 
An initial sample informed consent form is provided for the investigator to prepare the 
informed consent document to be used at his or her site.  Updates to the template are to 
be communicated formally in writing from the Amgen Study Manager to the investigator.  
The written informed consent form is to be prepared in the language(s) of the potential 
subject population. 
Before a subject’s participation in the clinical study, the investigator is responsible for 
obtaining written informed consent from the subject after adequate explanation of the 
aims, methods, anticipated benefits, and potential hazards of the study and before any 
protocol specific screening procedures or any investigational product(s) is/ are 
administered.   
The investigator is also responsible for asking the subject if the subject has a primary 
care physician and if the subject agrees to have his/her primary care physician informed 
of the subject’s participation in the clinical study.  If the subject agrees to such 
notification, the investigator is to inform the subject’s primary care physician of the 
subject’s participation in the clinical study.  If the subject does not have a primary care 
physician and the investigator will be acting in that capacity, the investigator is to 
document such in the subject’s medical record.  The acquisition of informed consent and 
the subject’s agreement or refusal of his/her notification of the primary care physician is 
to be documented in the subject’s medical records, and the informed consent form is to 
be signed and personally dated by the subject and by the person who conducted the 
informed consent discussion.  The original signed informed consent form is to be 
retained in accordance with institutional policy, and a copy of the signed consent form is 
to be provided to the subject. 

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If a potential subject is illiterate or visually impaired and does not have a legally 
acceptable representative, the investigator must provide an impartial witness to read the 
informed consent form to the subject and must allow for questions.  Thereafter, both the 
subject and the witness must sign the informed consent form to attest that informed 
consent was freely given and understood.   
14.2 
Institutional Review Board/Independent Ethics Committee 
A copy of the protocol, proposed informed consent form, other written subject-facing 
information, and any proposed advertising material must be submitted to the IRB/IEC for 
written approval.  A copy of the written approval of the protocol and informed consent 
form must be received by Amgen before recruitment of subjects into the study and 
shipment of Amgen investigational product. 
The investigator must submit and, where necessary, obtain approval from the IRB/IEC 
for all subsequent protocol amendments and changes to the informed consent 
document.  The investigator is to notify the IRB/IEC of deviations from the protocol or 
serious adverse events occurring at the site and other adverse event reports received 
from Amgen, in accordance with local procedures. 
The investigator is responsible for obtaining annual IRB/IEC approval /renewal 
throughout the duration of the study.  Copies of the investigator’s reports and the 
IRB/IEC continuance of approval must be sent to Amgen. 
14.3 
Subject Confidentiality 
The investigator must ensure that the subject’s confidentiality is maintained:   
 
Subjects are to be identified by a unique subject identification number.   
 
Where permitted, date of birth is to be documented and formatted in accordance with 
local laws and regulations.   
 
On the demographics page, in addition to the unique subject identification number, 
include the age at the time of enrollment.   

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 
For Serious Adverse Events reported to Amgen, subjects are to be identified by their 
unique subject identification number, initials (for faxed reports, in accordance with 
local laws and regulations), and date of birth (in accordance with local laws and 
regulations). 
 
Documents that are not submitted to Amgen (eg, signed informed consent forms) are 
to be kept in strict confidence by the investigator, except as described below. 
In compliance with governmental/ICH GCP Guidelines, it is required that the investigator 
and institution permit authorized representatives of the company, of the regulatory 
agency(s), and the IRB/IEC direct access to review the subject’s original medical records 
for verification of study related procedures and data.  Direct access includes examining, 
analyzing, verifying, and reproducing any records and reports that are important to the 
evaluation of the study.  The investigator is obligated to inform and obtain the consent of 
the subject to permit named such individuals to have access to his/her study related 
records, including personal information. 
14.4 
Investigator Signatory Obligations 
Each clinical study report is to be signed by the investigator or, in the case of  
multi-center studies, the coordinating investigator. 
The coordinating investigator, identified by Amgen, will be any or all of the following: 
 
a recognized expert in the therapeutic area 
 
an investigator who provided significant contributions to either the design or 
interpretation of the study 
 
an investigator contributing a high number of eligible subjects 
15. 
ADMINISTRATIVE AND LEGAL OBLIGATIONS 
15.1 
Protocol Amendments and Study Termination 
Amgen may amend the protocol at any time.  After Amgen amends the protocol, the 
Investigator is to return the signed Investigator’s Signature page confirming agreement 
to continue participation in the study according to the amendment.  The IRB/IEC must be 
informed of all amendments and give approval.  The investigator must send a copy of 
the approval letter from the IRB/IEC and amended protocol Investigator’s Signature 
page to Amgen prior to implementation of the protocol amendment at their site. 
Amgen reserves the right to terminate the study at any time.  Both Amgen and the 
investigator reserve the right to terminate the Investigator’s participation in the study 
according to the Clinical Trial Agreement.  The investigator is to notify the IRB/IEC in 
writing of the study’s completion or early termination and send a copy of the notification 
to Amgen. 

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Subjects may be eligible for continued treatment with Amgen investigational product by 
an extension protocol or as provided for by the local country’s regulatory mechanism.  
However, Amgen reserves the unilateral right, at its sole discretion, to determine 
whether to supply Amgen investigational product(s), and by what mechanism, after 
termination of the study and before it is available commercially. 
15.2 
Study Documentation and Archive 
The investigator is to maintain a list of appropriately qualified persons to whom he/she 
has delegated study duties.  All persons authorized to make entries and/or corrections 
on CRFs will be included on the Amgen Delegation of Authority Form. 
Source documents are original documents, data, and records from which the subject’s 
CRF data are obtained.  These include but are not limited to hospital records, clinical 
and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, 
and correspondence. 
The Investigator and study staff are responsible for maintaining a comprehensive and 
centralized filing system of all study related (essential) documentation, suitable for 
inspection at any time by representatives from Amgen and/or applicable regulatory 
authorities.   
Elements to include: 
 
Subject files containing completed CRF, informed consent forms, and subject 
identification list 
 
Study files containing the protocol with all amendments, Investigator’s Brochure, 
copies of prestudy documentation, and all correspondence to and from the IRB/IEC 
and Amgen 
 
Investigational product-related correspondence including Proof of Receipts (POR), 
Investigational Product Accountability Record(s), Return of Investigational Product 
for Destruction Form(s), Final Investigational Product Reconciliation Statement, as 
applicable. 
 
Non-investigational product(s), and/or medical device(s) or combination product(s) 
documentation, as applicable. 
In addition, all original source documents supporting entries in the CRFs must be 
maintained and be readily available. 
Retention of study documents will be governed by the Clinical Trial Agreement. 
15.3 
Study Monitoring and Data Collection 
The Amgen representative(s) and regulatory authority inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting the facilities and, 

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upon request, inspecting the various records of the clinical study (eg, CRFs and other 
pertinent data) provided that subject confidentiality is respected. 
The Clinical Monitor is responsible for verifying the CRFs at regular intervals throughout 
the study to verify adherence to the protocol; completeness, accuracy, and consistency 
of the data; and adherence to local regulations on the conduct of clinical research.  The 
Clinical Monitor is to have access to subject medical records and other study related 
records needed to verify the entries on the CRFs. 
The investigator agrees to cooperate with the clinical monitor to ensure that any 
problems detected in the course of these monitoring visits, including delays in 
completing CRFs, are resolved. 
In accordance with ICH GCP and the sponsor’s audit plans, this study may be selected 
for audit by representatives from Amgen’s Global Compliance Auditing function (or 
designees).  Inspection of site facilities (eg, pharmacy, protocol-required therapy storage 
areas, laboratories) and review of study related records will occur to evaluate the study 
conduct and compliance with the protocol, ICH GCP, and applicable regulatory 
requirements. 
Data capture for this study is planned to be electronic: 
 
All source documentation supporting entries into the electronic CRFs must be 
maintained and readily available. 
 
Updates to electronic CRFs will be automatically documented through the software’s 
“audit trail.” 
 
To ensure the quality of clinical data across all subjects and sites, a clinical data 
management review is performed on subject data received at Amgen.  During this 
review, subject data are checked for consistency, omissions, and any apparent 
discrepancies.  In addition, the data are reviewed for adherence to the protocol and 
GCP.  To resolve any questions arising from the clinical data management review 
process, data queries are created in the EDC system database for site resolution 
and subsequently closed by the EDC system or by an Amgen reviewer. 
 
The investigator signs only the Investigator Verification Form for this electronic data 
capture study.  This signature indicates that the investigator inspected or reviewed 
the data on the CRF, the data queries, and agrees with the content. 
15.4 
Investigator Responsibilities for Data Collection 
The investigator is responsible for complying with the requirements for all assessments 
and data collection (including subjects not receiving protocol-required therapies) as 
stipulated in the protocol for each subject in the study.  For subjects who withdraw prior 
to completion of all protocol-required visits and are unable or unwilling to continue the 

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Schedule of Assessments (Section 10.1), the investigator can search publicly available 
records (where permitted) to ascertain survival status.  This ensures that the data set(s) 
produced as an outcome of the study is/are as comprehensive as possible.   
15.5 
Language 
CRFs must be completed in English.  TRADENAMES (if used) for concomitant 
medications may be entered in the local language.   
All written information and other material to be used by subjects and investigative staff 
must use vocabulary and language that are clearly understood.   
15.6 
Publication Policy 
To coordinate dissemination of data from this study, the investigator will obtain input and 
assistance from Amgen staff as appropriate. 
To coordinate dissemination of data from this study, Amgen may facilitate the formation 
of a publication committee consisting of several investigators and appropriate Amgen 
staff, the governance and responsibilities of which are set forth in a Publication Charter.  
The committee is expected to solicit input and assistance from other investigators and to 
collaborate with authors and Amgen staff as appropriate as defined in the Publication 
Charter.  Membership on the committee (both for investigators and Amgen staff) does 
not guarantee authorship.  The criteria described below are to be met for every 
publication. 
Authorship of any publications resulting from this study will be determined on the basis 
of the International Committee of Medical Journal Editors (ICMJE) Recommendations for 
the Conduct of Reporting, Editing, and Publication of Scholarly Work in Medical 
Journals, which states: 
 
Authorship credit should be based on (1) substantial contributions to conception and 
design, acquisition of data, or analysis and interpretation of data; (2) drafting the 
article or revising it critically for important intellectual content; (3) final approval of the 
version to be published; and (4) agreement to be accountable for all aspects of the 
work in ensuring that questions related to the accuracy or integrity of any part of the 
work are appropriately investigated and resolved.  Authors should meet conditions 1, 
2, and 3 and 4. 
 
When a large, multicenter group has conducted the work, the group should identify 
the individuals who accept direct responsibility for the manuscript.  These individuals 
should fully meet the criteria for authorship defined above. 
 
Acquisition of funding, collection of data, or general supervision of the research 
group, alone, does not justify authorship. 

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 
All persons designated as authors should qualify for authorship, and all those who 
qualify should be listed. 
 
Each author should have participated sufficiently in the work to take public 
responsibility for appropriate portions of the content. 
All publications (eg, manuscripts, abstracts, oral/slide presentations, book chapters) 
based on this study must be submitted to Amgen for corporate review.  The Clinical Trial 
Agreement among the institution, investigator, and Amgen will detail the procedures for, 
and timing of, Amgen’s review of publications. 
15.7 
Compensation 
Any arrangements for compensation to subjects for injury or illness that arises in the 
study are described in the Compensation for Injury section of the Informed Consent that 
is available as a separate document. 

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incident metabolic syndrome and mortality. J Investig Med. 2016;64: 392-399. 
Paige E, Masconi KL, Tsimikas S, et al, Lipoprotein(a) and incident type-2 diabetes: 
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Date:  07 December 2021 
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17. 
APPENDICES 
Appendix A.  Additional Safety Assessment Information 
Adverse Event Grading Scale 
For all adverse events, the investigator must assess the severity according to the Amgen 
Standard Adverse Event Scale depicted below:  
 
Amgen Standard Adverse Event Grading Scale 
MILD 
Aware of sign or symptom, but easily tolerated 
MODERATE 
Discomfort enough to cause interference with usual activity 
SEVERE 
Incapacitating with inability to work or do usual activity 
Drug-induced Liver Injury Reporting & Additional Assessments  
Reporting 
To facilitate appropriate monitoring for signals of DILI, cases of concurrent AST or ALT 
and TBIL and/or INR elevation according to the criteria specified in Section 9.4 require 
the following: 
 
The event is to be reported to Amgen as a serious adverse event within 24 hours of 
discovery or notification of the event (ie, before additional etiologic investigations 
have been concluded) 
 
The appropriate eCRF (eg, Event eCRF) that captures information necessary to 
facilitate the evaluation of treatment-emergent liver abnormalities is to be completed 
and sent to the Amgen.  
Other events of hepatotoxicity and potential DILI are to be reported as serious adverse 
events if they meet the criteria for a serious adverse event defined in Section 12.2.1.2. 
Additional Clinical Assessments and Observation 
All subjects in whom investigational product(s) or protocol-required therapies is/are 
withheld (either permanently or conditionally) due to potential DILI as specified in 
Section 9.4 or who experience AST or ALT elevations  3 x ULN or 2-fold increase 
above baseline values for subjects with evaluated values before drug must undergo a 
period of “close observation” until abnormalities return to normal or to the subject’s 
baseline levels.  Assessments that are to be performed during this period include:  
 
Repeat AST, ALT, ALP, bilirubin (total and direct), and INR within 24 hours  
 
In cases of TBIL  2x ULN or INR  1.5, retesting of liver tests, bilirubin (total and 
direct), and INR is to be performed every 24 hours until laboratory abnormalities 
improve 

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 
Testing frequency of the above laboratory tests may decrease if the abnormalities 
stabilize or the investigational product(s) or protocol-required therapies has/have 
been discontinued AND the subject is asymptomatic. 
 
Initiate investigation of alternative causes for elevated AST or ALT and/or elevated 
TBIL.  The following are to be considered depending on the clinical situation: 
 
Complete blood count (CBC) with differential to assess for eosinophilia 
 
Serum total immunoglobulin IgG, Anti-nuclear antibody (ANA), Anti Smooth 
Muscle Antibody, and Liver Kidney Microsomal antibody 1 (LKM1) to assess for 
autoimmune hepatitis 
 
Serum acetaminophen (paracetamol) levels 
 
A more detailed history of:  
o Prior and/or concurrent diseases or illness 
o Exposure to environmental and/or industrial chemical agents  
o Symptoms (if applicable) including right upper quadrant pain,  
hypersensitivity-type reactions, fatigue, nausea, vomiting and fever 
o Prior and/or concurrent use of alcohol, recreational drugs and special diets 
o Concomitant use of medications (including non-prescription medicines and 
herbal and dietary supplements), plants, and mushrooms 
 
Viral serologies 
 
CPK, haptoglobin, LDH, and peripheral blood smear 
 
Appropriate liver imaging if clinically indicated 
 
Appropriate blood sampling for pharmacokinetic analysis if this has not already been 
collected  
 
Hepatology consult (liver biopsy may be considered in consultation with an 
hepatologist) 
 
Follow the subject and the laboratory tests (ALT, AST, TBIL, INR) until all laboratory 
abnormalities return to baseline or normal or considered stable by the investigator.  
The “close observation period” is to continue for a minimum of 4 weeks after 
discontinuation of all investigational product(s) and protocol-required therapies. 
The potential DILI event and additional information such as medical history, concomitant 
medications and laboratory results must be captured in corresponding CRFs. 

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Appendix B.  Serious Adverse Event Report Form  
 

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Appendix C.  Pregnancy Notification Form 
 
 

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Appendix D.  Lactation Notification Form 
 
 

Approval Signatures
Document Name:
Protocol Amendment olpasiran 20170544 7
Document Description:
AMG 890 Study 20170544 PA7 clean
Document Number:
CLIN-000007686
Approval Date:
08 Dec 2021
Type of Study Protocol:
Amendment
Protocol Amendment No.: 7
Document Approvals
Reason for Signing: Management
Name: 
Date of Signature: 07-Dec-2021 17:48:12 GMT+0000
Reason for Signing: Functional Area
Name: 
Date of Signature: 08-Dec-2021 17:34:40 GMT+0000

Product:  AMG 890 
Protocol Number:  20170544 
Date:  07 December 2021 
Page 1 of 6 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Amendment 7 
Protocol Title:  A Phase 1, Randomized, Double-blind, Placebo-controlled, Single 
Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a) 
 
Amgen Protocol Number (AMG 890) 20170544 
 
Amendment Date: 
07 December 2021 
 
Rationale: 
This protocol is being amended to enhance subject enrollment for cohort 9 by loosening 
eligibility restrictions on age, body mass index (BMI), and history of diabetes.  Accumulated data 
thus far confirm that modifying these eligibility criteria are not expected to have an adverse 
impact on subject safety, pharmacokinetics, or pharmacodynamics. 
Changes to the protocol text in Section 12 (safety) are in line with current Amgen protocol 
template. 

Product:  AMG 890 
Protocol Number:  20170544 
Date:  25 March 2021 
Page 1 of 7 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Superseding Amendment 6 
Protocol Title:  A Phase 1, Randomized, Double-blind, Placebo-controlled, Single 
Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a) 
 
Amgen Protocol Number (AMG 890) 20170544 
IND number BB-IND 136605 
Amendment Date: 
25 March 2021 
Rationale: 
This protocol is being amended to: 
 
Update made to the protocol to the Schedule of Assessments for cohorts 1 to 9 
 
Update the Pregnancy Notification Form  
 
Administrative, typographical, and formatting changes were made throughout the 
protocol. 

Product:  AMG890 
Protocol Number:  20170544 
Date:  21 December 2020 
Page 1 of 1 
Amgen Proprietary - Confidential 
Amendment 6 
Protocol Title:  A Phase 1, Randomized, Double-blind, Placebo-controlled, Single 
Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of AMG 890 in Subjects with Elevated Plasma Lipoprotein(a) 
 
Amgen Protocol Number AMG890 20170544 
 
Amendment Date: 
21 December 2020 
 
Rationale: 
This protocol was amended because editorial updates were needed to align with current 
safety language in the new template, change the vendor providing laboratory analyses, 
add urinalysis at day 85 for cohorts 8 and 9, clarify the enrollment status of cohorts 1-8, 
and make other administrative/editorial updates.  

Product:  AMG 890
Protocol Number:  20170544
Date:  13 December 2019
Page 1 of 27
CONFIDENTIAL
Amendment #5
Protocol Title:  A Phase 1, Randomized, Double-blind, Placebo-controlled, Single 
Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)
Amgen Protocol Number AMG 890 20170544
Amendment Date:
13 December 2019
Rationale:
The protocol is being amended to add 2 SAD cohorts evaluating 225 mg (cohort 8) and 
675 mg (cohort 9) in subjects with high baseline Lp(a) ≥200 nM. The highest doses of 
AMG 890 tested to date, which have been observed to be well tolerated with no safety
signals, are 225 mg in low baseline Lp(a) subjects (cohort 5) and 75 mg in high baseline 
Lp(a) subjects (cohort 7). In cohorts 1 to 7 of this study, considerable variability has been 
observed in PK and Lp(a) response between low and high baseline Lp(a) subjects.
Given these differences, the 225 mg and 675 mg cohorts in high baseline Lp(a) subjects 
(cohorts 8 and 9) will allow for more intensive and robust PK and Lp(a) data evaluation 
to support broader options for AMG 890 Ph 3 dose and regimen selection. The 675 mg 
dose (cohort 9), in turn, is also anticipated to provide a wide range of exposures with 
minimal overlap in exposure distributions across subjects with high baseline Lp(a) 
(~9 fold increase from 9 mg in cohort 6 to 675 mg in cohort 9), and to provide additional 
safety information at a higher dose and with longer durations of Lp(a) suppression. 
Also, administrative and typographical changes were made.

Product:  AMG 890
Protocol Number:  20170544
Date:  17 May 2019
Page 1 of 3
CONFIDENTIAL
Amendment #4
Protocol Title:  A Phase 1, Randomized, Double-blind, Placebo-controlled, Single 
Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)
Amgen Protocol Number AMG 890 20170544
Amendment Date:
17 May 2019
Rationale:
The protocol is being amended to clarify that Lp(a) samples are to be collected at days 
155 and 183 for cohorts 3 to 5.  Inadvertently, Lp(a) measurement collections were not 
noted on Table 5:  Schedule of Assessments – Post-Dosing for Cohorts 1-5 on study 
days 155 and 183, and the number of times and blood volume collected were not 
correctly reflected in the Informed Consent Form (ICF). Table 3: Tests & Procedures of 
the ICF does correctly state that blood tests for Lp(a) will be collected at Screening, 
days 1, 2, 4, 7, 15, and all visits through end of treatment for cohorts 3 to 5.  
Also, administrative and typographical changes were made.

Product:  AMG 890
Protocol Number:  20170544
Date:  02 May 2019
Page 1 of 7
CONFIDENTIAL
Amendment #3
Protocol Title:  A Phase 1, Randomized, Double-blind, Placebo-controlled, Single 
Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)
Amgen Protocol Number AMG 890 20170544
Amendment Date:
02 May 2019
Rationale:
The protocol is being amended for the following reasons:  to update key study contact 
personnel, to define the dose in cohort 7 as 75 mg and to update inclusion and exclusion 
criteria for cohorts 6 and 7.  Exclusion criterion 209 was updated to exclude subjects on 
stable dose of statin in cohorts 6 and 7 if the ALT or AST is > 1.5 the upper limit of 
normal of the laboratory’s reference at screening or at day -3 to -1.  In addition,
exclusion criterion 219 was updated to permit subjects in cohorts 6 and 7 to be on stable 
medications for chronic medical conditions not otherwise excluded.  These updates are 
not expected to impact the safety of the subjects.  Updates to the Schedule of 
Assessment tables were also made to correct the study hour for day 7 and to add vital 
sign measurements on day -3 to day -1 for cohorts 6 and 7.
Also, administrative, typographical and formatting changes were made throughout the 
protocol.

Protocol Number:  20170544
Product:  AMG 890
Date:  07 February 2019
Page 1 of 54
Confidential
Amendment #2
Protocol Title:  A Phase 1, Randomized, Double-blind, Placebo-controlled, Single 
Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)
Amgen Protocol Number AMG 890 20170544
Amendment Date:
07 February 2019
Rationale:
As of 6 February 2019, AMG 890 was administered as a single subcutaneous dose of 3, 
9, 30, 75, and 225 mg to 30 subjects (6 per dose level) with elevated Lp(a) levels 
subjects.  Doses up to 75 mg were reviewed by the dose level review team and found to 
be safe and tolerated to date.  At the time of this amendment, subjects in the 225 mg 
dose cohort have completed dosing and have been followed for 7 days without incident.  
Based on the preliminary pharmacodynamic results no further dose escalation (ie, to 675 
mg) is necessary, and monthly dosing will not be selected as a dosing regimen in future 
AMG 890 studies.  Therefore, the 675 mg single dose cohort and the multiple ascending 
dose cohorts (ie, AMG 890 or placebo Q4W x 3) have been removed from the protocol.
Changes implemented include:

Removing the multiple ascending dose (MAD) cohorts and SAD cohort 6 (675 
mg dose)

Adding two new SAD cohorts (6 and 7) that will enroll the same population that 
would have been assessed in the removed MAD cohorts

Increasing the number of sites participating in the study

Updating of the definitions of end of treatment visit and end of study visit

Updating the requirements for the follow-up of subjects who at the end of 
treatment visit have plasma Lp(a) levels that have not returned to ≥ 80% of 
baseline

Protocol Number:  20170544
Product:  AMG 890
Date:  07 February 2019
Page 2 of 54
Confidential

Updating the secondary endpoint to reflect that the assessment of change in 
Lp(a) levels will be through the end of treatment visit 

Specifying the planned primary and final analyses

Updating the definition of baseline for Lp(a)

Updating the inclusion and exclusion criteria  

Updating the Dose Level Review Team (DLRT)
The use of Self Evident Corrections is being removed according to current Amgen 
practice.  
Current Amgen forms have been updated for the following forms: electronic SAE 
Contingency Form, Lactation Notification Form, Pregnancy Form.
Also, administration, typographical and formatting changes were made throughout the 
protocol.

Product:  AMG 890
Protocol Number:  20170544
Date:  20 September 2018
Page 1 of 39
CONFIDENTIAL
Amendment #1
Protocol Title:  A Phase 1, Randomized, Double-blind, Placebo-controlled, Single 
and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics and Pharmacodynamics of AMG 890 in Subjects with Elevated 
Plasma Lipoprotein(a)
Amgen Protocol Number AMG 890 20170544
Amendment Date:
20 September 2018
Rationale:
This protocol is being amended to add additional safety laboratory and ECG 
assessments; to add two additional days for urine PK sampling; to clarify exclusion 
criteria; to implement operational changes; and to remove redundancy within the 
exploratory biomarker endpoints, 
 
. These changes will refine the protocol’s readability, 
allow for the implementation of operational changes, and will improve quality of data 
generation.
In addition, changes have been made to the protocol to improve the readability, the 
clarity, and the consistency throughout the protocol.
One of the Key Contacts for the study has been updated.