A Phase 2, Randomized, Double Blind, Placebo Controlled, Parallel Group, Multiple Center Study to Evaluate the Safety, Tolerability, and Efficacy of NGM282 Administered for 12 Weeks in Patients With Primary Sclerosing Cholangitis
Phase: PHASE2
Conditions: Primary Sclerosing Cholangitis
Sponsor: NGM Biopharmaceuticals, Inc

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 1 of 71 
 
 
 
 
 
 
 
A PHASE 2, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED, 
PARALLEL GROUP, MULTIPLE CENTER STUDY TO EVALUATE THE 
SAFETY, TOLERABILITY, AND EFFICACY OF NGM282 ADMINISTERED FOR 
12 WEEKS IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS (PSC) 
 
PROTOCOL NUMBER 15-0106 
 
for 
 
NGM Biopharmaceuticals, Inc. 
 
IND Number:  119,471 
EudraCT Number:  2015-003392-30 
 
Original Protocol – 30 July 2015 
Amendment 1 – 5 November 2015 
Amendment 2 – 27 May 2016 
 
Confidentiality Statement: 
This document contains proprietary and confidential information of NGM Biopharmaceuticals, Inc.  Acceptance 
of this document constitutes agreement by the recipient that no previously unpublished information contained 
herein will be published or disclosed without the prior written approval of NGM Biopharmaceuticals, Inc. with 
the exception that this document may be disclosed to study personnel under your supervision who need to know 
the contents for conducting the study and appropriate Institutional Review Boards/Ethics Committees under the 
condition that the personnel have agreed to keep this information confidential.  The foregoing shall not apply to 
disclosure r equired by  governmental r egulations or  l aws; h owever, N GM Biopharmaceuticals, Inc. shall b e 
promptly notified of any such disclosure. 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 3 of 71 
 
TABLE OF CONTENTS 
STUDY IDENTIFICATION ...............................................................................................2 
ABBREVIATIONS .............................................................................................................8 
1 SYNOPSIS ...................................................................................................................11 
2 INTRODUCTION .......................................................................................................15 
2.1 
BACKGROUND .............................................................................................15 
2.1.1 Primary Sclerosing Cholangitis (PSC) .....................................................15 
2.1.2 Treatment of PSC .....................................................................................16 
2.1.3 Therapeutic Rationale for NGM282 in PSC ............................................18 
2.2 
NONCLINICAL STUDIES .............................................................................19 
2.2.1 Nonclinical Safety Assessment ................................................................19 
2.3 
CLINICAL STUDIES .....................................................................................20 
2.4 
RATIONALE FOR DOSE SELECTION OF NGM282 FOR PSC ................20 
3 STUDY OBJECTIVES ................................................................................................22 
4 STUDY DESIGN.........................................................................................................23 
4.1 
STUDY STOPPING CRITERIA .....................................................................23 
5 SUBJECT SELECTION ..............................................................................................24 
5.1 
INCLUSION CRITERIA.................................................................................24 
5.2 
EXCLUSION CRITERIA ...............................................................................25 
5.3 
DISCONTINUATION OF STUDY TREATMENT IN AN INDIVIDUAL 
SUBJECT .........................................................................................................28 
5.4 
DISCONTINUATION OF SUBJECTS FROM STUDY PARTICIPATION.28 
5.5 
SCHEDULE OF STUDY PROCEDURES .....................................................29 
5.6 
STUDY VISIT PROCEDURES ......................................................................32 
5.6.1 Day –42 to Day –1 (Screening) Procedures .............................................32 
5.6.2 Day 1 Procedures ......................................................................................33 
5.6.3 Week 1 Procedures ...................................................................................34 
5.6.4 Week 2 Procedures ...................................................................................35 
5.6.5 Week 4 Procedures ...................................................................................36 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 4 of 71 
 
5.6.6 Week 8 Procedures ...................................................................................37 
5.6.7 Week 12 (End of Treatment)/Early Withdrawal Procedures ...................38 
5.6.8 Week 16 (End of Study) Procedures ........................................................39 
5.7 
CONCOMITANT MEDICATIONS ...............................................................40 
5.8 
DIET AND ACTIVITY CONTROL ...............................................................40 
5.9 
CLINICAL EVALUATIONS ..........................................................................41 
5.9.1 Colonoscopy .............................................................................................41 
5.9.2 Magnetic Resonance Cholangiopancreatography ....................................41 
5.9.3 Pharmacokinetic Blood Sample Collection and Processing .....................42 
5.9.4 Clinical Laboratory Assessments .............................................................42 
5.9.5 12-Lead Electrocardiograms ....................................................................43 
5.9.6 Vital Signs ................................................................................................43 
5.9.7 Physical Examinations .............................................................................43 
5.9.8 Weight ......................................................................................................43 
5.9.9 Local Injection-Site Symptom Assessments ............................................43 
5.9.10 Numeric Rating Scale for Pruritus and Fatigue ........................................44 
5.9.11 5-D Pruritus Scale ....................................................................................44 
5.9.12 Mayo Partial IBD Score ...........................................................................44 
6 STUDY DRUG ............................................................................................................46 
6.1 
CLINICAL SUPPLIES ....................................................................................46 
6.2 
STUDY DRUG ACCOUNTABILITY............................................................46 
6.3 
STUDY DRUG STORAGE ............................................................................46 
6.4 
DOSE PREPARATION AND ADMINISTRATION .....................................46 
6.5 
REMOVAL OF STUDY BLIND ....................................................................47 
7 ADVERSE EVENTS ...................................................................................................47 
7.1 
DEFINITION AND GRADING OF SEVERITY OF ADVERSE EVENTS .47 
7.2 
CRITERIA FOR DETERMINING RELATIONSHIP TO DRUG .................48 
7.3 
REPORTING ...................................................................................................49 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 5 of 71 
 
7.3.1 Serious Adverse Events Notification Requirements ................................50 
8 DATA ANALYSIS AND STATISTICAL CONSIDERATIONS ..............................52 
8.1 
SAMPLE SIZE ................................................................................................52 
8.2 
RANDOMIZATION........................................................................................53 
8.3 
TEST OF HYPOTHESIS AND SIGNIFICANCE LEVELS ..........................53 
8.4 
ANALYSIS SETS ...........................................................................................53 
8.4.1 Randomized Set ........................................................................................53 
8.4.2 Safety Set ..................................................................................................53 
8.4.3 Full Analysis Set ......................................................................................53 
8.4.4 Per Protocol Set ........................................................................................54 
8.4.5 Pharmacokinetic Set .................................................................................54 
8.5 
SUBJECT DISPOSITION ...............................................................................54 
8.6 
TREATMENT EXPOSURE ............................................................................54 
8.7 
PROTOCOL DEVIATIONS ...........................................................................54 
8.8 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........54 
8.9 
EFFICACY AND PHARMACODYNAMICS ...............................................55 
8.9.1 Efficacy and Pharmacodynamic Endpoints ..............................................55 
8.9.2 Analysis of Primary Efficacy Endpoint ....................................................55 
8.9.3 Analysis of Secondary Endpoints.............................................................56 
8.9.4 Analysis of Exploratory PD Endpoints ....................................................57 
8.10 
SAFETY AND TOLERABILITY ...................................................................57 
8.10.1 Adverse Events .........................................................................................57 
8.10.2 Clinical Laboratory Evaluations ...............................................................58 
8.10.3 Physical Examinations .............................................................................58 
8.10.4 Vital Signs ................................................................................................58 
8.10.5 Pregnancy Test .........................................................................................58 
8.10.6 Electrocardiogram ....................................................................................58 
8.10.7 Injection-Site Reactions ...........................................................................58 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 6 of 71 
 
8.10.8 Prior and Concomitant Medications .........................................................58 
8.10.9 Interim Analysis .......................................................................................59 
8.11 
PHARMACOKINETICS .................................................................................59 
9 DATA MANAGEMENT AND ELECTRONIC SYSTEMS ......................................59 
9.1 
DATA MANAGEMENT.................................................................................59 
9.2 
ELECTRONIC SYSTEMS ..............................................................................60 
10 ADMINISTRATIVE ASPECTS .................................................................................60 
10.1 
PROTOCOL ADHERENCE ...........................................................................60 
10.2 
DISCLOSURE .................................................................................................60 
10.3 
MONITORING ................................................................................................60 
10.4 
INSTITUTIONAL REVIEW BOARD/ETHICS COMMITTEE ....................61 
10.5 
INFORMED CONSENT .................................................................................61 
10.6 
RECORDS .......................................................................................................61 
10.7 
DATA MONITORING COMMITTEE ...........................................................62 
10.8 
FINANCING AND INSURANCE ..................................................................62 
INVESTIGATOR PROTOCOL REVIEW AND SIGNATURE FORM ..........................63 
SPONSOR PROTOCOL APPROVAL AND SIGNATURE PAGE ................................64 
REFERENCES ..................................................................................................................65 
APPENDIX A–FOOD AND DRUG ADMINISTRATION TOXICITY GRADING 
SCALE IN LOCAL INJECTION-SITE SYMPTOM ASSESSMENTS ..............68 
APPENDIX B—NUMERIC RATING SCALE FOR ITCH AND FATIGUE .................69 
APPENDIX C—5-D PRURITIS SCALE .........................................................................70 
APPENDIX D—MAYO PARTIAL IBD SCORE (INFLAMMATORY BOWEL 
DISEASE SCALE) ................................................................................................71 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 7 of 71 
 
TABLE OF TABLES 
Number 
Title 
Page 
2.2.1-1 
Estimated Safety Exposure Margin of NGM282 
20 
5.5-1 
Schedule of Study Procedures 
30 
 
 
 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 8 of 71 
 
ABBREVIATIONS 
AASLD 
American Association for the Study of Liver Diseases 
ACG 
American College of Gastroenterology 
ADA 
anti-drug antibody 
AE 
adverse event 
AIH 
autoimmune hepatitis 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCA 
anti-neutrophil cytoplasmic antibody 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC 
area under the concentration–time curve 
C2h post-dose 
concentration at 2 hours post-dose 
C4 
7-alpha-hydroxy-4-cholesten-3-one 
CA19-9 
carbohydrate antigen 19-9 
CHMP 
Committee for Medicinal Products for Human Use (European Medicines 
Agency) 
Cmax 
maximum drug concentration 
CRO 
contract research organization 
Ctrough 
trough concentration 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMC 
Data Monitoring Committee 
DVM 
data validation manual 
EASL 
European Association for the Study of the Liver 
EC 
Ethics Committee 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
ELF 
enhanced liver fibrosis 
EOS 
end of study 
EOT 
end of treatment 
ERCP 
endoscopic retrograde cholangiopancreatography 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 9 of 71 
 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FGF19 
fibroblast growth factor 19 
GGT 
gamma-glutamyl transpeptidase  
GLP 
Good Laboratory Practice 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HDL 
high-density lipoprotein 
HIV 
human immunodeficiency virus 
IA 
Interim Analysis 
IB 
Investigator’s Brochure 
IBD 
inflammatory bowel disease 
ICF 
Informed Consent Form 
IgG4 
immunoglobulin G4 
IRB 
Institutional Review Board 
ICH 
International Conference on Harmonisation 
INR 
International Normalized Ratio 
ISR 
injection-site reaction 
 
 
LDL 
low-density lipoprotein 
LISSA 
local injection-site symptom assessment 
LS 
least square 
LLT 
Lowest Level Term (MedDRA)   
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed-effect model repeated measures 
MRCP 
magnetic resonance cholangiopancreatography 
NAb 
neutralizing antibody 
NASH 
nonalcoholic steatohepatitis 
NGM 
NGM Biopharmaceuticals, Inc. 
NGM282 
a recombinant protein of 190 a mino acids; engineered variant of humanized 
FGF19 under development for the treatment of type 2 diabetes 
NOAEL 
no-observed-adverse-effect level 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 10 of 71 
 
NRS 
Numeric Rating Scale 
p-ANCA 
perinuclear anti-neutrophil cytoplasmic antibody 
PBC 
primary biliary cirrhosis 
PD 
pharmacodynamics; pharmacodynamic 
PI 
Principal Investigator 
PK 
pharmacokinetics; pharmacokinetic 
PPS 
Per Protocol Set 
PSC 
primary sclerosing cholangitis 
PT 
preferred term 
SAE 
serious adverse event 
SAERF 
Serious Adverse Event Report Form 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SC 
subcutaneous 
SD 
standard deviation 
SE 
standard error 
SOC 
system organ class 
SUSAR 
suspected, unexpected serious adverse reaction 
T2D 
type 2 diabetes 
TEAE 
treatment-emergent adverse event 
TNF 
tumor necrosis factor 
UA 
urinalysis 
UC 
ulcerative colitis 
UDCA 
ursodeoxycholic acid 
UK 
United Kingdom 
ULN 
upper limit of normal 
U.S. 
United States 
WHO-DD 
World Health Organization Drug Dictionary Enhanced 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 12 of 71 
 
Methodology/ 
Study Design: 
This is a multiple-center evaluation of NGM282 in a randomized, double-blind, 
placebo-controlled, parallel-group study when administered for 12 weeks as a daily 
subcutaneous (SC) injection in patients with PSC.  Approximately 60 patients will be 
randomized across approximately 40–45 sites worldwide. 
Patients to be studied will have confirmed PSC as defined by an elevated ALP and 
either cholangiography or liver histology consistent with PSC.  The presence of IBD is 
allowed as well as treatment with a stable regimen of biologic, immunosuppressant, or 
systemic corticosteroid therapy.  Ursodeoxycholic acid (UDCA) therapy is allowed at 
stable doses for at least 12 weeks and < 27 mg/kg/day.  Patients with decompensated 
cirrhosis, cholangiocarcinoma (diagnosed or suspected), acute cholangitis, or recently 
placed bile-duct stents will be excluded from this study.  All patients with concomitant 
IBD will be required to have had a colonoscopy within 12 months of Screening with no 
evidence of dysplasia.  All patients will undergo a magnetic resonance 
cholangiopancreatography (MRCP) at Screening. 
Patients will sign the Informed Consent Form (ICF) at or prior to the Screening Visit, 
and will undergo screening assessments to verify eligibility for the study (up to 
6 weeks).   
On Day 1, subjects will be randomized into one of the three treatment arms (NGM282 
1 mg, NGM282 3 mg, or placebo) in a 1:1:1 ratio.  Subjects will be stratified at 
randomization, according to concurrent UDCA or no-UDCA status to ensure an even 
distribution across the three groups.  Study-drug self-administration instructions and 
training will be provided to the subjects and a weekly study-drug kit will be dispensed.  
Treatment assignment will be blinded to the sites, subjects, Sponsor, and Medical 
Monitor throughout the study period. 
The first dose (Day 1) and doses at Weeks 1, 2, 4, 8, and 12 will be self-administered in 
the clinic, with all other doses through Week 12 self-administered at home.  
Self-administration should occur at approximately the same time in the morning for 
every dose in both the clinic and at home. 
Subjects will return to the clinic on Weeks 1, 2, 4, and 8 for on-treatment assessments 
and to receive weekly study-drug kits.  Week 12 will be the End of Treatment (EOT) 
clinic visit.  Subjects will return to the clinic at Week 16 (or 4 weeks after last dose) for 
an End of Study (EOS) follow-up visit.  
 
Number of Subjects: 
 
Approximately 60 subjects will be randomized. 
 
Number of Study 
Sites: 
Approximately 40–45 sites worldwide.   
Test Product(s), 
Dose, and 
Mode of 
Administration: 
The NGM282 final product will be supplied in pre-filled syringes intended to deliver 
0.3 mL of 1 mg NGM282, 3 mg of NGM282, or placebo for SC injection.  Subjects 
will be instructed to self-administer SC injections of study drug at approximately the 
same time in the morning.   
 
Duration of 
Treatment: 
Patients will sign the ICF at or prior to the Screening Visit, and will undergo screening 
assessments to verify eligibility for the study (up to 6 weeks).  All subjects will be 
treated with NGM282 or placebo for 12 weeks, and will be monitored after completing 
their final dose of NGM282 or placebo (4 weeks).  The total duration of individual 
participation will be approximately 22 weeks.    
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 14 of 71 
 
Statistical Methods: 
The primary efficacy analysis will consist of comparing each NGM282 treatment group 
against the placebo group, within a mixed-effect model repeated measures analysis of 
the primary efficacy endpoint.  
The primary efficacy analysis will be repeated for each continuous secondary efficacy 
endpoint.  
The categorical secondary efficacy endpoints will be analyzed using confidence 
intervals of treatment differences. 
The safety and tolerability endpoints will be summarized. 
At the planned interim analysis, the evidence regarding the safety and efficacy of 
NGM282 in the PSC indication will be assessed, in order to evaluate the 
appropriateness of continuing the study. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 15 of 71 
 
2 INTRODUCTION 
2.1 
BACKGROUND 
2.1.1 Primary Sclerosing Cholangitis (PSC) 
PSC is a chronic cholestatic liver disease that is characterized by diffuse inflammation and 
fibrosis of the bile ducts (Chapman et al. 2010).  The intra and/or extrahepatic bile ducts can 
be affected; ongoing destruction often leads to cholestasis, advanced fibrosis, liver cirrhosis, 
and eventually liver failure with its consequent complications such as portal hypertension and 
increased risk of malignancy, in particular cholangiocarcinoma (Ali et al. 2015).  PSC is 
frequently associated with inflammatory bowel disease (IBD), more frequently ulcerative 
colitis (UC) than Crohn’s disease, with the prevalence ranging from 21% to 80%, depending 
on screening programs and nationality (Tsaitas et al. 2014). 
The disease is slowly progressive and its course may be variable from one patient to another 
(Angulo and Lindor 1999).  Males are affected twice as often as females and are usually 
diagnosed with the disease in their fifth decade of life (Molodecky et al. 2011).  Patients are 
often diagnosed incidentally, and nearly 50% are asymptomatic at the time of diagnosis 
(Hirschfield et al. 2013).  Despite being asymptomatic, patients with PSC have a shorter 
average time of survival compared with matched controls from the general population.  
Various review articles that consider the epidemiology of PSC on a global basis note a high 
degree of variability in prevalence and incidence figures (0.02–1.6 per 10,000 and 
0–0.13 per 10,000, respectively) with the greatest incidence and prevalence in Scandinavia, 
the UK, and the U.S. (Boonstra et al. 2012).  Several studies have suggested an increasing 
trend in PSC incidence and prevalence rates.  However, these apparent increases are more 
likely due to increasing awareness of the disease, greater understanding of the coincidence 
with IBDs, and improved diagnostics revealing more patients at the asymptomatic stage of 
disease. 
The etiology of PSC remains unclear although it is likely caused by multiple factors.  These 
include autoimmunity, portal bacteremia, absorption of toxins, ischemic injury, viral 
infections, toxic bile acids, and a genetic predisposition (Hirschfield and Karlsen 2014).  The 
pathogenesis of PSC involves the exposure of genetically predisposed individuals to an 
environmental antigen that subsequently elicits an aberrant immune response, leading to 
development of the disease. 
The diagnosis of PSC is challenging as most patients are asymptomatic or display 
nonspecific symptoms (Andraus et al. 2011).  The diagnosis of PSC is typically achieved 
after a complication such as cholangitis or hepatic dysfunction occurs.  Patients may 
experience periods of remission.  The severity and symptoms can vary between individuals 
who suffer from PSC as it is made up of more than one disease subtype, which include 
small-duct PSC, classic PSC, and immunoglobulin G4 (IgG4) PSC.  A diagnosis of PSC is 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 16 of 71 
 
made in patients with unexplained elevated serum alkaline phosphatase (ALP) and 
gamma-glutamyl transpeptidase (GGT) and when magnetic resonance 
cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography 
(ERCP) show characteristic bile-duct changes with multifocal strictures and segmental 
dilatations, and causes of secondary sclerosing cholangitis and other cholestatic disorders are 
excluded (Lindor et al. 2015).  A marked increase in serum autoantibody levels occurs in 
patients with PSC as well, with anti-neutrophil cytoplasmic antibodies (ANCAs) in 87%, 
anticardiolipin antibodies in 66%, and antinuclear antibodies in 53%.  Patients who present 
with clinical, biochemical, and histological features compatible with PSC but have normal 
cholangiograms are classified as having small-duct PSC.  Where a patient presents with IBD 
with increased liver test values, they should be immediately suspected of having concurrent 
PSC.  However, these abnormal values do not reflect the severity of the underlying disease 
and at present there is no specific diagnostic serologic test for PSC.  
Changes observed from liver biopsies in PSC patients in general are nonspecific although 
periductal concentric (“onion skinning”) fibrosis is a typical finding and so may support the 
diagnosis of PSC (Chapman et al. 2010; Lindor et al. 2015).  If a patient is suspected of 
having small-duct PSC or there are concerns that the patient also has autoimmune hepatitis 
then liver biopsy can be used to help diagnose PSC.  PSC has been described to progress 
through four stages: 
• Stage 1:  Lymphocyte infiltration and epithelial cell degeneration of the bile duct in 
the portal triads 
• Stage 2:  Inflammatory infiltrates and early fibrogenesis in the periportal parenchyma 
with piecemeal necrosis and enlarged bile ducts with minimal ductopenia 
• Stage 3:  Portal-to-portal bridging fibrosis with severe degeneration of the ducts and 
ductopenia 
• Stage 4:  End-stage liver disease with frank cirrhosis 
 
The most frequent clinical symptoms in PSC are fatigue and pruritus, with other less 
common symptoms being abdominal discomfort, jaundice, and weight loss (Benito de Valle 
et al. 2012).  Other symptoms may include vitamin deficiencies and bone disease and, in 
advanced liver disease, portal hypertension, coagulopathy, and liver failure (Hirschfield et al. 
2013).  Secondary complications of PSC include bacterial cholangitis, gall stones, and 
malignancy—in particular cholangio- and hepatocellular carcinoma (Lindor et al. 2015).   
2.1.2 Treatment of PSC 
Currently, the primary therapy for PSC is endoscopic or radiologic dilatation or stenting of 
bile-duct strictures targeted at reducing or halting progression of the disease (Kaya et al. 
2001; Lindor et al. 2015).  Although there is no established or approved pharmacologic 
therapy for PSC, ursodeoxycholic acid (UDCA) has been studied in multiple prospective 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 17 of 71 
 
clinical studies and is considered the only pharmacologic treatment option with a significant 
biochemical response.  However, the data supporting a beneficial effect on clinical endpoints 
and long-term outcomes remain conflicting.  Several prospective, randomized controlled 
trials have evaluated different doses of UDCA ranging from 10–15 mg/kg/day to  
17–23 mg/kg/day and most recently up to 28–30 mg/kg/day (Triantos et al. 2011).  Currently, 
neither the American Association for the Study of Liver Diseases (AASLD) nor the 
European Association for the Study of the Liver’s (EASL) Clinical Guidelines makes a 
recommendation for general use of UDCA in PSC (Beuers et al. 2009; Chapman et al. 2010).  
However, recent American College of Gastroenterology (ACG) guidelines have put a 
limitation on doses only above 27 mg/kg/day with a suggestion that intermediate doses may 
offer an improved biochemical response associated with improved outcomes (Lindor et al. 
2015).  ALP is the traditional marker of cholestasis and biochemical response to UDCA in 
PSC and recent studies have demonstrated it as predictive of disease progression and 
outcomes of treated and untreated patients.  Patients with PSC and very high serum ALP 
activity usually fail to respond to UDCA therapy, whereas patients with PSC with low serum 
ALP activity treated with UDCA have an excellent long-term prognosis (Stanich et al. 2011).  
Guidance from clinical experts has suggested a trial of 6 months of UDCA and to continue 
treatment if the ALP is reduced by 40% from baseline or < 1.5 x upper limit of normal 
(ULN) and no significant tolerability or safety issues are observed (Tabibian and Lindor 
2014).  
A number of immunosuppressive (prednisolone, budesonide, azathioprine, cyclosporine, 
methotrexate, mycophenolate, tacrolimus), anti-inflammatory (pentoxifylline, etanercept, 
other anti-TNF monoclonal antibodies) and anti-fibrotic (colchicine, penicillamine, 
pirfenidone) agents approved for other indications have been evaluated as primary or 
adjunctive treatments for PSC (Hirschfield et al. 2013).  None of these agents have 
demonstrated a significant clinical benefit in the treatment of PSC.  Small pilot studies are 
currently studying the role of antibiotics in PSC, with liver enzyme reductions seen after 
treatment with metronidazole or oral vancomycin, but this approach is still considered 
experimental.  
Orthotopic liver transplantation remains the only clinically proven treatment, shown to 
prolong survival with 5-year survival rates of up to 80% (Williamson and Chapman 2015).  
However, PSC recurs in the donor liver in approximately 20%–25% of patients at 5 years.  
Additionally, patients with PSC have a 10%–15% lifetime risk of developing 
cholangiocarcinoma (Rizvi et al. 2015).  Liver transplantation has been a disappointment in 
the treatment of cholangiocarcinoma, with significantly lower patient survival due to 
recurrent disease (Neumann and Schmeding 2015).  Thus, most transplant centers are not 
transplanting these patients outside of study protocols. 
Therefore, a significant unmet medical need still exists for novel agents for the treatment of 
PSC and its subsequent complications. 

CONFIDENTIAL 
NGM Protocol 15-0106 
27 May 2016 
Page 18 of 71 
2.1.3 Therapeutic Rationale for NGM282 in PSC 
Fibroblast growth factor 19 (FGF19) is a naturally occurring protein selectively expressed 
and secreted in the gastrointestinal tract.  FGF19 functions as an ileal hormone that directly 
regulates the classic pathway of hydrophobic (“toxic”) bile acid synthesis by altering the 
activity of the CYP7A1 enzyme through binding to the FGFR4–β-klotho co-receptor 
complex in the liver (Goetz et al. 2007; Kurosu et al. 2007).  Hepatic bile acid synthesis is 
largely controlled by a complex enterohepatic feedback regulatory mechanism that is directly 
mediated by FGF19.  Changes in the FGF19 activity have been shown to significantly alter 
both the size and composition of the bile acid pool (Russell 2003).  Both nonclinical and 
clinical studies support the role of FGF19 in the regulation of classical bile acid synthetic 
pathways (Lundasen et al. 2006; Schaap et al. 2009; Kir et al. 2011; Lenicek et al. 2011; 
Pattni et al. 2012). Recent clinical data have demonstrated a relationship between FGF19 
levels and PSC.  FGF19 mRNA expression and gall bladder levels of FGF19 are reduced in 
PSC versus non-PSC patients (Zweers et al. 2012).  These reduced FGF19 levels in bile may 
contribute to chronic inflammation and fibrosis in both the intra- and extrahepatic bile ducts 
of PSC patients through the dysregulation of FGF19-mediated bile acid synthesis.     
NGM282 is a recombinant protein of 190 amino acids with a molecular weight of 21.3 kDa 
and an amino acid sequence 95.4% identical to that of human FGF19.  Extensive in vivo 
structure–activity relationship analyses have been conducted to define and manipulate the 
distinct functional domains in FGF19 protein that are responsible for its metabolic and 
proliferative features.  More than 160 variants of human FGF19 were engineered, of which 
NGM282 was selected as the clinical candidate based on robust efficacy with no evidence of 
the proliferative activity previously observed in db/db mice. 
NGM282 effectively mimics the actions of FGF19 on bile acid synthesis through the binding 
of FGFR4c–β-klotho co-receptor (Study 12-MP-NGM282-1006).  In vitro studies have 
demonstrated that NGM282 binds to human hepatocytes with affinity similar to that of 
FGF19 (Studies 11-MP-NGM282-1002 and 13-MP-NGM282-1005).  Additionally, NGM282 
specifically inhibits only CY7A1 activity without inhibiting other bile acid synthetic enzymes 
(Study 12-MP-NGM282-1006).  In vivo studies have shown that systemic administration 
NGM282 can potently and rapidly suppress the expression of the Cyp7a1 gene in db/db mice 
(Study 11-PD-NGM282-1001).  Serum levels of 
7-alpha-hydroxy-4-cholesten-3-one (C4), a key biomarker of CYP7A1 biologic activity, were 
also reduced in the 28-day monkey toxicology study (Study 11-TX-NGM282-1002) and the 
26-week toxicology study in monkeys (Study 13-TX-NGM282-1004).  Significant reductions 
in serum C4 levels were also observed after administration of NGM282 in normal volunteers 
(Study 12-0101) as well as in patients with primary biliary cirrhosis (PBC)
(Study 13-0103).  NGM282 has also demonstrated improvements in liver biochemistries and 
histology in the bile duct ligation and α-napthylisothiocyanate mouse models of severe 
cholestatic injury (Studies 14-PD-NGM282-1006 and 14-PD-NGM282-1007).  Similar 
improvements were seen in MDR2-deficient mice that develop liver histopathology and

CONFIDENTIAL 
NGM Protocol 15-0106 
27 May 2016 
Page 19 of 71 
injury similar to PSC in humans (Study 14-PD-NGM282-1009).  In humans, treatment with 
NGM282 also caused significant reductions in ALP and serum transaminases in PBC patients 
who were incomplete responders to UDCA, consistent with a decrease in hepatobiliary 
injury. 
Based on the identified pharmacologic activities in animals and humans as well as the 
favorable safety and tolerability profiles in normal volunteers and PBC patients, NGM282 
represents a potentially important therapeutic option for the treatment of other bile acid 
disorders such as PSC through pharmacologic FGF19 signaling to reduce the synthesis of 
toxic bile acids.   
2.2 
NONCLINICAL STUDIES 
NGM has completed a series of in vitro and in vivo nonclinical studies supportive of the 
clinical development of NGM282 in patients with PSC.  Please refer to the Investigator’s 
Brochure (IB) for additional information on these studies.   
2.2.1 Nonclinical Safety Assessment 
The nonclinical safety of NGM282 has been assessed in general toxicity studies in CD-1 
mice and cynomolgus monkeys for up to 26 weeks of treatment and in embryo–fetal toxicity 
studies in CD-1 mice and New Zealand White rabbits.  NGM282 was pharmacologically 
active in the mouse and monkey for up to 26 weeks of treatment. 
In the monkey, NGM282 was clinically well tolerated as clinical signs were limited to 
increased hair loss at doses ≥ 0.1 mg/kg and slight reductions in body-weight gain at 1 mg/kg 
at 26 weeks of treatment. In the mouse, NGM282 produced transient clinical signs (e.g., 
hypoactivity or partial eye closure) at doses ≥ 1 mg/kg that were not dose limiting and 
resolved with continued treatment for up to 26 weeks. In the mouse, microscopic findings 
limited to the liver (minimal to moderate hepatocellular hypertrophy) were associated with 
slight increases in albumin, total protein, and liver weight. These changes were not considered 
adverse and were reversible.  
In the mouse and rabbit, NGM282 did not produce any adverse effects on embryo–fetal 
development at the highest doses tested (10 mg/kg).  In the rabbit, the 
no-observed-adverse-effect level (NOAEL) was 1 mg/kg due to maternal toxicity associated 
with body-weight gain reduction and associated reduction in fetal uterine weight at 10 mg/kg.   
Based on the cumulative nonclinical safety profile of NGM282 for up to 26 weeks of 
treatment, the NOAELs in the mouse and monkey were determined to be 1 and 3 mg/kg, 
respectively.  A sufficient safety margin exists for NGM282 at the proposed maximal clinical 
dose of 6 mg (0.0864 mg/kg) where estimated exposure is estimated to be 2- or 14-fold below 
that at the NOAELs in the mouse or monkey, respectively (see Table 2.2.1-1). 

CONFIDENTIAL 
NGM Protocol 15-0106 
27 May 2016 
Page 20 of 71 
Table 2.2.1-1. 
Estimated Safety Exposure Margin of NGM282 
Nonclinical 
Species 
NOAEL 
(mg/kg) a 
Plasma AUC 
(hr  ng/mL) b 
Exposure Margin Relative to 
Maximum Human Therapeutic Dose c 
Monkey 
1 
6610 
̴ 14X 
Mouse 
3 
1062 
̴ 2X 
AUC = area under the concentration–time curve; hr = hour; NOAEL = no-observed-adverse-effect level. 
a  Determined from the 6-month chronic toxicity studies. 
b  Systemic exposure at Day 1 after a single dose was used as the most conservative estimate of exposure given 
the presence of anti-drug antibody formation with repeat dosing in animals leading to drug accumulation 
(plasma AUC 7-fold above Day 1 levels).  
c  Based on a maximal therapeutic dose of 6 mg (0.0864 mg/kg based on a 70-kg patient) where plasma AUC is 
projected to be 482 hr  ng/mL (Study 12-0101). 
2.3 
CLINICAL STUDIES 
NGM has conducted a Phase 1 clinical trial in normal volunteers as well as Phase 2a and 2b 
trials in PBC patients.  These studies are supportive of the clinical development of NGM282 
in patients with PSC.  Please refer to the IB for additional detailed information on these 
studies. 
2.4 
RATIONALE FOR DOSE SELECTION OF NGM282 FOR PSC 
The doses selected for the Phase 2 trial in PSC are supported by both the nonclinical and 
clinical data generated to date.  The dose range for the first-in-human Phase 1 clinical trial  
(0.1–30 mg) was based on a broad approach to dose calculation considering the 
pharmacology of FGF19, beyond sole reliance on the NOAEL obtained in the GLP 28-day 
toxicology program.  The dose range also took into consideration safe starting-dose 
principles for first-in-human administration as outlined in both FDA and CHMP guidance.  
Dose-proportional changes in pharmacokinetic (PK) parameters were observed with both 
single and multiple dosing in the Phase 1 trial, consistent with predictions from animal 
models.  All doses were safe and well tolerated, thus establishing the initial clinical safety of 
this dose range. 
The proposed doses of 1 and 3 mg for evaluation in patients with PSC are based on a 
cumulative broad approach to dose calculation considering the pharmacology of FGF19 in 
PSC, clinical data from normal volunteers and subjects with PBC, and exposure safety 
margins obtained in the GLP 26-week toxicology program relative to the clinical doses 
proposed.  The proposed doses of 1 and 3 mg are within the current safety margins in both 
monkeys and mice (Table 2.2.1-1).  The drug exposure is comparable between normal 
volunteers and all populations studied to date (type 2 diabetes [T2D], PBC) and, therefore, 
expected to be comparable in the PSC population. 
The selection of the 1- and 3-mg doses was based on the efficacy, safety, and tolerability 
observed in the PBC Phase 2a trial in which NGM282 doses of 0.3 and 3 mg were evaluated.  

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 21 of 71 
 
A total of 45 patients were enrolled and randomized into the three study arms of 0.3 mg 
(n = 14), 3.0 mg (n = 16), or placebo (n = 15).  A progressive and statistically significant 
decrease in mean absolute ALP from Baseline to Day 28 was noted in both active treatment 
groups (p < 0.025).  A dose-related response was observed in absolute change in ALP from 
Baseline to the respective visits, with greater decreases in ALP shown with the 
higher (3.0 mg) dose of NGM282 (absolute change from Baseline to Day 28:  –48.9 IU/L in 
the 0.3-mg group, –69.0 IU/L in the 3.0-mg group, and 3.9 IU/L in the placebo group).  
Statistically significant overall treatment effects were demonstrated for both 0.3-mg and 
3.0-mg doses for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 
whereas only for the 3.0-mg dose for GGT and serum C4 levels.  The majority of the 
treatment-emergent adverse events (TEAEs) reported in this study were either mild or 
moderate in intensity.  The frequency of related TEAEs was slightly higher in the 3.0-mg 
treatment group compared to the other two treatment groups.  Diarrhea was the most 
frequently reported and treatment-related TEAE; 3 of 14 subjects (21.4%) in the 0.3-mg 
group reported three events, 4 of 16 subjects (25.0%) in the 3.0-mg group reported 
six events, and 1 of 15 subjects (6.7%) in the placebo group reported two events.  Overall, 
the study drug was well tolerated by the subjects.  The majority of subjects in all treatment 
groups reported “no reaction” to the injection site.  Of those reported, all but one were mild 
and predominantly reported as erythema at the injection site.  No evidence of drug-induced 
pruritus was observed, as assessed through both the Visual Analogue Scale and the 
5D Pruritus Scale.  In summary, NGM282 demonstrated significant reductions in key 
markers of hepatobiliary injury and has a favorable safety and tolerability profile in PBC 
patients treated for 28 days.  
The PBC study subjects represent a population similar to the PSC population based on the 
underlying role of bile acids in the associated inflammation and hepatobiliary injury.  Based 
on the above data, the selected doses should allow a balance of optimizing the biologic 
activity versus safety and tolerability in the studied population.  

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 23 of 71 
 
4 STUDY DESIGN 
This is a multiple-center, randomized, double-blind, placebo-controlled, parallel-group study 
of NGM282 when administered for 12 weeks as a daily subcutaneous (SC) injection in 
patients with PSC.  Approximately 60 subjects will be randomized across approximately  
40–45 sites worldwide. 
Patients will sign the Informed Consent Form at or prior to the Screening Visit and will 
undergo screening assessments to verify eligibility for the study (up to 6 weeks).   
Patients to be studied will have confirmed PSC as defined by an elevated ALP and either 
liver histology or cholangiography consistent with PSC.  The presence of IBD is allowed as 
well as treatment with a stable regimen of biologic, immunosuppressant, or systemic 
corticosteroid therapy.  UDCA therapy is allowed at stable doses for at least 12 weeks and 
< 27 mg/kg/day.  Patients with decompensated cirrhosis, cholangiocarcinoma (diagnosed or 
suspected), acute cholangitis, or recently placed bile-duct stents will be excluded from this 
study.  All subjects with concomitant IBD will be required to have had a colonoscopy within 
12 months of Screening with no evidence of dysplasia.  All subjects will undergo MRCP at 
Screening. 
On Day 1, subjects will be randomized into one of the three treatment arms (NGM282 1 mg, 
NGM282 3 mg, or placebo) in a 1:1:1 ratio.  The randomization will be stratified according 
to concurrent UDCA or no-UDCA status to ensure an even distribution across the 
three groups.  Study-drug SC self-administration instructions and training will be provided to 
the subjects and a weekly study-drug kit will be dispensed.  Treatment assignment will be 
blinded to the sites, subjects, Sponsor, and Medical Monitor throughout the study period. 
The first dose (Day 1) and doses at Weeks 1, 2, 4, 8, and 12 will be self-administered in the 
clinic, with all other doses through Week 12 self-administered at home.  Self-administration 
should occur at approximately the same time in the morning for every dose in both the clinic 
and at home. 
Subjects will return to the clinic on Weeks 1, 2, 4, and 8 for on-treatment assessments and to 
receive weekly study-drug kits.  Week 12 will be the End of Treatment (EOT) clinic visit.  
Subjects will return to the clinic at Week 16 (or 4 weeks after last dose) for an End of Study 
(EOS) follow-up visit.  
4.1 
STUDY STOPPING CRITERIA 
The entire study may be discontinued at the discretion of the Sponsor based on the 
occurrence of the following: 
• Adverse events (AEs) with respect to their nature, frequency, severity, and/or duration 
• Medical or ethical reasons affecting the continued performance of the study 
• Difficulties in the recruitment of patients 
• Cancellation of drug development  

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 24 of 71 
 
The entire study will be discontinued by the sponsor if there are three or more related 
Grade 3 TEAEs of the same Common Terminology Criteria for Adverse Events (CTCAE) 
category. 
5 SUBJECT SELECTION 
5.1 
INCLUSION CRITERIA 
Patients who meet the following criteria may be included in the study: 
1. 
Males and females between 18 and 75 years of age inclusive who are able to 
comprehend instructions and follow the study procedures, and are willing to sign an 
Informed Consent Form (ICF). 
2. 
Confirmed diagnosis of PSC based any two of the following three criteria:  
a. Historical evidence of an elevated ALP > ULN from any laboratory 
b. Liver biopsy consistent with PSC 
i. Patients with small-duct PSC on liver biopsy must also have a 
concurrent diagnosis of IBD 
c. Abnormal cholangiography consistent with PSC as measured by MRCP, 
ERCP, or percutaneous transhepatic cholangiography  
3. 
Subjects must have certain additional laboratory parameters in specified ranges at 
Screening, as follows: 
a. ALP > 1.5 × ULN 
b. Total bilirubin ≤ 2.5 mg/dL  
c. ALT and AST < 5 × ULN 
d. Serum creatinine < 2 mg/dL or creatinine clearance > 60 mL/min by 
Cockroft-Gault calculation 
e. Platelets ≥ 100 K/uL 
f. International Normalized Ratio (INR) ≤ 1.3 (in the absence of warfarin or 
other anticoagulant therapy) 
g. Carbohydrate antigen 19-9 (CA19-9) ≤ 130 U/mL 
i. Patients with a CA 19-9 > 130 U/mL may be enrolled if they have 
two results a mínimum of 4 weeks but not greater than 1 year apart and 
not more than 50 U/mL difference between the two results 
4. 
Patients taking UDCA will be allowed to enroll if meeting the following criteria: 
a. Total daily dose of < 27 mg/kg/day 
b. Minimum of 12 weeks of treatment 
c. No significant dosage changes during 8 weeks prior to Screening 
d. Minimum of 12-week washout period prior to Screening if UDCA is stopped 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 25 of 71 
 
5. 
Patients with concomitant IBD are allowed to enroll upon meeting the following 
criteria: 
a. A colonoscopy within 12 months of Screening with no evidence of dysplasia 
b. No episode of an IBD flare or IBD flare–related bloody diarrhea within 
6 months of Screening and through Day 1 
c. Stable regimen of biologic treatments, immunosuppressive, or systemic 
corticosteroids (< 10 mg/day) for > 12 weeks prior to Screening and through 
Day 1 
i. Vedolizumab is an excluded biologic treatment 
6. 
Female patients are eligible for the study if they meet the following criteria: 
a. Are not pregnant or nursing 
b. Of non-childbearing potential defined as women who have had a 
hysterectomy, bilateral oophorectomy, medically documented ovarian failure, 
or are documented postmenopausal (follicle-stimulating hormone 
> 40 mIU/mL) 
OR 
Of childbearing potential defined as including women < 55 years of age with 
2 years of amenorrhea and both the following criteria: 
i. Both a negative serum pregnancy test at Screening and urine 
pregnancy test prior to Randomization  
ii. Correct and consistent use of one of the following methods of birth 
control in addition to a male partner using a condom from Screening to 
30 days after the last dose of study drug: 
1. hormone-containing contraceptive 
2. intrauterine device with a failure rate < 1% per year 
3. cervical cap or diaphragm with spermicidal agent 
4. tubal sterilization 
5. vasectomy in male partner 
7. 
Male subjects must agree to consistently and correctly use a condom in combination 
with one of the above methods of birth control from date of consent to 30 days after 
the last dose of study drug.   
8. 
Subjects must be able to comply with the SC self-administration instructions for study 
drug and be able to complete the study schedule of procedures.   
5.2 
EXCLUSION CRITERIA 
Any of the following will exclude potential subjects from the study: 
1. 
Clinically significant acute or chronic liver disease of an etiology other than PSC.  

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 26 of 71 
 
a. Patients with stable treated overlapping PSC and autoimmune hepatitis (AIH) 
will be allowed to enroll into the study. 
i. Stable treated overlapping PSC/AIH is defined as on a consistent 
regimen of immunosuppressive therapy for a minimum of 12 weeks 
and no evidence of a hepatic flare during that time period. 
2. 
Secondary or IgG4-related sclerosing cholangitis 
3. 
Presence of a dominant stricture of clinical concern on MRCP at Screening.  
a. Patients with dominant stricture can be enrolled if the investigator feels there 
is no evidence on magnetic resonance imaging or cholangiography indicative 
of cholangiocarcinoma or that the stricture will not result in significant 
fluctuations in ALP during Screening or Study period.  
b. Patients with a dominant stricture must have a total bilirubin of ≤ 2.5 mg/dL 
for at least 6 months prior to Screening. 
4. 
Placement of a bile-duct stent or percutaneous bile-duct drain within 3 months of 
Screening 
a. Patients who have undergone a balloon dilation procedure of a stricture will 
be allowed to enroll into the study after a minimum of 4 weeks 
post-procedure. 
5. 
History, evidence, or high suspicion of cholangiocarcinoma or other hepatobiliary 
malignancy based on imaging, screening laboratory values, and/or clinical symptoms 
6. 
Acute cholangitis within 12 weeks of Screening and through Day 1   
a. Chronic preventive antibiotics for cholangitis will be allowed in the study. 
b. Intermittent courses of antibiotics for the presumptive treatment of cholangitis 
are allowed if outside the 12-week window prior to Screening. 
7. 
Evidence of decompensated cirrhosis (Child-Pugh B or C) based on histology, 
relevant medical complications, or laboratory parameters.   
a. Patients with compensated cirrhosis will be allowed to enroll into the study. 
b. Patients with pre-sinusoidal esophageal varices with no history or evidence of 
bleeding may be enrolled as long as there is no other evidence of hepatic 
decompensation. 
8. 
Prior liver transplantation 
9. 
Any contraindication or inability to obtain a screening MRCP or colonoscopy (only in 
patients with concomitant IBD, if historical colonoscopy within the 12-month 
window is not available) 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 27 of 71 
 
10. 
Screening electrocardiogram (ECG) with clinically significant abnormalities as 
determined by the Investigator 
11. 
Positive for HBsAg, HCV-RNA, or anti-HIV 
12. 
History of malignancy diagnosed or treated within 2 years (recent localized treatment 
of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma 
in situ is allowed if appropriately treated prior to Screening); subjects under 
evaluation for malignancy are not eligible. 
13. 
Clinically-relevant drug or alcohol abuse within 12 months of screening.  A positive 
drug screen will exclude subjects unless it can be explained by a prescribed 
medication. 
14. 
Use of any prohibited concomitant medications as described in Section 5.7 within 
4 weeks of Day 1 visit 
15. 
Patients with severe allergic or anaphylactic reactions to recombinant therapeutic 
proteins, fusion proteins, or chimeric, human, or humanized antibodies 
16. 
Participation in a study of another investigational agent within 4 weeks or 
five half-lives of the investigational drug (whichever is longer) prior to Screening 
17. 
History of clinically significant unstable or untreated illness or any other major 
medical disorder that may interfere with subject treatment, assessment, or compliance 
with the protocol 
18. 
Any acute or chronic condition or other disease that, in the opinion of the 
Investigator, would limit the patient’s ability to complete and/or participate in this 
clinical study 
19. 
Presence of any other conditions (e.g., geographic or social), actual or projected, that 
the investigator feels would restrict or limit the patient’s participation for the duration 
of the study 
20. 
Employment by NGM, participating contract research organization (CRO), or study 
site (permanent, temporary contract worker, or designee responsible for the conduct 
of the study) or are immediate family of an NGM employee, participating CRO, or 
study-site employee (hence, conflict of interest issues).  Immediate family is defined 
as a spouse, parent, child, or sibling, whether biological or legally adopted. 
The Investigator has discretion to repeat assessments/procedures if he/she believes there is a 
good chance the results were spurious and do not accurately represent the subject’s true 
values.  Repeat assessments/procedures must be conducted within the 6-week Screening 
Period, prior to randomization, and a subject may only be rescreened for these labs a single 
time.    

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 28 of 71 
 
5.3 
DISCONTINUATION OF STUDY TREATMENT IN AN INDIVIDUAL 
SUBJECT 
Study treatment will be discontinued if any of the following CTCAE categories or abnormal 
elevations in liver function tests occurs on-treatment: 
• Any Grade 3 TEAE related to study drug 
• Any Grade 4 or higher TEAE 
• Elevation of ALT and total bilirubin > 2 times above subject-specific baseline value 
calculated using the median of the Screening and Day 1 value 
o ALT, AST, and total bilirubin must be re-tested within 72 hours.   
o Subjects with persistent elevations should be discontinued from treatment, 
independent of whether or not they are symptomatic. 
• Elevation of ALT > 2 times above subject-specific baseline  
o ALT, AST, and total bilirubin must be re-tested within 72 hours.   
o Subjects with persistent elevations who are asymptomatic may continue 
treatment under protocol-defined close observation criteria.  
o Subjects with persistent elevations who are symptomatic must discontinue 
treatment. 
o Subjects continuing treatment under close observation should implement 
study procedures and assessments as part of the study conduct: 
1. Repeat liver enzyme and serum bilirubin tests two or three times weekly. 
The frequency of retesting can decrease to once a week or less if 
abnormalities stabilize or the trial drug has been discontinued and the 
subject is asymptomatic.  
2. Repeat additional tests to evaluate liver synthetic function (e.g., INR, 
direct bilirubin) as appropriate. 
3. Obtain a detailed history of symptoms and prior or concurrent diseases. 
4. Obtain a history of concomitant drug use (including nonprescription 
medications and herbal and dietary supplement preparations), alcohol use, 
recreational drug use, environmental toxin exposure, and special diets. 
5. Rule out acute viral hepatitis and other acute or chronic hepatobiliary 
diseases. 
Dose reductions or increases are not allowed as part the study conduct. 
5.4 
DISCONTINUATION OF SUBJECTS FROM STUDY PARTICIPATION  
Patients will be informed that they are free to withdraw from the study at any time and for 
any reason.  The Principal Investigator (PI) may remove a subject from the study if, in the 
PI’s opinion, it is not in the best interest of the subject to continue the study.  Subjects may 
be discontinued due to subject’s personal withdrawal of consent, due to subject’s 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 29 of 71 
 
non-compliance of the study-drug prescription, due to a change in compliance with an 
inclusion/exclusion criterion that is clinically relevant and affects subject safety, due to a 
site/subject’s protocol deviation, due to subject being considered lost-to-follow-up, due to 
any code-breaking requested by investigator/safety, due to NGM opting to terminate study, 
due to a subject experiencing an AE(s), due to a subject experiencing a pregnancy, or due to 
an administration of non-permitted concomitant medication that might affect subject safety 
or study assessments/objectives.  Notification of discontinuation will be made immediately to 
the Sponsor’s Medical Monitor.  In case of premature discontinuation of study participation, 
efforts will be made to perform all final Week 12 (EOT) and Week 16 (EOS) 
visits/assessments.  The date the subject is withdrawn from the study and the reason for 
discontinuation will be recorded on the subject’s electronic Case Report Form (eCRF).  All 
withdrawn subjects will be followed until resolution of any AEs or until any unresolved AEs 
are judged by the PI to have stabilized. 
5.5 
SCHEDULE OF STUDY PROCEDURES 
The Schedule of Study Procedures is shown in Table 5.5-1.  The visits should occur as close 
to the intended dates as possible.  However, there is an acceptable ± 3-day window for 
individual scheduled visits.  Subjects attending any visits out of windows from Day 1 to 
Week 12/Early Withdrawal (EOT) Visit should be brought back into compliance with the 
overall study-visit schedule as soon as possible thereafter.  Subjects will then return to the 
clinic at Week 16 (or 4 weeks after last dose) for an EOS follow-up visit. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 30 of 71 
 
Table 5.5-1 
Schedule of Study Procedures  
Study Procedure 
Days –42 to –1 
(Screening) a 
Day 
1 
Wk 
1 
Wk 
2 
Wk 
4 
Wk 
8 
Wk 12 (EOT)/ 
Early Withdrawal 
Wk 16 
(EOS)/ 
Follow-up 
Informed consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
Body weight 
X 
X 
 
 
X 
X 
X 
X 
Physical exam 
X 
X  
 
X 
X 
X 
X 
X 
12-lead electrocardiogram 
X 
X 
 
 
 
 
X 
X 
Vital signs  
X 
X 
X 
X 
X 
X 
X 
X 
Colonoscopy b 
X 
 
 
 
 
 
 
 
MRCP c  
X 
 
 
 
 
 
 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization  
 
X 
 
 
 
 
 
 
Study drug 
self-administration training 
 
X 
X 
X 
X 
 
 
 
Dispense study drug 
 
X 
X 
X 
X 
X 
 
 
Study-drug compliance  
 
 
X 
X 
X 
X 
X 
 
Adverse event evaluations 
 
X 
X 
X 
X 
X 
X 
X 
LISSA evaluations d 
 
X 
X 
X 
X 
X 
X 
X 
PK blood samples e 
 
X 
X 
X 
X 
X 
X 
X 
NRS Itch/Fatigue f  
 
X 
X 
 
X 
 
X 
 
5-D Pruritus  
 
X 
X 
X 
X 
X 
X 
X 
Mayo Partial IBD Score g 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology  
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
 
 
X 
 
X 
X 
Lipid panel  
 
X 
 
 
 
 
X 
 
CA19-9 h 
X 
 
 
 
 
 
 
 
p-ANCA 
X 
 
 
 
 
 
 
 
ELF panel 
 
X 
 
 
 
 
X 
 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 32 of 71 
 
5.6 
STUDY VISIT PROCEDURES 
5.6.1 Day –42 to Day –1 (Screening) Procedures 
Patients will report to this visit fasted for 10 hours with only water allowed.  The following 
screening procedures will be performed for all potential subjects at a visit (or visits) 
conducted within 42 days prior to dosing: 
• Obtain informed consent. 
• Collect demographic data. 
• Review medical history. 
• Assess inclusion/exclusion criteria. 
• Measure height. 
• Measure body weight. 
• Conduct physical examination.  
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• In patients with concomitant IBD, obtain colonoscopy report from eligible historical 
colonoscopy or undergo a colonoscopy procedure to obtain a new report if outside the 
12-month window prior to MRCP. 
• Obtain historical MRCP or ERCP for PSC diagnosis and dominant stricture assessment. 
• Obtain new MRCP for baseline assessment. 
• Record prior and concomitant medications. 
• Perform Mayo Partial IBD Score. 
• Obtain ~10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• Hematology 
• INR 
• Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) 
• CA19-9 
• Serum pregnancy test (all female subjects) 
• HIV antibody and hepatitis screen 
• Obtain urine samples for the following: 
• Urinalysis (UA) 
• Selected drugs of abuse 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 33 of 71 
 
5.6.2 Day 1 Procedures 
Subjects will report to this visit fasted for 10 hours with only water allowed.  The following 
procedures will be performed at the Day 1 Visit: 
Pre-dose: 
• 
Reassess inclusion/exclusion criteria. 
• 
Measure body weight. 
• 
Conduct physical examination. 
• 
Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• 
Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• 
Assess for concomitant medications. 
• 
Assess for AEs from Screening period. 
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• Hematology 
• Lipids 
• C4 and serum bile acids 
• Vitamin D 
• INR 
• Enhanced liver fibrosis (ELF) panel 
• PK (pre-dose) 
• Anti-drug antibodies (ADAs) 
• Neutralizing antibodies (NAbs) 
• Exploratory biomarkers 
 
 
• Obtain urine samples for the following: 
• Pregnancy test 
• UA 
• Perform 5-D Pruritus Scale. 
• Perform Mayo Partial IBD Score. 
• Perform and then dispense Numeric Rating Scale (NRS) daily diary for Week 1 
assessments. 
 
In-clinic dosing: 
• 
Confirm inclusion/exclusion criteria. 
• 
Perform randomization. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 34 of 71 
 
• 
Dispense initial study-drug kit/diary (for recording of date/time of study-drug dosing). 
• 
Provide study-drug SC self-administration instructions/training. 
• 
Oversee subject study-drug SC self-administration. 
• 
Perform local injection-site symptom assessment (LISSA) evaluation. 
Before clinic discharge: 
• Obtain 2-hour post-dose PK sample. 
• Assess for AEs. 
• Schedule subject for Week 1 visit. 
• Instruct subjects to not self-administer their study drug until they are on-site. 
5.6.3 Week 1 Procedures 
Subjects will report to this visit fasted for 10 hours with only water allowed and undosed.  
The following procedures will be performed at the Week 1 visit: 
Pre-dose: 
• 
Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• 
Assess for concomitant medications. 
• 
Assess for AEs. 
• 
Perform LISSA evaluation. 
• Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• Hematology 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Exploratory biomarkers 
• Perform 5-D Pruritus Scale. 
• Perform Mayo Partial IBD Score. 
• 
Collect Week 1 NRS daily dairy.  
 
Dosing: 
• 
Collect old study-drug kit/diary and conduct reconciliation. 
• 
Dispense new study-drug kit/diary. 
• 
Oversee subject study-drug SC self-administration (from new kit).  
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 35 of 71 
 
Discharge (20 minutes after dosing): 
• Assess for AEs. 
• Schedule subject for Week 2 visit. 
• Instruct subjects to not self-administer their study drug until they are on-site. 
5.6.4 Week 2 Procedures 
Subjects will report to this visit fasted for 10 hours with only water allowed and undosed.  
The following procedures will be performed at the Week 2 visit: 
Pre-dose: 
• 
Conduct physical examination. 
• 
Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• 
Assess for concomitant medications. 
• 
Assess for AEs. 
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• Hematology 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Exploratory biomarkers 
• Perform LISSA evaluation. 
• Perform 5-D Pruritus Scale. 
• Perform Mayo Partial IBD Score. 
• Dispense NRS daily diary for Week 4 assessments. 
 
Dosing: 
• 
Collect old study-drug kit/diary and conduct reconciliation. 
• 
Dispense new study-drug kit/diary. 
• 
Oversee subject study-drug SC self-administration (from new kit). 
 
Discharge (20 minutes after dosing): 
• Assess for AEs. 
• Schedule subject for Week 4 visit. 
• Instruct subjects to not self-administer their study drug until they are on-site. 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 36 of 71 
 
5.6.5 Week 4 Procedures 
Subjects will report to this visit fasted for 10 hours with only water allowed and undosed.  
The following procedures will be performed at the Week 4 visit: 
Pre-dose: 
• 
Conduct physical examination. 
• 
Measure body weight. 
• 
Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• 
Assess for concomitant medications. 
• 
Assess for AEs. 
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• Hematology 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Exploratory biomarkers 
• Obtain urine samples for UA. 
• Perform LISSA evaluation. 
• Perform 5-D Pruritus Scale. 
• Perform Mayo Partial IBD Score. 
• Collect Week 4 NRS daily diary. 
 
Dosing: 
• 
Collect old study-drug kit/diary and conduct reconciliation. 
• 
Dispense new study-drug kit/diary. 
• 
Oversee subject study-drug self-administration (from new kit). 
 
Discharge (20 minutes after dosing): 
• Assess for AEs. 
• Schedule subject for Week 8 visit. 
• Instruct subjects to not self-administer their study drug until they are on-site. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 37 of 71 
 
5.6.6 Week 8 Procedures 
Subjects will report to this visit fasted for 10 hours with only water allowed and undosed.  
The following procedures will be performed at the Week 8 visit: 
Pre-dose: 
• 
Conduct physical exam. 
• 
Measure body weight. 
• 
Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• 
Assess for concomitant medications. 
• 
Assess for AEs. 
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• Hematology 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Exploratory biomarkers 
• 
Perform LISSA evaluation. 
• Perform 5-D Pruritus Scale. 
• Perform Mayo Partial IBD Score. 
• 
Dispense Week 12 NRS daily diary. 
 
Dosing: 
• 
Collect old study-drug kit/diary and conduct reconciliation. 
• 
Dispense new study-drug kit/diary. 
• 
Oversee subject study-drug SC self-administration (from new kit). 
 
Discharge (20 minutes after dosing): 
• Assess for AEs. 
• 
Schedule subject for Week 12 (End of Treatment) visit. 
• 
Instruct subjects to not self-administer their study drug until they are on-site. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 38 of 71 
 
5.6.7 Week 12 (End of Treatment)/Early Withdrawal Procedures 
Subjects will report to this visit fasted for 10 hours with only water allowed and undosed.  
The following procedures will be performed at the Week 12/Early Withdrawal Visit: 
Pre-dose: 
 
• 
Measure body weight. 
• 
Conduct physical examination. 
• 
Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• 
Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• 
Assess for concomitant medications. 
• 
Assess for AEs. 
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• Hematology 
• Lipid panel  
• C4 and serum bile acids 
• Vitamin D 
• INR 
• ELF panel 
• Serum pregnancy test (all female subjects) 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Exploratory biomarkers 
 
  
• Obtain urine sample for UA. 
• Perform LISSA evaluation. 
• Perform 5-D Pruritus Scale. 
• Perform Mayo Partial IBD Score. 
• Collect Week 12 NRS daily diary. 
 
Dosing: 
• 
Collect old study-drug kit/diary and conduct reconciliation. 
• 
Oversee subject study-drug SC self-administration (from old kit) (not applicable for 
Early Withdrawal subjects). 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 39 of 71 
 
Discharge: 
(NOTE:  Before-clinic-discharge assessments [PK sampling and AE recording evaluation] 
are not applicable for Early Withdrawal subjects.  However, Early Withdrawal subjects 
should be scheduled for a 4-week Follow-up Visit.)   
• 
Obtain 2-hour post-dose PK blood sample. 
• 
Assess for AEs. 
• 
Schedule subject for Week 16 (End of Study) Visit. 
5.6.8 Week 16 (End of Study) Procedures 
This visit will be performed 4 weeks after last dose of study medication.  Subjects will report 
to this visit fasted for 10 hours with only water allowed.  The following procedures will be 
performed at the Week 16 visit: 
• 
Measure body weight. 
• 
Conduct physical examination. 
• 
Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• 
Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• 
Record concomitant medications. 
• 
Record AEs. 
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• Hematology 
• PK  
• Vitamin D 
• INR 
• Serum pregnancy test (all female subjects) 
• ADAs 
• NAbs 
• Exploratory biomarkers 
• Obtain urine sample for UA. 
• Perform LISSA evaluation. 
• Perform 5-D Pruritus Scale. 
• Perform Mayo Partial IBD Score. 

CONFIDENTIAL 
NGM Protocol 15-0106 
27 May 2016 
Page 40 of 71 
5.7 
CONCOMITANT MEDICATIONS 
Any medication taken within 4 weeks prior to Screening and during the study period, as well 
as the reason for use, will be recorded in the source documents and the eCRFs. 
Subjects should refrain from the use of any new prescription medications or products or 
change in the dose or frequency of existing therapies within 4 weeks prior to Day 1 until 
EOS.  The Medical Monitor should be informed of any changes or addition of medications 
during this time period.  
The following medications are prohibited from 4 weeks prior to Day 1 and through the end of 
treatment: 
•
Investigational agents, other than NGM282, or devices for any indication
•
Known hepatotoxic agents
o
Concomitant medication can be screened at http://livertox.nih.gov
•
Agents which can increase or decrease ALP
o
Patients on stable doses of a medication that may impact ALP for a minimum 
of 12 weeks can be considered for enrollment.
o
Medications which decrease ALP (such as UDCA, fibrates, bile acid resins) 
should also be screened for and not be started at any time point during the 
screening or study period.
•
Agents used for the treatment of any condition listed in the exclusionary enrollment 
criteria (see Section 5.2)
•
Off-label use of therapies for PSC such as oral vancomycin, other antibiotics, or 
vedolizumab within 12 weeks of Screening through the EOS visit
•
Any herbal medications other than standard vitamin supplements 
In addition: 
•
Subjects taking medications for IBD must have been on a stable regimen of these
medications for at least 12 weeks prior to Day 1 and should maintain if possible a stable
dose during the study period.
•
Subjects taking UDCA are eligible but must have been on stable doses of < 27 mg/kg/day
for at least 12 weeks prior to their Screening.  No significant dosage changes should be
made during 8 weeks prior to Screening and a minimum 8-week washout period should
occur prior to Screening if UDCA is stopped.  Subjects not taking UDCA should not start
it during the study period.
5.8 
DIET AND ACTIVITY CONTROL 
Subjects should maintain their normal level of physical activity, diet, and lifestyle throughout 
the entire study (i.e., will not begin a new exercise program or participate in any unusually 
strenuous physical exertion).  

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 41 of 71 
 
5.9 
CLINICAL EVALUATIONS 
5.9.1 Colonoscopy 
Due to the high risk of colonic dysplasia in UC patients with PSC, a 2010 guideline from the 
AASLD recommends that patients with PSC and IBD undergo surveillance colonoscopy 
every 1–2 years from the time of diagnosis of PSC (Chapman et al. 2010).  Patients with PSC 
without IBD should undergo surveillance colonoscopy every 5 years.  If surveillance biopsies 
and flow cytometry show no evidence of dysplasia or aneuploidy, follow-up colonoscopy can 
be performed in 2–3 years.  A possible exception would be those patients with > 20 years' 
duration of colitis; in such patients it is reasonable to perform annual surveillance 
colonoscopy because of the high risk of dysplasia.  If surveillance biopsies show no evidence 
of dysplasia, but flow cytometry is not available, a repeat colonoscopy is recommended 
annually.  If surveillance biopsies reveal indefinite dysplasia, repeat surveillance 
colonoscopy is recommended every 6–12 months.  If low-grade dysplasia is detected, a 
variety of options may be considered, including total colectomy.  It would also be reasonable 
to repeat a surveillance colonoscopy within 3–6 months to confirm a diagnosis of low-grade 
dysplasia.  If there are multiple sites of low-grade dysplasia or multiple inflammatory polyps 
that preclude adequate surveillance, colectomy should be recommended.  However, if 
low-grade dysplasia is present in only one biopsy specimen, repeat surveillance colonoscopy 
in 6–12 months may also be considered.  If high-grade dysplasia is detected, colectomy 
should be strongly recommended.  
Because of the increased risk of dysplasia and colon cancer in PSC, all subjects with 
concomitant IBD in Study 15-0106 should have a colonoscopy with no evidence of dysplasia 
within 12 months of Screening (Table 5.5-1). 
5.9.2 Magnetic Resonance Cholangiopancreatography 
MRCP is a noninvasive technique for evaluating the intrahepatic and extrahepatic bile ducts 
and the pancreatic duct.  Unlike conventional ERCP, MRCP does not require contrast 
material to be administered into the ductal system; thus, the morbidity associated with 
endoscopic procedures and contrast materials is avoided.  However, MRCP does not permit 
interventions to be performed such as stone extraction, stent insertion, or biopsy.  The 
optimal protocol to perform MRCP has not been defined; variation continues across centers.  
As a general rule, the protocol depends upon the specific magnetic resonance magnet being 
used, including its field strength (e.g., 1.5 versus 3T) and the manufacturer, as well as 
institutional experience and preferences.  However, all acquisition protocols obtain heavily 
T2-weighted images as thick slabs and the images are reformatted in planes to optimize 
depiction of the extrahepatic ducts.  Volume-rendered images may be used to depict the 
intra- and extrahepatic bile ducts.  
In Study 15-0106, MRCP can be performed as one of the criteria for the diagnosis of PSC 
and will be performed in all subjects during Screening as a baseline assessment (Table 5.5-1).  

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 42 of 71 
 
5.9.3 Pharmacokinetic Blood Sample Collection and Processing 
Blood samples for PK analysis of NGM282 levels will be collected before dosing on Day 1 
and Weeks 1, 2, 4, 8, 12, and 16 (no dose administered) as outlined in the Schedule of Study 
Procedures (Table 5.5-1).  On Day 1 and Week 12, an additional PK blood sample will be 
collected 2 hours post-dose.   
Processing, storage, and shipping instructions for these PK blood samples will be presented 
in a separate Lab Manual. 
5.9.4 Clinical Laboratory Assessments 
Clinical laboratory evaluations including chemistry (fasted at least 10 hours), hematology, 
and UA will be collected as outlined in the Schedule of Study Procedures (Table 5.5-1).  
Laboratory assessments of lipid panel (total cholesterol, LDL, HDL, and triglyceride) will be 
performed as outlined in the Schedule of Study Procedures (Table 5.5-1). 
Laboratory assessments for C4 and serum bile acids will be performed as outlined in the 
Schedule of Study Procedures (Table 5.5-1). 
Laboratory assessments for changes in bile-mediated absorption as measured by vitamin D 
and INR will be performed as outlined in the Schedule of Study Procedures (Table 5.5-1). 
CA19-9 and p-ANCA will be collected at Screening as outlined in the Schedule of Study 
Procedures (Table 5.5-1). 
ELF panel will be performed as outlined in the Schedule of Study Procedures (Table 5.5-1). 
Hepatitis screen and HIV antibody screen will be performed at Screening.   
A urine screen for drugs of abuse will be performed at Screening.  
A stool sample will be collected at Day 1 and Week 12.  If necessary, in order to obtain a 
sample, kits will be provided to patients for at-home collection and aliquoting, for return to 
clinic at Day 1 and Week 12 visits.  Stool samples will be analyzed for calprotectin, 
microbiome (bacterial composition), and fecal fat content. 
A serum qualitative pregnancy test (all female subjects) will be performed at Screening and 
Weeks 12 and 16.  A urine pregnancy test (all female subjects) will be performed at Day 1. 
Samples for analysis of ADAs, NAbs, and exploratory biomarkers will be collected as 
outlined in the Schedule of Study Procedures (Table 5.5-1).  All NAb samples will be 
collected as scheduled and analyzed only if necessary based on ADA results.   
Processing, storage, and shipping instructions for the above will be presented in a separate 
Lab Manual. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 43 of 71 
 
5.9.5 12-Lead Electrocardiograms 
12-lead ECGs will be performed after the subject has been supine for at least 5 minutes, and 
as outlined in the Schedule of Study Procedures (Table 5.5-1). 
5.9.6 Vital Signs 
Vital signs (including temperature, respiratory rate, and seated blood pressure and pulse) will 
be obtained at Screening and at all study visits as outlined in the Schedule of Study 
Procedures (Table 5.5-1). 
Seated blood pressure and pulse will be measured after the subject has been seated for at least 
5 minutes. 
5.9.7 Physical Examinations 
A routine physical examination will be performed at Screening, Day 1, and Weeks 2, 4, 8, 
12, and 16 as outlined in the Schedule of Study Procedures (Table 5.5-1).  The physical 
examination may be performed by a physician, trained physician’s assistant, or a nurse 
practitioner, as acceptable according to local regulation.  
5.9.8  Weight 
Subjects will be weighed at Screening, Day 1, and Weeks 4, 8, 12, and 16 as outlined in the 
Schedule of Study Procedures (Table 5.5-1).   
5.9.9 Local Injection-Site Symptom Assessments 
Injection-site evaluation will be made and documented (including photographs, as needed) by 
the PI or clinic staff using a LISSA (Appendix A).   
The LISSA is to be administered pre-dose at Day 1 and Weeks 1, 2, 4, 8, 12, and 16 (End of 
Study) as outlined in the Schedule of Study Procedures (Table 5.5-1).   
The instructions below are to be followed for the pre-dose LISSA: 
• The injection-site area(s) should be examined for any injection-site reaction (ISR) at 
every visit. 
• If a single ISR is observed, the LISSA should be used to rate that ISR. 
• If multiple ISRs are observed, the LISSA should be used to rate the most severe ISR. 
• The study visit note should document the total number of ISRs seen on examination. 
The LISSA is intended to be a “snapshot” of the ISRs at the time of clinic assessment.  The 
LISSA is not intended to capture ISR data (frequency, severity, duration, etc.) in between 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 44 of 71 
 
clinic visits.  As with any other potential AE, Investigator judgment should be used as to 
whether any ISR is recorded as an AE.  
In addition to this, Mild to Severe Reactions (LISSA Grade 1–3) are reported as AEs at the 
discretion of the investigator unless standard serious adverse event (SAE) criteria are met and 
then must be reported as an SAE.  Life-threatening (LISSA Grade 4) meet SAE criteria and 
must be reported as such. 
LISSAs may be performed if necessary and as clinically indicated by the PI to capture ISRs 
outside of the routine scheduled assessment time points. 
The 2007 FDA Toxicity Grading Scale (Appendix A) will be used to assess any ISRs 
(U.S. Department of Health and Human Services 2007).  The documented record will include 
all of the symptoms, severity, and any local reaction (including pain, tenderness, redness, and 
swelling) and size of injection-site skin reactions identified and observed by the subject or 
clinic personnel.  LISSA scores will be documented on the subject’s eCRF.  
5.9.10 Numeric Rating Scale for Pruritus and Fatigue 
An 11-point numeric rating scale for both pruritus and fatigue will be completed by subjects 
as a daily diary during Day 1 and Weeks 1, 4, and 12 as outlined in the Schedule of Study 
Procedures (Table 5.5-1).  Diary will be dispensed at the study visit prior to the collection 
week.  Subject will use the scale (Appendix B) to rate severity ranging from 0 “none” to 10 
“worst possible.”    
5.9.11 5-D Pruritus Scale 
The 5-D Pruritus Scale (Appendix C) is a modified version of the Total Neuropathy Scale 
(Elman et al. 2010).  It is a brief multidimensional questionnaire used to measure the chronic 
itch.  The instrument claims to serve as a monitoring instrument for the long-term course of 
pruritus.  This instrument has not been validated in numerous cohorts of subjects with either 
primary or secondary pruritus; none had PBC.  The 5-D Pruritus Scale has five questions that 
assess degree, duration, direction, disability, and distribution of pruritic symptoms.   
The 5-D Pruritus Scale is to be administered pre-dose at Day 1 and Weeks 1, 2, 4, 8, 12, and 
16 (End of Study) as outlined in the Schedule of Study Procedures (Table 5.5-1).   
5.9.12 Mayo Partial IBD Score 
The Mayo Partial IBD Score (Appendix D) is a non-invasive 9-point partial Mayo score used 
as an outcome measure for clinical trials assessing therapy for ulcerative colitis 
(Lewis et al. 2008).  The partial score evaluates changes in stool frequency, rectal bleeding, 
and physician assessment of disease severity, with defined changes in the score correlating 
with clinical responses to treatment.  The Mayo Partial IBD Score will be assessed by 
study-site personnel at all study visits in all subjects, including Screening and EOS. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 45 of 71 
 
The Mayo Partial IBD Score is to be administered pre-dose at Day 1 and Weeks 1, 2, 4, 8, 
12, and 16 (End of Study) as outlined in the Schedule of Study Procedures (Table 5.5-1).   

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 46 of 71 
 
6 STUDY DRUG 
6.1 
CLINICAL SUPPLIES 
 
 
 
 
  
 
   
6.2 
STUDY DRUG ACCOUNTABILITY 
The PI is responsible for ensuring that a current record of inventory/drug accountability is 
maintained.  Inventory records must be readily available for inspection by the study monitor 
and are open to inspection by regulatory authorities at any time.  Each shipment of drug 
supply for the study will contain a shipping manifest to assist the PI in maintaining current 
and accurate inventory records. 
Upon receipt of the investigational drug, the designated site personnel will visually inspect 
the shipment, verify the number and condition of study drug received, and confirm receipt of 
study drug.  Study-drug reconciliation will be performed based on the study-drug kits and the 
remaining returned syringes and compared to recorded results in the study-drug diary. 
At the completion of the study, all unused study-drug supplies will be returned to the Sponsor 
(or designee) or disposed of by the clinic, per the Sponsor’s (or designee’s) written 
instructions. 
6.3 
STUDY DRUG STORAGE 
At the clinical site, study drug is to be stored refrigerated at 2°C–8°C (36°F–46°F) in a 
secure, controlled-access location protected from light.   
At the subject’s home, study drug is to be stored refrigerated at 2°C–8°C (36°F–46°F) in a 
location protected from light (e.g., their refrigerator).  Subjects will be instructed to take care 
in keeping study drug out of the reach of children and other family members who may have 
access to the storage location. 
6.4 
DOSE PREPARATION AND ADMINISTRATION 
Subjects will be instructed to self-administer/dose at approximately the same time each 
morning over the 12-week treatment period.  Study-drug syringes for SC injection should be 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 47 of 71 
 
brought to room temperature prior to use.  Study drug will be administered as a SC injection 
in the abdomen.  On Day 1, subjects will be trained on self-administering a SC injection.  On 
Weeks 1, 2, 4, 8, and 12, self-administration will occur in the clinic under observation by 
clinic staff.  Re-training will be provided as required.  Written preparation and study drug 
self-administration instructions will be provided to each subject.  Subjects will be required to 
complete a daily study-drug administration diary.  
6.5 
REMOVAL OF STUDY BLIND 
This will be a double-blind, placebo-controlled study.  Breaking of the blind will be available 
to the PI through an 
.  The subject’s 
treatment assignment will be available to the PI in the event of a medical emergency or an 
AE that necessitated identification of the study drug for the welfare of that subject.  Except in 
the case of a medical emergency, the PI and clinic staff will remain blinded during the 
conduct of the study and until such time that all discrepancies in the clinical database are 
resolved (i.e., at the time of the database lock).  The date and time when the PI removed the 
study blind for an individual subject will be documented by the 
 and an automated 
notification will be sent to the Sponsor.  The contracted CRO’s pharmacovigilance team may 
also be required to break the blind for regulatory reporting purposes. 
7 ADVERSE EVENTS 
7.1 
DEFINITION AND GRADING OF SEVERITY OF ADVERSE EVENTS 
An AE is defined as any untoward medical occurrence in a subject of clinical investigational 
participation administered a pharmaceutical product, whether or not considered drug related.  
A TEAE is an AE that is reported after administration of a dose of study drug. 
AEs include the following: 
• Unfavorable changes in general condition 
• Subjective or objective signs/symptoms 
• Concomitant diseases or accidents 
• Clinically relevant adverse changes in laboratory parameters observed in a subject in 
the course of a clinical study 
AEs comprise all disturbances of general health status, subjective and objective disease 
symptoms (including laboratory abnormalities), and accidents observed in the context of a 
clinical trial, irrespective of a possible causal relationship with the administration of the trial 
substance.  Events occurring in the framework of a clinical trial during drug-free and 
post-treatment periods or under placebo are also to be designated as AEs. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 48 of 71 
 
All AEs, regardless of how identified (e.g., volunteered, elicited, noted on physical 
examination), will be recorded throughout the study (i.e., from time of consent until final 
Follow-up visit).  
Subjects will be followed for resolution of AEs, by querying the subjects for an ongoing AE 
until resolved or until any unresolved AEs are judged by the PI to have stabilized or if lost to 
follow-up.  Resolution of all AEs will be promptly documented by the clinic on the subject’s 
eCRF. 
Any pregnancy diagnosed during the study must be reported immediately to the PI and 
Sponsor, including pregnancy in female partners of male subjects.  The pregnancy will be 
followed to term and/or outcome and this outcome must be reported to the Sponsor.  
Pregnancy, in and of itself, is not regarded as an AE or SAE unless the birth results in a 
congenital anomaly/birth defect or there is suspicion that the study drug may have interfered 
with the effectiveness of a contraceptive medication or method. 
Medication overdose may have occurred when an additional dose of a medication is known 
or suspected to have been taken (accidentally or intentionally) or when the dose administered 
exceeds the dose mandated by the protocol.  An overdose can involve any study medication 
and should be reported whether or not there is an associated AE.  An overdose is only 
considered an SAE if any of the defined criteria are met.  Associated AEs should be recorded 
and assessed in the standard manner defined by the protocol.  In cases of a discrepancy in 
drug accountability, an overdose will only be established when it is clear the subject has 
taken an extra dose or the investigator has reason to suspect additional doses were taken.  
The PI will rate the severity of AEs using the CTCAE v4.03.  Each CTCAE v4.03 term is a 
Medical Dictionary for Regulatory Activities (MedDRA) Lowest Level Term (LLT).  The 
CTCAE displays Grades 1–5 with unique clinical descriptions of severity for each AE.  Not 
all Grades are appropriate for all AEs.  Therefore, some AEs are listed with fewer than 
five options for Grade selection.  Grade 5 (Death) is not appropriate for some AEs and, 
therefore, is not an option.   
7.2 
CRITERIA FOR DETERMINING RELATIONSHIP TO DRUG 
The PI will make a blinded determination of the relationship of the AE to the study drug 
(including placebo) using a four-category system (not related, possible, probable, definite) 
according to the following guidelines: 
• NOT RELATED = an AE that does not follow a reasonable temporal sequence from 
administration of the drug and that can be reasonably explained by other factors, 
including underlying disease, complications, concomitant drugs, or concurrent 
treatment; 
• POSSIBLE = an AE that follows a reasonable temporal sequence from the 
administration of the drug (including the course after withdrawal of the drug) and that 
cannot be excluded as being possibly caused by the drug (e.g., existence of similar 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 49 of 71 
 
reports attributed to the drug and/or its analogues; reactions attributable to the 
pharmacological effect of the drug), although other factors such as underlying 
disease, complications, concomitant drugs, or concurrent treatment are presumable; 
• PROBABLE = an AE that follows a reasonable temporal sequence from 
administration of the drug (including the course after withdrawal of the drug) and that 
can be excluded as being possibly caused by other factors, such as underlying disease, 
complications, concomitant drugs, or concurrent treatment. 
• DEFINITE = an AE that follows a reasonable temporal sequence from administration 
of the drug (including the course after withdrawal of the drug), follows a known or 
hypothesized cause–effect relationship, and (if appropriate) satisfies the following: 
o Positive results obtained in drug sensitivity tests 
o Toxic level of the drug present in blood or other body fluids 
7.3 
REPORTING 
An SAE is any untoward medical occurrence at any dose that results in any of the following 
outcomes: 
• Death 
• A life-threatening event (i.e., places the subject, in the view of the PI, at immediate 
risk of death) 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
An unexpected adverse drug event is any adverse drug event the specificity or severity of 
which is not consistent with the current IB or, if an IB is not required or available, the 
specificity or severity of which is not consistent with the risk information described in the 
general investigational plan or elsewhere in the current application. 
An AE is associated with the use of the drug if a reasonable possibility exists that the event 
may have been caused by the drug. 
SAEs that are unexpected and related are reportable to Regulatory Authorities.  Reportable 
SAEs will be reported by the PI to the Sponsor and the responsible Institutional Review 
Board (IRB) or Ethics Committee (EC). 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 50 of 71 
 
The Sponsor’s assigned Safety Representative will be electronically notified via the 
Medidata system.  The reporting in the system must be completed by study personnel within 
24 hours of when an SAE is first recognized or reported.  Written reports should only be used 
if the site has issues accessing Medidata.  The Safety Representative will subsequently notify 
the Sponsor and the Sponsor’s assigned Medical Monitor of all reported SAEs. 
7.3.1 Serious Adverse Events Notification Requirements 
Any SAE must be reported by the Investigator, immediately or within 24 hours of awareness 
of the event, through data entry in the Adverse Event eCRF via the Medidata Rave® 
electronic data capture system.  If the Investigator does not become aware of the SAE 
immediately (e.g., study subject seeks initial treatment elsewhere), he/she is to report the 
event within 24 hours after learning of it and document the time he/she first learned of the 
SAE. 
Immediate notification to NGM (via the contracted CRO’s pharmacovigilance safety hotline 
telephone number) must occur if the SAE is fatal or life-threatening, irrespective of the 
extent of available AE information. 
In the rare case the Medidata Rave system is not available, the paper Serious Adverse Event 
Report Form (SAERF) should be used and faxed to the contracted CRO’s pharmacovigilance 
safety hotline fax number, according to the instructions provided in the study-specific 
regulatory binder.  Once the Medidata Rave system is available the event details should be 
entered as soon as possible. 
For all SAEs, the Investigator is obligated to pursue and provide detailed information to 
NGM in accordance with the timeframes for reporting specified above.  In addition, the 
Investigator may be required to obtain additional follow-up information in an expedited 
fashion.   
At the time of first notification, the Investigator or designee should provide the following 
information, if available.  
• 
Protocol number 
• 
Reporter (study site and investigator) 
• 
Patient’s study number 
• 
Patient’s date of birth 
• 
Patient’s gender 
• 
Date of first dose of investigational product 
• 
Date of last dose of investigational product, if applicable 
• 
Action taken with investigational product 
• 
Adverse Event term 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 51 of 71 
 
• 
Time and date of occurrence of the event (start and stop dates if known) 
• 
Severity 
• 
Outcome 
• 
A brief description of the event, outcome to date, and any actions taken 
• 
The seriousness criteria (on) that were met 
• 
Concomitant medication at onset of the event, if known 
• 
Relevant past history information 
• 
Relevant laboratory test findings 
• 
Investigator’s opinion of the relationship to investigational product. (“Is there a 
reasonable possibility that the investigational product caused the SAE? Yes or No?”) 
If requested by the contracted CRO’s pharmacovigilance unit, any missing or additional 
relevant information concerning the SAE should be entered into the Medidata Rave system 
or faxed to the safety hotline fax number.  The Investigator is required to comply with 
applicable regulations (including local laws and guidances) regarding the notification of 
his/her health authorities, IRB, principal and coordinating Investigators, study Investigators, 
and institutions.  
NGM or its designee is responsible for submitting expedited safety reports to the appropriate 
regulatory agency for all confirmed suspected, unexpected serious adverse reactions 
(SUSARs).  These reports will comply with the applicable regulatory requirements and with 
the International Conference on Harmonisation (ICH) Guideline for Clinical Safety Data 
Management:  Definitions and Standards for Expedited Reporting (E2A).  In the case of a 
fatal or life-threatening SUSAR, NGM or its designee will notify the appropriate regulatory 
agency as soon as possible but in no case later than 7 calendar days after NGM's initial 
receipt of the information.  For a non–life-threatening SUSAR, the report will be submitted 
no later than 15 days after NGM is made aware of the event. 
An SAE may qualify for expedited reporting to regulatory authorities if it is determined to be 
a SUSAR. 
 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 52 of 71 
 
8 DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
Details of statistical parameters and methods to be applied will be provided in a detailed 
Statistical Analysis Plan (SAP) prior to database lock (unblinding). 
8.1 
SAMPLE SIZE 
A sample size of 20 subjects randomized per treatment group was chosen in light of logistical 
needs and so as to accumulate sufficient safety data on NGM282.  The associated power to 
detect a treatment difference in the primary efficacy analysis, for either NGM282 comparison 
versus placebo, is at least 90%, based on the following assumptions: 
A. ALP Population Mean Change from Baseline: 
 
NGM282 
(either 1 mg or 3 mg) 
Placebo 
Subjects taking UDCA at Baseline 
–75 
0 
Subjects not taking UDCA at Baseline 
–475 
0 
UDCA = ursodeoxycholic acid. 
 
 
 
B. Equal numbers of completing subjects for each of the four cells above 
C. Population (not sample) standard deviation (SD) between subjects within each of the 
four cells above:  200 
D. Analysis of variance with treatment, UDCA (yes/no), treatment with UDCA (all as 
classification variables), and baseline value (as a continuous covariate) in the model 
E. 20% dropout rate, from randomization to Week 12, yielding 16 completing subjects 
per treatment group 
F. Dunnett’s 1-step adjustment for multiplicity, requiring a type 1 error rate of 0.027 
(2-sided) for each comparison versus placebo 
Assumptions underlying the means and SDs are based on studies evaluating UDCA as a 
first-line therapy and in studies where secondary or combination therapies with UDCA have 
been utilized.  The power in the primary efficacy analysis may be slightly higher, since it 
incorporates Dunnett’s step-down adjustment and utilizes repeated measures to reduce the 
power losses due to dropouts.  On the other hand, power may decrease slightly, to the degree 
that unequal numbers of subjects are randomized taking and not taking UDCA.  In addition, 
the probability that the observed least square (LS) mean treatment difference exceeds 30% of 
the placebo LS mean change has not been examined. 
To randomize 60 subjects, approximately 90 will be screened. 
If, in contrast, the population SD is 300, the power is roughly 81% for each NGM282 
comparison versus placebo.  

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 53 of 71 
 
8.2 
RANDOMIZATION 
At Day 1, all eligible subjects will be randomized 
 to one of the three treatment 
arms (NGM282 1 mg, NGM282 3 mg, or placebo) in a 1:1:1 ratio.  The randomization will 
be stratified by UDCA status (yes/no), to ensure an even distribution across the 
three treatment groups.  That status will be based on concomitant medication history.  
Additional randomization specifications will be detailed in the randomization plan.   
8.3 
TEST OF HYPOTHESIS AND SIGNIFICANCE LEVELS 
The null hypothesis being tested for this study will be that there is no difference between the 
active (1 mg or 3 mg NGM282, as applicable) and the Placebo treatment groups at Week 12 
in the population mean change from Baseline in ALP.  However, trial success will depend on 
both rejection of that null hypothesis at the 5% two-sided significance level, and observing 
the difference between either of the NGM282 groups and the placebo group, in the LS mean 
changes from Baseline of at least 30% of the placebo LS mean change from Baseline. 
8.4 
ANALYSIS SETS 
The analysis sets are detailed below.  Details of any others will be described in the SAP. 
8.4.1 Randomized Set 
All randomized subjects will be included in the Randomized Set.  In analyses using this set, 
subjects will be grouped according to randomized treatment if this differs from actual 
treatment received. 
8.4.2 Safety Set 
All randomized subjects who receive at least one dose (full or partial) of study drug and have 
at least one post-dose safety evaluation will be included in the Safety Set.  In analyses using 
this set, subjects will be grouped according to actual treatment received if this differs from 
the randomized treatment. 
8.4.3 Full Analysis Set 
All randomized subjects who receive at least one dose (full or partial) of study drug and have 
at least one valid, non-missing post-dose efficacy/PD parameter value will be included in the 
Full Analysis Set (FAS).  This will be the set for the primary analyses of efficacy and PD 
endpoints.  In FAS analyses, subjects will be grouped according to randomized treatment if 
this differs from actual treatment received.  

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 54 of 71 
 
8.4.4 Per Protocol Set 
The Per Protocol Set (PPS) will constitute a subset of the FAS.  It will include subjects who 
have at least one valid, non-missing post-dose ALP measurement.  In addition, FAS subjects 
who deviate from the conduct of the study or have an AE deemed by the Medical Monitor to 
be impactful on the primary endpoint will be excluded from the PPS.  In associated analyses, 
subjects will be grouped according to actual treatment received, if it differs from the 
randomized treatment. 
8.4.5 Pharmacokinetic Set 
All randomized participants who receive at least one dose (full or partial) of blinded drug, 
had a pre-dose (Baseline) blood draw, and provided at least one qualified (above the limit of 
quantification) post-dose sample will be included in the PK Set.  Subjects with protocol 
violations will be assessed by the medical monitor for inclusion in this set.  In associated 
analyses, subjects will be grouped according to the actual treatment received, if it differs 
from that to which the subject was randomized. 
8.5 
SUBJECT DISPOSITION 
Individual data listings for subject disposition will be presented for each subject, including 
enrollment date, treatment start date, treatment discontinuation date, discontinuation reason, 
and analysis set flags.  The number and percentage of subjects entering and discontinuing the 
study will be presented by treatment group.  The reasons for discontinuation will also be 
summarized.  Subject disposition will be summarized using the FAS. 
8.6 
TREATMENT EXPOSURE 
Measures of extent of treatment exposure include the total number of doses per subject and 
compliance.  Treatment compliance is defined as the number of doses administered per 
protocol/number of doses prescribed per protocol.  These measures will be summarized using 
the Safety Set. 
8.7 
PROTOCOL DEVIATIONS 
Protocol deviations will be summarized using the FAS. 
8.8 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS 
Demographics, medical history, and other Baseline characteristics will be summarized using 
the Randomized Set, FAS, and Safety Set.   

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 56 of 71 
 
As secondary analyses within the same MMRM, the linear combinations  
µ1 - µ3 
and  
(µ1+µ3)/2 - µp  
will be estimated, where µ1, µ3, and µp are the population LS means for the primary efficacy 
endpoint of the 1 mg NGM282, 3 mg NGM282, and placebo groups, respectively.  
Further explanatory variables may be included in additional modeling using the FAS, similar 
to the primary efficacy analysis, depending on the relevance to the endpoint; such modeling 
will be specified in the SAP. 
If strong evidence of marked deviations from normality is noted in the distribution of the 
residuals of the primary MMRM ANCOVA, then FAS analyses using data transformations 
of the primary efficacy endpoint, and/or non-parametric approaches, will be explored. 
As sensitivity analyses,  
a. The primary analysis for the primary endpoint will be repeated for the PPS. 
b. The treatments will be compared with respect to the population mean of the 
primary endpoint using the FAS and an ANCOVA model having treatment 
group, UDCA (yes/no), and treatment by UDCA interaction as classification 
variables, and the baseline value as the continuous covariate.  The overall 
type 1 error rate for the two pairwise comparisons versus placebo will be 
controlled using the step-down Dunnett multiple-testing procedure.  Missing 
data will be imputed using the last post-baseline observation carried forward 
methodology.  Subjects with no post-baseline observations will be excluded. 
8.9.3 Analysis of Secondary Endpoints 
The analysis of secondary endpoints will be based on the FAS. 
The primary efficacy analysis will be repeated for each continuous secondary efficacy 
endpoint.  Further explanatory variables may be included in the modeling depending on the 
relevance to the endpoint analyzed and will be specified in the SAP. 
In addition, for each NGM282 treatment group, the LS mean rate (slope, per week) of change 
in ALP during Weeks 1–4 will be compared to that during Weeks 5–12; the changes in 
slopes will be estimated.  This estimation will be performed using a MMRM similar to that 
of the primary efficacy analysis.  It will also be repeated using percent change in ALP. 
Categorical secondary efficacy endpoints (reflecting incidence and severity of 
IBD-associated symptoms and acute cholangitis) will be analyzed using confidence intervals 
of differences of population treatment proportions.   

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 57 of 71 
 
8.9.4 Analysis of Exploratory PD Endpoints 
The analysis of exploratory PD endpoints will be based on the FAS. 
The primary efficacy analysis will be repeated for each continuous exploratory PD endpoint.  
Further explanatory variables may be included in the modeling depending on the relevance to 
the endpoint analyzed and will be specified in the SAP. 
8.10 
SAFETY AND TOLERABILITY 
Safety and tolerability will be assessed by clinical review and summaries of the following 
parameters:   
1. AEs 
2. Clinical laboratory test results 
3. Physical examination results 
4. LISSAs 
5. ECG results 
6. ISRs 
7. Changes and percent changes in total cholesterol, HDL cholesterol, LDL cholesterol, and 
triglycerides 
8. Vital signs 
All safety and tolerability analyses will be conducted using the Safety Set. 
8.10.1 Adverse Events 
AEs, including SAEs, will be coded using the MedDRA.  The number and percentage of 
subjects experiencing an AE will be summarized for each system organ class (SOC) and 
preferred term (PT) by treatment group.  In addition, AEs will be tabulated according to 
severity, causality, and relation to the study drug.   
All AE summaries will be restricted to TEAEs only, defined as AEs that commence on or 
after the time of start of first study-drug administration and before 30 days after the last dose 
of blinded drug.  AEs without an onset date or time will be defined as treatment emergent, 
except if an incomplete date (e.g., month and year) clearly indicates that the event started 
prior to the start of first administration of study drug or if the AE stop date indicates that the 
event started or stopped prior to the start of first administration of study drug. 
For the summaries of AEs, subjects who experience the same AE (in terms of the MedDRA 
preferred term) more than once will be counted only once for that event.  Separate summaries 
will be provided for AEs by severity, causality, and relationship to study drug.  
All AEs will be listed.  SAEs will be summarized and listed. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 58 of 71 
 
8.10.2 Clinical Laboratory Evaluations 
The values and percentage changes from Baseline at Week 12 of total cholesterol, HDL 
cholesterol, and LDL cholesterol will be summarized. 
Observed values and absolute changes from Baseline for routine chemistry, hematology, and 
urinalysis values will be summarized at each per-protocol time point for each treatment 
group and overall.  Shift tables may also be presented for select chemistry and hematology 
parameters, as identified in the SAP.  
In data listings, laboratory values will be compared to normal ranges; out-of-range and 
clinically significant laboratory values will be identified. 
8.10.3 Physical Examinations 
Physical examination results will be listed for each subject. 
8.10.4 Vital Signs 
Observed values as well as changes from Baseline will be summarized for all vital-sign 
parameters, by time point and treatment group.   
8.10.5 Pregnancy Test 
Urine and serum pregnancy test data will be listed for each female subject. 
8.10.6 Electrocardiogram 
Observed values as well as changes from Baseline will be summarized for all ECG 
parameters, by time point and treatment group.   
8.10.7 Injection-Site Reactions 
Frequency tabulations of ISRs will be presented at each time point by treatment group.  
8.10.8 Prior and Concomitant Medications 
Non-study medications will be classified as prior and concomitant, and coded using the 
current version of the World Health Organization Drug Dictionary Enhanced (WHO-DD). 
Prior medications are defined as those taken at least once during the 28 days before 
Screening.  Concomitant medications are defined as those taken at least once from 28 days 
prior to Screening through the EOS visit.  Medications stopped in the 28 days prior to the 
Screening time point will not be considered concomitant. 
Prior medications and concomitant medications will be listed separately.  In addition, 
concomitant medications will be summarized by Anatomical Therapeutic Chemical (ATC) 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 59 of 71 
 
class and PT using frequency counts and percentages.  For the summaries of concomitant 
medications, subjects who take the same medication (in terms of PT) more than once will be 
counted only once for that medication. 
8.10.9 Interim Analysis 
An unblinded interim analysis (IA) will be conducted when approximately 24 subjects (a 
minumum of 8 subjects per arm) have completed the Week 12 visit.  At the IA, the evidence 
regarding the safety and efficacy of NGM282 in the PSC indication will be assessed, in order 
to evaluate the appropriateness of continuing the study.  
A separate SAP for the IA will be generated, describing the conduct of the IA in detail. 
8.11 
PHARMACOKINETICS  
The following PK parameters will be calculated using the PK Set and the validated PK 
software, Phoenix WinNonlin, Version 5.3 (or higher; Certara Corporation; Princeton, NJ, 
U.S.): 
• Day 1; Weeks 1, 2, 4, 8, and 12:  trough concentration (Ctrough) 
• Day 1 and Week 12:  Ctrough; concentration at 2 hours post-dose (C2h post-dose) 
PK data will be used to evaluate the accumulation of NGM282 in the plasma of PSC patients 
following multiple-dose administration at 1 and 3 mg per day.  This will be done by 
comparing the steady-state trough NGM282 levels in PSC subjects to results obtained on 
Day 1 in the same subject and, more generally, in the dosing cohort.  In addition, 
determination of NGM282 concentrations 2 hours post-dose on Day 1 and Week 12 will 
enhance information obtained on accumulation and provide an indication of expected 
maximum drug concentration (Cmax) in patients.  This information will be directly compared 
to Phase 1 results obtained in healthy volunteers (Study 12-0101) and with other medical 
conditions (PBC, nonalcoholic steatohepatitis [NASH], and T2D).  In addition, PK data will 
be used to explore PK/PD correlations in terms of drug efficacy and toxicity, where data 
allow.  Actual sample times will be used in the data analysis. 
The exposure of 1 mg and 3 mg of NGM282 will also be evaluated. 
9 DATA MANAGEMENT AND ELECTRONIC SYSTEMS 
9.1 
DATA MANAGEMENT 
A data validation manual (DVM) will specify all relevant aspects of data processing and 
handling for the study, including how data will be managed and cleaned.  Relevant sections 
of the DVM includes the following:  standard operating procedures to be followed; eCRF 
data entry and flow, tracking and filing; coding and coding review plan; reconciliation of 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 60 of 71 
 
SAEs; external and vendor data integration, import, and reconciliation; and general listing 
review. 
9.2 
ELECTRONIC SYSTEMS 
Electronic systems used to collect and process data in this study will include the following: 
• Contracted CRO’s
 randomization and dispensing study-drug supply 
• Medidata Rave for general data capture 
• PreClarus – real-time study data and analysis 
• Statistical Analysis Software (SAS) – data reconciliation/packaging and statistical 
analysis and review 
10  
ADMINISTRATIVE ASPECTS 
10.1 
PROTOCOL ADHERENCE 
The PI must adhere to the protocol as detailed in this document and agree that the Sponsor 
must approve any changes to the protocol prior to seeking approval from the EC.  
No alterations in the protocol will occur without agreement between the Sponsor and the PI.  
No alterations in the protocol affecting subject safety will occur without the express written 
approvals of the Sponsor, PI, and EC. 
10.2 
DISCLOSURE 
All information provided regarding the study as well as all information collected/documented 
during the course of the study will be regarded as confidential.  The PI agrees not to disclose 
such information in any way without prior written permission from the Sponsor. 
Any publication of the results either in part or in total (articles in journals or newspapers, oral 
presentations, abstracts, etc.) by the PI or their representative(s) shall require prior 
notification and review within a reasonable time frame by the Sponsor and cannot be made in 
violation of the Sponsor’s confidentiality restrictions or to the detriment of the Sponsor’s 
intellectual property rights. 
10.3 
MONITORING 
The Sponsor’s or designee’s monitor (i.e., “the monitor”) will be responsible for monitoring 
this clinical trial.  The monitor will review the study conduct, proper eCRF and source 
documentation completion and retention, and accurate study-drug accountability.  To this 
end, the monitor will visit the study site at suitable intervals and be in frequent contact 
through verbal and written communication.  The PI will grant access to all documents 
(related to the study and the individual subjects) at any time these are requested by the 
sponsor or designee.  In turn, the monitor will adhere to all requirements for subject 
confidentiality as outlined in the ICF.  The PI and PI’s staff will be expected to cooperate 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 61 of 71 
 
with the monitor, to be available during a portion of the monitoring visit to answer questions, 
to resolve discrepancies, and to provide any missing information. 
10.4 
INSTITUTIONAL REVIEW BOARD/ETHICS COMMITTEE 
This protocol, the informed consent document, and all relevant supporting data must be 
submitted to the IRB/EC for approval.  IRB/EC approval of the protocol, informed consent 
document, and any advertisement used to recruit study subjects must be obtained before the 
study may be initiated. 
The PI is responsible for keeping the IRB/EC advised of the progress of the study and of any 
changes made to the protocol as deemed appropriate but, in any case, at least once a year.  
The PI is also responsible for notifying the IRB/EC of any reportable AEs that occur during 
the study. 
10.5 
INFORMED CONSENT 
This study will be conducted in compliance with ICH E6 Good Clinical Practice:  
Consolidated Guidelines pertaining to informed consent.  At the first visit, prior to initiation 
of any study-related procedures, patients must give their written consent to participate in the 
study after having been informed about the nature and purpose of the study, 
participation/termination conditions, and risks and benefits.  The informed consent document 
must be signed and dated by the patient and PI, or designee, prior to study participation.  
A copy of the informed consent document must be provided to the subject.  Signed consent 
forms must remain in the subject’s study file and be available for verification by Sponsor or 
its representative at any time. 
10.6 
RECORDS 
The results from Screening and data collected during the study will be recorded in the 
subject’s eCRF.  To maintain confidentiality, the subjects will be identified only by numbers 
and initials. 
The completed eCRFs will be transferred to the Sponsor or designee.  Copies of each eCRF 
will be retained by the PI.  All source documents, records, and reports will be retained by the 
clinic. 
All primary source data or copies thereof (e.g., laboratory records, eCRFs, data sheets, 
correspondence, photographs, and computer records) that are a result of the original 
observations and activities of the study and are necessary for the reconstruction and 
evaluation of any study report will be retained in the clinic archives. 
Sponsor will inform the PI of the time period for retaining these records to comply with all 
applicable regulatory requirements.  The minimum retention time will meet the strictest 
(longest) standard applicable to that site for the study, as dictated by any institutional 
requirements or local laws or regulations, or Sponsor standards/procedures; otherwise, the 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 62 of 71 
 
retention period will default to the retention period of 15 years following completion of the 
clinical trial.   
10.7 
DATA MONITORING COMMITTEE 
A Data Monitoring Committee (DMC) will be established in order to protect subject welfare, 
preserve study integrity, and provide recommendations as needed regarding study conduct. 
The DMC will be comprised of two external liver disease clinical experts as well as a 
statistician and a medical team member from the sponsor.  The DMC will meet at predefined 
time points and on an as-needed basis based on enrollment, treatment milestones, and safety. 
Formal minutes and recommendations will provided by the DMC to the sponsor regarding 
additional data requests and the continuation of the conduct of the study as outlined in the 
current protocol.  The DMC will operate under the guidance of an agreed-upon charter. 
10.8 
FINANCING AND INSURANCE 
The financing and insurance for this study are outlined in the Clinical Trial Research 
Agreement.  

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 63 of 71 
 
INVESTIGATOR PROTOCOL REVIEW AND SIGNATURE FORM 
Protocol Number: 
15-0106 
 
Protocol Title:  A Phase 2, Randomized, Double Blind, Placebo Controlled, Parallel Group, 
Multiple Center Study to Evaluate the Safety, Tolerability, and Efficacy of NGM282 
Administered for 12 Weeks in Patients with Primary Sclerosing Cholangitis (PSC)  
 
I have read the above-mentioned Protocol Amendment 2 dated 27 May 2016. 
 
I agree to conduct the study as detailed herein and in compliance with ICH Guidelines for 
Good Clinical Practice and applicable regulatory requirements, and to inform all who assist 
me in the conduct of this study of their responsibilities and obligations.  
 
 
 
 
 
__________________________________________ 
Principal Investigator (Please PRINT) 
 
 
 
__________________________________________ 
__________________ 
Principal Investigator (Signature) 
 Date 
 
 
__________________________________________ 
Name of Institution (Please PRINT) 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 65 of 71 
 
REFERENCES  
Ali AH, Carey EJ, Lindor KD. Mini-review: current research on the treatment of primary 
sclerosing cholangitis. Intractable Rare Dis Res 2015;4:1–6. 
Andraus W, Haddad L, Nacif LS, et al. Case report: the best approach for diagnosing primary 
sclerosing cholangitis. Clinics 2011;66:1987–9. 
Angulo P, Lindor KD. Primary sclerosing cholangitis. Hepatology 1999;30:325–32. 
Benito de Valle M, Rahman M, Lindkvist B, et al. Factors that reduce health-related quality 
of life in patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol 
2012;10:769–75. 
Beuers U, Boberg KM, Chapman RW, et al. EASL Clinical Practice Guidelines: 
management of cholestatic liver diseases. J Hepatol 2009;51:237–67. 
Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and 
primary biliary cirrhosis: a systematic review. J Hepatol 2012;56:1181–8. 
Chapman R, Fevery J, Kalloo A, et al. Diagnosis and management of primary sclerosing 
cholangitis. Hepatology 2010;51:660–78. 
Dmitrienko A, D'Agostino R, Sr. Traditional multiplicity adjustment methods in clinical 
trials. Stat Med 2013;32:5172–218. 
Elman S, Hynan LS, Gabriel V, et al. The 5-D itch scale: a new measure of pruritus. Brit J 
Dermatol 2010;162:587–93. 
Goetz R, Beenken A, Ibrahimi OA, et al. Molecular insights into the Klotho-dependent, 
endocrine mode of action of fibroblast growth factor 19 subfamily members. Mol Cell Biol 
2007;7:3417–28. 
Hirschfield GM, Karlsen TH, Lindor KD, et al. Primary sclerosing cholangitis. Lancet 
2013;382:1587–99.  
Hirschfield GM, Karlsen TH. Genetic risks link autoimmune hepatitis to other autoimmune 
liver disease. Gastroenterology 2014;147:270–3. 
Kaya M, Petersen BT, Angulo P, et al. Balloon dilation compared to stenting of dominant 
strictures in primary sclerosing cholangitis. Am J Gastroenterol 2001;96:1059–66. 
Kir S, Beddow SA, Samuel VT, et al. FGF19 as a postprandial, insulin-independent activator 
of hepatic protein and glycogen synthesis. Science 2011;331:1621–4. 
Kurosu H, Choi M, Ogawa Y, et al. Tissue-specific expression of beta-Klotho and fibroblast 
growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. 
Biol Chem 2007;282:26687–95. 
Lenicek M, Duricova D, Komarek V, et al. Bile acid malabsorption in inflammatory bowel 
disease: assessment by serum markers. Inflamm Bowel Dis 2011;17:1322–7. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 66 of 71 
 
Lewis JD, Chuai S, Nessel L, et al. Use of the noninvasive components of the Mayo score to 
assess clinical response in ulcerative colitis. Inflamm Bowel Dis 2008;14:1660–6. 
Lindor KD, Kowdley KV, Harrison ME. ACG clinical guideline: primary sclerosing 
cholangitis. Am J Gastroenterol 2015;110:646–59.  
Lundasen T, Gälman C, Angelin B, et al. Circulating intestinal fibroblast growth factor 19 
has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man. J Intern 
Med 2006;260:530–6.  
Molodecky NA, Kareemi H, Parab R, et al. Incidence of primary sclerosing cholangitis: a 
systematic review and meta-analysis. Hepatology 2011;53:1590–9. 
Neumann UP, Schmeding M. Role of surgery in cholangiocarcinoma: from resection to 
transplantation. Best Pract Res Clin Gastroenterol 2015;29:295–308. 
Pattni S, Brydon WG, Dew T, et al. Fibroblast growth factor 19 and 
7a-hydroxy-4-cholesten-3-one in the diagnosis of patients with possible bile acid diarrhea. 
Clin Transl Gastroenterol 2012;3:1–7. 
Rizvi S, Eaton JE, Gores GJ. Primary sclerosing cholangitis as a pre-malignant biliary tract 
disease: surveillance and management. Clin Gastroenterol Hepatol 2015 Jun 4. pii: 
S1542-3565(15). 
Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Ann Rev Biochem 
2003;72:137–74. 
Schaap FG, van der Gaag NA, Gouma DJ, et al. High expression of the bile salt-homeostatic 
hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis. 
Hepatology 2009;49:1228–35. 
Stanich PP, Bjornsson E, Gossard AA, et al. Alkaline phosphatase normalization is 
associated with better prognosis in primary sclerosing cholangitis. Dig Liver Dis 
2011;43:309–13. 
Tabibian JH, Lindor KD. Ursodeoxycholic acid in primary sclerosing cholangitis: if 
withdrawal is bad, then administration is good (right?). Hepatology 2014;60:785–8. 
Triantos CK, Koukias NM, Nikolopoulou VN, et al. Meta-analysis: ursodeoxycholic acid for 
primary sclerosing cholangitis. Aliment Pharmacol Ther 2011;34:901–10. 
Tsaitas C, Semertzidou A, Sinakos E. Update on inflammatory bowel disease in patients with 
primary sclerosing cholangitis. World J Hepatol 2014;6:178–87. 
U.S. Department of Health and Human Services, Food and Drug Administration, Center for 
Biologics Evaluation and Research. Guidance for industry: toxicity grading scale for healthy 
adult and adolescent volunteers enrolled in preventive vaccine clinical trials. September 
2007. 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 67 of 71 
 
Williamson KD, Chapman RW. Primary sclerosing cholangitis: a clinical update. Br Med 
Bull 2015;114:53–64. 
Zweers SJLB, Shiryaev A, Karlsen TH, et al. Reduced FGF19 level in bile and decreased 
FGF19 expression in the gallbladder of patients with primary sclerosing cholangitis. J Hepat 
2012;56 (Suppl2):S145 (abstract presented at EASL International Liver Congress, Barcelona, 
Spain 18–22 April 2012). 
 
 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 68 of 71 
 
APPENDIX A–FOOD AND DRUG ADMINISTRATION TOXICITY GRADING 
SCALE IN LOCAL INJECTION-SITE SYMPTOM ASSESSMENTS 
Local Reaction to 
Injection Product 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially  
Life-Threatening 
(Grade 4) 
Pain 
Does not 
interfere with 
activity 
Repeated use of 
non-narcotic pain 
reliever more than 
24 hours or interferes 
with activity 
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity 
Emergency room 
visit or 
hospitalization 
Tenderness 
Mild discomfort 
to touch 
Discomfort with 
movement 
Significant 
discomfort at 
rest 
Emergency room 
visit or 
hospitalization 
Erythema/Redness a 
2.5–5 cm 
5.1–10 cm 
> 10 cm 
Necrosis or 
exfoliative 
dermatitis 
Induration/Swelling b 
2.5–5 cm and 
does not 
interfere with 
activity 
5.1–10 cm or interferes 
with activity 
> 10 cm or 
prevents daily 
activity 
Necrosis 
Notes:  The FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers enrolled in Preventive 
Vaccine Clinical Trials can be found at: 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/ 
Vaccines/ucm074775 htm. 
a 
In addition to grading the measured local reaction at the greatest single diameter, the measurements should 
be recorded as a continuous variable. 
b 
Induration or swelling should be evaluated and graded using the functional scale as well as the actual 
measurement. 
 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 69 of 71 
 
APPENDIX B—NUMERIC RATING SCALE FOR ITCH AND FATIGUE 
 
ITCH SEVERITY 
Instructions:  
Please clearly mark an ‘x’ in the box (
) that best describes your itching in the past 
24 hours. 
No Itching 
 
 
 
Worst Imaginable 
Itching 
▼ 
 
 
 
▼ 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Physically 
Tired At All 
Extremely 
Physically Tired 
    ▼ 
▼ 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 70 of 71 
 
APPENDIX C—5-D PRURITIS SCALE 
 
 
 

 
CONFIDENTIAL 
NGM Protocol 15-0106  
 
27 May 2016  
Page 71 of 71 
 
APPENDIX D—MAYO PARTIAL IBD SCORE (INFLAMMATORY BOWEL 
DISEASE SCALE) 
Components of the Partial Mayo Score 
Stool Frequency 
 0 = Normal 
 1 = 1–2 stools/day more than normal 
 2 = 3–4 stools/day more than normal 
 3 = >4 stools/day more than normal 
Rectal bleeding a 
 0 = None 
 1 = Visible blood with stool less than half the time 
 2 = Visible blood with stool half of the time or more 
 3 = Passing blood alone 
Physician rating of disease activity 
 0 = Normal 
 1 = Mild 
 2 = Moderate 
 3 = Severe 
a 
A score of 3 for bleeding required patients to have at least 50% of bowel motions 
accompanied by visible blood and at least one bowel motion with blood alone.