Clinical trial NCT03883607
Conditions: Non Alcoholic Steatohepatitis
Keywords: Pediatric Pharmacokinetics
Sponsor: Genfit
Start date: 2019-06-25; Completion date: 2020-06-16
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The study was being conducted in order to assess the pharmacokinetics and the safety of elafibranor following once daily administration of two dose levels of elafibranor (80 milligrams \[mg\] and 120mg) during 3 months in children and adolescent population (8 to 17 years of age) with non alcoholic steatohepatitis (NASH).

Detailed description:

Arms: arm 1: Participants received Elafibranor 80 mg tablet orally once daily for 12 weeks. arm 2: Participants received Elafibranor 120 mg tablet orally once daily for 12 weeks.
Interventions: intervention 1: Elafibranor 80mg intervention 2: Elafibranor 120mg
Intervention descriptions: intervention 1: Once daily oral intake of elafibranor 80 mg during 3 months intervention 2: Once daily oral intake of elafibranor 120 mg during 3 months

Protocol documents:
Prot_000.pdf: 
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C L I N I C A L P R O T O C O L –  P H A S E 2 A  
P R O T O C O L N ° G F T 5 0 5 E -2 1 8 -1  
I N D N U M B E R : 1 1 5 0 2 8 
A M E N D M E N T  3 : F I N A L  4 .0  - R E L E A S E D A T E :  2 0  A P R I L 2 0 2 0   
S u p ers e d es pr e vi o u s V ersi o n 3 . 0 - R el e as e d at e 2 1  F e br u ar y 2 0 2 0  
A n O p e n L a b el, R a n d o miz e d, M ulti c e nt er St u d y t o Ass ess  t h e P h ar m a c o ki n eti c  a n d 
P h ar m a c o d y n a mi c Pr ofil e  a n d t h e S af et y a n d T ol er a bilit y of T w o D os e L e v els of 
El afi br a n or  (8 0 m g a n d 1 2 0 m g ) i n C hil dr e n a n d A d ol es c e nts, 8 t o 1 7 Y e ars of A g e, wit h 
N o n al c o h oli c  St e at o h e p atitis ( N A S H)  
 
 
S p o n s or  
 
 
G E N FI T  
 
P ar c E ur a s a nt é  
8 8 5, a v e n u e E u g è n e A vi n é e  
5 9 1 2 0 L O O S  
Fr a n c e  
 
R e pr e s e nt e d b y:  
, M D 
 
P h o n e:  
  
E -m ail:
 
 
 
 
 
 
P P D
P P D
P P D
P P D


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S I G N A T U R E P A G E  
Pr ot o c ol Titl e:  
A n O p e n L a b el, R a n d o miz e d, M ulti c e nt er 
St u d y t o Ass ess t h e P h ar m a c o ki n eti c a n d 
P h ar m a c o d y n a mi c Pr ofil e a n d t h e S af et y 
a n d T ol er a bilit y of T w o D os e L e v els of 
El afi br a n or ( 8 0 m g a n d 1 2 0 m g) i n 
C hil dr e n a n d A d ol es c e nts, 8 t o 1 7 Y e ars 
of A g e, wit h N o n al c o h oli c St e at o h e p atitis 
( N A S H) 
Pr ot o c ol C o d e:  
G F T 5 0 5 E -2 1 8 -1  
I N D N u m b er:  
1 1 5 0 2 8  
V er si o n:  
4 .0  
R el e a s e D at e:  
2 0 A pril 2 0 2 0  
 
 
 
 
O n b e h alf of (t h e S p o n s or) : 
G E N FI T  
P ar c E ur as a nt é  
8 8 5, a v e n u e E u g è n e A vi n é e  
5 9 1 2 0 L O O S –  Fr a n c e  
, M D 
 
Pri nt N a m e  
 
 
 
 
Si g n at u r e 
 
D at e  
 
P P D


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CLINICAL STUDY PROTOCOL - INVESTIGATOR SIGNATURE PAGE 
 
Protocol Title: 
An Open Label, Randomized, Multicenter Study to 
Assess the Pharmacokinetic and Pharmacodynamic 
Profile and the Safety and Tolerability of Two Dose 
Levels of Elafibranor (80 mg and 120 mg) in Children 
and Adolescents, 8 to 17 Years of Age, with 
Nonalcoholic Steatohepatitis (NASH)  
Protocol Code: 
GFT505E-218-1 
IND Number: 
115028 
Clinical Phase: 
2a 
Version: 
4.0 
Release Date: 
20 April 2020 
 
Sponsor: 
GENFIT 
Parc Eurasanté, 
885 avenue Eugène Avinée, 
59120 Loos – France 
 
I have read this protocol, agree that the protocol contains all the information necessary to conduct the study 
and with my signature confirm that I’ll conduct the study according to it and that all staff members involved 
in the conduct of this study are informed about their obligations in meeting the above commitments. 
 
 
Investigator Name:  
 
 
Institution Name: 
 
 
 
Institution 
Address: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
Date  
 
 


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S T U D Y C O N T A C T S  
P R O T O C O L N °:  G F T 5 0 5 E -2 1 8 -1 / I N D N ° 1 1 5 0 2 8   
 
S p o n s or  
 
  
G E N FI T  
 
P ar c E ur a s a nt é  
8 8 5, a v e n u e E u g è n e A vi n é e  
5 9 1 2 0 L O O S –  Fr a n c e  
 
 
, M D 
 
P h o n e: 
   
E -M ail:  
 
 
C R O f or 
M o nit ori n g  a n d 
P K P ar a m et er 
A n al y si s  
 
C R O f or D at a -
M a n a g e m e nt & 
St ati sti c s  
 
P h ar m a c o -
vi gil a n c e  
St u d y Dr u g 
S u p pli er  
C e ntr al 
L a b or at or y  
C R O f or P K 
T e sti n g  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P P D
P P D
P P D
P P D
P P D


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Summary of changes to the protocol: 
 
Section 
New Text (additions in bold; deletions in strikethrough) 
Section 5.2.1 
Due to the COVID-19 crisis, the screening window (i.e., the time from the 
signing of consent / screening visit 1 to randomization) can be extended to 
be up to 8 weeks if no onsite visit is possible earlier. 
 
Section 5.3.3 
• 
Off-site study procedures in case of crisis situation 
Based on assessment of risk, and to ensure patient safety and minimize risks 
to trial integrity, the sponsor determined that the following optional off-site 
study procedures can be performed in case a study participant cannot attend 
an on-site visit during the COVID-19 crisis:  
 
• 
Safety assessment via phone call  
• 
Local lab assessment 
• 
Delivery of the study treatment to patient 
• 
Visit to patient’s home  
 
These options apply to all on-site study visits except for the randomization 
visit (Visit 1).  Visit 1 must occur on-site as per section 5.2.2.   
 
These solutions can be applied after Medical Monitor approval and depending 
on the investigator’s judgment of each case and the patient/parent(s)’s 
agreement.  The alternative solutions can be implemented in response to the 
COVID-19 crisis prior to the notification or submission to and approval of 
regulatory agencies and ethics committees. 
 
Before implementing any of these options for a patient, the site will contact 
the patient and parent(s) to check whether they agree with the off-site 
procedures.    
 
The patient will be invited to attend an on-site visit to complete the study 
procedures as per protocol, as soon as the situation allows it. 
 
5.3.3.1 
Safety and drug compliance procedures 
 
 
The following procedures will be performed if applicable for the visit via either 
a phone contact, or, if safe and possible, a direct visit to the patient:  
 
• 
Check for AEs  
• 
Collection of any lifestyle modifications 
• 
Check concomitant/prior medication  
• 
Check of compliance (review of dosing diary with the 
patient/parent(s)) 
• 
Physical examination if possible with a direct visit to the patient or 
using video (described in Section 6.2.1)  
• 
Record vital signs, waist circumference and weight if possible with a 
direct visit to the patient (described in Section 6.2.1 and Section 6.2.2) 
 
5.3.3.2 Local lab assessment  


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The patient will be asked if he/she can access a local lab in the few days after 
the phone contact to obtain hematology and biochemistry testing.  
 
If a direct visit to the patient is safe and possible, the appropriate lab 
parameters corresponding to the on-site study visit will be collected. 
 
5.3.3.3 Delivery of study treatment to the patient 
 
The study treatment can be shipped to the patient or delivered directly to the 
patient by the site study staff if safe and possible as per the site procedure. 
 
As per the usual study visit, the patient will be instructed to continue taking 
the available tablets from the existing kit until he/she receives the new kit. 
 
The study drug compliance and study drug accountability will be performed 
as described in Section 7.7 and_Section 7.8 once brought to the study 
site/study pharmacy. 
 
5.3.3.4 Completion of Missed Study Procedures  
 
As soon as the situation allows it, the site will schedule the patient’s on-site 
visit to complete the missed study procedures (those that could not be 
performed during the phone calls/visit to patient) as per protocol. 
 
 
 


Clinical Trial GFT505E-218-1 
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CLINICAL TRIAL SYNOPSIS 
 
Sponsor 
GENFIT 
 
Study Drug 
Elafibranor (GFT505) 
Protocol Number 
GFT505E-218-1 
Title of the study 
An Open Label, Randomized, Multicenter Study to Assess the Pharmacokinetic and Pharmacodynamic 
Profile and the Safety and Tolerability of Two Dose Levels of Elafibranor (80 mg and 120 mg) in Children 
and Adolescents, 8 to 17 Years of Age, with Nonalcoholic Steatohepatitis (NASH) 
Phase: 2a 
Indication: Treatment of Nonalcoholic Steatohepatitis (NASH) 
Study Design and dose levels 
This study is an open-label, randomized, multicenter, sequential cohort study that will assess the 
pharmacokinetics (PK), safety, and pharmacodynamics (PD) and explore the relationship between PK and 
PD response following 12 weeks of once daily oral administration of elafibranor at doses of 80 mg and 
120 mg in children and adolescents, 8 to 17 years of age (inclusive), with histologically confirmed 
(historical biopsy) nonalcoholic steatohepatitis (NASH). The target population will include patients with 
NASH with and without fibrosis. Of the 20 patients that will be enrolled and dosed with elafibranor, at 
least 4 patients ≥12 to ≤17 years of age, and at least 2 patients ≥8 to ≤11 years of age, will have 
significant fibrosis [i.e., fibrosis stage 2 or 3]). 
Two patient cohorts will be dosed sequentially. Cohort 1 will consist of approximately 12 patients who are 
≥12 to ≤17 years of age and will be enrolled first. Once 10 (80%) patients in cohort 1 have been evaluated 
for PK and safety through Visit 4 by the Data Safety Monitoring Board (DSMB), and if agreed upon by the 
DSMB, enrollment will be open to patients ≥8 to ≤11 years of age. Cohort 2 will consist of approximately 
8 patients who are ≥8 to ≤11 years of age.   
Potential patients will be screened within 28 days (Day -28 [Week -4] to Day -7 [Week -1]) prior to Day 
1. Day 1 will include randomization and dosing with study drug. After signing the informed consent form 
(ICF) (parent/legal guardian) and the assent (patient) documents, patients will undergo screening 
procedures to confirm study eligibility. The patient (and parent/legal guardian) will be given counselling 
regarding a diet and exercise regimen to be maintained starting from the screening visit. 
Eligible patients will return to the clinic on Day 1. Baseline evaluations1 will be obtained prior to study 
drug administration. Patients will be randomized (1:1) to receive either 80 mg or 120 mg once daily for 
12 weeks. The patient (and parent/legal guardian) will again be counselled on dietary and exercise 
regimen requirements that will be maintained throughout the study period. Patients will be dispensed a 
1-month supply of study drug and dosing diary and will be scheduled for their next visit on Day 15 (± 2 
days) for safety evaluations and compliance check1. 
The patient will return on Day 29 (± 2 days)/Week 4 for safety, PD (biological laboratory assessments), 
PK assessments, and compliance check1. A 1-month supply of study drug and dosing diary will be 
dispensed. The patient will return the following day for collection of the 24-hour (±10 minutes) post-dose 
sample (prior to the next daily dose).  The patient will return to the clinic on Day 57 (± 2 days)/Week 8 
and Day 85 (± 2 days)/Week 12, for safety, PD (biological laboratory assessments) and compliance 
evaluations.  On Day 57 (± 2 days)/Week 8, in addition to safety and PD, a 1-month supply of study drug 
and dosing diary will be dispensed. At the End of Treatment (EOT) visit, Day 85 (± 2 days)/Week 12, 
quality of life will be assessed, the final PK sample will be collected, and unused study drug and completed 
diary will be collected. A final safety evaluation will be conducted at the End of Study (EOS) visit, Day 113 
(± 2 days)/Week 16. 
1Refer to General Study Assessment Schedule and Section 5 – Trial Procedures for detailed procedure 
listings. 


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R o ut e o f A d mi nistr ati o n: Or al  
D os e L e v els : T w o d os e l e v els will b e e v al u at e d i n t his st u d y; 8 0 m g a d mi ni st er e d o n c e d ail y  f or 1 2 w e e ks 
a n d 1 2 0 m g a d mi ni st er e d o n c e d ail y  f or 1 2 w e e ks. 
St u d y O bj e cti v e s  
Pri m ar y O bj e cti v e  
•  
T o ass ess t h e p h ar m a c o ki n eti cs of el afi br a n or a n d its  a cti v e  m et a b olit e G F T 1 0 0 7, f oll o wi n g o n c e 
d ail y or al a d mi ni str ati o n of t w o d os e l e v els of el afi br a n or ( 8 0 m g a n d 1 2 0 m g) t o c hil dr e n a n d 
a d ol es c e nts, 8 t o 1 7 y e ars of a g e  (i n cl usi v e).  
S e c o n d ar y O bj e cti v es  
P h ar m a c o d y n a mi c  
•  
T o ass ess c h a n g es  i n s er u m al a ni n e a mi n otr a n sf er a s e ( A L T), as p art at e a mi n otr a nsf er a s e ( A S T), 
g a m m a -gl ut a m yl tr a nsf er a s e ( G G T), a n d al k ali n e p h os p h at as e ( A L P)  a n d ot h er li v er m ar k ers ; 
•  
T o ass ess c h a n g es i n m ar k ers of gl u c os e h o m e ost a si s (h o m e ost ati c m o d el ass ess m e nt f or i ns uli n 
r e sist a n c e ( H O M A-I R) a n d f asti n g i ns uli n); 
•  
T o ass ess c h a n g es i n s er u m li pi d p ar a m et ers ; 
•  
T o ass ess c h a n g e s i n b o d y w ei g ht a n d Bo d y M ass In d e x ( B MI)  z-s c or e ; 
•  
T o ass ess c h a n g e s i n w aist cir c u mf er e n c e; 
•  
T o ass ess c h a n g e s i n i nfl a m m at or y m ar k ers;  
•  
T o ass ess t h e c h a n g e i n  t h e p e di atri c q u ali ty of lif e ( P e ds Q L ™) s c or e as c o m pl et e d b y t h e 
c hil d/ a d ol es c e nt a n d t h e p ar e nt /l e g al g u ar di a n. 
S af et y  
•  
T o ass ess t h e s af et y a n d t ol er a bilit y pr ofil e of t w o d o s e l e v els of el afi br a n or ( 8 0  m g a n d 1 2 0 m g) 
i n c hil dr e n a n d a d ol e s c e nts, 8 thr o u g h  1 7 y e ars of a g e.  
E x pl or at or y O bj e cti v e s  
•  
 
  
P ati e nt P o p ul ati o n   
C hil dr e n a n d a d ol es c e nts, 8 t o 1 7 y e ars of a g e (i n cl u si v e), wit h hist ol o gi c al l y c o nfir m e d ( hist ori c al bi o ps y) 
N A S H . T h e t ar g et p o p ul ati o n will i n cl u d e p ati e nts wit h N A S H , wit h a n d  wit h o ut  fi br osis. At l e ast 4  p ati e nts 
≥1 2 t o ≤1 7 y e ars  of a g e , a n d at l e ast 2  p ati e nt s ≥8 t o ≤1 1 y e ars of a g e , will h a v e  hist or y of si g nifi c a nt 
fi br osis (i. e., fi br osis st a g e 2 or  3).  
C CI


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Randomization 
Number of Randomized Patients (planned): A total of 20 patients will be enrolled across the two cohorts.  
• 
Cohort 1: ≥12 to ≤17 years of age. A total of approximately 12 patients will be randomized in this 
cohort.   
• 
Cohort 2: ≥8 to ≤11 years of age. A total of approximately 8 patients will be randomized in this 
cohort.  Enrollment in this cohort will not start until 80% of the patients in cohort 1 have been 
evaluated through Visit 4 by the DSMB. 
Patients will be randomized 1:1 to receive either dose (80 or 120 mg). 
Considering that at least 4 patients ≥12 to ≤17 years of age and at least 2 patients ≥8 to ≤11 years of 
age with fibrosis stage 2 or 3 will be enrolled and to achieve balance between dosing groups according 
to the fibrosis severity, randomization will be stratified within each cohort based upon the patient’s 
historical (liver biopsy used for study qualification) fibrosis severity stage (stratum 1: fibrosis stage 0 to 1 
and stratum 2: fibrosis stage 2 to 3). 
Number of participating centres (planned): Two (2)  
Number of participating countries: One (1) United States (US) 
Study Duration Per Patient 
Each patient will participate in the study for up to approximately 20 weeks (screening through final follow-
up visit). 
Study Schedule 
• 
Screening:  
• 
Screening Visit 1 Week -4 to Week -1 (SV1): Day -28 to Day -7 
• 
Screening Visit 2 Week -1 (SV2): Day -5 (±2 days) (telephone contact only) 
• 
Randomization and Treatment: Day 1 to Day 85 (±2 days)  
• 
Visit 1 Week 0 (Randomization): Day 1 
• 
Visit 2 Week 2: Day 15 (±2 days) 
• 
Visit 3 Week 4: Day 29 (±2 days) 
• 
Visit 4 Week 4: Day 30 (24h PK sample collection) 
• 
Visit 5 Week 8: Day 57 (±2 days) 
• 
Visit 6 Week 12 (EOT): Day 85 (±2 days) 
• 
Follow-up: Day 86 to Day 113 (±2 days) (Week 12 to Week 16) 
• 
Visit 7 Week 16 (EOS): Day 113 (±2 days) 
Inclusion Criteria 
For a study patient to be evaluated for study participation:  
1. Parent(s)/Legal Guardian(s) must provide written Informed Consent (including the Health 
Insurance Portability and Accountability Act [HIPAA]) prior to the conduct of any study related 
procedures to permit participation of a minor in a clinical research study in accordance with 
federal and local laws. Additionally, assent from a minor child will be obtained in accordance 
with federal and local laws as well as in compliance with the recommendations of the approving 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC). 
Study patients will be eligible for inclusion in the study if they meet all the following criteria at Screening 
and up to the time of Randomization (Visit 1) as applicable: 


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2. Are male or female between 8 and 17 years of age (inclusive) at the time of Screening Visit 1 
(when consent for study participation is given) and at the time of Randomization (Visit 1). 
3. Diagnosis of non-alcoholic steatohepatitis (NASH) confirmed by histological evaluation (with or 
without fibrosis) from a liver biopsy obtained within 24 months prior to Randomization (Visit 
1/Day 1). 
4. Has adhered to a minimum of 3 months of lifestyle modification to treat NASH, prior to 
Screening (SV1), and agrees to adhere to lifestyle modifications (diet and exercise) throughout 
the study period (Screening through final visit [Visit 7/Day 113]).  
5. Has an alanine aminotransferase (ALT) level greater than (>) 50 IU/L, at Screening (SV1). 
6. Has a Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ≥ 5, at Screening (SV1). 
7. Has a Body Mass Index z-score (BMI z-score) (also referred to as BMI-for-age percentile) 
greater than or equal to (≥) 85th percentile for age and gender at Screening (SV1). 
8. Has a Hemoglobin A1C (HbA1c) less than or equal to (≤) 8.5%. If the patient has Type 2 
diabetes and is taking anti-diabetic therapy (e.g., metformin or insulin), treatment must have 
been started at least 3 months prior to Screening (SV1) and the dose must be stable for at least 
3 months prior to Screening (SV1) and should remain stable through Randomization (Visit 1/Day 
1).   
9. If patient is taking medications or supplements to treat non-alcoholic fatty liver disease/non-
alcoholic steatohepatitis (NAFLD/NASH) (Vitamin E, ursodeoxycholic acid, polyunsaturated fatty 
acids [PUFAs]), the dose must be stable for at least 3 months prior to Screening Visit 1 and 
should remain stable through Randomization (V1/Day 1) and planned to remain stable through 
EOS. 
10. Sexually active female participants of childbearing potential must agree to utilize a highly 
effective method of contraception per the Clinical Trial Facilitation Group (CTFG) Guidelines 
(refer to Appendix IV), from Screening through 30 days after the last dose of study drug (1 
month after the end of treatment (EOT), and agree to monthly pregnancy testing during the 
study up to and including EOS.  
11. The Parent(s)/Legal guardian(s) and study patient are willing and able to follow all study-related 
procedures, including but not limited to daily study drug administration, pharmacokinetic (PK) 
sampling, be willing and able to return to the study clinic for study visits and be accessible by 
phone or e-mail for study related communications. 
12. Patient agrees not to consume alcohol or use illicit drugs during the study up to and including 
EOS. 
Exclusion Criteria 
A study patient will be excluded from the study if they meet any of the following criteria at Screening 
(SV1) or prior to Randomization (Visit 1/Day 1): 
1. Has history of bariatric surgery or planned surgery during the study period. 
2. Has known history of heart disease. 
3. Has uncontrolled hypertension evidenced by sustained elevation in systolic blood pressure >140 
mmHg or diastolic blood pressure >90 mmHg despite treatment with antihypertensive therapy, 
prior to Randomization (Visit 1/Day 1). 
4. Has a known history of Type 1 diabetes. 
5. Has a known history of acquired immunodeficiency syndrome or positive screening for human 
immunodeficiency virus (HIV) antibodies at Screening Visit 1. 
6. Has a documented weight loss of more than 5% during the 6-month period prior to 
Randomization (Visit 1/Day 1). 


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7. Has a history of renal disease defined as an estimated glomerular filtration rate (eGFR) <90 
mL/min/1.73 m2 using the Schwartz Bedside GFR Calculator for Children or present at Screening 
Visit 1. 
8. History of, significant alcohol consumption or inability to reliably quantify alcohol intake, and/or 
use of illicit drugs.  
9. Has clinical and/or historical evidence of cirrhosis, included by not limited to: 
a. Abnormal low hemoglobin as deemed clinically significant by the investigator (with the 
exception of females with a documented history of a low hemoglobin during 
menstruation); 
b. White blood cell count < 3,500 cells/mm3 of blood; 
c. Platelet count <150,000 cells/mm3 of blood; 
d. Direct bilirubin >0.3 mg/dL; 
e. Total bilirubin >1.3 mg/dL unless the patient has a diagnosis of Gilbert disease in which 
case direct bilirubin and reticulocyte count do not exceed the upper limit of normal (ULN) 
and haemoglobin is greater than the lower limit ofnormal; 
f. 
Serum albumin <3.5 g/dL; 
g. International normalized ratio (INR) >1.4. 
10. Has evidence of chronic liver disease other than NASH, defined by any one of the following: 
a. Biopsy consistent with histological evidence of autoimmune hepatitis; 
b. Serum hepatitis A antibody (anti-HAV IgM) positive; 
c. Serum hepatitis B surface antigen (HBsAg) positive; 
d. Serum hepatitis C antibody (anti-HCV) positive; 
e. Serum hepatitis E antibody (anti-HEV) positive; 
f. 
History of or current positive Anti-Mitochondrial Antibody (AMA)Test; 
g. Known or current Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) > 
45% with histological evidence of iron overload; 
h. Known or current Alpha-1-antitrypsin (A1AT) phenotype/genotype ZZ or SZ; 
i. 
Diagnosis of Wilson's disease. 
11. Has a creatine phosphokinase (CPK) greater than the upper limit of normal (ULN) at Screening 
Visit 1. This test may be repeated , if necessary, to confirm eligibility. 
12. Has AST and/or ALT >8 x ULN. 
13. Has used any prohibited medication(s) within the specified timeframe (Refer to Appendix III, 
non-permitted medications):  
a. Within 12 months prior to Screening Visit 1 up to Randomization (Visit 1/Day 1) 
i. Chronic use (defined as treatment longer than 3 consecutive months) of 
medications known to cause hepatic steatosis or steatohepatitis (including but 
not limited to systemic chronic glucocorticoids, tetracycline, valproic acid, 
salicylates, tamoxifen, methotrexate).  
b. Within 12 weeks prior to Screening Visit 1 up to Randomization (Visit 1/Day 1) 
i. Use of Thiazolidinediones (glitazones [pioglitazone & rosiglitazone]).  
c. Within 8 weeks prior to Screening Visit 1 up to Randomization (Visit 1/Day 1) 


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i. Fibrates medications. Patients taking statins or ezetimibe prior to Screening Visit 
1 may participate if the dose has been stable for 3 months prior to Screening 
Visit 1 and no dose adjustments are anticipated.   
14. Is currently taking drugs that could interfere with study medication absorption, distribution, 
metabolism or excretion or could lead to induction or inhibition of microsomal enzymes, e.g., 
indomethacin. 
15. Is pregnant, lactating or is planning to become pregnant during the study. 
16. Is participating in any other study and have received any other investigational drug or device 
within 30 days prior to Screening or are taking part in a non-medication study which, in the 
opinion of the Investigator, would interfere with study compliance or outcome assessments. 
17. Has symptoms of clinical depression. 
18. Has other concurrent medical (e.g., immunological, neoplastic, endocrine, hematological, 
gastrointestinal or neurological) or psychiatric condition, which, in the opinion of the 
Investigator, would place the patient at increased risk, preclude obtaining voluntary 
consent/assent or compliance with required study procedures, or would confound the objectives 
of study. 
19. Has known allergy to the study drug or any of its components. 
Primary Endpoint 
• 
Plasma concentrations of elafibranor and its active metabolite GFT1007. 
Secondary Endpoints 
Pharmacodynamic 
• 
Change from baseline in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) and other liver markers; 
• 
Change from baseline in glucose homeostasis makers (Homeostatic Model Assessment of Insulin 
Resistance [HOMA-IR] and fasting insulin), as a continuous measure;  
• 
Change from baseline in serum lipid parameters; 
• 
Change from baseline in body weight and BMI z-score; 
• 
Change from baseline in waist circumference; 
• 
Change from baseline in inflammatory markers;  
• 
Change from baseline in pediatric quality of life (PedsQL™) score. 
Safety 
• 
Incidence and severity of treatment emergent adverse events (TEAEs) and their relationship to 
study drug; 
• 
Incidence of clinically meaningful changes from baseline in safety laboratory parameters, physical 
examination, electrocardiogram (ECG) and vital signs. 
Exploratory Endpoint 
• 
 
  


Clinical Trial GFT505E-218-1 
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Study Duration (planned): estimated 20 months (First patient first visit [FPFV] to Last patient last visit 
[LPLV]) 
• 
Regulatory/Ethics Committee submission: January 2019 
• 
Initiation visits: March 2019 - April 2019  
• 
FPFV: March 2019 
• 
LPLV: November 2020 
Data Safety Monitoring Board (DSMB) 
A DSMB will be established to monitor the progress of the study and to perform safety data reviews as 
designated in the DSMB Charter, in order to protect patient welfare. The DSMB charter will define the 
role, responsibilities, rules and tasks, schedule, and format of meetings and data review and reporting 
requirements.  
The DSMB considers study-specific data as well as relevant background knowledge about the disease, 
test agent, or patient population under study. The primary responsibilities of the DSMB are to 1) review 
and evaluate the accumulated study data for participant safety, study conduct and progress, and 2) make 
recommendations concerning the continuation (i.e. proceeding with enrollment of patients in cohort 2), 
modification, or termination of the trial. All DSMB discussions, decisions, and recommendations will be 
communicated promptly to the sponsor as described in the DSMB Charter.  
The DSMB will consist of two independent clinicians with relevant expertise in related NAFLD/NASH 
pediatric clinical trials and 1 statistician with expertise in clinical trial and interim data analysis.  
At a minimum, safety data will be summarized by the statistician after every 5th patient completes visit 4 
or available data at the end of each quarter (at approximately 3-month intervals), whichever comes first 
throughout the study.  The DSMB will also review safety and PK data once 80% of the patients in Cohort 
1 have completed through Visit 4. Enrollment in Cohort 2 will commence as recommended by the DSMB.  
Statistical Considerations 
Sample Size  
The primary objective of this study is to characterize individual PK parameters in children and adolescents 
8 to 17 years of age (inclusive), by collecting rich PK samples to support non-compartmental analysis 
(NCA). Inter-patient variability of PK parameters in adults was low to moderate (coefficient of variation 
[CV]% ranged from 23.3% to 68.3%). Assuming a similar degree of variability in pediatric population, a 
sample size of 20 patients is set to target a 95% CI [confidence interval] within 60% and 140% of the 
geometric mean estimates of clearance and volume of distribution for elafibranor with at least 80% power 
(Wang et al., 2012). Additionally, 20 patients should be sufficient to evaluate the safety and tolerability 
and explore the responsiveness (efficacy) of once daily oral dosing of 80 mg and 120 mg of elafibranor 
for up to 12 weeks. 
Analysis Populations 
Three populations will be used for analysis: safety, PK and intent-to-treat. The definition of these 
populations follows: 
• 
Safety Population: All patients who received at least one dose of study drug and have at least one 
post-baseline safety assessment. 
• 
Pharmacokinetic Population: All patients who received at least one dose of study drug, do not 
have protocol deviations or adverse events which may significantly affect PK, and have at least 
one post-dose PK sample. 
• 
Intent-to-Treat (ITT) Population: All randomised patients who received at least one dose of study 
drug. 
PK and safety data will be analysed based respectively on the PK population and the safety population. 
Efficacy data will be analysed based on the ITT population.   


Cli ni c al Tri al G F T 5 0 5 E -2 1 8 -1  
Pr ot o c ol V 4. 0 2 0  A pril 2 0 2 0  
 
G E N F I T  
 
P a g e  1 4  of 8 3  
 
Pri m ar y a n d S e c o n d ar y A n al ysis  
P h ar m a c o ki n eti cs  
I n di vi d u al pl as m a c o n c e ntr ati o ns f or el afi br a n or  a n d its a cti v e m et a b olit e G F T 1 0 0 7 , will b e s u m m ariz e d 
d es cri pti v el y  (i. e., n u m b er of o bs er v ati o ns, arit h m eti c  m e a n,  st a n d ar d d e vi ati o n  (S D) , % 
c o effi ci e nt of 
v ari ati o n  ( C V %), m e di a n, mi ni m u m a n d  m a xi m u m , g e o m etri c m e a n , a n d %  c o effi ci e nt of v ari ati o n of t h e 
g e o m etri c m e a n (C V % G e o m etri c M e a n ) b y pl a n n e d ti m e p oi nts f or e a c h d os e gr o u p.  I n di vi d u al pl a s m a 
c o n c e ntr ati o n -ti m e pr ofil es of el afi br a n or will b e pl ott e d o n b ot h li n e ar a n d s e mi-l o garit h mi c  s c al es. M e a n 
v al u es o v er ti m e b y d o s e pl ots will als o b e pr e s e nt e d gr a p hi c all y . 
P h ar m a c o ki n eti c p ar a m et ers  of  el afi br a n or  a n d G F T 1 0 0 7  will b e esti m at e d usi n g n o n c o m p art m e nt al 
a n al ysis m et h o d s  i n P h o e ni x 
Wi n N o nli n  8. 0 or hi g h er , usi n g a ct u al el a ps e d ti m e fr o m d osi n g.  Pl as m a 
c o n c e ntr ati o ns e q u al t o or gr e at er t h a n t h e q u ali fi e d l o w er li mit of t h e ass a y ( L O Q) will b e us e d i n t h e 
p h ar m a c o ki n eti c a n al ysis.  T h e f oll o wi n g c al c ul at e d P K  p ar a m et ers will i n cl u d e, b ut n ot li mit e d t o : 
•  
M a xi m u m c o n c e ntr ati o n ( C m a x ); 
•  
T i m e t o m a xi m u m c o n c e ntr ati o n ( Tm a x ); 
•  
A r e a u n d er t h e pl a s m a c o n c e ntr atio n ti m e c ur v e o v er 2 4 h o urs ( A U C[0 -2 4 ]); 
•  
Tr o u g h c o n c e ntr ati o ns i n pl as m a ( C tr o u g h). 
T h e  a n al ysis pl a n will b e f urt h er d et ail e d i n t h e P K S t atisti c al A n al ysi s P l a n ( P K-S A P).  
S af et y  
•  
S af et y e v al u ati o ns 
will c o nsist of a d v ers e e v e nts ( A Es), vit al si g ns, E C G, a n d l a b or at or y 
m e as ur e m e nts ( h e m at ol o g y , c o a g ul ati o n,  bi o c h e mistr y, a n d uri n al y sis)  a n d will b e s u m m ariz e d b y 
d os e gr o u p  a n d o v er all . F ull d et ails will b e s p e cifi e d i n t h e S A P. 
Effi c a c y  
•  
Effi c a c y e v al u ati o ns will b e s u m m ariz e d b y  d os e gr o u p a n d b y ti m e p oi nt usi n g d es cri pti v e st atisti cs  
a n d  will b e b a s e d o n t h e c h a n g e fr o m b as eli n e . F ull d et ails will b e s p e cifi e d i n t h e S A P.  
E x pl or at or y  A n al y sis  
•  
 
  
C CI


Clinical Trial GFT505E-218-1 
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Page 15 of 83 
 
 
 
GENERAL STUDY ASSESSMENT SCHEDULE 
Visit 
Screening Period 
Treatment Period 
Follow-up Period 
SV1 
SV2 
V1 
V2 
V3 
V4 
V5 
V6/End of Treatment1 
V7/End of Study7 
 
Week 
-4 to -1 
-1 week 
0 
2 
4 
4 
8 
12 
16 
Visit Day with Permitted Margin 
-28 to -7 
-5 (±2 days) 
1 
15 (±2 days)  
29 (±2 days)  
Day 30 
57 (±2 days) 
85 (±2 days)  
113 (±2 days) 
Obtain informed consent / assent  
x 
 
 
 
 
 
 
 
 
Medical history / demographics 
x 
 
 
 
 
 
 
 
 
Check inclusion / exclusion criteria 
x 
 
x 
 
 
 
 
 
 
Lifestyle modifications (diet and 
exercise recommendations) 
  
Physical examination  
x 
 
x 
x 
x 
 
x 
x 
x 
Vital signs, height and weight 
measurement (calculation of BMI z-
score) 
x 
 
x 
x 
x 
 
x 
x 
x 
Waist circumference 
x 
 
x 
x 
x 
 
x 
x 
x 
12-Lead electrocardiogram  
 
 
x 
 
 
 
 
x 
 
Pediatric Quality of Life (PedsQL™) 
 
 
x 
 
 
 
 
x 
 
Lab evaluation (see table “study 
biological assessment schedule”) 
x 
 
x 
x 
x 
 
x 
x 
x 
PK blood sampling  
 
 
x2 
 
x2 
x2 
 
x2 
 
Phone call to the patient 
 
x 
 
 
 
 
 
 
 
Randomization 
 
 
x 
 
 
 
 
 
 
Review prior/concomitant 
medication 
x 
 
x 
x 
x 
 
x 
x 
x 
Adverse events 
 
Study drug dispensing  
 
 
x 
 
x 
 
x 
 
 
Study drug dosing 
 
 
Daily3 
 
 
Compliance check  
(pill count and dosing diary) 
 
 
 
x 
x 
 
x 
x 
 


Clinical Trial GFT505E-218-1 
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GENFIT 
 
Page 16 of 83 
 
 
 
BIOLOGICAL ASSESSMENT SCHEDULE 
Visit 
Screening 
period 
Treatment Period 
Follow-up 
period 
SV1 
V1 
V2 
V3 
V4 
V5 
V6/EOT1 
V7/EOS7 
Week 
(-4 to -1) 
0 
2 
4 
4 
8 
12 
16 
Visit Day with Permitted Margin 
-28 to -7 
1 
15 ± 2 days  
29 ± 2 days  
30 
57 ± 2 days 
85 ±2 days  
113 ± 2 days 
Labs – hematology and coagulation parameters 
hemoglobin, hematocrit, RBC, WBC, differential count, 
platelet count, reticulocytes count, prothrombin time 
(PT) and international normalized ratio (INR)  
x 
x 
x 
x 
 
x 
x 
x 
Labs- urine pregnancy testing4 
x 
x 
x 
x 
 
x 
x 
x 
Labs – serology 
HIV, HAV, HBs, HCV and HEV serology 
x 
 
 
 
 
 
 
 
Labs – other parameters for eligibility assessment 5 
Antimitochondrial Antibody (AMA), Alpha-1-
Antitrypsin Phenotype, Ceruloplasmin, Ferritin, 
Transferrin Saturation (Serum Iron, Total Iron Binding 
Capacity) 
x5 
 
 
 
 
 
 
 
Labs – biochemistry 
 
 
 
 
 
 
 
 
creatinine, creatinine clearance (eGFR), total protein, 
albumin, electrolytes (sodium, potassium, chloride, 
calcium), uric acid, urea, CPK, AST, ALT, GGT, alkaline 
phosphatase, total and conjugated bilirubin, hsCRP, 
fasting plasma glucose, fasting insulin, HOMA-IR, 
fructosamine, C-peptide, FFA, HbA1c, TSH, Cystatin C, 
eGFR from Cystatin C 
x 
x 
x 
x 
 
x 
x 
x 
Labs – lipids 
 
 
 
 
 
 
 
 
Total Cholesterol, Non HDL-C, HDL-C, TG, calculated 
VLDL-C, ApoAI, ApoB, LDL-C 
x 
x 
x 
x 
 
x 
x 
x 
Inflammatory markers 
fibrinogen, haptoglobin, TNF-, IL-6, PAI-1 
 
x 
 
x 
 
x 
x 
x 
Liver markers: 
CK18 (M65 & M30), adiponectin, ferritin, FGF19 & 
FGF21, 2 macroglobulin, hyaluronic acid, PIIINP, 
TIMP-1 
 
x 
 
x 
 
x 
x 
x 


Clinical Trial GFT505E-218-1 
Protocol V4.0 20 April 2020 
 
GENFIT 
 
Page 17 of 83 
 
 
 
Visit 
Screening 
period 
Treatment Period 
Follow-up 
period 
SV1 
V1 
V2 
V3 
V4 
V5 
V6/EOT1 
V7/EOS7 
Week 
(-4 to -1) 
0 
2 
4 
4 
8 
12 
16 
Visit Day with Permitted Margin 
-28 to -7 
1 
15 ± 2 days  
29 ± 2 days  
30 
57 ± 2 days 
85 ±2 days  
113 ± 2 days 
Urinalysis  
α1 microglobulin, β-NAG, N-Gal, albumin, creatinine, 
microscopic analysis 6 
 
x 
 
x 
 
x 
x 
x 
Labs – Urinalysis (dipstick) 
Specific gravity, pH, protein, glucose, ketones, 
bilirubin, urobilinogen, blood, nitrite, leukocytes 
 
x 
 
x 
 
x 
x 
x 
Labs – Additional samples 
x 
x 
 
 
 
 
x 
 
Blood Volume Collected Each Visit 
30.3 mL 
33 mL 
17.3 mL 
37.5 mL 
1 mL 
29.5 mL 
32 mL 
29.5 mL 
Total Volume of Blood Collected Over the Study Period: 210.1 mL 
1: If a patient prematurely discontinues, EOT visit procedures must be performed and patient will be encouraged to return for EOS one month later. 
2: PK sample collected on Day 1 To (prior to first dose), Day 29, T0 (trough), 0.5 hour (±2 minutes), 1 hour (±2 minutes), 1.5 hour (±2 minutes), 2 hours (±5 minutes), 4 hours (±5 minutes), 6 hours (±10 
minutes), and 8 hours (±10 minutes) post dose, Day 30, 24 hours (±10 minutes) after the dose administered  the previous day, and Day 85 24 hours (±10 minutes) after the dose administered  the previous day. 
3: From V1 to V5 the study dosing occurs at site during the visit. 
4: Females of childbearing potential (FOCBP) only. 
5: Parameters to be analyzed at SV1 only if not screened in the past for these tests (with available results in source documentation). 
6: Microscopic analysis is performed centrally in case urinalysis dipstick is abnormal. 
7 : If A safety lab parameter is abnormal at visit 7 and is at least 10% higher than the highest reported values obtained between SV1 and V1, an additional visit should be scheduled one month later to repeat 
those affected parameters. 
 


Clinical Trial GFT505E-218-1 
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Figure 1: Study Schematic 
 A: Enrollment 
 
 
B: Visit Schedule 
 
 


Clinical Trial GFT505E-218-1 
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Page 19 of 83 
 
Table of Contents 
 
CLINICAL TRIAL SYNOPSIS ............................................................................................. 7 
General Study Assessment Schedule .......................................................................... 15 
Biological Assessment Schedule ................................................................................... 16 
Table of Contents ............................................................................................................. 19 
Table of Tables .................................................................................................................. 23 
Table of Figures ................................................................................................................ 23 
1. 
INTRODUCTION ...................................................................................................... 24 
1.1. Background ...................................................................................................................... 24 
1.2. Mechanism of Action ...................................................................................................... 24 
1.3. Pediatric Non-alcoholic Steatohepatitis .................................................................... 24 
1.3.1. 
Overview ................................................................................................................................ 24 
1.3.2. 
Natural History ...................................................................................................................... 24 
1.3.3. 
Diagnosis ................................................................................................................................ 25 
1.3.4. 
Prevalence .............................................................................................................................. 26 
1.4. Summary of Studies with Elafibranor ........................................................................ 26 
1.4.1. 
Nonclinical Experience .......................................................................................................... 26 
1.4.2. 
Clinical Experience ................................................................................................................ 27 
1.5. Rationale for Elafibranor in Pediatric Population .................................................... 28 
1.5.1. 
Rationale for Elafibranor in Pediatric NASH ...................................................................... 28 
1.5.2. 
Rationale for the Study Population .................................................................................... 28 
1.5.3. 
Justification of the Selected Dose ...................................................................................... 29 
1.5.4. 
Rationale for the Study ........................................................................................................ 29 
2. 
TRIAL OBJECTIVES ................................................................................................. 29 
2.1. Primary Objective ........................................................................................................... 29 
2.2. Secondary Objectives .................................................................................................... 29 
2.3. Safety Secondary Objective ......................................................................................... 30 
2.4. Exploratory Objective .................................................................................................... 30 
3. 
TRIAL DESIGN ......................................................................................................... 30 
3.1. Study Schedule................................................................................................................ 31 
3.2. Randomization ................................................................................................................ 31 
4. 
PATIENT SELECTION .............................................................................................. 31 
4.1. Inclusion Criteria ............................................................................................................ 31 
4.2. Exclusion Criteria ............................................................................................................ 32 
5. 
TRIAL PROCEDURES .............................................................................................. 34 
5.1. Lifestyle Recommendations and Study Recommendations .................................. 34 
5.1.1. 
Diet and Lifestyle Recommendations ................................................................................. 34 
5.1.2. 
Dietary, Fluid and Lifestyle Restrictions ............................................................................ 34 
5.2. Trial Procedures at Each Visit ...................................................................................... 35 
5.2.1. 
Screening Visit 1/Week -4 to Week -1 (Day -28 to Day -5 (±2 days)) ........................ 35 
5.2.2. 
Visit 1/Week 0/ Day 1 (Randomization) ............................................................................ 36 
5.2.3. 
Visit 2/Week 2 (Day 15 ±2 days) ....................................................................................... 37 


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5.2.4. 
Visit 3/Week 4 (Day 29 ±2 days) ....................................................................................... 37 
5.2.5. 
Visit 4/Week 4 (Day 30)....................................................................................................... 38 
5.2.6. 
Visit 5/Week 8 (Day 57 ±2 days) ....................................................................................... 38 
5.2.7. 
Visit 6/EOT Week 12 (Day 85 ±2 days) ............................................................................ 39 
5.2.8. 
Visit 7/EOS Week 16 (Day 113 ±2 days) .......................................................................... 40 
5.3. Other Visit ........................................................................................................................ 40 
5.3.1. 
Retesting Screening Visit ..................................................................................................... 40 
5.3.2. 
Safety follow-up visit ............................................................................................................ 40 
5.3.3. 
Off-site study procedures in case of crisis situation ........................................................ 40 
5.4. Patient Withdrawal and Discontinuation .................................................................. 42 
5.4.1. 
Early Termination .................................................................................................................. 42 
5.4.2. 
Replacement .......................................................................................................................... 42 
5.4.3. 
Lost to Follow-up .................................................................................................................. 42 
5.5. Safety Oversight ............................................................................................................. 43 
5.5.1. 
Investigator ............................................................................................................................ 43 
5.5.2. 
Data and Safety Monitoring Board ..................................................................................... 43 
6. 
ASSESSMENTS ......................................................................................................... 43 
6.1. Efficacy and Safety Assessments ................................................................................ 43 
6.1.1. 
Biological Assessments ......................................................................................................... 43 
6.1.2. 
Pharmacokinetics Evaluation ............................................................................................... 45 
6.2. Other Safety Assessments and On-going Safety Monitoring ................................ 46 
6.2.1. 
Physical Examination ............................................................................................................ 46 
6.2.2. 
Vital Signs .............................................................................................................................. 46 
6.2.3. 
12-Lead ECG .......................................................................................................................... 47 
6.2.4. 
Pediatric Quality of Life (PedsQL™) ................................................................................... 47 
6.3. Important Specific Biological Considerations and Patient Discontinuation 
Rules ............................................................................................................................................ 47 
6.3.1. 
Creatine Phosphokinase ....................................................................................................... 47 
6.3.2. 
Liver Function Monitoring .................................................................................................... 47 
6.3.3. 
Renal Function Monitoring ................................................................................................... 48 
6.3.4. 
Additional Monitoring ........................................................................................................... 48 
6.4. Guidance for Investigators ........................................................................................... 48 
6.4.1. 
Summary of Safety Data ...................................................................................................... 48 
6.4.2. 
Potential Risks ....................................................................................................................... 50 
6.4.3. 
Risk Benefit Analysis ............................................................................................................. 50 
7. 
TREATMENTS ........................................................................................................... 51 
7.1. Description of Study Drug ............................................................................................ 51 
7.2. Packaging and Labeling ................................................................................................ 52 
7.2.1. 
Packaging ............................................................................................................................... 52 
7.2.2. 
Labeling .................................................................................................................................. 52 
7.3. Storage Conditions ......................................................................................................... 52 
7.4. Dispensing and Administration of treatment ........................................................... 52 
7.5. Procedure for Blinding ................................................................................................... 52 
7.6. Procedure for Unblinding .............................................................................................. 52 
7.7. Study Drug Compliance ................................................................................................. 53 
7.8. Treatment Accountability, Retrieval and Destruction ............................................ 53 
7.9. Other Medication ............................................................................................................ 53 
7.9.1. 
Handling of Concomitant Medication ................................................................................. 53 
7.9.2. 
Non-Permitted Medication ................................................................................................... 53 


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7.9.3. 
Permitted Medication Under Conditions ............................................................................ 54 
8. 
Adverse Event / Serious adverse event Reporting ......................................... 54 
8.1. Definitions ........................................................................................................................ 54 
8.1.1. 
Adverse Event (AE) ............................................................................................................... 54 
8.1.2. 
Serious Adverse Events (SAE)............................................................................................. 55 
8.1.3. 
Clarification on Serious Adverse Events ............................................................................ 56 
8.1.4. 
Adverse Drug Reaction ........................................................................................................ 56 
8.1.5. 
Unexpected Adverse Event .................................................................................................. 56 
8.2. Assessments .................................................................................................................... 57 
8.2.1. 
Intensity Assessment ........................................................................................................... 57 
8.2.2. 
Relation to the Study Treatment ........................................................................................ 57 
8.2.3. 
Action Taken and Outcome ................................................................................................. 57 
8.3. Reporting .......................................................................................................................... 58 
8.3.1. 
Reporting an Adverse Event ................................................................................................ 58 
8.3.2. 
Reporting a Serious Adverse Event .................................................................................... 58 
8.3.3. 
Follow-up ................................................................................................................................ 60 
8.4. Post Study Reporting Requirements .......................................................................... 60 
8.5. Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events ......................................................................... 60 
8.6. Special Situation Reports ............................................................................................. 60 
8.6.1. 
Pregnancy .............................................................................................................................. 60 
8.6.2. 
Medication Error .................................................................................................................... 60 
8.6.3. 
Misuse ..................................................................................................................................... 61 
8.6.4. 
Overdose ................................................................................................................................ 61 
8.6.5. 
Abuse ...................................................................................................................................... 61 
9. 
Statistical Methods and Data Analysis ............................................................... 61 
9.1. Randomization and Treatment Assignment ............................................................. 61 
9.2. Endpoints .......................................................................................................................... 61 
9.2.1. 
Primary Endpoint................................................................................................................... 61 
9.2.2. 
Secondary Endpoints ............................................................................................................ 61 
9.2.3. 
Exploratory Endpoint ............................................................................................................ 62 
9.3. Sample Size Estimate .................................................................................................... 62 
9.4. Analysis Sets .................................................................................................................... 62 
9.5. Analysis of Primary Endpoint ....................................................................................... 62 
9.6. Other Statistical Analysis .............................................................................................. 63 
9.6.1. 
Safety ...................................................................................................................................... 63 
9.6.2. 
Efficacy ................................................................................................................................... 64 
9.6.3. 
Pharmacokinetic/Pharmacodynamic Analysis ................................................................... 64 
10. Data Handling and Record Keeping .................................................................... 64 
10.1. CRF and Source Documents ......................................................................................... 64 
10.2. Retention of Records ..................................................................................................... 65 
11. Quality Control and Quality Assurance .............................................................. 65 
11.1. Quality Control & Monitoring Procedures ................................................................. 65 
11.2. Quality Assurance ........................................................................................................... 66 
12. Ethics and regulatory ............................................................................................. 66 
12.1. Ethical Principles ............................................................................................................ 66 
12.2. Institutional Review Board/Independent Ethics Committee (IRB/IEC) ........... 66 


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12.3. Competent Authority ..................................................................................................... 67 
12.4. Informed Consent .......................................................................................................... 67 
12.4.1. 
General Provisions ............................................................................................................. 67 
12.4.2. 
Written Parental/Legal Guardian Consent ..................................................................... 67 
12.4.3. 
When Parents/Legal Guardian Disagree ........................................................................ 68 
12.4.4. 
Assent ................................................................................................................................. 68 
12.4.5. 
Documenting the Consent/Assent Process .................................................................... 68 
12.5. Confidentiality ................................................................................................................. 68 
12.6. Retained Blood Samples ............................................................................................... 69 
12.7. Definition of the End of the Research ........................................................................ 69 
13. Financing and insurance ....................................................................................... 69 
13.1. Financial Issues .............................................................................................................. 69 
13.2. Insurance ......................................................................................................................... 69 
14. Study results and publication policy .................................................................. 69 
14.1. Study Report .................................................................................................................... 69 
14.2. Confidentiality and Ownership of Data, Use of the Study Results and 
Publication ................................................................................................................................. 69 
15. REFERENCE LIST ..................................................................................................... 71 
16. Appendices ............................................................................................................... 73 
16.1. Appendix I – World Medical Association Declaration of Helsinki ........................ 73 
16.1.1. 
Preamble ............................................................................................................................. 73 
16.1.2. 
General Principles .............................................................................................................. 73 
16.1.3. 
Risks, Burdens and Benefits ............................................................................................ 74 
16.1.4. 
Vulnerable Groups and Individuals ................................................................................. 74 
16.1.5. 
Scientific Requirements and Research Protocols .......................................................... 74 
16.1.6. 
Research Ethics Committees ........................................................................................... 75 
16.1.7. 
Privacy and Confidentiality ............................................................................................... 75 
16.1.8. 
Informed Consent ............................................................................................................. 75 
16.1.9. 
Use of Placebo ................................................................................................................... 76 
16.1.10. Post-Trial Provisions .......................................................................................................... 76 
16.1.11. Research Registration and Publication and Dissemination of Results ....................... 76 
16.1.12. Unproven Interventions in Clinical Practice ................................................................... 76 
16.2. Appendix II – Dosing Diary (Sample) ........................................................................ 77 
16.3. Appendix III: Non-permitted and Permitted Medications .................................... 78 
16.4. Appendix IV: Clinical Trial Facilitation Group (CTFG) Highly Effective Methods 
of Birth Control ......................................................................................................................... 80 
16.5. Appendix V – List of Abbreviations ............................................................................. 81 
 
 
 
 
 


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Table of Tables 
 
Table 1 Overview of the Common Non-Serious Adverse Reactions (>1% of 
Patients Treated with Elafibranor) by System Organ Class Reported in 
Completed Elafibranor Clinical Studies with Repeated Administration 
of Elafibranor (at Least 14 Days) From 80 mg/Day up to 300 mg/Day 
(MTD) ................................................................................................................... 49 
Table 2 Overview of Suspected Unexpected Serious Adverse Reactions 
(SUSARs) by System Organ Class Reported in Completed Elafibranor 
Clinical Studies ................................................................................................... 49 
Table 3 Formulation of Elafibranor 120 mg Coated Tablet and Elafibranor 80 
mg Coated Tablet .............................................................................................. 51 
 
 
Table of Figures 
 
Figure 1: Study Schematic ............................................................................................. 18 
 
 
 


Cli ni c al Tri al G F T 5 0 5 E -2 1 8 -1  
Pr ot o c ol V 4 . 0 2 0  A pril 2 0 2 0  
 
G E N F I T  
 
P a g e  2 4  of 8 3  
 
1.  
I N T R O D U C T I O N  
1. 1.  B a c k gr o u n d  
El afi br a n or ( G F T 5 0 5) , is a n or all y a d mi nist er e d, li v er -t ar g et e d dru g c a n di d at e , b ei n g d e v el o p e d b y G e nfit 
f or t h e tr e at m e nt of n o n -al c o h oli c  st e at o h e p atitis ( N A S H) wit h fi br osis  i n a d ults, a n d f or t h e tr e at m e nt of 
pri m ar y bili ar y c h ol a n gitis ( P B C). El afi br a n or is c urr e ntl y i n P h as e 3 of d e v el o p m e nt f or N A S H wit h fi br o sis  
i n a n a d ult p o p ul ati o n, u n d er 
, ori gi n all y fil e d i n J u n e 2 0 1 2, a n d i n P h as e 2 a f or P B C u n d er  
 
, fil e d i n S e pt e m b er 2 0 1 6. P h as e 1 a n d 2 cli ni c al st u di es wit h el afi br a n or h a v e b e e n c o n d u ct e d i n 
E ur o p e a n d t h e U nit e d St at es ( U S) a n d a m ult i-n ati o n al P h as e 3 r e gistr ati o n st u d y is o n g oi n g u n d er I N D 
1 1 5 0 2 8. A m ulti -n ati o n al P h as e 2 a st u d y i s o n g oi n g i n P B C u n d er 
.  
1. 2.  M e c h a ni s m of A cti o n  
El afi br a n or is a d u al p er o xis o m e pr olif er at or -a cti v at e d r e c e pt or ( P P A R) α ,δ  a g o nist, wit h a 5 -f ol d s el e cti vit y 
f or a cti vati o n of P P A R α  o v er P P A R δ . G F T 1 0 0 7 is t h e m ai n m et a b olit e of el afi br a n or a n d s h o ws si mil ar 
a cti v ati o n of P P A R α ,δ  (R atzi u et al ., 2 0 1 6). El afi br a n or i m pr o v es i ns uli n s e n siti vit y, gl u c o s e h o m e ost a si s, 
a n d li pi d m et a b olis m a n d r e d u c es i nfl a m m ati o n.  
1. 3.  P e di at ri c N o n -al c o h oli c St e at o h e p atiti s   
1. 3. 1.  
O v er vi e w  
P e di atri c n o n -al c o h oli c f att y li v er dis e as e ( N A F L D) is d efi n e d a s  t h e f ull s p e ctr u m of dis e as e c hr o ni c h e p ati c 
st e at osis i n c hil dr e n ( 1 8 y e ars or y o u n g er), w hi c h is n o t s e c o n d ar y t o g e n eti c/ m et a b oli c dis or d ers, 
i nf e cti o ns, us e of st e at o g e ni c m e di c ati o n s, al c o h ol c o n s u m pti o n, or m al n utriti o n (V os et al ., 2 0 1 7). I n m ost 
c hil dr e n, N A F L D  is ass o ci at e d wit h i ns uli n r esist a n c e, c e ntr al or g e n er aliz e d o b esit y, a n d d ysli pi d e mi a 
c h ar a ct eriz e d b y hi g h tri gl y c eri d e a n d l o w hi g h  d e n sit y li p o pr ot ei n ( H D L) c h ol e st er ol l e v els ( V os et al ., 
2 0 1 7 ). N A F L D is t h e m ost c o m m o n c a us e of c hr o ni c li v er dis e as e i n c hil dr e n i n t h e U nit e d St at es ( U S ) 
(S c h wi m m er et al ., 2 0 0 6). 
B a s e d o n hi st ol o g y, N A F L D c a n b e di vi d e d i nt o n o n al c o h oli c f att y li v er ( N A F L), w hi c h d e n ot e s bl a n d 
st e at osis, a n d n o n al c o h oli c st e at o h e p atitis ( N A S H), w hi c h is m ar k e d b y st e at osis a n d l o b ul ar i nf l a m m ati o n 
a n d h e p at o c ell ul ar i nj ur y ( V os et al ., 2 0 1 7). N A S H is a pr o gr essi v e f or m of li v er di s e as e t h at m a y l e a d t o 
a d v a n c e d fi br osis, ci rr h osis, a n d h e p at o c ell ul ar c ar ci n o m a i n a s u bs et of aff e ct e d i n di vi d u als ( L o o m b a et 
al ., 2 0 0 9). C hil dr e n wit h N A S H ar e at t h e gr e at est ris k f or t h e m ost s e v er e o ut c o m es. H o w e v er, n ot all 
c hil dr e n wit h N A F L D will d e v el o p N A S H ( P ar d e e et al ., 2 0 0 9).  
N A F L D m a y b e s us p e ct e d b as e d o n n o ni n v asi v e t es ts, alt h o u g h n o n e of t h es e disti n g uis h b et w e e n c hil dr e n 
w h o h a v e N A S H v ers us c hil dr e n w h o h a v e N A F L b ut n ot N A S H ( i. e., mil d er f or ms of N A F L D). Li v er bi o p s y is 
r e q uir e d f or t h e d efi niti v e di a g n osis of N A F L D a n d t h e d et er mi n ati o n of t h e pr e s e n c e of N A S H ( P ar d e e et 
al ., 2 0 0 9). P e di atri c N A S H h as fr e q u e ntl y b e e n o bs er v e d t o s h o w diff er e nt p att er ns of i nfl a m m ati o n a n d 
fi br osis t h a n t h at s e e n i n a d ults, wit h pr e d o mi n a ntl y p ort al hist ol o gi c al c h a n g es (S c h w i m m er et al ., 2 0 0 5; 
R as hi d a n d R o b erts, 2 0 0 0 ; S c h wi m m er et al ., 2 0 0 3).  
T h e pr e v al e n c e of N A F L D i n t h e g e n er al p o p ul ati o n is esti m at e d at 3 0 % (M c P h ers o n et al ., 2 0 1 5). 
H o w e v er, t h e pr e v al e n c e of p e di atri c N A F L D i s still n ot w ell d efi n e d (D e ll a C ort e et al ., 2 0 1 2). 
1. 3. 2.  
N at ur al Hi st or y   
N A F L D i n c hil dr e n is disti n ct fr o m N A F L D i n a d ults i n p at h o p h y si ol o g y, cli ni c al c o urs e, a n d tr e at m e nt 
r e s p ons e ( S c h wi m m er et al ., 2 0 0 5). T h es e diff er e n c es m a y b e d u e i n p art t o t h e o c c urr e n c e of h e p ati c 
m et a b oli c d er a n g e m e nts t y pi c a l of N A F L D d uri n g p eri o ds of a cti v e gr o wt h (i nf a n c y, mi d-c hil d h o o d a n d 
p u b ert y) ( R o b erts, 2 0 0 7 ). M or e o v er, h or m o n al c h a n g es d uri n g p u b ert y m a y p ot e nti at e f at a c c u m ul ati o n i n 
t h e li v er (L o o m b a  et al ., 2 0 0 9 ) (G o y al a n d S c h wi m m er  2 0 1 6 ) (Q uir os -T ej eir a et al ., 2 0 0 7) (M o di et al. , 
2 0 1 1 ).  
C CI
C CI
C CI


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Among the adult population, it is believed that simple hepatic steatosis is generally non-progressive, while 
NASH may lead to progressive liver disease (Fazel et al., 2016). In the adult population, the progression of 
NASH can take years to manifest. In this context, the presence of type 2 diabetes and the severity of 
histologic features such as ballooning degeneration of hepatocytes can be important predictors of fibrosis 
progression, but only the stage of fibrosis predicts liver mortality (Liou and Kowdley, 2006). Similarly, 
evidence suggests that that among the pediatric population, insulin resistance and obesity are important 
predictors of progression (Schwimmer et al., 2003). A longitudinal follow-up study on former pediatric 
NAFLD patients indicated a high rate of type 2 diabetes (30%) and the persistence of obesity into young 
adulthood (Cioffi et al., 2017).  Factors that account for differences between children with NASH versus 
children with milder forms of NAFLD are unclear (Pardee et al., 2009).  
At diagnosis, 10–25% of children can have advanced fibrosis. In the most severe cases, children can 
progress within a few years to cirrhosis and end-stage liver disease. Quality longitudinal data of the natural 
history of pediatric NAFLD are limited. However, available data suggest that children with NAFLD are at risk 
for higher mortality rates as young adults (Goyal and Schwimmer, 2016). 
The natural history of pediatric NAFLD in the setting of lifestyle counselling was represented by the placebo 
arm of the treatment of non-alcoholic fatty liver disease in children (TONIC) trial, a 2-year randomized 
control trial designed to compare vitamin E, metformin, and placebo with liver biopsies at baseline and at 
2-year follow-up. All 3 arms received nutrition and physical activity (lifestyle) advice. In the placebo cohort, 
28% had resolution of NASH, 40% improved fibrosis, 40% improved steatosis, and 43% improved lobular 
inflammation. Progression of disease was seen in 25% (Lavine et al., 2011).  
Although limited, the pediatric data on the natural history of pediatric NAFLD support some conclusions. 
Fifteen percent of children with NAFLD have stage 3 fibrosis or higher at diagnosis (Schwimmer et al., 
2014) and disease in children appears to be more severe compared with adults (Holterman et al., 2013). 
Given that pediatric disease is by definition early onset disease, it may represent an aggressive phenotype 
of the disease. Reports show that a few children have rapid progression to clinical events from NAFLD 
(death, transplant, diabetes, CVD). Because such clinical events from pediatric NAFLD typically do not 
occur under the age of 21 years, studies determining clinical outcomes from pediatric NAFLD will require 
long-term follow-up into adulthood (Vos et al., 2017). 
1.3.3. 
 Diagnosis 
The diagnosis of NASH begins with the clinical suspicion of liver disease in a child. NAFLD may be 
suspected on the basis of an elevated serum alanine aminotransferase (ALT), hepatomegaly, or an 
abnormal imaging study consistent with fatty liver. In children, NAFLD is typically diagnosed between the 
ages of 10–13 years but the actual onset of disease for most children is not known (Goyal and Schwimmer, 
2016).  
Interpretation of liver histology is required to confirm a diagnosis of NAFLD, and to identify the presence 
and severity of NASH (Pardee et al., 2009). Not all children with NAFLD will develop NASH (Pardee et al., 
2009).  
Pediatric NASH is a histological diagnosis divided into two types: 
• 
Type 1: Liver biopsies consistent with adult histology. Defined as presence of steatosis with 
ballooning degeneration and/or perisinusoidal fibrosis, without portal involvement. 
• 
Type 2: Liver biopsies are unique in appearance. Defined as the presence of steatosis with portal 
inflammation and/or fibrosis, in the absence of ballooning degeneration or perisinusoidal 
involvement.  
Though the biological mechanisms behind the subtypes are currently unknown, these findings highlight a 
potentially important distinction between adult and pediatric NASH (Pardee et al., 2009). Identification of 
fibrosis in children with NASH and NAFLD is important because these phenotypes are expected to be more 
likely to progress to cirrhosis (Loomba and Chalasani, 2015). Overt signs and symptoms of advanced 
fibrosis or cirrhosis are, however, uncommon in children with NAFLD and NASH (Vos et al., 2017). 


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1.3.4. 
Prevalence 
Prevalence of NAFLD varies by race/ethnicity. US studies have revealed a 4-fold increased risk of hepatic 
steatosis in Hispanic, compared with non-Hispanic adolescents (11–22 years old) (Rehm et al., 2014). 
White and Asian children also have high prevalence, compared to African American children (Schwimmer et 
al., 2006). The prevalence also differs by sex, with most studies showing higher percentages in male 
compared to females (Pardee et al., 2009). However, males and females appear to be equally likely to 
have NASH (Goyal and Schwimmer, 2016). Prevalence is higher in obese children compared with normal 
weight, although not all children with NAFLD are obese (Schwimmer et al., 2006).  
Anderson et al (Anderson et al., 2015), conducted a systematic review and meta-analysis of all studies 
reporting a prevalence of NAFLD based on any diagnostic method (i.e. biopsy, ultrasound, magnetic 
resonance imaging or other scans or liver enzymes) in participants 1–19 years old, regardless of whether 
assessing NAFLD prevalence was the main aim of the study. The commonest serum biomarkers used to 
assess NAFLD prevalence in research settings and to identify patients who may benefit from further 
investigation in clinical settings are alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 
(Golberg, 1980 [reported in Anderson et al., 2015]). Both liver enzymes have been reported to correlate 
with the degree of liver fat infiltration, inflammation (Anderson et al., 2015). Prevalence of NAFLD ranges 
from 9 to 37% (Jou, 2008; Hesham, 2009 [reported in Anderson et al., 2015]). In one study of NAFLD in 
children, about 23% had NASH (Schwimmer et al., 2006). 
1.4. 
Summary of Studies with Elafibranor 
1.4.1. 
Nonclinical Experience 
No safety issues were identified when assessing the potential effects of elafibranor on the cardiovascular, 
respiratory, and central nervous systems.  In animal studies, elafibranor was well and rapidly absorbed 
although absolute bioavailability was moderate (about 20% to 40%). Elafibranor is extensively metabolized 
and the activity is mainly carried by the active metabolite GFT1007. In all species, maximal plasma 
concentrations and exposure for both elafibranor and GFT1007 increase with the dose after single or 
repeated administrations. Elafibranor and its metabolites are rapidly cleared from the plasma and are 
mainly excreted by the fecal route, with urinary excretion as a secondary route of elimination. In the rat, 
elafibranor and/or its metabolites are rapidly excreted into the bile and undergo an extensive entero-
hepatic cycle, giving support for liver targeting of elafibranor and/or GFT1007. Tissue distribution studies in 
rodents and monkeys support the liver targeting of elafibranor and/or its metabolites.  
The toxicology program performed according to ICH guidelines demonstrates that elafibranor has no 
genotoxic or mutagenicity potential. According to acute toxicity study results, it can be concluded that 
elafibranor is safe when administered as single oral doses in rat and mouse, since no sign of toxicity was 
detected up to the dose of 1000 mg/kg. The safety of elafibranor has been assessed in multiple preclinical 
toxicology studies with repeated-dose oral administration for up to 6 months in rats and 12 months in 
monkeys.  
Two-year repeated-dose carcinogenicity studies in mice and rats have been completed. The only consistent 
safety concern raised by these studies is the expected PPARα-associated hepatomegaly, hepatocellular 
hypertrophy, and liver carcinoma in rodent species (mice and rats). However, it is well known that, 
compared to nonhuman primates and humans, rodents are highly sensitive to PPARα agonist induced 
peroxisome proliferation and associated liver side effects. Thus, available information on this class of drug, 
which includes marketed fibrates, together with the lack of any liver side effects in monkeys treated with 
high doses of elafibranor for 1 year, support the nonrelevance to humans (Cattley, 1998). Overall, these 
studies did not reveal any other safety issues up to the highest doses tested. Notably, elafibranor did not 
show any of the known PPARγ-related concerns such as excess weight gain, hemodilution, edema, 
cardiomegaly, adiponectin induction, or urinary bladder carcinoma. 
The phototoxic potential of elafibranor has been assessed by the in vitro 3T3 NRU phototoxicity test and 
the ultraviolet (UV)-Local Lymph Node Assay (LLNA) test in mice. Elafibranor, but not its major metabolite 
GFT1007, showed UVA-dependent cytotoxicity in vitro. The UV-LLNA test was performed in mice with oral 
dosing for 3 days at up to 800 mg/kg/day elafibranor. Although a very conservative NOEL was set at 400 


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mg/kg/day based on isolated findings at the highest dose, it is considered that data are more in favour of 
an absence of phototoxic effect, given the tissue distribution of elafibranor, and absence of phototoxicity 
signal in all clinical studies. 
To support dosing in children, a juvenile toxicity study has recently been performed in rats, with 
administration of elafibranor from post-natal day (PND) 21 to PND 63 (6 weeks). An assessment of delayed 
onset toxicity and/or reversibility of toxicity was made following a 4 week recovery period. Overall, changes 
observed during the study were either minor and monitorable (and at least partially reversible), or 
recognized adaptive changes associated with the PPARα agonist class of compound in the rat. Therefore, 
the no observed adverse effect level (NOAEL) for male and female juvenile rats was considered to be 100 
mg/kg/day elafibranor. 
1.4.2. 
Clinical Experience 
Overall, a total of 2511 subjects have been randomized in the elafibranor clinical program, of which it is 
estimated that 1704 were exposed to elafibranor (based upon actual exposure data from completed clinical 
trials and the enrollment/randomization schemes for ongoing trials). These studies have been conducted in 
adult patients aged 18 to 75 years of age. 
Overall, 549 healthy subjects, 60 obese but otherwise healthy subjects, 37 patients with mixed 
hyperlipidaemia (type IIb Frederickson), 94 patients with atherogenic dyslipidaemia and abdominal obesity, 
47 patients with impaired glucose tolerance and abdominal obesity, 109 diabetes mellitus type 2 patients, 
22 patients with insulin resistance and abdominal obesity, 1548 NASH patients and 45 PBC patients were 
randomized and treated in clinical trials to date. Of these, 406 healthy subjects, 45 obese but otherwise 
healthy subjects, 24 patients with mixed hyperlipidaemia, 63 patients with atherogenic dyslipidaemia and 
abdominal obesity, 23 patients with impaired glucose tolerance and abdominal obesity, 59 diabetes 
mellitus type II patients, 22 patients with insulin resistance and abdominal obesity, and an estimated 1032 
NASH patients and 30 PBC patients received elafibranor, based upon actual exposure data from completed 
clinical trials and the enrollment/randomization schemes for ongoing trials. 
Clinical data have confirmed the potential beneficial effect of elafibranor in subjects with metabolic 
disorders and NASH. 
Phase 2 studies in subjects with cardiometabolic disorders and NASH have demonstrated consistent 
reductions in ALP compared to placebo. The reduction in ALP was associated with relevant reductions in 
markers of liver injury such as GGT and ALT and in inflammatory markers. These data are encouraging to 
consider elafibranor as a potential drug candidate to treat PBC. 
In addition, the Phase 2b trial in adult NASH patients demonstrated the efficacy of elafibranor at the 
therapeutic dose of 120 mg on a clinically meaningful primary endpoint, resolution of histological NASH 
without worsening of fibrosis, in patients with active disease (NAS ≥4). While the trial was short and not 
designed for antifibrotic endpoints, it nonetheless showed that elafibranor, at 120 mg daily, improved 
fibrosis indirectly through the resolution of NASH. Importantly, elafibranor 120 mg concomitantly improved 
the cardiometabolic risk profile of the patients by decreasing plasma triglycerides, total and low density 
lipoprotein-cholesterol (LDL-C), increasing high density lipoprotein-cholesterol (HDL-C), and improving 
inflammation, insulin resistance, and glucose homeostasis. Together, these results position elafibranor as a 
drug candidate to treat NASH with the objective to block fibrosis evolution and ultimately avoid long term 
liver outcomes while reducing cardiovascular risk. 
A Phase 3 study in subjects with NASH and fibrosis is ongoing with up to 2224 patients to be enrolled and, 
to date, more than half of the subjects have been randomized. In this study, subjects are receiving 120 
mg/day elafibranor or placebo for up to 72 weeks during the first treatment period, followed by a 
long-term treatment period to assess efficacy on progression to cirrhosis, all-cause mortality, and 
liver-related clinical outcomes – as measured by the onset of any of the listed adjudicated events of portal 
hypertension or cirrhosis-related events.  
These studies have highlighted the good safety profile of elafibranor and no major safety concerns have 
been raised. Based on the cumulative experience gathered to date, gastrointestinal disorders and asthenia/ 


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fatigue are considered common non-serious adverse reactions reasonably associated with elafibranor. Most 
of them are of mild to moderate intensity. Laboratory increases in serum creatinine or CPK should be 
monitored throughout clinical trials as this has been observed in Phase 2 studies to date and is a known 
PPARα agonist effect. Elevation of transaminases should also be monitored as well as drug-induced liver 
injury. In the absence of human pregnancy data, highly effective contraception should be maintained for 
women of childbearing potential participating in clinical trials with elafibranor treatment, up to 1 month 
after end of study treatment. A DSMB has been reviewing the safety data of the ongoing phase 3 study 
every 6 months in an unblinded manner and has not raised any safety signal. 
In conclusion, the safety data and the current knowledge on elafibranor confirm the favourable balance 
between anticipated efficacy/benefits and risks. 
For additional detailed information see current version of Investigator’s Brochure.  
1.5. 
Rationale for Elafibranor in Pediatric Population 
1.5.1. 
Rationale for Elafibranor in Pediatric NASH 
The goal of treatment of pediatric NAFLD and NASH is to stop and reverse liver injury (Nobili et al., 2014). 
Lifestyle modification is the current first-line therapy for pediatric NAFLD and NASH, even though it is 
difficult to obtain and to maintain (Della Corte et al., 2014). There is no approved pharmacological therapy 
for NAFLD and NASH in children or adults (Loomba et al., 2009). 
As described above, pre-clinical studies have shown that elafibranor reverses histological NASH and liver 
fibrosis in multiple pre-clinical models of NAFLD/NASH, reducing hepatic inflammation and normalizing liver 
enzymes. In addition, elafibranor improves dyslipidemia in numerous preclinical models, and has insulin-
sensitizing and glucose-lowering properties in experimental models of type 2 diabetes. 
Possible PPAR-related side-effects have been considered in order to assess the benefit-risk of the use of 
elafibranor in pediatric populations. Most of the PPAR-related safety concerns described in humans are 
associated with the PPAR γ isoform, notably those reported with PPAR γ agonists on cardiovascular risks. 
They are therefore not relevant to elafibranor, which shows no evidence of PPAR γ -associated activity in 
vivo. In particular, there is no evidence of cardiomegaly or increased risk of cardiac insufficiency that have 
been associated with PPAR γ agonists (Nesto et al., 2003). 
PPARα associated liver and related tumors observed in two-year rodent carcinogenicity studies with 
elafibranor are rodent specific and are not considered relevant to humans.  
The proposed 3-month study in the 8-17 year old pediatric population will allow to obtain the PK/PD profile 
and the safety data under close monitoring in highly-recognized academic settings.  
Overall, the non-clinical data, along with clinical studies to date, support the use of elafibranor for the 
treatment of fatty liver diseases (NAFLD/NASH) and hepatic fibrosis, with associated benefit on atherogenic 
dyslipidemia (high triglycerides, low HDL-cholesterol), glucose homeostasis and insulin resistance, and 
inflammatory status. 
There is currently no evidence to suggest that the therapeutic activity of elafibranor may be different in 
children compared to the adult. Taking into account, the prevalence of NAFLD in children, and the 
beneficial effects of elafibranor on liver damage and on the various components of the metabolic 
syndrome, we therefore propose NAFLD as a treatment indication for elafibranor in children. 
1.5.2. 
Rationale for the Study Population 
Patients enrolled in this study are children and adolescents (8 to 17 years old, inclusive) will be 
representative of the pediatric population with NASH that will include patients without fibrosis and some 
with significant (stage 2 or 3) fibrosis. In addition, they have metabolic abnormalities, suffer from 
overweight (BMI z-score > 85th percentile) and insulin resistance (HOMA-IR ≥ 5). These abnormalities 


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represent the basis for the development of their liver disease, with insulin resistance being the central 
element of progression of NAFLD. 
As elafibranor has consistently demonstrated clear efficacy on metabolic parameters, insulin resistance and 
inflammation in the phase 2a program and in the phase 2b, it is expected that the patients will all have a 
clinical benefit with elafibranor treatment, which addresses the metabolic abnormalities present at the early 
stage of NAFLD. 
The safety will be closely monitored in high level academic sites. 
1.5.3. 
Justification of the Selected Dose 
The results obtained in the phase 2 program showed that both doses of elafibranor 80mg and 120mg 
beneficially affect the metabolic parameters such as plasma lipids, glucose homeostasis, and insulin 
resistance in the adult population. 
In all studies currently performed (including the ongoing phase 3 study monitored by a DSMB), a good 
safety profile of elafibranor has been demonstrated. Due to the overweight/obese profile of the targeted 
population in this first pediatric study (inclusion criteria related to minimum BMI z-score), dose intended to 
be used on this study are similar to the ones used in phase 2b and phase 3 studies. 
Therefore, given the good safety profile and the efficacy of elafibranor 80 and 120mg, both doses will be 
tested in this pediatric study. 
The PK data obtained in this study will be used to confirm the dose to be used in future studies in children 
and adolescents (8 to 17 years old). 
1.5.4. 
Rationale for the Study 
The present short-term study will provide important preliminary information related to pharmacokinetics, 
safety, tolerability, and efficacy (including metabolic function) in this pediatric population. The study results 
will inform the development of the pediatric formulation and optimize the design of future studies. 
2. 
TRIAL OBJECTIVES 
2.1. 
Primary Objective  
To assess the pharmacokinetic profile of elafibranor and its active metabolite GFT1007, following once 
daily oral administration of two dose levels of elafibranor (80 and 120 mg) to children and adolescents, 8 
to 17 years of age (inclusive).  
2.2. 
Secondary Objectives  
• 
To assess changes in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) and other liver markers; 
• 
To assess changes in markers of glucose homeostasis (homeostatic model assessment for insulin 
resistance (HOMA-IR) and fasting insulin); 
• 
To assess changes in serum lipid parameters; 
• 
To assess changes in body weight and BMI z-score; 
• 
To assess changes in waist circumference; 
• 
To assess changes in inflammatory markers;  
• 
To assess the change in the pediatric quality of life (PedsQL™) score as completed by the 
child/adolescent and the parent/legal guardian. 


Cli ni c al Tri al G F T 5 0 5 E -2 1 8 -1  
Pr ot o c ol V 4 . 0 2 0  A pril 2 0 2 0  
 
G E N F I T  
 
P a g e  3 0  of 8 3  
 
2. 3.  S af et y  S e c o n d ar y O bj e cti v e  
T o ass ess t h e s af et y a n d t ol er a bilit y pr ofil e of t w o d o s e l e v els of el afi br a n or (8 0 m g a n d 1 2 0 m g) i n 
c hil dr e n a n d a d ol es c e nts, 8 t hr o u g h  1 7 y e ars of a g e.  
2. 4.  E x pl or at or y O bj e cti v e  
 
  
3.  
T R I A L D E S I G N  
T his st u d y is a n o p e n -l ab el, r a n d o miz e d, m ulti c e nt er, s e q u e nti al c o h ort st u d y t h at will ass ess t h e 
p h ar m a c o ki n eti cs ( P K), s af et y, a n d p h ar m a c o d y n a mi c s ( P D) a n d e x pl or e t h e r el ati o ns hi p b et w e e n P K a n d 
P D r e s p o n s e f oll o wi n g 1 2 w e e ks of o n c e d ail y or al a d mi nistr ati o n of el afi br a n or at d os es of 8 0 m g a n d 1 2 0 
m g i n c hil dr e n a n d a d ol es c e nts, 8 t o 1 7 y e ars of a g e (i n cl u si v e), wit h hist ol o gi c all y c o nfir m e d ( hist ori c al 
bi o ps y) n o n al c o h oli c  st e at o h e p atitis ( N A S H). T h e t ar g et p o p ul ati o n will i n cl u d e p ati e nts wit h N A S H wit h 
a n d wit h o ut fi br os i s. Of t h e 2 0 p ati e nts t h at will b e e nr oll e d a n d d os e d wit h el afi br a n or, at l e ast 4 p ati e nts 
≥1 2 t o ≤1 7 y e ars of a g e a n d at l e ast 2 p ati e nts ≥8 t o ≤1 1 y e a rs of a g e will h a v e si g nifi c a nt fi br osis [i. e., 
fi br osis st a g e 2 or 3]). 
T w o p ati e nt c o h orts will b e d os e d s e q u e nti all y. C o h ort 1 will c o nsist of a p pr o xi m at el y 1 2 p ati e nts w h o ar e 
≥1 2 t o ≤1 7 y e ars of a g e a n d will b e e nr oll e d first. O n c e 1 0 ( 8 0 %) p ati e nts i n c o h ort 1 h a v e b e e n 
e v al u at e d f or P K a n d s af et y t hr o u g h Visit 4 b y t h e D at a S af et y M o nit ori n g B o ar d ( D S M B),  a n d if a gr e e d 
u p o n b y t h e D S M B,  e nr oll m e nt will b e o p e n t o p ati e nts ≥8 t o ≤1 1 y e ars of a g e. C o h ort 2 will c o nsist of 
a p pr o xi m at el y 8 p ati e nts w h o ar e ≥8 t o ≤1 1 y e ars of a g e.  
P ot e nti al p ati e n ts will b e s cr e e n e d wit hi n 2 8 d a y s (-2 8 [ W e e k -4] t o -7 [ We e k -1]) pri or t o D a y 1 . D a y 1 
will i n cl u d e  r a n d o miz ati o n a n d d osi n g wit h st u d y dr u g. Aft er si g ni n g t h e I C F (p ar e nt/ l e g al g u ar di a n ) a n d 
ass e nt (p ati e nt ) d o c u m e nts, p ati e nt s will u n d er g o s cr e e ni n g pr o c e d ur es t o c o nfir m st u d y eli gi bilit y.  T h e 
p ati e nt  (a n d  p ar e nt/ g u ar di a n ) will b e gi v e n c o u ns elli n g r e g ar di n g a di et a n d e x er ci s e r e gi m e n t o b e 
m ai nt ai n e d st arti n g fr o m t h e S cr e e ni n g  visit.  
Eli gi bl e p ati e nt s will r et ur n t o t h e cli ni c o n D a y 1 . B as eli n e e v al u ati o n s i n cl u di n g c o nfir m ati o n of c o nti n u e d 
st u d y eli gi bi lit y, p h ysi c al e x a mi n ati o n, h ei g ht/ w ei g ht a n d w aist cir c u mf er e n c e, vit al si g ns, 1 2-l e a d s af et y 
el e ctr o c ar di o gr a m ( E C G), cli ni c al l a b or at or y e v al u ati o n s (i n cl u di n g pr e -d os e p h ar m a c o ki n eti c ( P K) s a m pl e, 
bi ol o gi c al a ss ess m e nts a n d s af et y ass ess m e nt s), c oll e ct i o n of a d v ers e e v e nts ( A Es) a n d c o n c o mit a nt 
m e di c ati o ns, b as eli n e P e di atri c Q u alit y of Lif e ( P e ds Q L ™) c o m pl et e d b y t h e p ati e nt a n d t h e p ar e nt /l e g al 
g u ar di a n ], a n d pr e g n a n c y t est (f or f e m al es of c hil d b e ari n g p ot e nti al [F O C B P] ), will b e o bt ai n e d pri or t o 
st ud y dr u g a d mi nistr ati o n. P ati e n ts will b e r a n d o miz e d ( 1: 1) t o r e c ei v e eit h er 8 0 m g or 1 2 0 m g o n c e d ail y 
f or 1 2 w e e ks. T h e p ati e n t ( a n d p ar e nt/ l e g al g u ar di a n ) will a g ai n b e c o u ns ell e d o n di et ar y a n d e x er cis e  
r e gi m e n r e q uir e m e nts t h at will b e m ai nt ai n e d t hr o ug h o ut t h e st u d y p eri o d.  P ati e nt s will b e dis p e ns e d a 1 -
m o nt h s u p pl y of st u d y dr u g  a n d d osi n g di ar y  a n d will b e s c h e d ul e d  f or t h eir n e xt visit o n D a y 15  ( ± 2 
d a ys) f or s af et y, P D ( bi ol o gi c al l a b or at or y ass ess m e nts) e v al u ati o n  a n d c o m pli a n c e c h e c k.  
T h e p at i e nt will r et ur n o n D a y 29  ( ± 2 d a ys)/ W e e k 4  f or s af et y, P D ( bi ol o gi c al l a b or at or y ass ess m e nt s), P K 
ass ess m e nts, a n d c o m pli a n c e c h e c k. A pr e -d os e P K s a m pl e will b e o bt ai n e d, a n d t h e d ail y d os e of st u d y 
dr u g will b e gi v e n i n t h e cli ni c. P K s a m pl es will b e c oll e ct e d at 0. 5  h o ur s ( ± 2 mi n ut es), 1 -h o ur  ( ± 2 
mi n ut es),  1. 5 h o urs ( ± 2  mi n ut es), 2  h o urs ( ± 5 mi n ut e s),  4  h o urs ( ± 5 mi n ut es), 6 h o urs  ( ± 1 0 mi n ut es), 
a n d 8 h o urs ( ± 1 0  mi n ut es)  p ost d os e. A 1 -m o nt h s u p pl y of st u d y dr u g a n d d osi n g di ar y will b e dis p e ns e d. 
T h e p ati e n t will r et ur n t h e f oll o wi n g d a y f or c oll e cti o n of t h e 2 4 h o ur ( ±1 0 mi n ut e ) p ost -d os e s a m pl e ( pri or 
t o n e xt d ail y d o s e). T h e p ati e nt s will r et ur n t o t h e cli ni c o n D a y 5 7  ( ± 2 d a ys)/ W e ek 8  a n d D a y 8 5  ( ± 2 
d a ys)/ W e e k 1 2  E O T visit , f or s af et y a n d P D ( bi ol o gi c al l a b or at or y ass ess m e nts) e v al u ati o ns a n d c o m pli a n c e 
e v al u ati o n s.   O n D a y 5 7 , i n a d diti o n t o s af et y a n d P D, a 1 -m o nt h s u p pl y of st u d y dr u g a n d d o si n g di ar y 
will b e dis p e ns e d.  At t h e E n d of Tr e at m e nt ( E O T) visit, D a y 8 5 ( ±  2 d a ys) /W e e k 1 2 , q u alit y o f lif e will b e 
ass ess e d , t h e fi n al P K s a m pl e will b e c oll e ct e d, a n d u n us e d st u d y dr u g a n d c o m pl et e d d osi n g di ar y will b e 
c oll e ct e d.  A fi n al s af et y e v al u ati o n will b e c o n d u ct e d o n E O S visit, D a y 1 1 3  ( ± 2 d a ys)/ W e e k 16 . 
C CI


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3.1. 
Study Schedule 
Each patient may participate in the study for up to approximately 20 weeks (Screening through final 
follow-up visit). 
• 
Screening:  
o 
SV1 Week -4 to Week -1: Day -28 to Day -7 
o 
SV2 Week -1: Day -5 (±2 days) (telephone contact only) 
• 
Randomization and Treatment: Day 1 to Day 85 (±2 days)  
o 
V1 Week 0 (Randomization): Day 1 
o 
V2 Week 2: Day 15 (±2 days) 
o 
V3 Week 4: Day 29 (±2 days) 
o 
V4 Week 4: Day 30 (24h PK sample collection) 
o 
V5 Week 8: Day 57 (±2 days) 
o 
V6 Week 12 (EOT): Day 85 (±2 days) 
• 
Follow-up: Day 86 to Day 113 (±2 days) (Week 12 to Week 16) 
o 
V7 Week 16 (EOS): Day 113 (±2 days) 
3.2. 
Randomization 
Number of Randomized Patients (planned): A total of 20 patients will be enrolled across the two cohorts.  
• 
Cohort 1: ≥12 to ≤17 years of age.  A total of approximately 12 patients will be randomized in this 
cohort.   
• 
Cohort 2: ≥8 to ≤11 years of age.  A total of approximately 8 patients will be randomized in this 
cohort.  Enrollment in this cohort will not start until 80% of the patients in cohort 1 have been 
evaluated through Visit 4 by the Data Safety Monitoring Board and a recommendation by the 
DSMB to continue the study has been made. 
Patients will be randomized 1:1 to receive either dose (80 or 120 mg). 
Considering that at least 4 patients ≥12 to ≤17 years of age and at least 2 patients ≥8 to ≤11 years of 
age with fibrosis stage 2 or 3 will be enrolled and to achieve balance between dosing groups according to 
the fibrosis severity, randomization will be stratified within each cohort based upon screening fibrosis 
severity stage (stratum 1:fibrosis stage 0 to 1 and stratum 2: fibrosis stage 2 to 3). 
4. 
PATIENT SELECTION 
4.1. 
Inclusion Criteria 
For a study patient to be evaluated for study participation:  
1. Parent(s)/Legal Guardian(s) must provide written Informed Consent (including HIPAA) prior to the 
conduct of any study related procedures to permit participation of a minor in a clinical research 
study in accordance with federal and local laws. Additionally, assent from a minor child will be 
obtained in accordance with federal and local laws as well as in compliance with the 
recommendations of the approving Institutional Review Board (IRB)/Independent Ethics 
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Study patients will be eligible for inclusion in the study if they meet all the following criteria at Screening 
and up to the time of Randomization (Visit 1) as applicable: 
2. Are male or female between 8 and 17 years of age (inclusive) at the time of Screening Visit 1 
(when consent for study participation is given) and at the time of Randomization (Visit 1). 
3. Diagnosis of non-alcoholic steatohepatitis (NASH) confirmed by histological evaluation (with or 
without fibrosis) from a liver biopsy obtained within 24 months prior to Randomization (Visit 
1/Day 1). 
4. Has adhered to a minimum of 3 months of lifestyle modification to treat NASH, prior to Screening 
(SV1), and agrees to adhere to lifestyle modifications (diet and exercise) throughout the study 
period (Screening through final visit [Visit 7/Day 113]).  
5. Has an alanine aminotransferase (ALT) level greater than (>) 50 IU/L, at Screening (SV1). 
6. Has a Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ≥ 5, at Screening (SV1). 
7. Has a Body Mass Index z-score (BMI z-score) (also referred to as BMI-for-age percentile) greater 
than or equal to (≥) 85th percentile for age and gender at Screening (SV1). 
8. Has a Hemoglobin A1C (HbA1c) less than or equal to (≤) 8.5%. If the patient has Type 2 diabetes 
and is taking anti-diabetic therapy (e.g., metformin or insulin), treatment must have been started 
at least 3 months prior to Screening (SV1) and the dose must be stable for at least 3 months prior 
to Screening (SV1) and should remain stable through Randomization (Visit 1/Day 1).   
9. If patient is taking medications or supplements to treat NAFLD/NASH (Vitamin E, ursodeoxycholic 
acid, PUFAs), the dose must be stable for at least 3 months prior to Screening Visit 1 and should 
remain stable through Randomization (V1/Day 1) and planned to remain stable through EOS. 
10. Sexually active female participants of childbearing potential must agree to utilize a highly effective 
method of contraception per the Clinical Trial Facilitation Group (CTFG) Guidelines (refer to 
Appendix IV), from Screening through 30 days after the last dose of study drug (1 month after 
the end of treatment (EOT), and agree to monthly pregnancy testing during the study up to and 
including EOS. 
11. The Parent(s)/Legal guardian(s) and study patient are willing and able to follow all study-related 
procedures, including but not limited to daily study drug administration, pharmacokinetic (PK) 
sampling, be willing and able to return to the study clinic for study visits and be accessible by 
phone or e-mail for study related communications. 
12. Patient agrees not to consume alcohol or use illicit drugs during the study up to and including 
EOS. 
4.2. 
Exclusion Criteria 
A study patient will be excluded from the study if they meet any of the following criteria at Screening (SV1) 
or prior to Randomization (Visit 1/Day 1): 
1. Has history of bariatric surgery or planned surgery during the study period 
2. Has known history of heart disease. 
3. Has uncontrolled hypertension evidenced by sustained elevation in systolic blood pressure >140 
mmHg or diastolic blood pressure >90 mmHg despite treatment with antihypertensive therapy, 
prior to Randomization (Visit 1/Day 1). 


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4. Has a known history of Type 1 diabetes. 
5. Has a known history of acquired immunodeficiency syndrome or positive screening for human 
immunodeficiency virus antibodies at Screening Visit 1. 
6. Has a documented weight loss of more than 5% during the 6-month period prior to 
Randomization (Visit 1/Day 1). 
7. Has a history of renal disease defined as an estimated glomerular filtration rate (eGFR) <90 
mL/min/1.73 m2 using the Schwartz Bedside GFR Calculator for Children or present at Screening 
Visit 1. 
8. History of, significant alcohol consumption or inability to reliably quantify alcohol intake, and/or 
use of illicit drugs.  
9. Has clinical and/or historical evidence of cirrhosis, included by not limited to: 
a. Abnormal low hemoglobin as deemed clinically significant by the investigator (with the 
exception of females with a documented history of a low hemoglobin during 
menstruation); 
b. White blood cell count < 3,500 cells/mm3 of blood; 
c. Platelet count <150,000 cells/mm3 of blood; 
d. Direct bilirubin >0.3 mg/dL; 
e. Total bilirubin >1.3 mg/dL unless the patient has a diagnosis of Gilbert disease in which 
case direct bilirubin and reticulocyte count do not exceed the upper limit of normal (ULN) 
and haemoglobin is greater than the lower limit of normal; 
f. 
Serum albumin <3.5 g/dL; 
g. International normalized ratio (INR) >1.4. 
10. Has evidence of chronic liver disease other than NASH, defined by any one of the following: 
a. Biopsy consistent with histological evidence of autoimmune hepatitis; 
b. Serum hepatitis A antibody (anti-HAV IgM) positive; 
c. Serum hepatitis B surface antigen (HBsAg) positive; 
d. Serum hepatitis C antibody (anti-HCV) positive; 
e. Serum hepatitis E antibody (anti-HEV) positive; 
f. 
History of or current positive Anti-Mitochondrial Antibody (AMA)Test; 
g. Known or current Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) > 
45% with histological evidence of iron overload; 
h. Known or current Alpha-1-antitrypsin (A1AT) phenotype/genotype ZZ or SZ; 
i. 
Diagnosis of Wilson's disease. 
11. Has a creatine phosphokinase (CPK) greater than the upper limit of normal (ULN) at Screening 
Visit 1.  This test may be repeated , if necessary, to confirm eligibility. 


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12. Has AST and/or ALT >8 x ULN. 
13. Has used any prohibited medication(s) within the specified timeframe (Refer to Appendix III, non-
permitted medications):  
a. Within 12 months prior to Screening Visit 1 up to Randomization (Visit 1/Day 1) 
i. Chronic use (defined as treatment longer than 3 consecutive months) of 
medications known to cause hepatic steatosis or steatohepatitis (including but not 
limited to systemic chronic glucocorticoids, tetracycline, valproic acid, salicylates, 
tamoxifen, methotrexate).  
b. Within 12 Weeks prior to Screening Visit 1 up to Randomization (Visit 1/Day 1) 
i. Use of Thiazolidinediones (glitazones [pioglitazone & rosiglitazone]).  
c. Within 8 Weeks prior to Screening Visit 1 up to Randomization (Visit 1/Day 1) 
i. Fibrates medications. Patients taking statins or ezetimibe prior to Screening Visit 1 
may participate if the dose has been stable for 3 months prior to Screening Visit 1 
and no dose adjustments are anticipated.   
14. Is currently taking drugs that could interfere with study medication absorption, distribution, 
metabolism or excretion or could lead to induction or inhibition of microsomal enzymes, e.g., 
indomethacin. 
15. Is pregnant, lactating or is planning to become pregnant during the study. 
16. Is participating in any other study and have received any other investigational drug or device 
within 30 days prior to Screening or are taking part in a non-medication study which, in the 
opinion of the Investigator, would interfere with study compliance or outcome assessments. 
17. Has symptoms of clinical depression. 
18. Has other concurrent medical (e.g., immunological, neoplastic, endocrine, hematological, 
gastrointestinal or neurological) or psychiatric condition, which, in the opinion of the Investigator, 
would place the patient at increased risk, preclude obtaining voluntary consent/assent or 
compliance with required study procedures, or would confound the objectives of study. 
19. Has known allergy to the study drug or any of its components. 
5. 
TRIAL PROCEDURES 
The procedures performed at each visit are summarized in Section 5.2 and in the General Study 
Assessment Schedule and Biological Assessment Schedule. However, a patient may be seen at any time for 
safety reasons and will be recorded as an unscheduled visit. 
5.1. 
Lifestyle Recommendations and Study Recommendations  
5.1.1. 
Diet and Lifestyle Recommendations 
Standard diet and exercise recommendation given by the Investigator during Screening Visit 1 will be given 
at the beginning of each patient’s participation and will be maintained throughout the study. 
These recommendations will be based on the latest recommendations from the American Academy of 
Pediatrics (AAP) (Birch et al., 2006). 
5.1.2. 
Dietary, Fluid and Lifestyle Restrictions 


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The following restrictions apply to patients in this trial from Screening Visit 1 through the end of the study: 
• 
Patients will be required to fast (no food or drink other than water) for at least 10 hours prior to 
blood sampling (except for the post-dose PK blood sampling). As such, patients should not 
consume any breakfast or take study medication in the morning prior to the blood sampling. In 
case the patient does not fast before a visit, a new appointment will be scheduled to occur within 4 
days. 
• 
On each study visit day (with the exception of Visit 4/ Day 30), study treatment will be taken 
under fasting conditions after the blood sampling. 
• 
During the 48 hours preceding each study visit, patients should not perform strenuous exercise. 
• 
Alcohol should not be consumed during the study (through EOS visit). 
• 
Illicit drugs should not be used during the study (through EOS visit). 
5.2. 
Trial Procedures at Each Visit  
The procedures and assessments to be performed at each visit are indicated in the General Study 
Assessment Schedule, Biological Assessment Schedule, and Figure 1: Study Schematic. When planning 
study visits, all subsequent visits should be calculated based off of Visit 1 (Day 1).  An estimated time for 
the conduct of each visit is provided as a guide only to the study site personnel and study patient and 
parent/legal guardian for planning purposes. Note: it will not be considered a departure from the protocol 
if the visit length is shorter or longer than anticipated. 
5.2.1. 
Screening Visit 1/Week -4 to Week -1 (Day -28 to Day -5 (±2 days)) 
The screening visit can occur up to 4 weeks prior to randomization but should occur at least 1 week prior 
to planned randomization to ensure the results of laboratory test are available to verify inclusion/exclusion 
criteria. Due to the COVID-19 crisis, the screening window (i.e., the time from the signing of consent / 
screening visit 1 to randomization) can be extended to be up to 8 weeks if no onsite visit is possible earlier. 
 It is estimated that this visit will take approximately 2 hours to complete the visit. 
• 
Informed Consent Process 
o 
The parent(s)/legal guardian (s) must provide written informed consent prior to any study 
procedure being done; and 
o 
The patient must provide assent to participate in the study. 
• 
Interview 
o 
Evaluate Inclusion/Exclusion Criteria; 
o 
Review and record demographic information;  
o 
Review and record prior medications (those taken within the last 12 months and current 
medications); 
o 
Review prior medical and surgical histories; 
o 
Assess potential alcohol intake by AUDIT questionnaire interview of patient. 
• 
Assessments 
o 
Measure and record height, weight, waist circumference, and calculate BMI z-score; 
o 
Obtain and record vital signs; 
o 
Perform a complete physical examination. 
• 
Sample Collection 


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o 
Collect fasting blood samples as indicated on the General Study Assessment Schedule;  
o 
Collect urine sample for urinalysis (UA) and urine pregnancy test (if applicable). 
• 
Instructions 
o 
Inform Parent/legal guardian and patient that they will be contacted within approximately 1 
week regarding study qualification and will be scheduled for Visit 1 (as applicable).  
o 
Counselling regarding a diet and exercise regimen that should be maintained starting from 
the screening visit. 
• 
Screen Visit 2 – Phone Contact Week -1 
o 
Inform Parent/legal guardian and patient of qualification status and schedule for Day 1 
(randomization). 
o 
When Visit 1 is scheduled inform the parent/guardian the patient must present for Visit 1 in 
a fasted state (nothing to eat or drink (except water) for 10 hours prior to the visit). 
5.2.2. 
Visit 1/Week 0/ Day 1 (Randomization)  
It is estimated that this visit will take approximately 2 hours to complete the visit. 
• 
Interview 
o 
Confirm patient continues to meet Inclusion/Exclusion Criteria; 
o 
Review of adverse events; 
o 
Review concomitant medications. 
• 
Assessments 
o 
Measure and record height, weight, waist circumference, and calculate BMI z-score; 
o 
Obtain and record vital signs; 
o 
Obtain 12-lead Electrocardiogram (ECG); 
o 
Perform a complete physical examination; 
o 
Patient and parent/legal guardian to self-complete the PedsQL™ questionnaire individually. 
• 
Sample Collection 
o 
Collect fasting blood samples as indicated on the General Study Assessment Schedule; 
o 
Collect urine sample for UA and for urine pregnancy testing (as applicable and locally tested). 
• 
Randomization and Dosing 
o 
Randomize patient to study treatment; 
o 
Administer the first dose of study drug in the clinic. Dose will be given with a minimum of 
50 mL of water and check that study drug is swallowed. 
• 
Instructions 
o 
Counselling regarding a diet and exercise regimen that should be maintained starting from 
the screening visit. 
o 
Review dosing procedure and completion of dosing diary (refer to Appendix II) and dispense 
1-month supply of study drug.  Patient’s should be instructed not to discard used wallet 
cards, rather, the used wallet cards should be kept and returned with the box to the study 
site at the next study visit (Visit 2).    
o 
Remind the parent/legal guardian/patient to present for Visit 2 in a fasted state (nothing to 
eat or drink (except water) for 10 hours prior to the visit). 
o 
Remind the patient to not take any dose the day of Visit 2 before presenting to the clinic. 


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5.2.3. 
Visit 2/Week 2 (Day 15 ±2 days) 
It is estimated that this visit will take approximately 1 hour to complete the visit. 
• 
Interview 
o 
Review of adverse events; 
o 
Review concomitant medications. 
• 
Assessments 
o 
Measure and record height, weight, waist circumference, and calculate BMI z-score; 
o 
Obtain and record vital signs; 
o 
Perform a complete physical examination. 
• 
Sample Collection 
o 
Collect fasting blood samples as indicated on the General Study Assessment Schedule;  
o 
Collect urine sample for urine pregnancy testing (as applicable and locally tested). 
• 
Compliance Check  
o 
Pill count; 
o 
Review diary; 
o 
Administration of dose in the clinic. Dose will be administered with approximately 50 mL of 
water and check that study drug is swallowed.  
• 
Instructions 
o 
Counselling regarding a diet and exercise regimen that should be maintained throughout the 
study. 
o 
Review dosing procedure and completion of dosing diary (refer to Appendix II).  Re-dispense 
study drug to the patient. 
o 
Remind the parent/legal guardian/patient to present for Visit 3 in a fasted state (nothing to 
eat or drink (except water) for 10 hours prior to the visit). 
o 
Remind the patient not to take any dose of study medication the day of Visit 3 before 
presenting to the clinic. 
5.2.4. 
Visit 3/Week 4 (Day 29 ±2 days) 
It is estimated that the total visit time will be approximately 8-1/2 hours. Patients will remain in the clinic 
for the collection of PK samples through hour 4. Patients may leave the clinic and return for the 6 hour and 
8-hour PK sample collection at the discretion of the investigator or study coordinator.  
• 
Interview 
o 
Review of adverse events; 
o 
Review concomitant medications. 
• 
Assessments 
o 
Measure and record height, weight, waist circumference, and calculate BMI z-score; 
o 
Obtain and record vital signs; 
o 
Perform a complete physical examination. 
• 
Sample Collection 
o 
Collect fasting blood samples as indicated on the General Study Assessment Schedule; 


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o 
Collection of PK samples (T0) prior to dose, and at 0.5 hours (±2 minutes), 1-hour (±2 
minutes), 1.5-hour (±2 minutes), 2-hour (±5 minutes), 4 (±5 minutes), 6 (±10 minutes) 
and 8 hours (± 10 minutes) post dose; 
o 
Collect urine sample for UA and for urine pregnancy testing (as applicable and locally tested). 
• 
Dosing and Compliance Check (collect carton previously dispensed at visit 1) 
o 
Conduct a pill count; 
o 
Review diary; 
o 
Administration of dose in the clinic. Dose will be administered with approximately 50 mL of 
water and check that study drug is swallowed.  
• 
Instructions 
o 
Counselling regarding a diet and exercise regimen that should be maintained throughout the 
study. 
o 
Review dosing procedure and completion of dosing diary and dispense 1-month supply of 
study drug (refer to Appendix II). 
o 
Remind the patient not to take any dose of study medication the day of V4 before presenting 
to the clinic. 
5.2.5. 
Visit 4/Week 4 (Day 30) 
It is estimated the visit will take approximately 30 minutes to complete. 
• 
Interview 
o 
Review of adverse events. 
• 
Sample Collection 
o 
Collect 24-hour (± 10 minutes) post Day 29 dose PK blood sample.  
• 
Dosing  
o 
Administration of dose in the clinic. Dose will be administered with approximately 50 mL of 
water and check that study drug is swallowed.  
• 
Instructions 
o 
Review dosing procedure and completion of dosing diary and dispense 1-month supply of 
study drug (refer to Appendix II). 
o 
Remind the patient not to take any dose of study medication the day of V5 before presenting 
to the clinic. 
o 
Remind the parent/legal guardian/patient to present for Visit 5 in a fasted state (nothing to 
eat or drink (except water) for 10 hours prior to the visit). 
5.2.6. 
Visit 5/Week 8 (Day 57 ±2 days) 
It is estimated that the visit will take about 1 hour to complete.  
• 
Interview 
o 
Review of adverse events; 
o 
Review concomitant medications. 
• 
Assessments 
o 
Measure and record height, weight, waist circumference, and calculate BMI z-score; 
o 
Obtain and record vital signs; 


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o 
Perform a complete physical examination. 
• 
Sample Collection 
o 
Collect fasting blood samples as indicated on the General Study Assessment Schedule; 
o 
Collect urine sample for UA and for urine pregnancy testing (as applicable and locally tested); 
• 
Dosing and Compliance Check (collect the carton previously dispensed at visit 3) 
o 
Conduct a pill count; 
o 
Review diary; 
o 
Administration of dose in the clinic. Dose will be administered with approximately 50 mL of 
water and check that study drug is swallowed.  
• 
Instructions 
o 
Counselling regarding a diet and exercise regimen that should be maintained throughout the 
study. 
o 
Review dosing procedure and completion of dosing diary and dispense 1-month supply of 
study drug (refer to Appendix II). 
o 
Remind the parent/legal guardian/patient to present for Visit 6 in a fasted state (nothing to 
eat or drink (except water) for 10 hours prior to the visit). 
o 
Remind the patient not to take any dose of study medication the day of V6. 
5.2.7. 
Visit 6/EOT Week 12 (Day 85 ±2 days) 
It is estimated that visit will take about 2 hours to complete.  
• 
Interview 
o 
Review of adverse events; 
o 
Review concomitant medications; 
• 
Assessments 
o 
Measure and record height, weight, waist circumference, and calculate BMI z-score; 
o 
Obtain and record vital sign; 
o 
Obtain 12-lead ECG; 
o 
Perform a complete physical examination. 
• 
Patient and parent/legal guardian to self-complete the PedsQL™ questionnaire individually. 
• 
Sample Collection 
o 
Collect fasting blood samples as indicated on the General Study Assessment Schedule; 
o 
Collect urine sample for UA and for urine pregnancy testing (as applicable and locally tested); 
o 
Collect PK samples approximately 24 hours after the last dose (dose taken on day 84). 
• 
Compliance Check (collect the carton previously dispensed at visit 5) 
o 
Conduct a pill count; 
o 
Review diary; 
o 
Retrieve unused and used wallets of study drug. 
• 
Instructions 
o 
Counselling regarding a diet and exercise regimen that should be maintained throughout the 
study (final visit). 


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o 
Remind the parent/legal guardian/patient to present for Visit 7 in a fasted state (nothing to 
eat or drink (except water) for 10 hours prior to the visit). 
In case of early termination at any time after Visit 1 the next visit the patient will complete will be Visit 6/EOT 
procedures. 
5.2.8. 
Visit 7/EOS Week 16 (Day 113 ±2 days) 
It is estimated that visit will take about 2 hours to complete.  
• 
Interview 
o 
Review of adverse events; 
o 
Review concomitant medications. 
• 
Assessments 
o 
Measure and record height, weight, weight circumference, and calculate BMI z-score; 
o 
Obtain and record vital signs; 
o 
Perform a complete physical examination. 
• 
Sample Collection 
o 
Collect fasting blood samples as indicated on the General Study Assessment Schedule; 
o 
Collect urine sample for UA and for urine pregnancy testing (as applicable and locally tested). 
5.3. 
Other Visit 
5.3.1. 
Retesting Screening Visit 
Upon receipt of result from biological assessment done at Screening Visit 1, and in case a retesting is 
needed according to the selection criteria, an additional visit will be scheduled according to the 
recommended timeframe for retesting. 
Permitted retest in case of abnormal value at Screening Visit 1 is: 
• 
CPK: can be repeated prior to randomization (Day 1). 
Any other retest deemed necessary by the investigator at any time during the study should be discussed 
with the study medical monitor. 
5.3.2. 
Safety follow-up visit 
If at V7/EOS any safety lab parameter is abnormal and at least 10% higher than the highest reported 
values obtained between SV1 and V1, an additional visit should be scheduled one month later to repeat 
those affected parameters. 
The safety lab parameters are defined as hematology, coagulation biochemistry, lipids and inflammatory 
markers. 
5.3.3. 
Off-site study procedures in case of crisis situation 
Based on assessment of risk, and to ensure patient safety and minimize risks to trial integrity, the sponsor 
determined that the following optional off-site study procedures can be performed in case a study 
participant cannot attend an on-site visit during the COVID-19 crisis:  
 
• 
Safety assessment via phone call  
• 
Local lab assessment 
• 
Delivery of the study treatment to patient 
• 
Visit to patient’s home  
 


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These options apply to all on-site study visits except for the randomization visit (Visit 1).  Visit 1 must occur 
on-site as per section 5.2.2.   
 
These solutions can be applied after Medical Monitor approval and depending on the investigator’s judgment 
of each case and the patient/parent(s) ’s agreement.  The alternative solutions can be implemented in 
response to the COVID-19 crisis prior to the notification or submission to and approval of regulatory 
agencies and ethics committees. 
 
Before implementing any of these options for a patient, the site will contact the patient and parent(s) to 
check whether they agree with the off-site procedures.    
 
The patient will be invited to attend an on-site visit to complete the study procedures as per protocol, as 
soon as the situation allows it. 
 
5.3.3.1. 
Safety and drug compliance procedures 
 
 
The following procedures will be performed if applicable for the visit via either a phone contact, or, if safe 
and possible, a direct visit to the patient:  
 
• 
Check for AEs  
• 
Collection of any lifestyle modifications 
• 
Check concomitant/prior medication  
• 
Check of compliance (review of dosing diary with the patient/parent(s)) 
• 
Physical examination if possible with a direct visit to the patient or using video (described in 
Section 6.2.1)  
• 
Record vital signs, waist circumference and weight if possible with a direct visit to the patient 
(described in Section 6.2.1 and Section 6.2.2) 
 
5.3.3.2. 
Local lab assessment  
 
The patient will be asked if he/she can access a local lab in the few days after the phone contact to obtain 
hematology and biochemistry testing.  
 
If a direct visit to the patient is safe and possible, the appropriate lab parameters corresponding to the on-
site study visit will be collected. 
 
5.3.3.3. 
Delivery of study treatment to the patient 
 
The study treatment can be shipped to the patient or delivered directly to the patient by the site study staff 
if safe and possible as per the site procedure. 
 
As per the usual study visit, the patient will be instructed to continue taking the available tablets from the 
existing kit until he/she receives the new kit. 
 
The study drug compliance and study drug accountability will be performed as described in Section 7.7 
and Section 7.8 once brought to the study site/study pharmacy. 
 
 


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5.3.3.4. 
Completion of Missed Study Procedures  
 
As soon as the situation allows it, the site will schedule the patient’s on-site visit to complete the missed 
study procedures (those that could not be performed during the phone calls/visit to patient) as per protocol. 
 
 
 
5.4. 
Patient Withdrawal and Discontinuation  
5.4.1. 
Early Termination 
A patient or the patient’s parent/legal guardian may withdraw the patient from treatment or from the study 
at any time at their request or may be withdrawn at any time at the discretion of the Investigator or 
Sponsor for safety, behavioral, or administrative reasons. Upon withdrawal, the study drug should be 
permanently discontinued. 
5.4.1.1. 
Discontinuation for Treatment 
A patient must be permanently discontinued from the study drug for any of the following reasons: 
• 
The patient becomes pregnant; 
• 
Allergic or adverse reaction to the study drug; 
• 
Per section 6.3 of the protocol referring to Important specific biological considerations for patient 
discontinuation related to reported lab values; 
• 
Clinically significant adverse event, which in the opinion of the Investigator, would put the patient 
at unnecessary risk if dosing was continued; or 
• 
If a patient is discontinued from treatment at any time after Visit 1, they should complete the Visit 
6/EOT visit and will be encouraged to return one month later for Visit 7/EOS visit. 
5.4.1.2. 
Discontinuation from Study 
A patient must be discontinued from the study drug and from the study for the following reason: 
• 
The patient/parent/legal guardian withdraws consent. From the time consent is withdrawn, no 
additional data should be collected. However, the Sponsor may retain and continue to use data 
collected before such withdrawal of consent.  
5.4.2. 
Replacement 
Patient replacement will be at the discretion of the Sponsor.   
5.4.3. 
Lost to Follow-up 
A patient is considered to have been lost to follow-up if he/she [patient or parent/legal guardian] cannot 
be contacted by the Investigator (or designee). The Investigator (or designee) will document efforts to 
attempt to reach the patient twice by telephone and will send a certified letter before considering the 
patient lost to follow-up.  The end of participation for a patient lost to follow-up is documented as the 
delivery date of the certified letter. 
 


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5.5. 
Safety Oversight 
5.5.1. 
Investigator 
The Principal Investigator must have access and be available to promptly review the results of all safety 
assessments (i.e., clinical laboratory testing), electrocardiogram (ECG) results, vital signs and adverse 
events (AEs) including application site assessment information throughout the study. Safety assessments 
must be promptly (should be within 48 hours of notification of event) entered into the Electronic Data 
Capture (EDC) system. Clinical laboratory data will be evaluated by the Principal Investigator and clinical 
relevance will be assessed for abnormal values and the assessment will be documented on the laboratory 
report. A copy of the reports will be maintained as part of the source documentation.  
5.5.2. 
 Data and Safety Monitoring Board 
A DSMB will be established to monitor the progress of the study and to perform safety data reviews as 
designated in the DSMB charter, in order to protect patient welfare. The DSMB charter will define the role, 
responsibilities, rules and tasks, schedule, and format of meetings and data review and reporting 
requirements.  
The DSMB considers study-specific data as well as relevant background knowledge about the disease, test 
agent, or patient population under study. The primary responsibilities of the DSMB are to 1) review and 
evaluate the accumulated study data for participant safety, study conduct and progress, and 2) make 
recommendations concerning the continuation (i.e. proceeding with enrollment of patients in cohort 2), 
modification, or termination of the trial. All DSMB discussions, decisions, and recommendations will be 
communicated promptly to the Sponsor as described in the DSMB charter.  
The DSMB will consist of two independent clinicians with relevant expertise in related NAFLD/NASH 
pediatric clinical trials and 1 statistician with expertise in clinical trial and interim data analysis.  
At minimum, safety data will be summarized by the statistician after every 5th patient completes visit 4 or 
available data at the end of each quarter (at approximately 3-month intervals), whichever comes first 
throughout the study.  The DSMB will also review safety and PK data once 80% of the patients in Cohort 1 
have completed through Visit 4. Enrollment in Cohort 2 will commence as recommended by the DSMB. 
6. 
ASSESSMENTS 
6.1. 
Efficacy and Safety Assessments 
6.1.1. 
Biological Assessments 
All blood samples for efficacy and/or for safety assessment will be analyzed by the central laboratory. The 
Laboratory Manual will outline the collection process and shipping requirements. Blood will be taken a total 
of 15 times over a 16-week period. On Days 29 and 30 blood samples will be collected 9 times over a 24-
hour period. Refer to the Laboratory Manual for exact amounts of blood required for each test. 
6.1.1.1. 
Collection Procedure 
Blood sampling will be performed by trained personnel at each site. Use of diversional activities (E.g., cell 
phone or tablet) or use of a topical anesthetic (e.g., EMLA cream) should be considered in order to reduce 
pain associated with venipuncture.  An indwelling catheter may be inserted for repeat sample collection, 
while to patient is in the clinic. The catheter should be flushed with saline between sampling.   
6.1.1.2. 
Reporting 
For all visits, laboratory results will be available to sites approximately 24 hours after receipt of samples by 
the central laboratory.  Laboratory reports should be reviewed, signed and dated by the Investigator as 
soon as received. The Investigator should comment upon out of range parameters and assess clinical 
significance.  


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6.1.1.3. 
Sample Retention 
 
Blood samples may be retained indefinitely by the Sponsor for future testing for the purpose of 
investigating the study drug’s safety and effectiveness in support of future clinical research and/or to 
answer regulatory authority questions related to safety and effectiveness at the time of registration. 
Samples will only be identified by the patient number. Blood samples will not be shared with other 
research institutions for purposes outside of the protocol. 
6.1.1.4. 
Hematology and Coagulation Parameters 
The following parameters will be collected after fasting (nothing to eat or drink except water) for a 
minimum of 10 hours: Hemoglobin, hematocrit, red blood cells RBC), white blood cells (WBC) platelet 
count, differential count, reticulocyte count and prothrombin (PT) and international normalized ratio (INR). 
6.1.1.5. 
Pregnancy Test 
A pregnancy test is required for female patients of childbearing potential. Results must be negative at 
Screening Visit 1. Additionally, a urine pregnancy test (Clinical Laboratory Improvement Amendment - CLIA 
waived) will be done prior to Randomization (Visit 1) and at each study visit, with the exception of visit 4.  
Serum confirmation will be completed for all positive urine pregnancy tests. 
6.1.1.6. 
Serology 
All patients will be screened for HIV, hepatitis A antibody (anti-HAV), hepatitis B surface antigen (HBsAg), 
hepatitis C antibody (anti-HCV), and hepatitis E antibody (anti-HEV). Evaluation for HIV seropositivity will 
consist of enzyme-linked immunosorbent assay (ELISA) and, if positive, will be confirmed by the Bio Rad 
Multispot HIV-1/2 antibody differential test. Appropriate counseling will be made available to the patient in 
the event of a positive finding. Notification of state and federal authorities, as required by law, will be the 
responsibility of the Investigator. 
6.1.1.7. 
Other Parameters for Eligibility Assessment 
In case patient hasn’t been screened for the following parameters: Antimitochondrial Antibody (AMA), 
Alpha-1-Antitrypsin Phenotype, Ceruloplasmin, Ferritin, Transferrin Saturation (Serum Iron, Total Iron 
Binding Capacity), these parameters will be tested centrally at screening visit 1. 
6.1.1.8. 
Biochemistry 
The following parameters will be collected after fasting (nothing to eat or drink except water) for a 
minimum of 10 hours: creatinine, creatinine clearance (eGFR), total proteins, albumin, electrolytes 
(sodium, potassium, chloride, calcium), uric acid, urea, creatine phosphokinase (CPK), AST, ALT, gamma-
glutamyl transferase (GGT), alkaline phosphatase (ALP), total and conjugated bilirubin, high sensitivity C-
reactive protein (hsCRP), fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin 
resistance (HOMA-IR), fructosamine, C-peptide, free fatty acids (FFA), hemoglobin A1c (HbA1c), thyroid 
stimulating hormone (TSH). Cystatin C, eGFR from Cystatin C. 
6.1.1.9. 
Lipid Profile 
The following parameters will be collected after fasting (nothing to eat or drink accept water) for a 
minimum of 10 hours: total cholesterol [TC], non high-density lipoprotein cholesterol [non-HDL-C], HDL-C, 
low-density lipoprotein-cholesterol [LDL-C], triglycerides [TG]), calculated very low-density lipoprotein 
(VLDL-C), apolipoprotein A-I (ApoAI), and Apolipoprotein B (ApoB)). 
6.1.1.10. 
Urinalysis 
A urine sample will be collected and a macroscopic urinalysis (by urine dipstick) will be done by Medpace 
Reference Laboratory.  The following test will be done centrally via this method, specific gravity, pH, 


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protein, glucose, ketones, bilirubin, urobilinogen, blood, nitrite and leukocytes.  Should any result from the 
urine dip stick be positive, a urine microscopic exam will be performed.  Other urine parameters will be 
tested by the central laboratory include: α1 microglobulin, β-NAG, N-Gal, albumin and creatinine.  
6.1.1.11. 
Liver Markers 
The following parameters will be collected after fasting (nothing to eat or drink except water) for a 
minimum of 10 hours: CK18 (M65 & M30), adiponectin, ferritin, FGF19 & FGF21, 2 macroglobulin, 
hyaluronic acid, PIIINP, TIMP-1. 
6.1.1.12. 
Inflammatory Markers 
The following parameters will be collected after fasting (nothing to eat or drink except water) for a 
minimum of 10 hours: fibrinogen, haptoglobin, TNF-α, IL-6, PAI-1   
6.1.1.13. 
Other Parameters 
Additional tubes of serum will be collected for the purpose of research about pediatric NASH and 
biomarker. 
6.1.2. 
Pharmacokinetics Evaluation 
6.1.2.1. 
Description of Pharmacokinetic Evaluation Parameters  
Pre-dose PK sample will be collected prior to first dose administration on Day 1 (Visit 1). 
Pharmacokinetic samples will be collected on Day 29 (± 2 days) at T0 (prior to morning dose, 0.5 (±2 
minutes), 1 (±2 minutes), 1.5 (±2 minutes), 2 (±5 minutes), 4 (±5 minutes), 6 (±10 minutes), 8 (±10 
minutes) and 24 hours (±10 minutes) and on Day 85 (± 2 days) approximately 24 hours (±10 minutes) 
after the last study drug administration to determine PK parameters for assessment of elafibranor and its 
active metabolite GFT1007, at steady state.  
Details regarding collection, processing, storage and shipment will be described in the Laboratory Manual.  
6.1.2.2. 
Pharmacokinetic Analysis 
The PK analysis will be conducted at Eurofins ADME BIOANALYSES (75A Avenue de Pascalet 30310 
Vergèze FRANCE) in compliance with the Standard Operating Procedures in use at Eurofins ADME 
BIOANALYSES. 
Elafibranor and GFT1007 will be assayed by measuring concentrations according to an analytical method 
previously developed and validated by Eurofins ADME BIOANALYSES. 
6.1.2.3. 
Pharmacokinetic Blood Sampling Timepoints 
Blood sampling will be performed for elafibranor and main active metabolite GFT1007 plasma 
concentration measurements at the following timepoints: 
• 
Visit 1/Day 1: Pre dose;  
• 
Visit 3/Day 29 (± 2 days): T0 (prior to morning dose under fasting conditions), 0.5 (±2 minutes), 1 
(±2 minutes), 1.5 (±2 minutes), 2 (±5 minutes), 4 (±5 minutes), 6 (±10 minutes), 8 (±10 
minutes); 
• 
Visit 4/Day 30: 24 hours (±10 minutes) post dose administered at V3 (and prior to next dose of 
study drug); 


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• 
Visit 6/Day 85 (± 2 days): PK sample approximately 24 hours (±10 minutes) after last study drug 
administration. 
6.1.2.4. 
Pharmacokinetic Blood Handling Procedures 
Blood samples will be collected into 1mL lithium heparin tubes protected from light with foil and plasma will 
be separated in a refrigerated centrifuge (ca.4°c) at 1500 g for 15 minutes and a volume of 250µl will be 
dispensed in a polypropylene opaque tube for both aliquots 1 and 2. 
The plasma will be stored at -20°c ±5°C at the site facilities. 
Thereafter, the plasma will be transported in dry ice, first to the central laboratory where they will be 
stored at -20°C ±5°C until shipped to Eurofins ADME BIOANALYSE for analysis. 
6.2. 
Other Safety Assessments and On-going Safety Monitoring 
6.2.1. 
Physical Examination 
A physical examination will be performed at each visit. The physical examination will include an 
examination of general appearance, skin, eyes, ears, nose, throat, neck/thyroid, lungs, heart, upper/lower 
extremities, lymph nodes, abdomen, musculoskeletal system and basic neurological assessment. Additional 
systems will be evaluated as needed. Physical exam findings must be recorded in the source 
documentation and include the date and name of the individual conducting the examination. Physical 
examinations must be performed by an individual licensed to conduct standard physical examinations. 
6.2.2. 
Vital Signs 
Blood pressure [BP (mmHg)] and pulse rate [PR (BPM)] will be measured at each visit (with the exception 
of Visit 4) according to the “Recommendations for Blood Pressure Measurement in Humans and 
Experimental Animals” published in an AHA scientific statement.  
It is important that vital signs be taken before any invasive procedures (e.g., venipuncture).  Each 
measurement should be recorded in the source document and recorded in the electronic case report form 
(eCRF).  
Important Points for Clinical Blood Pressure Measurement: 
• 
The patient should be seated comfortably with the back supported and the upper arm bared 
without constrictive clothing. The legs should not be crossed.  It is recommended the same arm be 
used for the collection of blood pressure readings throughout the patient’s participation. 
• 
The arm should be supported at heart level, and the bladder of the cuff should encircle at least 
80% of the arm circumference. 
• 
When using a mercury sphygmomanometer, the mercury should be deflated at 2 to 3 mm/s, and 
the first and last audible sounds should be taken as systolic and diastolic pressure. The column 
should be read to the nearest 2 mmHg. 
• 
Neither the patient nor the observer should talk during the measurement. 
• 
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) will be measured after 5 minutes 
of rest in the seated position with a standard mercury sphygmomanometer or a validated 
sphygmomanometer. Validated manometer has to be the same for a given patient throughout the 
visits. 
 
 


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6.2.3. 
12-Lead ECG 
All investigative sites will perform ECG using a calibrated ECG machine. Site personnel must assess the 
quality of the ECG while the patient is still at the investigative site in the event that additional ECGs need to 
be performed (i.e., if artifact is present).  
Any potential clinical significance of ECG will be determined by the Investigator with relation to the 
patient’s medical history, physical examination and concomitant medication and recorded in the eCRF. 
For younger children, the parent/legal guardian may need to practice, prior to the study visit, lying still.  
Suggest use of a timer to help the child understand how long to hold still.  If possible, have the patient rest 
quietly for at least 10 minutes. Refer to Study Procedure Manual for additional details regarding data 
collection and transmission. 
6.2.4. 
Pediatric Quality of Life (PedsQL™)  
The child, adolescent and parent/legal guardian PedsQL™ (Version 4.0) Generic Core Scales will be used in 
this study. The scale validated for use in the pediatric populations; child version for 8-12 years of age and 
teen version for 13 to 18 years of age and a parent version for each respective age group. It is composed 
of 23 items comprising 4 dimensions. A copy of the scales and instructions for scoring will be provided to 
the site. The Sponsor has secured the required licensing for use of the scale in this study.  The PedsQL™ 
(Version 4.0) will be completed on paper by the patient and by a parent/legal guardian individually.   This 
information will then be entered on the eCRF page by study site staff.  The patient/ parent or legal 
guardian will complete the same version of the questionnaire throughout the study. 
6.3. 
Important Specific Biological Considerations and Patient Discontinuation 
Rules 
6.3.1. 
Creatine Phosphokinase 
If at any visit during the treatment periods, a patient experiences diffuse myalgia, muscle tenderness, and 
marked increase in muscle CPK values higher than 2 x ULN, the patient must be discontinued from study 
drug immediately and followed up as described in Section 5.4.1.1. 
If at any visit during the treatment periods, a patient experiences marked increase in muscle CPK values 
>2x ULN without symptoms or if associated with vigorous exercise, an additional visit and test should be 
done within approximately 48 to 72 hours. If during that visit CPK elevations persist, the patient must be 
discontinued from study treatment immediately and followed up as described in Section 5.4.1.1. 
6.3.2. 
Liver Function Monitoring 
• 
Increase in aminotransferase (AT) of <3 x baseline value: no additional action required, schedule 
next visit as per assessment schedule. 
• 
Liver function monitoring requirements for all patients with increased in AT > 3x baseline value: 
o 
Increase in AT of >3 x baseline value but less than 10 x ULN: retest after 48 to 72 hours. 
o 
AT remains >3 x baseline value and <5 x the baseline, or 10 x ULN: continue the drug 
with close serial monitoring (once a week). 
o 
AT increases >5 x baseline value will lead to permanent discontinuation of the patient 
from study drug and schedule EOT Visit (refer to Section 5.2.7). 
o 
An increase of AT >10 x ULN will lead to immediate permanent discontinuation of the 
patient from study drug, and scheduling of EOT visit (refer to Section 5.2.7). 
Patients will permanently discontinue from study drug (refer to Section 5.2.8 and 5.4.1.1) if at any visit 
during the treatment periods they exhibit any of the following: 


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• 
Increase in AT >3 x baseline value AND increase in total bilirubin >2 ULN; 
• 
Increase in AT >3 x baseline value AND increase in INR>1.5; or 
• 
Increase in AT >3 x baseline value AND fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, and/or eosinophilia (>5%). 
6.3.3. 
Renal Function Monitoring 
• 
Decrease in eGFR of 15ml/min/1.73m² or more compared to baseline value associated with 
cystatin C > ULN: retest of serum creatinine, cystatin C and eGFR within approximately 48 to 72 
hours. 
• 
If decrease in eGFR and increase in cystatin C persists, permanent discontinuation from study drug  
will be considered and discussed with the Medical Monitor(see Section 5.2.8 and 5.4.1.1). 
• 
In case of an increase of creatinine or Cystatin C >20% from baseline: retest every two weeks 
until two consecutive results are <20% from baseline. A retest visit should be considered and 
discussed with the Medical Monitor if no protocol required visit is planned within the next two 
weeks. 
• 
Decrease of eGFR at a value less than 60 ml/min/1.73m²: permanently discontinue patient from 
study drug and schedule EOT Visit (refer to Section 5.2.7). 
6.3.4. 
Additional Monitoring 
• 
Decrease in haemoglobin greater than 2mg/dL from baseline: retest within 48 to 72 hours. 
• 
If haemoglobin decline is persistent or worsening and unexplained by other causes, permanently 
discontinue patient from study drug and schedule EOT Visit (refer to Section 5.2.7). 
6.4. 
Guidance for Investigators 
6.4.1. 
Summary of Safety Data 
6.4.1.1. 
 Non-Serious Adverse Drug Reactions 
For all completed studies to date with repeated administration of elafibranor (at least 14 days) from 80 
mg/day up to 300 mg/day (MTD), numbers and percentages of frequency of adverse drug reactions (ADR, 
adverse events reported by investigators as possibly related or related to study drug) have been calculated 
compared to the total number of subjects treated with elafibranor and the total number of subjects treated 
with placebo.  
Only non-serious adverse reactions with frequency > 1% are considered for reporting. Given the small 
numbers for each adverse reaction identified with a frequency >1%, an imbalance in frequency of 
occurrence compared to placebo is reported when the relative delta is ≥ 30%. 
The common non-serious adverse drug reactions reported with repeated doses of at least 80 mg 
elafibranor per day are thus summarized in Table 1. 
Among the non-serious adverse reactions, the most frequent were gastro-intestinal disorders and general 
disorders. The first ones in term of frequency consisted mostly of diarrhea and vomiting. For general 
disorders, the main symptoms were fatigue / asthenia.  
Other non-serious adverse reactions reported in more than 1% of patients concerned changes in biological 
parameters such as liver enzymes increase (mainly transaminases), CPK elevation, or increase of creatinine 
(reported by investigators as renal failure and/or impairment due to the calculation of creatinine clearance 


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by Modification of Diet in Renal Disease (MDRD) based on creatinine). Myalgia, decrease of appetite, and 
rash were also reported in more than 1% of patients but remain limited.  
Table 1 
Overview of the Common Non-Serious Adverse Reactions (>1% of Patients Treated 
with Elafibranor) by System Organ Class Reported in Completed Elafibranor Clinical 
Studies with Repeated Administration of Elafibranor (at Least 14 Days) From 80 
mg/Day up to 300 mg/Day (MTD) 
System Organ Class 
Adverse Reaction 
Severity 
Number of cases 
(Frequency %) 
Gastrointestinal disorders  
Diarrhea 
Mild to moderate 
17 (2.9%) 
Vomiting 
Mild to moderate 
9 (1.5%) 
General disorders and 
administration site conditions  
Fatigue / Asthenia 
Mild to moderate 
17 (2.9%) 
Investigations  
Hepatic enzymes increased 
(mainly transaminases) 
Mild to severe 
11 (1.9%) 
Blood creatine phosphokinase 
increased 
Mild to moderate 
6 (1.0%) 
Musculoskeletal and connective 
tissue disorders  
Myalgia 
Mild to severe 
9 (1.5%) 
Metabolism & nutrition disorders  
Decreased appetite 
Mild to severe 
9 (1.5%) 
Skin and subcutaneous tissue 
disorders 
Rash 
Mild to moderate 
8 (1.4%) 
Renal and urinary disorders 
Renal failure/impairment 
Mild to moderate 
7 (1.2%) 
6.4.1.2. 
Serious Adverse Drug Reactions 
The 9 serious adverse reactions (serious adverse events reported by investigators as possibly related or 
related to study drug) reported in 6 patients treated with elafibranor in completed clinical studies are 
summarized in Table 2. 
Table 2 
Overview of Suspected Unexpected Serious Adverse Reactions (SUSARs) by System 
Organ Class Reported in Completed Elafibranor Clinical Studies 
System Organ Class 
Adverse Reaction 
Severity 
Number of cases 
(Frequency %) 
Cardiac disorders 
Atrial fibrillation 
Moderate 
1 (0.12%) 
Gastrointestinal disorders 
Acute pancreatitis 
Mild 
1 (0.12%) 
 
Pancreatitis* 
Moderate 
1 (0.12%) 
Hepatobiliary disorders 
Acute cholecystitis* 
Moderate 
1 (0.12%) 
Nervous system disorders 
Ataxia** 
Moderate 
1 (0.12%) 
 
Tremor** 
Moderate 
1 (0.12%) 
 
Involuntary muscle 
contractions** 
Moderate 
1 (0.12%) 
 
Parkinson’s disease 
Moderate 
1 (0.12%) 
Pregnancy, puerperium and 
perinatal conditions 
Spontaneous abortion 
Mild 
1 (0.12%) 
*all in one patient 
**all in one patient 
All 9 serious adverse reactions were reported as suspected unexpected serious adverse reactions 
(SUSARs). However, for atrial fibrillation, acute cholecystitis and pancreatitis, and Parkinson’s disease, after 
later investigations, given the medical history of the patients or the time of occurrence of the event, these 
events were considered as having no reasonable causal relationship to elafibranor by the Sponsor.  


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For the other cases of possibly related serious adverse events (SAEs), the causality assessment to 
elafibranor was considered as having a reasonable possibility both by the investigator and by the Sponsor 
as there was no way to rule out a relationship to study drug. 
6.4.2. 
Potential Risks 
In toxicology studies, the only consistent safety concern was the expected PPAR-associated 
hepatomegaly, hepatocellular hypertrophy, and liver carcinoma in rodent species (mice and rats). 
However, it is well known that, compared to nonhuman primates and humans, rodents are highly sensitive 
to PPAR agonist induced peroxisome proliferation and associated liver side effects. Thus, available 
information on this class of drug, which includes marketed fibrates, together with the lack of any liver side 
effects in monkeys treated with high doses of elafibranor for 1 year, support the nonrelevance to humans 
[Cattley et al., 1998]. Elafibranor did not show any of the known PPAR-related concerns such as excess in 
weight gain, hemodilution, edema, cardiomegaly, adiponectin induction, or urinary bladder carcinoma. 
Regarding specific monitoring, although no signal for increase in CPK has been observed in clinical trials, 
given the known effects of PPAR agonists on the increase of CPK enzyme, this parameter is monitored in 
clinical trials. For this reason, it is recommended that investigators review these lab results in the course of 
clinical trials.  
Other known effects of PPAR agonists include an increase of creatinine, which was observed in Phase 2 
trials with elafibranor, and corresponded to an increase of 5-10% that was reversible at end of treatment. 
This should also be monitored in clinical trials. 
Liver enzymes are also monitored in clinical trials, with specific attention paid to drug-induced liver injury. 
Based on the findings of non-clinical reproductive and developmental toxicity studies performed to date, 
and in the absence of human pregnancy data, elafibranor may be classed in the “Possible human 
teratogenicity/fetotoxicity in early pregnancy” risk category according to the Clinical Trial Facilitation Group 
(CTFG) document “Recommendations related to contraception and pregnancy testing in clinical trials” 
(September 2014).  
As such, all clinical trials with elafibranor including women of childbearing potential require a negative 
pregnancy test before randomization, with highly effective contraceptive measures throughout the study. It 
is recommended to maintain the contraception up to 1 month after end of treatment. Pregnancy tests 
should be repeated as stated within the Study General Assessment schedule.  
6.4.3. 
Risk Benefit Analysis  
Clinical data have confirmed the potential beneficial effect of elafibranor in adult subjects with NASH.  
Phase 2 studies in subjects with cardiometabolic disorders and NASH have demonstrated consistent 
reductions in ALP compared to placebo. The reduction in ALP was associated with relevant reductions in 
markers of liver injury such as GGT and ALT and in inflammatory markers. These data are encouraging to 
consider elafibranor as a potential drug candidate to treat PBC. 
 In addition, the Phase 2b trial in NASH patients demonstrated the efficacy of elafibranor at the therapeutic 
dose of 120 mg on a clinically meaningful primary endpoint, resolution of histological NASH without 
worsening of fibrosis, in patients with active disease (NAS ≥4). While the trial was short and not designed 
for antifibrotic endpoints, it nonetheless showed that elafibranor, at 120 mg daily, improved fibrosis 
indirectly through the resolution of NASH. Importantly, elafibranor 120 mg concomitantly improved the 
cardiometabolic risk profile of the patients by decreasing plasma triglycerides, total and LDL-cholesterol, 
increasing HDL-C, and improving inflammation, insulin resistance, and glucose homeostasis. Together, 
these results position elafibranor as a drug candidate to treat NASH with the objective to block fibrosis 
evolution and ultimately avoid long term liver outcomes while reducing cardiovascular risk.  
Moreover, these studies have highlighted the good safety profile of elafibranor and no major safety 
concerns have been raised. 


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Based on the cumulative experience gathered to date, gastrointestinal disorders and asthenia / fatigue are 
considered common non-serious adverse reactions reasonably associated with elafibranor. Most of them 
are of mild to moderate intensity. Laboratory increases in serum creatinine or CPK should be monitored 
throughout the clinical trials as this has been observed in Phase 2 studies to date and is a known PPARα 
agonist effect. Elevation of transaminases should also be monitored as well as drug-induced liver injury. In 
the absence of human pregnancy data, highly effective contraception should be maintained for women of 
childbearing potential participating in clinical trials with elafibranor treatment, up to 1 month after end of 
study treatment. 
In conclusion, the safety data and the current knowledge on elafibranor confirm the favorable balance 
between anticipated efficacy/benefits and risks.  
7. 
TREATMENTS 
7.1. 
Description of Study Drug  
Elafibranor (propanoic acid, 2-[2,6-dimethyl-4-[3-[4-(methylthio)phenyl]-3-oxo-1(E)-propenyl] phenoxy]-2-
methylpropanoic acid) will be supplied as 80 mg or 120 mg white to off-white round coated tablets (of 
different size) with no printed inscription. The tablet contains elafibranor and inactive ingredients 
(microcrystalline cellulose, povidone, croscarmellose, anhydrous colloidal silica, magnesium stearate, 
opadry II HP 85F18422). 
The safety of elafibranor is supported by non-clinical toxicity data (adult and juvenile toxicity studies) for 
the youngest/lightest patients at the two dosage strengths for the expected duration of treatment.  
The excipients used in the manufacture of elafibranor 80 mg and 120 mg coated tablets have been 
commonly used in drug oral forms for decades both in adult and pediatric formulations. All of them are 
compliant with the European and US Pharmacopeia (including all components of the coating) (refer to 
Table 3). 
Elafibranor tablets formulation does not contain any excipient with known adverse effects such as 
preservatives, coloring agents, sugars, and sweeteners. 
Table 3 
Formulation of Elafibranor 120 mg Coated Tablet and Elafibranor 80 mg Coated 
Tablet 
Excipient 
% w/w 
Elafibranor 120 mg 
Tablet 
Elafibranor   80 
mg Tablet 
mg/tablet 
mg/tablet 
Core tablet 
 
 
 
Elafibranor 
38.217 
120.0 
80.0 
Microcrystalline cellulose  
45.669 
143.4 
95.6 
Povidone  
4.777 
15.0 
10.0 
Croscarmellose  
5.732 
18.0 
12.0 
Anhydrous colloidal silica  
0.191 
0.6 
0.4 
Magnesium stearate 
0.955 
3.0 
2.0 
Coating 
 
 
 
Opadry II HP 85F18422® 
4.459 
14.0 
9.3 
Purified Water 
- 
- 
- 
Total fill weight (mg) 
100.0 
314.0 
209.3 
Dosage strength 
- 
120.0 
80.0 
For additional information see Investigator’s Brochure. 


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7.2. 
Packaging and Labeling 
7.2.1. 
Packaging  
The primary packaging is composed of opaque polyamide/aluminum/PVC complex and aluminum foil 
blisters. This has been shown to be a suitable primary packaging for tablets. 
For elafibranor 120 mg, blisters containing 8 tablets each, will be packed in child proof wallets. 
• 
Each child proof wallet will contain 1 blister.  
• 
Five wallets will be packaged inside a carton. 
For elafibranor 80 mg blisters containing 7 tablets each, will be packed in child proof wallets. 
• 
Each child proof wallet will contain 1 blister.  
• 
Five wallets will be packaged inside a carton. 
7.2.2. 
Labeling 
All labels for study drugs meet all applicable requirements of the US Food and Drug Administration (FDA) 
and the EU annex 13 of Good Manufacturing Practices: Manufacture of Investigational Medicinal Products 
(July 2003) and /or other local regulations, as applicable. 
Distribution of study drug will be performed according to the Good Distribution Practices. 
Product cartons will be labelled with the protocol number, Sponsor’s name and address, description of 
contents, storage conditions, expiry date, dosage instructions, and any other applicable items required by 
national and regional guidelines/regulations.  
The label will contain the statements “For clinical trial use only” or other similar/appropriate statements as 
well as the following instructions “Please return empty packaging and unused products to your doctor at 
your next visit.”  
7.3. 
Storage Conditions  
Elafibranor should be stored between +15°C and +25°C (59°F and 77°F). Storage conditions are specified 
on the label. 
7.4. 
Dispensing and Administration of treatment  
Treatment (dose group) assignment will be provided via the central randomization procedure. The drug 
inventory is open label and will be distinctly labelled with respect to dose level. Study personnel will select 
the next available corresponding kit (1-month supply) in inventory at the appropriate dose level and will 
immediately record the assigned kit in the eCRF.  Patients will be informed to take one tablet per day of 
elafibranor 80 mg or 120 mg orally before breakfast with a glass of water each morning. 
7.5. 
Procedure for Blinding  
Not applicable 
7.6. 
Procedure for Unblinding  
Not applicable


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7.7. 
Study Drug Compliance 
From Visit 1 and at each subsequent visit while the patient is being treated with study drug up to the EOT 
visit, the patient will be instructed to bring back all used and unused cartons and wallets containing 
blisters. Compliance will be checked by the Investigator or their designee during those visits and recorded 
in the eCRF. 
If treatment is interrupted, whatever the cause, duration and reason for the interruption should be 
documented in the dosing diary and on the source documentation. 
7.8. 
Treatment Accountability, Retrieval and Destruction 
The Investigator or pharmacist will sign a receipt for each study treatment on the day of receipt. A drug 
accountability record should be maintained by the person responsible for dispensing the trial medication to 
the patient. 
All partially used or unused treatments will be inventoried by the monitor during and at the conclusion of 
the study. 
On Sponsor request, all treatments (used or unused) may be destroyed on site per acceptable site Drug 
Destruction Standard Operating Procedure or the Drug Distribution Centre will organize the retrieval of all 
treatments (used or unused) and will proceed to their destruction after the Sponsor provides written 
authorization. 
7.9. 
Other Medication 
7.9.1. 
Handling of Concomitant Medication 
In a general manner, patients should be discouraged from starting any new medication without consulting 
the investigator unless the new medication is required for emergency purpose. In the same way, any 
qualitative or quantitative change in concomitant therapy should be avoided when possible (Appendix III) 
In the event that it becomes necessary during the study, this should be recorded by the Investigator in the 
eCRF (including concomitant medications taken within 3 months prior to screening) and information should 
be communicated to the Medical Monitor. 
This includes drugs used on a chronic as well as on an ‘as needed’ basis. 
7.9.2. 
Non-Permitted Medication  
The following medications are not allowed: 
• 
Thiazolidinediones (glitazones [pioglitazone & rosiglitazone]): From 3 months (12 weeks) prior to 
Screening Visit 1 (SV1) up to End of Study (Visit 7); 
• 
Fibrates: From 2 months (8 weeks) prior to Screening Visit 1 up to End of Study (Visit 7); 
• 
Indomethacin: From Randomization (V1/Day 1) to End of Treatment (V6). 
Chronic use of the following medication is not permitted):  
• 
Methotrexate, tamoxifen, chronic systemic glucocorticoid, tetracycline, valproic acid, salicylates: 
• 
From 12 months prior to screening (Screening Visit 1) up to Randomization (Visit 1): chronic use 
defined as treatment longer than 3 consecutive months. 
If it is identified that these non-permitted drugs have been administered to a patient within the excluded 
timeframes, the site will discuss the continuation of the patient with the Medical Monitors of the study.


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7.9.3. 
Permitted Medication Under Conditions 
The following medications are permitted under the condition of no qualitative change and stable dose for 3 
months prior to Screening Visit 1 up to Randomization (Visit 1/Day 1): 
• 
Statins, ezetimibe, and other nonfibrate lipid lowering medications; 
• 
Anti-diabetic as insulin, metformin, Gliptins, Sulfonylureas, glucagon-like peptide 1 (GLP-1) agonist, 
sodium/glucose cotransporter 2 (SGLT2) inhibitor; 
• 
Medication to treat NAFLD/NASH such as Vitamin E, ursodeoxycholic acid, PUFAs. 
During the study (from V1 to V7), qualitative change and dose change should be avoided as much as 
possible.  All qualitative and dose changes must be captured in the source and eCRF. 
Chronic use (defined as treatment longer than 2 consecutive weeks) of the following medication should be 
avoided if possible, from V1 to V7: 
• 
Methotrexate, tamoxifen, chronic systemic glucocorticoid, tetracycline, valproic acid, salicylates.  
8. 
ADVERSE EVENT / SERIOUS ADVERSE EVENT REPORTING 
8.1. 
Definitions 
8.1.1. 
Adverse Event (AE) 
Any untoward medical occurrence in a patient or clinical investigation patient administered a 
pharmaceutical (investigational) product and which does not necessarily have to have a causal relationship 
with this treatment will be considered as an AE. The term AE is synonymous with the term “adverse 
experience” as used by the Food and Drug Administration (FDA). 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding or 
physiological observation, for example), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not considered related to the medicinal product. 
Examples of AE include (but are not limited to): abnormal test findings; clinically significant symptoms and 
signs; changes in physical examination findings; hypersensitivity; progression/worsening of pre-existing 
condition or underlying disease; recurrence of a pre-existing condition; lack of effect, complication, and 
termination of pregnancy. 
Additionally, they may include the signs or symptoms resulting from: drug overdose, drug withdrawal, drug 
abuse, drug misuse, drug interactions, drug dependency, extravasation, exposure in utero. 
The criteria for determining whether an abnormal objective test finding should be reported as an AE are as 
follows: 
• 
Test result is associated with accompanying symptoms; 
• 
Test result requires additional diagnostic testing or medical/surgical intervention; 
• 
Test result leads to a change in trial dosing or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy; 
• 
Test result is considered to be an AE by the Investigator or Sponsor. 
Repeating an abnormal test, in the absence of any of the above conditions, does not constitute an AE. Any 
abnormal test result that is determined to be an error does not require reporting as an AE. 


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An AE does not include the following: 
• 
Medical or surgical procedures performed; the condition that leads to the procedure may be an AE 
if applicable; 
• 
Pre-existing disease, condition or laboratory abnormalities present or detected before the 
Screening Visit that do not worsen; 
• 
Overdose without clinical sequelae; 
• 
Any medical condition or clinically significant laboratory abnormality with an onset before the 
consent form is signed. Such a medical condition is pre-existing and should be documented on the 
medical history of the eCRF; 
• 
Uncomplicated pregnancy; 
• 
An induced elective abortion to terminate a pregnancy without medical reason. 
The questions concerning whether the condition existed before the start of the active phase of the study 
and whether it has increased in severity and/or frequency will be used to determine whether an event is a 
treatment-emergent AE. An AE is considered to be treatment emergent if (1) it is not present when the 
active phase of the study begins and is not a chronic condition that is part of the patient’s medical history, 
or (2) it is present at the start of the active phase of the study or as part of the patient’s medical history, 
but the severity or frequency increases during the active phase. The active phase of the study begins at 
the time of the first dose of the study drug. The active phase of the study ends at the last study visit. 
 
8.1.2. 
Serious Adverse Events (SAE) 
A SAE is any untoward medical occurrence that at any dose: 
• 
Results in death; 
• 
Is life-threatening (see Section 8.1.2.1); 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization (see Section 8.1.2.2); 
• 
Results in persistent or significant disability/incapacity (see Section 8.1.2.3); 
• 
Is a congenital anomaly/birth defect (including fetal malformations associated with spontaneous 
abortions or elective abortions); or 
• 
Is another medically important condition (see Section 8.1.2.4). 
In addition, any illnesses reported before starting active treatment that have worsened after ICF signed or 
AE meeting the criteria of seriousness (as defined above) must be reported as an SAE. 
8.1.2.1. 
Life-Threatening Adverse Events 
A life-threatening AE in the definition of "serious" refers to an event in which the patient was at risk of 
death at the time of the event; it does not refer to an event which hypothetically might have caused death 
if it were more severe. 
8.1.2.2. 
In-Patient or Prolonged Hospitalization  
An inpatient hospitalization or prolongation of a hospitalization means that the patient stays overnight in 
the hospital. Visits to the emergency room will not be considered hospital admission. Pre-planned hospital 
stays or hospital stays for nonmedical social reasons will not be considered as hospitalization, for example: 
• 
Hospitalization or prolongation of hospitalization is needed for a procedure required by the 
protocol. 


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• 
Hospitalization or prolongation of hospitalization is part of a routine procedure followed by the 
study center (e.g., stent removal after surgery). This should be recorded in the study file. 
• 
Hospitalization for survey visits or annual physicals fall in the same category. 
• 
Hospitalization planned before the start of the study for a pre-existing condition that has not 
worsened does not constitute an SAE (e.g., elective hospitalization for a total knee replacement 
due to a pre-existing condition of osteoarthritis of the knee that has not worsened during the 
study). 
8.1.2.3. 
Significant or Incapacitating Disability 
Only a persistent or significant or incapacitating disability is intended. This item refers to a substantial 
disruption of a person’s ability to conduct normal life functions. Thus, disability is not intended to include 
experiences of relatively minor medical significance such as headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma. 
8.1.2.4. 
Medically Important Condition 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is appropriate 
in other situations, such as important medical events that may not be immediately life-threatening or result 
in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the 
other outcomes listed in the definition above. These should usually be considered serious. 
Examples of such events are: 
• 
Intensive treatment in an emergency room or at home for allergic bronchospasm. 
• 
Blood dyscrasias or convulsions that do not result in hospitalization. 
• 
Development of drug dependency or drug abuse. 
8.1.3. 
Clarification on Serious Adverse Events 
• 
Death is an outcome of an AE, not an AE. 
• 
An SAE may occur even if the patient was not being treated with the investigational medicinal 
product at the occurrence of the event. 
• 
Life-threatening means that patient is at immediate risk of death. This does not include an event 
that might have led to death if it had occurred with greater severity. 
• 
Complications that occur during hospitalizations are AEs. If a complication prolongs the 
hospitalization, it is a SAE. 
• 
Patient hospitalization means that the patient stays overnight in the hospital. Pre-planned hospital 
stays or hospital stays for nonmedical social reasons will not be considered as hospitalization. 
• 
A procedure for protocol/disease-related investigations should not be reported as SAE. 
Hospitalization or prolonged hospitalization for a complication of such procedures should be 
reported as SAE. 
8.1.4. 
Adverse Drug Reaction 
An adverse drug reaction (ADR) is defined as a response to a medicinal product which is noxious and 
unintended and that is considered causally related to an investigational medicinal product. A serious 
adverse drug reaction (SADR) is an ADR which meets the seriousness criteria. 
8.1.5. 
Unexpected Adverse Event 
Expectedness is assessed by the Sponsor. An unexpected AE is defined as an event that has a nature of 
severity or specificity that is not consistent with the applicable Investigator Brochure or that is 


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symptomatically and pathophysiologically related to a known toxicity but differs because of a greater 
severity or specificity. 
“Unexpected” refers to an ADR that has not been previously observed and reported rather than an event 
that has not been anticipated based on the properties of the drug. 
8.2. 
Assessments 
The Investigator will establish whether or not any AEs have occurred at each visit from the date of consent 
through the EOS visit (or 30 days after the last drug intake whichever is later). The patient will be 
questioned in a general manner to determine specific symptoms without offering the patient any 
suggestion. 
8.2.1. 
Intensity Assessment 
The intensity of the AE will be graded as follows: 
• 
Mild: Awareness of signs or symptoms, but easily tolerated and are of minor irritant type causing 
no loss of time from normal activities. Symptoms do not require therapy or a medical evaluation; 
signs and symptoms are transient. 
• 
Moderate: Events introduce a low level of inconvenience or concern to the participant and may 
interfere with daily activities but are usually improved by simple therapeutic measures; moderate 
experiences may cause some interference with functioning. 
• 
Severe: Events interrupt the participant’s normal daily activities and generally require systemic 
drug therapy or other treatment; they are usually incapacitating. 
8.2.2. 
Relation to the Study Treatment 
The Investigator will make a clinical and scientific judgment regarding whether or not the AE was related 
to study treatment. The Investigator will evaluate any changes in laboratory values and make a 
determination as to whether or not the change is clinically important, and whether or not the changes 
were related to study drug. However, even if the Investigator feels there is no relationship to the study 
drug, the AE or clinically significant laboratory abnormality must be recorded in the eCRF. 
The Investigator will record the relation to the study treatment according to the following causality terms: 
• 
Related: the AE follows a reasonable temporal sequence from the time of drug administration, 
and it cannot be explained by the patient's clinical state or the study procedures/conditions. The 
AE abates upon discontinuation of the study drug and reappears when the study drug is 
introduced. 
• 
Possibly related: the AE follows a reasonable temporal sequence from the time of drug 
administration but could have been produced by the patient's clinical state or the study 
procedures/conditions. 
• 
Unlikely related: the temporal association between the AE and the study drug is such that the 
study drug is not likely to have any reasonable association with the AE. The relationship is not 
likely because of other plausible explanations. 
• 
Not related: the AE must definitely be caused by the patient's clinical state or the study 
procedure/conditions. A reasonable explanation must be given, e.g., no study drug taken, 
preplanned elective medical intervention, or incompatible temporal relationship. 
• 
Not assessable: the report suggesting an adverse reaction cannot be judged because information 
is insufficient or contradictory and data cannot be supplemented or verified. 
 
8.2.3. 
Action Taken and Outcome 


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The Investigator will record the action taken with drug and outcome of the event for each AE according to 
the following:Action taken with investigational drug 
• 
Drug permanently withdrawn – in case a patient is permanently withdrawn from the study drug 
• 
Drug temporarily withdrawn – in case the study drug is temporarily withdrawn 
• 
Dose not changed – in case no action is taken regarding the study drug 
• 
Unknown 
• 
Not applicable – an AE started before initiation of treatment with study drug, the treatment had 
been completed prior to reaction/event, or the patient has died. 
Outcome 
• 
Recovered/resolved 
• 
Recovering/resolving 
• 
Not recovered/not resolved 
• 
Recovered/resolved with sequelae 
• 
Fatal 
• 
Unknown 
Note: In case of irreversible congenital anomalies the choice not recovered/not resolved should be used. 
“Fatal” should be used when death is possibly related to the reaction/event. 
8.3. 
Reporting 
8.3.1. 
Reporting an Adverse Event 
All AEs regardless of seriousness or relationship to study drug, including those occurring during the 
Screening Period, are to be recorded on the corresponding page(s) of the eCRF and in the patient’s 
medical record from the ICF signature until the EOS visit (or 30 days after last drug intake, whichever is 
later). Whenever possible, symptoms should be grouped as a single syndrome or diagnosis. The 
Investigator should specify the date of onset, maximal intensity, action taken with respect to study drug, 
corrective therapy given, outcome, and his/her opinion as to whether there is a reasonable possibility that 
the AE was caused by the study drug. 
Adverse event reporting begins from signature of the patient ICF at the first Screening Visit and ends at 
the EOS visit (or 30 days after last drug intake, whichever is later). 
8.3.2. 
Reporting a Serious Adverse Event  
Serious AE reporting begins from signature of the patient ICF and ends at the EOS visit (or 30 days after 
last drug intake, whichever is later). Any SAE that is brought to the attention of the Investigator at any 
time after the reporting period and which is considered by him/her to be caused by the study drug within a 
reasonable possibility, should be reported. 
Investigators must notify, by fax or e-mail, the Sponsor designated representative SGS Life Sciences 
Services Medical Affairs of all SAEs IMMEDIATELY (within 24 hours of the Investigator becoming 
aware of the event).


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ANY SERIOUS ADVERSE EVENTS, WHETHER OR NOT RELATED TO THE STUDY DRUG, MUST BE 
REPORTED IMMEDIATELY (WITHIN 24 HOURS) TO SGS Life Science Services MEDICAL AFFAIRS 
AT THE FOLLOWING FAX NUMBERS: 
FAX numbers: +32 (0)15 29 93 94 or 1-800-746-6618 
Contact Person: SGS Life Science Services Medical Affairs Department 
E-mail: be.life.saefax-ma@sgs.com 
 
All SAEs independent of the circumstances or suspected cause must be reported in ENGLISH on a SAE 
Form. The SAE Form should include a clearly written narrative describing signs, symptoms, and treatment 
of the event, diagnostic procedures, as well as any relevant laboratory data and any sequelae, in order to 
allow a complete medical assessment of the case and independent determination of the possible causality. 
The Investigator is also required to submit follow-up SAE reports to SGS Life Science Services Medical 
Affairs within 24 hours of becoming aware of additional information such as diagnosis, outcome, causality 
assessment, results of specific investigations, and any new significant information that has not been 
previously reported. 
It is critical that the information provided on the initial or follow-up SAE Form matches the information 
recorded in the source documents and the eCRF for the same event. 
Copies of additional laboratory tests, consultation reports, postmortem reports, hospital case reports, 
autopsy reports, and other documents relevant to the reported SAE should be sent when requested and 
applicable. All provided reports must be anonymized. 
Follow-up reports relative to the patient’s subsequent course must be submitted to SGS Life Science 
Services Medical Affairs until the event has subsided or, in case of permanent impairment, until the 
condition stabilizes. 
The Sponsor or its designated representative will report all the relevant safety information to the 
concerned Competent Authorities and to the concerned IRB/IEC according to the country-specific 
requirements. 
Investigator must fulfill his/her regulatory obligations to the Regulatory Authorities and/or to the Ethics 
Committee in accordance with local regulations. 
Depending on local regulations in different regions and countries, the Sponsor or designated clinical 
research organization (CRO) may be required to expedite report to the Regulatory Authorities for: 
• 
SAEs (including events related to study procedures) 
• 
SADRs 
• 
Suspected unexpected serious adverse reactions (SUSARs) 
Each SAE report received from the Investigators will be evaluated by the designated CRO for 
pharmacovigilance who will assess the seriousness of the event. Each SAE report will be evaluated by the 
Sponsor and/or his designees who will assess the relationship to study procedure or study treatment and 
the expectedness of the event. Expectedness will be assessed using the reference safety information 
included in the Investigator Brochure. 
Any unexpected safety issue that changes the risk benefit analysis and is likely to have an impact on the 
patients who have participated in the trial will be reported by the Sponsor as soon as possible to the 
concerned Competent Authority(ies) together with proposed actions. 
 


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8.3.3. 
Follow-up 
The Investigator should take all appropriate measures to ensure the safety of the patients, notably he/she 
should follow up the outcome of any AE until the return to normal or until stabilization of the patient’s 
condition, even if this goes beyond the EOS visit. 
The patient must be followed up until clinical recovery is complete and laboratory results have returned to 
normal, or until progression has been stabilized. This may imply that follow-up will continue after the 
patient has left the study and that additional investigations may be requested by the Sponsor. This 
information should be documented in the patient’s medical records. 
8.4. 
Post Study Reporting Requirements 
Any SAEs and deaths that occur within 30 days of the last dose of the study drug, regardless of causality, 
should be reported. 
Any SAE that is brought to the attention of the Investigator at any time after the reporting period and 
which is considered by him/her to be caused by the study drug within a reasonable possibility, should be 
reported. 
8.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events 
Laboratory abnormalities are not necessarily recorded as AEs or SAEs. However, laboratory abnormalities 
that are considered clinically relevant by the Investigator must be recorded as an AE or SAE as applicable. 
8.6. 
Special Situation Reports 
Special situations reports include pregnancy reports, reports of medication error, abuse, misuse or 
overdose, and reports associated with product complaints. 
8.6.1. 
Pregnancy 
In case of pregnancy a communication will be sent by the Investigator to SGS Life Science Services Medical 
Affairs by faxing a completed pregnancy form within 24 hours of his/her knowledge of the pregnancy. 
Pregnancies of female partners of male patients exposed to study medication should also be reported to 
SGS Life Science Services Medical Affairs using the corresponding pregnancy form. 
Female patients must be instructed to discontinue the study drug immediately and inform the Investigator 
as soon as possible once they are aware of being pregnant or suspect that they are pregnant during the 
study or within 30 days of the last dose of the study drug. 
Female patients will be requested, as part of the general ICF, to provide informed consent to allow 
reasonable attempts to be made to obtain information on any possible medicinal product exposure to an 
embryo or fetus and to follow up on the outcome of the pregnancy. 
The Investigator will contact the patient at the expected time of delivery for follow-up. If the outcome of 
pregnancy meets the criteria for immediate classification of an SAE (e.g., spontaneous or therapeutic 
abortion, stillbirth, neonatal death, congenital anomaly, birth defect), the Investigator should follow the 
procedure for reporting SAEs as detailed in Section 8.3.2. 
The pregnancy itself is not considered an AE. 
8.6.2. 
Medication Error 
Medication error is defined as an unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the healthcare professional, patient, or consumer. All medication 


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errors will be documented in the eCRF and, in case of any potential risk to patient safety, would be 
reported as appropriate (see Section 8.6). 
8.6.3. 
Misuse 
This refers to situations where the medicinal product is intentionally and inappropriately used not in 
accordance with the protocol. In case of any potential risk to patient safety, would be reported as 
appropriate (see Section 8.6). 
8.6.4. 
Overdose 
This refers to the administration of a quantity of a medicinal product given per administration or 
cumulatively, which is above the highest dose of the protocol. Clinical judgment should always be applied. 
8.6.5. 
Abuse 
This corresponds to the persistent or sporadic, intentional excessive use of a medicinal product, which is 
accompanied by harmful physical or psychological effects. 
9. 
STATISTICAL METHODS AND DATA ANALYSIS 
9.1. 
Randomization and Treatment Assignment 
Number of Randomized Patients (planned): A total of 20 patients will be enrolled across the two cohorts.  
• 
Cohort 1: ≥12 to ≤17 years of age.  A total of approximately 12 patients will be randomized in this 
cohort.   
• 
Cohort 2: ≥8 to ≤11 years of age.  A total of approximately 8 patients will be randomized in this 
cohort.  Enrollment in this cohort will not start until 80% of the patients in cohort 1 have been 
evaluated through Visit 4 by the Data Safety Monitoring Board. 
Patients will be randomized 1:1 to receive either dose (80 or 120 mg). 
Considering that at least 4 patients ≥12 to ≤17 years of age and at least 2 patients ≥8 to ≤11 years of 
age with fibrosis stage 2 or 3 will be enrolled and to achieve balance between dosing groups according to 
the fibrosis severity, randomization will be stratified within each cohort based upon screening fibrosis 
severity stage (stratum 1:fibrosis stage 0 to 1 and stratum 2: fibrosis stage 2 to 3). 
The randomization procedure will be further described in the Study Procedure Manual. 
9.2. 
Endpoints 
9.2.1. 
Primary Endpoint 
Plasma concentrations of elafibranor and its active metabolite GFT1007.  
9.2.2. 
Secondary Endpoints 
9.2.2.1. 
Efficacy 
• 
Change from baseline in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) and other liver markers; 
• 
Change from baseline in serum lipid parameters; 
• 
Change from baseline in glucose homeostasis makers (Fasting plasma glucose, Homeostatic Model 
Assessment of Insulin Resistance [HOMA-IR] and fasting insulin); 


Cli ni c al Tri al G F T 5 0 5 E -2 1 8 -1  
Pr ot o c ol V 4 . 0 2 0  A pril 2 0 2 0  
 
G E N F I T  
 
P a g e  6 2  of 8 3  
 
•  
C h a n g e fr o m b as eli n e i n b o d y w ei g ht a n d B MI z-s c or e ; 
•  
C h a n g e fr o m b as eli n e i n w aist cir c u mf er e n c e ; 
•  
C h a n g e fr o m b as eli n e i n i nfl a m m at or y m ar k ers ;  
•  
C h a n g e fr o m b as eli n e i n p e di atri c q u ali ty of lif e ( P e ds Q L ™) s c or e.  
9. 2. 2. 2.  
S af et y  
•  
I n ci d e n c e a n d s e v erit y of tr e at m e nt e m er g e nt a d v ers e e v e nts ( T E A E s) a n d t h eir r el ati o ns hi p t o 
st u d y dr u g ;  
•  
I n ci d e n c e of cli ni c all y m e a ni n gf ul c h a n g es fr o m b a s eli n e i n s af et y l a b or at or y p ar a m et ers, p h ysi c al 
e x a mi n ati o n, E C G a n d vit al si g ns.  
9. 2. 3.  
E x pl or at or y E n d p oi nt  
 
 
9. 3.  S a m pl e Si z e  E sti m at e  
T h e pri m ar y o bj e cti v e of t hi s st u d y i s t o c h ar a ct eriz e i n di vi d u al P K p ar a m et ers i n c hil dr e n a n d a d ol e s c e nts 
8 t o 1 7 y e ars of a g e  (i n cl usi v e), b y c oll e cti n g ri c h P K s a m pl es t o s u p p ort n o n c o m p art m e nt al a n al ysis. I nt er-
s u bj e ct v ari a bilit y of P K p ar a m et ers i n a d ults w as l o w t o m o d er at e ( c o effi ci e nt of v ari ati o n [ C V] % r a n g e d 
fr o m 2 3. 3 % t o 6 8. 3 %). A ss u mi n g a si mil ar d e gr e e of v ari a bilit y i n p e di atri c p o p ul ati o n, a s a m pl e siz e of 2 0 
p ati e nts is s et t o t ar g et a 9 5 % CI [ c o nfi d e n c e i nt er v al] wit hin 6 0 % a n d 1 4 0 % of t h e g e o m etri c m e a n 
esti m at es of cl e ar a n c e a n d v ol u m e of distri b uti o n f or el afi br a n or wit h at l e ast 8 0 % p o w er ( W a n g  et al ., 
2 0 1 2 ). A d diti o n all y, 2 0 p ati e nts s h o ul d b e s uffi ci e nt t o e v al u at e t h e s af et y a n d t ol er a bili t y a n d e x pl or e t h e 
r e s p o nsi v e n ess ( effi c a c y) of o n c e d ail y or al d osi n g of 8 0 m g a n d 1 2 0 m g of el afi br a n or f or u p t o 1 2 w e e ks.  
9. 4.  A n al y si s S et s  
T hr e e p o p ul ati o ns will b e u s e d f or a n al ysis: s af et y, P K a n d i nt e nt -t o-tr e at. T h e d efi niti o n of t h es e 
p o p ul ati o ns ar e  as f oll o ws: 
•  
S af et y P o p ul ati o n: All p ati e nts w h o r e c ei v e d at l e ast o n e d os e of st u d y dr u g a n d h a v e at l e ast o n e 
p ost -b a s eli n e s af et y ass ess m e nt.  
•  
P h ar m a c o ki n eti c P o p ul ati o n: All p ati e nts w h o r e c ei v e d at l e ast o n e d os e of st u d y dr u g, d o n ot h a v e 
pr ot o c ol d e v i ati o ns or a d v ers e e v e nts w hi c h m a y si g nifi c a ntl y aff e ct P K, a n d h a v e at l e ast o n e 
p ost -d os e P K s a m pl e.  
•  
I nt e nt-t o-Tr e at (I T T) P o p ul ati o n:  All r a n d o mis e d p ati e nts w h o r e c ei v e d at l e ast o n e d os e of st u d y 
dr u g . 
P K a n d s af et y d at a will b e a n al ys e d  b a s e d o n t h e  s af et y p o p ul ati o n. Effi c a c y d at a will b e a n al ys e d  b as e d o n 
t h e I T T p o p ul ati o n. 
9. 5.  A n al y si s of P ri m ar y E n d p oi nt 
I n di vi d u al pl a s m a c o n c e ntr ati o ns f or el afi br a n or a n d it s a cti v e  m et a b olit e G F T 1 0 0 7, will b e s u m m ariz e d 
d es cri pti v el y (i. e., n u m b er of o bs er v ati o ns,  arit h m eti c m e a n, S D , C V %, m e di a n, mi ni m u m a n d m a xi m u m, 
g e o m etri c m e a n a n d C V % G e o m etri c M e a n b y pl a n n e d ti m e  p oi nts f or e a c h d os e gr o u p. I n di vi d u al pl a s m a 
c o n c e ntr ati o n -ti m e pr ofil es of el afi br a n or will b e pl ott e d o n b ot h li n e ar a n d s e mi-l o g arit h mi c s c al es. M e a n 
v al u es o v er ti m e b y d o s e pl ots will als o b e pr e s e nt e d gr a p hi c all y.  
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Pharmacokinetic parameters of elafibranor and GFT1007 will be estimated using NCA methods in Phoenix 
WinNonlin 8.0 or higher, using actual elapsed time from dosing. Plasma concentrations equal to or greater 
than the qualified lower limit of the assay (LOQ) will be used in the pharmacokinetic analysis. The following 
calculated PK parameters will include, but not limited to: 
• 
Maximum concentration (Cmax); 
• 
Time to maximum concentration (Tmax); 
• 
Area under the plasma concentration time curve over 24 hours (AUC[0-24]); 
• 
Trough concentrations in plasma (Ctrough). 
The analysis plan will be further detailed in the PK Statistical Analysis Plan (PK-SAP).   
9.6. 
Other Statistical Analysis 
9.6.1. 
Safety 
Safety evaluations will consist of adverse events (AEs), physical examinations, vital signs, ECGs, and 
laboratory measurements (hematology, coagulation parameters, biochemistry, and urinalysis). Full details 
will be specified in the SAP.  A general description of the planned analysis is as follows:  
• 
Laboratory parameters will be descriptively summarized (mean, SD, median, minimum, maximum) 
by dose group, for values at each visit and for changes from baseline at each subsequent visit. In 
addition, at each post baseline visit, parameter status (low, normal, high) will also be summarized 
as shift tables vs. baseline status.  
• 
Vital signs will be summarized similarly as for laboratory parameters but without shift tables. 
• 
Descriptive statistics and frequency tables will be prepared as appropriate for physical 
examinations, vital signs and ECG. 
• 
Adverse Events 
o 
AEs descriptions will be mapped to standard terms according to the Medical Dictionary for 
Regulatory Activity (MedDRA). 
o 
AEs that start prior to first study drug dose and that worsen after, and the AEs that start 
on or after first study drug dose will be considered a treatment emergent adverse event 
(TEAE).  
o 
The number of events, the number and proportion of patients reporting at least one event 
will be tabulated overall and by severity. Each patient will be counted only once according 
to the worst severity reported over the treatment period.  
o 
Separate tables will be constructed by dose group and overall for (a) all reported TEAEs, 
(b) protocol treatment related TEAEs, (c) serious TEAEs, and (d) TEAEs leading to protocol 
treatment discontinuation. 
o 
The non TEAEs will be listed separately and will not be included in the AE tabulations. 
• 
Concomitant medications will be mapped according to the World Health Organization (WHO) Drug 
Dictionary (WHODD) and will be presented in data listings.


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P a g e  6 4  of 8 3  
 
9. 6. 2.  
Effi c a c y  
•  
D es cri pti v e s u m m ari es will b e pr o vi d e d  b y d os e gr o u p  f or t h e effi c a c y e n d p oi nts (li v er m ar k ers, 
i nfl a m m at or y m ar k ers, li pi d s, bi o c h e mistr y p ar a m et ers a n d li v er f u n cti o n [e. g., A L T, A S T , C P K, 
G G T, A L P] , gl u c os e h o m e ost a sis p ar a m et ers  (f asti n g pl as m a gl u c os e, H O M A -I R a n d f asti n g 
i ns uli n), b o d y w ei g ht, B MI z-s c or e, w aist cir c u mf er e n c e a n d P e ds Q L ™).  V al u e at e a c h visit a n d 
c h a n g e fr o m b a s eli n e will b e s u m m ariz e d  b y d o s e gr o u p , a n d b y a g e g r o u p a n d o v er all. 
•  
D es cri pti v e st atisti cs f or c o nti n u o us v ari a bl es will b e n u m b er of p ati e nts, m e a n, S D, m e di a n, 
mi ni m u m a n d m a xi m u m a n d f or c at e g ori c al  v ari a bl es, fr e q u e n c y c o u nts a n d p er c e nt a g es  b y d os e 
gr o u p, a n d b y a g e gr o u p a n d o v er all .  
•  
If a p pr o pri at e, s hift t a bl es vs. b as eli n e st at us will b e pr o vi d e d b y d os e  gr o u p  a n d b y a g e gr o u p  a n d 
o v er all , t o d e s cri b e c h a n g e o v er ti m e d e p e n di n g o n r el e v a nt t hr es h ol ds.  
•  
Missi n g effi c a c y d at a will n ot b e i m p ut e d f or a n y a n al y s es.  T h e S A P will c o nt ai n f ull d et ails.  
 
 
 
 
 
1 0.  D A T A H A N D L I N G A N D R E C O R D K E E P I N G  
1 0. 1.  C R F a n d S o ur c e D o c u m e nt s  
A  c as e r e p ort f or m  (C R F ) i s r e q uir e d an d s h o ul d b e c o m pl et e d f or e a c h s cr e e n e d p ati e nt . T h e c o m pl et e d 
C R Fs ar e t h e s ol e pr o p ert y of t h e S p o ns or a n d s h o ul d n ot b e m a d e a v ail a bl e i n a n y f or m t o t hir d p arti es, 
e x c e pt f or a ut h oriz e d S p o n s or’ s r e pr e s e nt ati v es or a p pr o pri at e R e g ul at or y A ut h oriti es, wit h o ut writt e n 
p er missi o n fr o m t h e S p o ns or.  
T h e I n v esti g at or will e n s ur e t h at all d at a ar e e nt er e d pr o m ptl y, l e gi bl y, c o m pl et el y, a c c ur at el y a n d c o nf or m 
t o s o ur c e d o c u m e nts, i n a c c or d a n c e wit h s p e cifi c i nstr u cti o ns a c c o m p a n yi n g t h e C R Fs, d esi g n e d s p e cifi c all y 
f or t his st u d y. T h e C R F b ei n g us e d f or t hi s st u d y is a n el e ctr o ni c C R F t h at h as b e e n f ull y c ertifi e d a s b ei n g 
c o m pli a nt wit h t h e F D A c o d e of f e d er al r e g ul ati o ns ( C F R) at 2 1 C F R P art 1 1.  
All p ati e nt d at a g e n er a t e d d uri n g t h e st u d y will b e r e c or d e d i n t h e e C R F. P ati e nts will n ot b e i d e ntifi e d b y 
n a m e i n t h e e C R F or o n a n y st u d y d o c u m e nts t o b e c oll e ct e d b y t h e S p o ns or ( or d esi g n e e) b ut will b e 
i d e ntifi e d b y a p ati e nt n u m b er . 
T h e I n v esti g at o r will r e vi e w, a p pr o v e a n d d at e e a c h c o m pl et e d C R F  el e ctr o ni c all y ; t h e I n v esti g at or’s 
v ali d ati o n s er vi n g a s att est ati o n of t h e I n v esti g at or’s r es p o nsi bilit y f or e ns uri n g t h at all cli ni c al a n d 
l a b or at or y d at a e nt er e d o n t h e e C R F ar e c o m pl et e, a c c ur at e a n d a ut h e nti c.  
S h o ul d a c or r e cti o n b e m a d e, t h e c orr e ct e d i nf or m ati o n will b e r e c or d e d o n t h e e C R F b y t h e a ut h oriz e d 
p ers o n a n d e x pl ai n e d (if n e c ess ar y) . All c orr e ct e d d at a will b e tr a c k e d el e ctr o ni c all y t hr o u g h a n a u dit tr ail. 
It is t h e I n v esti g at or’ s o bli g ati o n t o e ns ur e d o c u m e nt ati o n of all r el e v a nt d at a i n t h e p ati e nt’s m e di c al fil e 
[ m e di c al hist or y, c o n c o mit a nt dis e as es, p ati e nt i d e ntifi c ati o n n u m b er, d at e of i nf or m e d c o ns e nt / ass e nt, 
visit d at es, a d mi nistr ati o n of st u d y m e di c ati o n, A d v ers e E v e nts (st art a n d st o p d at es) a n d all c o n c o mit a nt 
m e di c ati o ns (st art a n d st o p d at es)]. All d at a r e c or d e d i n t h e e C R F will b e d o c u m e nt e d b y s o ur c e d at a .
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10.2. Retention of Records 
The Investigator must maintain adequate and accurate records to enable the conduct of the study to be 
fully documented and the study data to be subsequently verified. 
The Investigator will be provided with a study file, which should be used to file the Investigator Brochure, 
protocol/amendments, drug accountability records, sample informed consent, staff curriculum vitae, 
correspondence with the IRB/IEC, Sponsor, and other study-related documents. 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator agrees to 
keep records, including the identity of all participating patients, all original signed ICFs, copies of all eCRFs, 
source documents, and detailed records of treatment disposition. 
The Investigator must retain the study documentation until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical 
development of the study drug. However, these documents should be retained for a longer period if 
required by the applicable regulatory requirements or by an agreement with the Sponsor. All hospital 
records will be archived according to local regulation. 
The Sponsor should be notified if the Investigator relocates, retires, or for any reason withdraws from the 
trial. The trial records must be transferred to an acceptable designee, such as another Investigator, 
another institution, or to the Sponsor. 
11. QUALITY CONTROL AND QUALITY ASSURANCE 
11.1. Quality Control & Monitoring Procedures 
It is the responsibility of the Investigator to ensure that the study is conducted in accordance with the 
protocol, Good Clinical Practice (ICH topic E6), applicable regulatory requirements, and the current 
Declaration of Helsinki (Appendix I) and that valid data are entered into the eCRFs. 
To achieve this objective, the Study Monitor’s duties are to aid the Investigator and, at the same time, the 
Sponsor in the maintenance of complete, legible, well-organized, and easily retrievable data. 
Before enrolling any patients in this study, the Study Monitor will review the protocol, the Investigator’s 
Brochure, the eCRFs and instructions for their completion and return, the procedure for obtaining informed 
consent, and the procedure for reporting AEs and SAEs with the Investigator. In addition, the Study 
Monitor will explain the Investigator’s reporting responsibilities and all applicable regulations concerning 
the clinical evaluation of the study drug. 
The Investigator will permit the representatives of Sponsor to monitor the study as frequently as the 
Sponsor deems is necessary to determine that data recording and protocol adherence are satisfactory. A 
Study Monitor from the CRO will be responsible for monitoring this clinical trial. To this end, the Study 
Monitor will visit the study site at suitable intervals and be in frequent contact through verbal and written 
communication. The eCRFs and related source documents, as well as drug accountability will be reviewed 
in detail by the monitor at each visit, in accordance with relevant Standard Operating Procedures and Good 
Clinical Practice (GCP; ICH topic E6) regulations. This includes results of tests performed as a requirement 
for participation in this study and any other medical records required to confirm information contained in 
the eCRFs, such as past medical history and secondary diagnoses. 
It is essential that the Study Monitor has access to all documents (related to the study and the individual 
participants) at any time these are requested. In turn, the Study Monitor will adhere to all requirements for 
patient confidentiality as outlined in the ICF. The Investigator and Investigator’s staff will be expected to 
cooperate with the Study Monitor, to be available during a portion of the Monitoring Visit to answer 
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All monitoring activities, including interim monitoring visit reports will be reported and archived in the Trial 
Master File. 
11.2. Quality Assurance 
For the purpose of ensuring compliance with the protocol, GCP and applicable regulatory requirements, the 
Investigator should permit auditing by the Sponsor and/or designee and inspection by applicable regulatory 
authorities. The Investigator agrees to allow the auditors/inspectors to have direct access to his/her study 
records for review, being understood that these personnel will adhere to all requirements for patient 
confidentiality, and as such will not disclose any personal identity or personal medical information. 
As soon as the Investigator is notified of a future inspection by the Authorities, he/she will inform the 
Sponsor and authorize the Sponsor to participate at this inspection. 
The confidentiality of the data verified, and the anonymity of the patients should be respected during these 
inspections. 
Clinical data manager from the Sponsor or sponsor’s representative will review the data for completeness 
and logical consistency. Additionally, the clinical data associates will use automated validation programs to 
help identify missing data, selected protocol violations, out of range data, and other data inconsistencies. 
Requests for data clarification or correction will be electronically provided to the investigative site for 
resolution. Clinical data associates will assure that corrections have been applied properly. 
12. ETHICS AND REGULATORY 
12.1. Ethical Principles 
This protocol complies with the principles laid down by the 18th World Medical Assembly (Helsinki, 1964) 
and all applicable amendments laid down by the World Medical Assemblies (Appendix I), and the GCP 
guideline. 
This trial also complies with applicable local regulatory requirements and laws of each country in which the 
study is performed, as well as any applicable guidelines. 
12.2. Institutional Review Board/Independent Ethics Committee (IRB/IEC) 
The GCP guidelines and the US CFR Title 21 Section 56 (21 CFR 56) require that approval must be 
obtained from an Institutional Review Board/ Independent Ethics Committee (IRB/IEC) prior to 
participation of human patients in research studies. Prior to the study onset, the protocol, ICF, assent, 
advertisements to be used for patient recruitment, and any other written information regarding this study 
to be provided to the patient or the patient’s legally acceptable representative must be approved by the 
IRB/IEC. The Sponsor will supply relevant material for the Investigator to submit to the IRB/IEC for the 
protocol’s review and approval. Verification of the IRB’s unconditional approval of the protocol and the 
written ICF statement will be transmitted to the Investigator. Documentation of the relevant IRB/IEC 
approval and of the IRB/IEC compliance with GCP guideline will be maintained by the site and will be 
available for review by the Sponsor or its designee or by the authorized members of regulatory agencies. 
The Applicant must supply the Sponsor with written documentation of the initial favorable opinion of the 
clinical research before the start of the trial. The study will not commence until favorable opinion has been 
obtained from the appropriate IRB/IEC. 
If any alterations, other than changes of administrative nature only, are made to the study protocol, a 
formal protocol amendment will be issued. The IRB/IEC will be informed by the Investigator of subsequent 
protocol amendments and of SUSARs. Approval for protocol amendments will be transmitted in writing to 
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The amendment will not be implemented until IRB/IEC approval, except in cases where immediate 
implementation is necessary to eliminate or prevent imminent hazard to the patients. A protocol change 
intended to eliminate an apparent immediate hazard must be documented in an amendment, reported to 
the IRC/IEC within 5 working days, and submitted to the appropriate regulatory agencies in the required 
time frame. 
If requested, the Investigator will permit audits by the IRB/IEC and regulatory inspections by providing 
direct access to source data/documents. 
The Investigator will provide the IRB/IEC with progress reports at appropriate intervals (not to exceed one 
year) and a Study Progress Report following the completion, termination, or discontinuation of the 
Investigator’s participation in the study. 
12.3. Competent Authority 
In the same way, when required by national regulation, approval from Competent Authorities (CA) should 
be granted before the beginning of the study. If applicable, Amendments will also be submitted to CA for 
approval. 
12.4. Informed Consent 
12.4.1. 
General Provisions 
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH GCP, US Code of 
Federal Regulations for Protection of Human Subjects (21 CFR 50.25[a,b], CFR 50.27, and CFR Part 56, 
Subpart A), HIPAA (if applicable), and local regulations. 
The Investigator (or designee) will prepare the Informed Consent Form, Assent and HIPAA authorization, 
as applicable, and provide the documents to the Sponsor or designee for approval prior to submission to 
the IRB/IEC. The consent/assent forms generated by the Investigator must be acceptable to the Sponsor 
and be approved by the IRB/IEC.  The written consent document will embody the elements of informed 
consent as described in the International Conference on Harmonization and will also comply with local 
regulations. The Investigator will send an IRB/IEC-approved copy of the Informed Consent Form and 
Assent Form to the Sponsor (or designee) for the study file. 
A properly executed, written, informed consent will be obtained from the patient’s legally authorized 
representative (parent(s) or legal guardian(s)) prior to entering the patient into the trial and conducting 
any Screening procedures. Information should be given in both oral and written form and study patients 
and their parent(s)/legally authorized representative(s) must be given ample opportunity to inquire about 
details of the study. In accordance with the requirements of the approving IRB/IEC, assent from the study 
patient will also be obtained. A copy of the signed consent form (and assent) will be given to the study 
patient or legal representative of the study patient and the original will be maintained with the study 
patient’s records. 
12.4.2. 
Written Parental/Legal Guardian Consent 
Adequate provisions must be made for soliciting the permission of the child’s (less than 18 years of age) 
parent(s) or legal guardian. If a patient turns 18 years of age during the course of the study, written 
informed consent will be obtained from the patient. 
The process for obtaining oral and/or written consent for children and adolescents is similar to that of 
obtaining consent for adults. An effective informed consent process involves at minimum these elements: 
• 
Conducting the process in a manner and location that ensures privacy; 
• 
Giving adequate information about the study in a language understandable to the parent/legal 
guardian and child/adolescent; 


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• 
Providing adequate opportunity for the parent/legal guardian and child to consider all options; 
• 
Responding to the parent(s)/legal guardian(s) and child’s questions; 
• 
Ensuring the parent/legal guardian and child has understood the information provided; 
• 
Obtaining the parent/legal guardian and child voluntary agreement to participate, and  
• 
Continuing to provide information as the parent(s)/legal guardian(s), child, or research requires. 
12.4.3. 
When Parents/Legal Guardian Disagree 
If there are two parents/legal guardians available to give permission but they disagree about allowing their 
child to participate in the study, the child may not be enrolled unless that disagreement can be resolved. 
This applies to all permissible categories, even if only one parent or legal guardian’s signature is required, 
when both parents/guardians are involved in the decision, they must agree for the child to be enrolled. If a 
parent or legal guardian who was not involved or available for the original consent later becomes involved 
or available, the two parents/legal guardians must then agree. 
12.4.4. 
Assent 
The Investigator should carefully consider and propose adequate provisions for obtaining assent of children 
and adolescents prior to their participating in research. In general assent is usually obtained from a child ≥ 
7 years of age, however the approving IRB/IEC will determine whether or how assent will be obtained. The 
child should be provided with essential information and asked if they wish to participate in the research 
study.  
12.4.5. 
Documenting the Consent/Assent Process 
Consent/Assent MUST be obtained and documented PRIOR to initiation of any study procedures. The 
Investigator or his/her approved designee must explain the nature of the study and associated risks to the 
parent(s)/legal guardian and study patient. The date/time that the ICF and Assent is signed, a brief 
description of the consent/assent process (e.g., questions asked by the patient), and the name of the 
individual who obtained consent/assent will be recorded in the source record. A copy of the signed and 
dated ICF and Assent should be provided to the parent(s)/legal guardian(s). Depending on the approving 
IRB/IEC and local requirements, an assent form may be included as part of the consent and may or may 
not be required to be signed by the child. Investigators must adhere to their local requirements for proper 
documentation of consent/assent. A summary of assent procedures for execution of this study must be 
maintained in the Investigator Essential Regulatory File. It is the responsibility of the Investigator to ensure 
that any individual delegated the responsibility for obtaining consent/assent are familiar and adhere to the 
applicable consent/assent requirements. 
12.5. Confidentiality 
The Sponsor will affirm and uphold the principle of the patient’s right to protection against the invasion of 
privacy. Throughout this study and any subsequent data analyses, all data will be identified only by 
protocol number and patient number. 
All unpublished information that the Sponsor gives to the Investigator shall be kept confidential and shall 
not be published or disclosed to a third party without the prior written consent of the Sponsor. 
When the Sponsor generates reports for presentations to regulatory agencies, one or more of the 
Investigators who has/have contributed significantly to the study will be asked to endorse the final report. 
The endorsement is required by some regulatory agencies. 
The Investigator shall not make a patent application based on the results of this study and shall not assist 
any third party in making such an application without the written authorization of the Sponsor unless 
otherwise specified in the Clinical Trial Agreement.


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12.6. Retained Blood Samples 
Blood samples collected during the study for biological assessments may be retained for future testing as 
necessary. Patient confidentiality will be maintained and only the site and patient number will identify the 
sample. No other linked or identifying information is maintained by the Sponsor.   
12.7. Definition of the End of the Research 
End of the research corresponds to the end of participation of the last patient participating in the research 
and to the last close-out of study sites. 
13. FINANCING AND INSURANCE 
13.1. Financial Issues 
Financial contracts will be signed between the Sponsor and the Investigator / Institution before initiation of 
the study. 
13.2. Insurance 
The patients taking part in the trial will be covered by the insurance taken by the Sponsor for this trial, if 
they were to suffer any prejudice as a result of taking part in the trial. 
In general, if a patient is injured as a direct result of the study drug, the Sponsor will pay for reasonable 
and necessary medical treatment for the injury, to the extent the expenses are not covered by the 
patient’s medical insurance, a government program, or other responsible third party. If laws or regulations 
of the locality in which the trial is taking place require additional payment of expenses, the Sponsor shall 
comply with such law or regulation. 
The Sponsor certifies to have taken out an insurance policy to cover the financial consequences of its civil 
liability and that of everyone involved in the research, and notably that of the Investigators and their 
colleagues with regard to any accidents or damage concerning the administration of the drug or 
paraclinical examinations directly linked to the performance of the trial. 
14. STUDY RESULTS AND PUBLICATION POLICY 
14.1. Study Report 
The final report will be written in ENGLISH upon completion of study and statistical analysis according to 
ICH E3 guideline. The report or part of it must be submitted to relevant authorities if applicable. 
14.2. Confidentiality and Ownership of Data, Use of the Study Results and 
Publication 
All materials, information (oral or written), and unpublished documentation provided to the Investigators 
(or any company/institution acting on their behalf), including this protocol, the patient eCRFs, and the 
Investigator's Brochure, are the exclusive property of the Sponsor and may not be published, given, or 
disclosed, either in part or in whole, by the Investigator or by any person under his/her authority to any 
third party without the prior express consent of the Sponsor. 
However, the submission of this protocol and other necessary documentation to the Institutional Review 
Board/Independent Ethics Committee (IRB/IEC) and the Competent Authority (if applicable) is expressly 
permitted, their members having the same obligation of confidentiality. 
The Investigator shall consider all information, results, discoveries, records (accumulated, acquired, or 
deduced) in the course of the study, other than that information to be disclosed by law, as confidential and 


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shall not disclose any such results, discoveries, or records to any third party without the Sponsor’s prior 
written consent. 
The Sponsor retains exclusive ownership of all data, results, reports, findings, discoveries, and any other 
information collected during this study. Therefore, the Sponsor reserves the right to use the data from the 
present study, either in the form of eCRFs (or copies of these), or in the form of a report, with or without 
comments and with or without analysis, in order to submit them to the Health Authorities of any country. 
When the Sponsor generates reports for presentations to regulatory agencies, one or more of the 
Investigators who has/have contributed significantly to the study will be asked to endorse the final report. 
The endorsement is required by some regulatory agencies. 
Furthermore, in the event that the study generates patentable results, the Investigator (or entity acting on 
his/her behalf according to local requirements) shall refrain from filing patent application(s) on such 
results, which will be filed by the Sponsor or its designees in its own name and at its expense. 
Clinical study will be registered on the open access website http://www.clinicaltrials.gov before the 
screening of the first patient in the study. 
It is the policy of the Sponsor to encourage the presentation and/or publication of the results of their 
studies, using only clean, checked, and validated data in order to ensure the accuracy of the results. 
The publication of study results will be agreed between the Sponsor and the Investigators. 
At least 45 days in advance of proposed submission, the Investigator should forward a copy of the 
manuscript or abstract for review by the Sponsor, and, if necessary, delay publication or communication for 
a limited time in order to protect the confidentiality or proprietary nature of any information contained 
therein. The Sponsor may also request that the Sponsor’s name and/or names of one or several of its 
employees appear or not appear in such publication. 
 
 


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15. REFERENCE LIST  
Anderson EL, Howe LD, Jones HE, et al. The prevalence of non-alcohol fatty liver disease in children 
and adolescents: A systematic review and meta-analysis. PLOSOne. 2015;10(10):e0140908. 
Birch LL, Daniels SR, Gilman MW, et al. Dietary recommendations for children and adolescents: A guide 
for practitioners. Pediatrics. 2006;117;544-559. 
Cattley RC, DeLuca J, Elcombe C, et al. Do peroxisome proliferating compounds pose a 
hepatocarcinogenic hazard to humans? Regul Toxicol Pharmacol. 1998;27:47-60. 
Cioffi CE, Welsh JA, Cleeton RL, et al. Natural history of NAFLD diagnosed in childhood: A single-center 
study. Children. 2017;4:34. 
Clinical Trial Facilitation Group (CTFG). Recommendations related to contraception and pregnancy 
testing in clinical trials. 2014. Accessed 20SEP2018 at 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf 
Della Corte C, Alisi A, Saccari A, et al. Nonalcoholic fatty liver disease in children and adolescents: An 
overview. J Adol Health. 2012;51:305-312. 
Della Corte C, Ferrari F, et al. Current pharmacotherapy for treating pediatric nonalcoholic fatty liver 
disease. Expert Opin Pharmacother. 2014;15(17):2501-2511. 
Fazel Y; Koenig AB, Sayiner M, et al. Epidemiology and natural history of non-alcoholic fatty liver 
disease. Metabolism. 2016;65:1017–1025. 
Goldberg DM. Structural, functional, and clinical aspects of gamma-glutamyltransferase. CRC Crit Rev 
Clin Lab Sci. 1980;12:1–58. 
Goyal NP, Schwimmer JB. The progression and natural history of pediatric nonalcoholic fatty liver 
disease. Clin Liver Dis. 2016;20(2):325-338. 
Hesham A-K. Nonalcoholic fatty liver disease in children living in the obeseogenic society. World J 
Pediatr. 2009; 5:245–254. 
Holterman AX, Guzman G, Fantuzzi G, et al. Nonalcoholic fatty liver disease in severely obese 
adolescent and adult patients. Obesity. 2013;21:591–597. 
Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin 
Liver Dis. 2008;28:370–379. [cited in Anderson, 2015] 
Lavine JE, Schwimmer JB, Van Natta ML, et al. Effect of vitamin E or metformin for treatment of 
nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled 
trial. JAMA. 2011;305:1659–68. 
Liou I, Kowdley KV. Natural history of nonalcoholic steatohepatitis. J. Clin. Gastroenterol. 2006;40 
(Suppl. 1):S11–S16. 
Loomba R, Sirlin CB, Schwimmer JB, Lavine JE. Advances in pediatric nonalcoholic fatty liver disease. 
Hepatology (Baltimore, Md). 2009;50(4):1282-1293.  
Loomba R, Chalasani N. The hierarchical model of NAFLD: prognostic significance of histologic features 
in NASH. Gastroenterology. 2015;149:278–81. 
McPherson S, Hardy T, Henderson E, et al. Evidence of NAFLD progression from steatosis to fibrosing-
steatohepatitis using paired biopsies: Implications for prognosis and clinical management.  J 
Hepatology. 2015;62:1148–1155. 
Modi N, Murgasova D, Ruager-Martin R, et al. The influence of maternal body mass index on infant 
adiposity and hepatic lipid content. Pediatr Res. 2011;70(3):287–291. 
Nesto RW, Bell D, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a 
consensus statement from the American heart association and American diabetes association.  
Circulation. 2003Dec9;108(23):2941-2948. 


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Nobili V, Cutrera R, Liccardo D, et al. Obstructive sleep apnea syndrome affects liver histology and 
inflammatory cell activation in pediatric nonalcoholic fatty liver disease, regardless of 
obesity/insulin resistance. Am J Respir Crit Care Med. 2014;189:66–76. 
Pardee PE, Lavine JE, Schwimmer JB. Diagnosis and treatment of pediatric nonalcoholic steatohepatitis 
and the implications for bariatric surgery. Semin Ped Surg. 2009;18(3):144-151. 
Quiros-Tejeira RE, Rivera CA, Ziba TT, et al. Risk for nonalcoholic fatty liver disease in Hispanic youth 
with BMI >or =95th percentile. J Pediatr Gastroenterol Nutr. 2007;44(2):228–236. 
Rashid M, Roberts EA. Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr. 2000; 
30(1):48-53. 
Ratziu V, Harrison SA, Francque S, et al. Elafibranor, an agonist of the peroxisome 
proliferator−activated receptor−α and −δ, induces resolution of nonalcoholic steatohepatitis 
without fibrosis worsening. Gastroenterology. 2016;150(5):1147-1159.e5. 
Rehm JL, Connor EL, Wolfgram PM, et al. Predicting hepatic steatosis in a racially and ethnically 
diverse cohort of adolescent girls. J Pediatr. 2014;165:319.e1–25.e1 
Roberts EA. Pediatric nonalcoholic fatty liver disease (NAFLD): A “growing” problem? Hepatology. 
2007;46:1133-1142. 
Schwimmer JB, Deutsch R, Rauch JB, et al. Obesity, insulin resistance, and other clinicopathological 
correlates of pediatric nonalcoholic fatty liver disease. J. Pediatr. 2003;143:500–505. 
Schwimmer JB, Behling C, Newbury R, et al. Histopathology of pediatric nonalcoholic fatty liver 
disease. Hepatology. 2005;42:641–649. 
Schwimmer JB, Deutsch R, Kahen T, et al. Prevalence of fatty liver in children and adolescents. 
Pediatrics. 2006;118:1388–1393. 
Schwimmer JB, Zepeda A, Newton KP, et al. Longitudinal assessment of high blood pressure in children 
with nonalcoholic fatty liver disease. PLoSOne. 2014;9:e112569. 
Varni JW. Scaling and Scoring of the Pediatric Quality of Life Inventory™ PedsQL™. Mapi Research 
Trust. Version 17. May 2017. 
Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN clinical practice guideline for the diagnosis and 
treatment of nonalcoholic fatty liver disease in children” Recommendations from the expert 
committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology 
hepatology and Nutrition (NASPGHAN). JPGN. 2017;64(2):319-334. 
Wang Y, Jadhav PR, Lala M, et al. Clarification on precision criteria to derive sample size when 
designing pediatric pharmacokinetic studies. J Clin Pharmacol .2012;52:1601-1606. 
 
 


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16. APPENDICES 
16.1. Appendix I – World Medical Association Declaration of Helsinki 
ETHICAL PRINCIPLES FOR MEDICAL RESEARCH INVOLVING HUMAN 
SUBJECTS - WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI 
 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 
and amended by the: 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
53rd WMA General Assembly, Washington DC, USA, October 2002 (Note of Clarification 
added) 
55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification added) 
59th WMA General Assembly, Seoul, Republic of Korea, October 2008 
64th WMA General Assembly, Fortaleza, Brazil, October 2013 
16.1.1. 
Preamble 
1.         The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of 
ethical principles for medical research involving human subjects, including research on identifiable human 
material and data. 
The Declaration is intended to be read as a whole and each of its constituent paragraphs should be applied 
with consideration of all other relevant paragraphs. 
2.         Consistent with the mandate of the WMA, the Declaration is addressed primarily to physicians. The 
WMA encourages others who are involved in medical research involving human subjects to adopt these 
principles. 
16.1.2. 
General Principles 
3.         The Declaration of Geneva of the WMA binds the physician with the words, “The health of my 
patient will be my first consideration,” and the International Code of Medical Ethics declares that, “A 
physician shall act in the patient’s best interest when providing medical care.” 
4.         It is the duty of the physician to promote and safeguard the health, well-being and rights of 
patients, including those who are involved in medical research. The physician’s knowledge and conscience 
are dedicated to the fulfilment of this duty. 
5.         Medical progress is based on research that ultimately must include studies involving human 
subjects. 
6.         The primary purpose of medical research involving human subjects is to understand the causes, 
development and effects of diseases and improve preventive, diagnostic and therapeutic interventions 
(methods, procedures and treatments). Even the best proven interventions must be evaluated continually 
through research for their safety, effectiveness, efficiency, accessibility and quality. 
7.         Medical research is subject to ethical standards that promote and ensure respect for all human 
subjects and protect their health and rights. 
8.         While the primary purpose of medical research is to generate new knowledge, this goal can never 
take precedence over the rights and interests of individual research subjects. 
9.         It is the duty of physicians who are involved in medical research to protect the life, health, dignity, 
integrity, right to self-determination, privacy, and confidentiality of personal information of research 
subjects. The responsibility for the protection of research subjects must always rest with the physician or 
other health care professionals and never with the research subjects, even though they have given consent. 
10.       Physicians must consider the ethical, legal and regulatory norms and standards for research 
involving human subjects in their own countries as well as applicable international norms and standards. 


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No national or international ethical, legal or regulatory requirement should reduce or eliminate any of the 
protections for research subjects set forth in this Declaration. 
11.       Medical research should be conducted in a manner that minimises possible harm to the 
environment. 
12.       Medical research involving human subjects must be conducted only by individuals with the 
appropriate ethics and scientific education, training and qualifications. Research on patients or healthy 
volunteers requires the supervision of a competent and appropriately qualified physician or other health 
care professional. 
13.       Groups that are underrepresented in medical research should be provided appropriate access to 
participation in research. 
14.       Physicians who combine medical research with medical care should involve their patients in 
research only to the extent that this is justified by its potential preventive, diagnostic or therapeutic value 
and if the physician has good reason to believe that participation in the research study will not adversely 
affect the health of the patients who serve as research subjects. 
15.       Appropriate compensation and treatment for subjects who are harmed as a result of participating 
in research must be ensured. 
16.1.3. 
Risks, Burdens and Benefits 
16.       In medical practice and in medical research, most interventions involve risks and burdens. 
Medical research involving human subjects may only be conducted if the importance of the objective 
outweighs the risks and burdens to the research subjects. 
17.       All medical research involving human subjects must be preceded by careful assessment of 
predictable risks and burdens to the individuals and groups involved in the research in comparison with 
foreseeable benefits to them and to other individuals or groups affected by the condition under 
investigation. 
Measures to minimise the risks must be implemented. The risks must be continuously monitored, assessed 
and documented by the researcher. 
18.       Physicians may not be involved in a research study involving human subjects unless they are 
confident that the risks have been adequately assessed and can be satisfactorily managed. 
When the risks are found to outweigh the potential benefits or when there is conclusive proof of definitive 
outcomes, physicians must assess whether to continue, modify or immediately stop the study. 
16.1.4. 
Vulnerable Groups and Individuals 
19.       Some groups and individuals are particularly vulnerable and may have an increased likelihood of 
being wronged or of incurring additional harm. 
All vulnerable groups and individuals should receive specifically considered protection. 
20.       Medical research with a vulnerable group is only justified if the research is responsive to the health 
needs or priorities of this group and the research cannot be carried out in a non-vulnerable group. In 
addition, this group should stand to benefit from the knowledge, practices or interventions that result from 
the research. 
16.1.5. 
Scientific Requirements and Research Protocols 
21.       Medical research involving human subjects must conform to generally accepted scientific principles, 
be based on a thorough knowledge of the scientific literature, other relevant sources of information, and 
adequate laboratory and, as appropriate, animal experimentation. The welfare of animals used for research 
must be respected. 
22.       The design and performance of each research study involving human subjects must be clearly 
described and justified in a research protocol. 
The protocol should contain a statement of the ethical considerations involved and should indicate how the 
principles in this Declaration have been addressed. The protocol should include information regarding 
funding, sponsors, institutional affiliations, potential conflicts of interest, incentives for subjects and 
information regarding provisions for treating and/or compensating subjects who are harmed as a 
consequence of participation in the research study. 
In clinical trials, the protocol must also describe appropriate arrangements for post-trial provisions. 
 


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16.1.6. 
Research Ethics Committees 
23.       The research protocol must be submitted for consideration, comment, guidance and approval to 
the concerned research ethics committee before the study begins. This committee must be transparent in 
its functioning, must be independent of the researcher, the sponsor and any other undue influence and 
must be duly qualified. It must take into consideration the laws and regulations of the country or countries 
in which the research is to be performed as well as applicable international norms and standards but these 
must not be allowed to reduce or eliminate any of the protections for research subjects set forth in this 
Declaration. 
The committee must have the right to monitor ongoing studies. The researcher must provide monitoring 
information to the committee, especially information about any serious adverse events. No amendment to 
the protocol may be made without consideration and approval by the committee. After the end of the 
study, the researchers must submit a final report to the committee containing a summary of the study’s 
findings and conclusions. 
16.1.7. 
Privacy and Confidentiality 
24.       Every precaution must be taken to protect the privacy of research subjects and the confidentiality 
of their personal information. 
16.1.8. 
Informed Consent 
25.       Participation by individuals capable of giving informed consent as subjects in medical research 
must be voluntary. Although it may be appropriate to consult family members or community leaders, no 
individual capable of giving informed consent may be enrolled in a research study unless he or she freely 
agrees. 
26.       In medical research involving human subjects capable of giving informed consent, each potential 
subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of 
interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study 
and the discomfort it may entail, post-study provisions and any other relevant aspects of the study. The 
potential subject must be informed of the right to refuse to participate in the study or to withdraw consent 
to participate at any time without reprisal. Special attention should be given to the specific information 
needs of individual potential subjects as well as to the methods used to deliver the information. 
After ensuring that the potential subject has understood the information, the physician or another 
appropriately qualified individual must then seek the potential subject’s freely given informed consent, 
preferably in writing. If the consent cannot be expressed in writing, the non-written consent must be 
formally documented and witnessed. 
All medical research subjects should be given the option of being informed about the general outcome and 
results of the study. 
27.       When seeking informed consent for participation in a research study the physician must be 
particularly cautious if the potential subject is in a dependent relationship with the physician or may consent 
under duress. In such situations the informed consent must be sought by an appropriately qualified 
individual who is completely independent of this relationship. 
28.       For a potential research subject who is incapable of giving informed consent, the physician must 
seek informed consent from the legally authorised representative. These individuals must not be included 
in a research study that has no likelihood of benefit for them unless it is intended to promote the health of 
the group represented by the potential subject, the research cannot instead be performed with persons 
capable of providing informed consent, and the research entails only minimal risk and minimal burden. 
29.       When a potential research subject who is deemed incapable of giving informed consent is able to 
give assent to decisions about participation in research, the physician must seek that assent in addition to 
the consent of the legally authorised representative. The potential subject’s dissent should be respected. 
30.       Research involving subjects who are physically or mentally incapable of giving consent, for 
example, unconscious patients, may be done only if the physical or mental condition that prevents giving 
informed consent is a necessary characteristic of the research group. In such circumstances the physician 
must seek informed consent from the legally authorised representative. If no such representative is 
available and if the research cannot be delayed, the study may proceed without informed consent provided 
that the specific reasons for involving subjects with a condition that renders them unable to give informed 


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consent have been stated in the research protocol and the study has been approved by a research ethics 
committee. Consent to remain in the research must be obtained as soon as possible from the subject or a 
legally authorised representative. 
31.       The physician must fully inform the patient which aspects of their care are related to the research. 
The refusal of a patient to participate in a study or the patient’s decision to withdraw from the study must 
never adversely affect the patient-physician relationship. 
32.       For medical research using identifiable human material or data, such as research on material or 
data contained in biobanks or similar repositories, physicians must seek informed consent for its collection, 
storage and/or reuse. There may be exceptional situations where consent would be impossible or 
impracticable to obtain for such research. In such situations the research may be done only after 
consideration and approval of a research ethics committee. 
16.1.9. 
Use of Placebo 
33.       The benefits, risks, burdens and effectiveness of a new intervention must be tested against those 
of the best proven intervention(s), except in the following circumstances: 
Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; or 
Where for compelling and scientifically sound methodological reasons the use of any intervention less 
effective than the best proven one, the use of placebo, or no intervention is necessary to determine the 
efficacy or safety of an intervention 
and the patients who receive any intervention less effective than the best proven one, placebo, or no 
intervention will not be subject to additional risks of serious or irreversible harm as a result of not receiving 
the best proven intervention. 
Extreme care must be taken to avoid abuse of this option. 
16.1.10. 
Post-Trial Provisions 
34.       In advance of a clinical trial, sponsors, researchers and host country governments should make 
provisions for post-trial access for all participants who still need an intervention identified as beneficial in 
the trial. This information must also be disclosed to participants during the informed consent process. 
16.1.11. 
Research Registration and Publication and Dissemination of Results 
35.       Every research study involving human subjects must be registered in a publicly accessible database 
before recruitment of the first subject. 
36.       Researchers, authors, sponsors, editors and publishers all have ethical obligations with regard to 
the publication and dissemination of the results of research. Researchers have a duty to make publicly 
available the results of their research on human subjects and are accountable for the completeness and 
accuracy of their reports. All parties should adhere to accepted guidelines for ethical reporting. Negative 
and inconclusive as well as positive results must be published or otherwise made publicly available. Sources 
of funding, institutional affiliations and conflicts of interest must be declared in the publication. Reports of 
research not in accordance with the principles of this Declaration should not be accepted for publication. 
16.1.12. 
Unproven Interventions in Clinical Practice 
37.       In the treatment of an individual patient, where proven interventions do not exist or other known 
interventions have been ineffective, the physician, after seeking expert advice, with informed consent from 
the patient or a legally authorised representative, may use an unproven intervention if in the physician’s 
judgement it offers hope of saving life, re-establishing health or alleviating suffering. This intervention 
should subsequently be made the object of research, designed to evaluate its safety and efficacy. In all 
cases, new information must be recorded and, where appropriate, made publicly available. 
 


Clinical Trial GFT505E-218-1 
Protocol V4.0 20 April 2020 
 
GENFIT 
 
Page 77 of 83 
 
16.2. Appendix II – Dosing Diary (Sample) 
 
 


Clinical Trial GFT505E-218-1 
Protocol V4.0 20 April 2020 
 
GENFIT 
 
Page 78 of 83 
 
16.3. Appendix III: Non-permitted and Permitted Medications 
 
NON-PERMITTED MEDICATION AND CONDITION 
Medications 
When 
Same pharmacological class (PPAR agonists) 
Thiazolidinediones (glitazones [pioglitazone and rosiglitazone]) 
From 3 months (12 weeks) prior to Screening Visit 
1 up to end of study (EOS) Visit 7 
Fibrates 
From 2 months (8 weeks) prior to Screening (SV1) 
up to end of study (EOS) Visit 7 
 
Medication that may induce steatosis/steatohepatitis  
Corticosteroids (parenteral & oral chronic administration) 
No chronic use of more than 3 consecutive months 
permitted from 12 months prior to Screening (SV1) 
up to Randomization (Visit 1/Day 1). 
Tamoxifen 
Methotrexate 
Tetracycline 
Valproic acid 
Salicylates 
Medication that may interact with absorption, metabolism, etc.  
Indomethacin 
From Randomization (Visit 1/Day 1) up to EOT Visit 
6 


Clinical Trial GFT505E-218-1 
Protocol V4.0 20 April 2020 
 
GENFIT 
 
Page 79 of 83 
 
PERMITTED MEDICATION AND CONDITION 
Medications 
When 
Antidiabetic therapy 
Insulin 
No qualitative change (i.e., no initiation of a new drug) from at 
least 3 months prior Screening (SV1) 
 
Dose stability required from at least 3 months prior to Screening 
Visit 1 up to Randomization (Visit1/Day 1) 
 
From Randomization Visit 1 to EOS Visit 7, qualitative change and 
dose change should be avoided as much as possible 
Metformin 
Gliptins 
Sulfonylureas 
GLP-1 agonists 
SGLT2- inhibitors  
Lipid lowering therapy 
Statins 
Dose stability required from at least 3 months prior to Screening 
Visit up to Randomization (Visit 1/Day 1). 
From Randomization (Visit 1/Day 1) to EOS V7, qualitative change 
and dose change should be avoided as much as possible. 
Ezetimibe 
Other nonfibrate lipid lowering therapies 
Medication that may induce steatosis/steatohepatitis 
Corticosteroids (parenteral & oral chronic 
administration) 
From Randomization (Visit 1/Day 1) to EOS Visit 7, chronic use of 
more than 2 consecutive weeks should be avoided as much as 
possible. 
Tamoxifen 
Methotrexate 
Tetracycline 
Valproic acid 
Salicylates 
Others 
Vitamin E  
Dose stability required from at least 3 months prior to Screening 
Visit 1) up to Randomization (Visit 1/Day 1).  
From Randomization (Visit 1/day 1) to EOS Visit 7, qualitative 
change and dose change should be avoided as much as possible 
PUFAs 
ursodeoxycholic acid 
GLP-1 =glucagon-like peptide 1; PUFA = polyunsaturated fatty acids; SGLT2 = sodium/glucose cotransporter 2. 


Clinical Trial GFT505E-218-1 
Protocol V3.0 21February2020 
 
GENFIT 
 
Page 80 of 83 
 
16.4. Appendix IV: Clinical Trial Facilitation Group (CTFG) Highly Effective 
Methods of Birth Control  
For the purpose of this guidance, methods that can achieve a failure rate of less than 1% per year when 
used consistently and correctly are considered as highly effective birth control methods. Such methods 
include: 
• 
combined (estrogen and progestogen containing) hormonal contraception associated with inhibition 
of ovulation1 
o 
oral 
o 
intravaginal 
o 
transdermal 
• 
progestogen-only hormonal contraception associated with inhibition of ovulation1 
o 
oral 
o 
injectable 
o 
implantable2 
• 
intrauterine device (IUD)2 
• 
intrauterine hormone-releasing system (IUS)2 
• 
bilateral tubal occlusion2 
• 
vasectomised partner2,3 
• 
sexual abstinence4 
 
1Hormonal contraception may be susceptible to interaction with the investigational medicinal product (IMP), 
which may reduce the efficacy of the contraception method. 
2Contraception methods that in the context of this guidance are considered to have low user dependency. 
3Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual 
partner of the woman of childbearing potential (WOCBP) trial participant and that the vasectomised partner 
has received medical assessment of the surgical success. 
4 In the context of this guidance sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study 
treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the subject. 
Source: Clinical Trial Facilitation Group (CTFG). Recommendations related to contraception and pregnancy 
testing in clinical trials. 2014, section 4, p. 9 


Clinical Trial GFT505E-218-1 
Protocol V3.0 21February2020 
 
GENFIT 
 
Page 81 of 83 
 
16.5. Appendix V – List of Abbreviations 
Abbreviation 
Definition 
A1AT 
Alpha-1-antitrypsin 
AAP 
American Academy of Pediatrics 
ADR 
Adverse drug reaction 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AMA 
Antimitochondrial Assay 
ApoAI 
Apolipoprotein A-I 
ApoB 
Apolipoprotein B 
AST 
Aspartate aminotransferase 
AT 
Aminotransferase 
AUC(0-24) 
Area under the plasma concentration time curve over 24 hours 
BMI 
Body mass index 
BP 
Blood pressure 
BPM 
Beats per minute 
CA  
Competent Authorities 
CFR  
Code of Federal Regulations 
CK 
Creatine kinase 
CPK 
Creatinine phosphokinase 
CI 
Confidence interval 
Cmax 
Maximum concentration observed 
COA 
Certificate of Analysis 
COVID-19 
Coronavirus disease of 2019 
CRF 
Case report form 
CRO 
Contract Research Organization 
CTFG 
Clinical Trial Facilitation Group 
CV 
Coefficient of Variation 
DBP 
Diastolic blood pressure 
dL 
Deciliter 
DSMB 
Data Safety and Monitoring Board 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
EOS 
End of Study 
EOT 
End of Treatment 
ELISA 
Enzyme-linked immunosorbent assay 
EU 
European Union 
FDA 
Food and Drug Administration 
FFA 
Fatty free acids 
FOCBP 
Females of childbearing potential 
FPFV 
First patient/first visit 
GLP-1 
Glucagon-like peptide 1 
GCP 
Good Clinical Practice 
GGT 
Gamma glutamyl transferase 
HAV 
Hepatitis A virus 
HbA1c 
Hemoglobin A1C 
HBsAg 
Hepatitis B surface antigen 
hsCRP 
High sensitivity C-reactive protein 
HCV 
Hepatitis C virus 
HDL 
High-density lipoprotein 


Clinical Trial GFT505E-218-1 
Protocol V4.0 20 April 2020 
 
GENFIT 
 
Page 82 of 83 
 
Abbreviation 
Definition 
HDL-C 
High-density lipoprotein cholesterol 
HEV 
Hepatitis E virus 
HIV 
Human immunodeficiency virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HOMA-IR 
Homeostasis Model Assessment of Insulin Resistance 
ICF or IC 
Informed Consent Form 
ICH 
International Council on Harmonization 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug Application 
INR 
International normalized ration 
IRB 
Institutional Review Board 
ITT 
Intent to treat 
IU 
International Unit 
L 
Liter 
LDL-C 
Low-density lipoprotein cholesterol 
LLNA 
Local Lymph node assay 
LOQ 
Lower limit of assay 
LPLV 
Last patient last visit 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mg/dL  
Milligram per deciliter 
mL 
Milliliter 
mm 
Millimeter 
mmHg 
Millimeter of mercury 
MTD 
Maximum tolerated dose 
NAFL 
Nonalcoholic fatty liver 
NAFLD 
Nonalcoholic fatty liver disease 
NASH 
Nonalcoholic steatohepatitis 
NCA 
Non compartmental analysis 
PBC 
Primary biliary cholangitis 
PD 
Pharmacodynamic 
PedsQL™ 
Pediatric Quality of Life 
PK 
Pharmacokinetic(s) 
PND 
Post-natal day 
PPAR 
Peroxisome proliferator-activated receptor 
PR 
Pulse rate 
PUFAs 
Polyunsaturated fatty acids 
RBC 
Red blood cells 
SADR 
Serious adverse drug reaction 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic blood pressure 
SD 
Standard deviation 
SGLT2 
Sodium/glucose cotransporter 2 
SUSAR 
Suspected unexpected serious adverse reaction 
TC 
Total cholesterol 
Tmax 
Time to maximum concentration 
TEAE 
Treatment emergent adverse event 
TIBC 
Total iron binding capacity 
TG 
Triglycerides 
TSH 
Thyroid stimulation hormone 
UA 
Urinalysis 
ULN 
Upper limit of normal 
UV 
Ultraviolet 
US 
United States 


Clinical Trial GFT505E-218-1 
Protocol V4.0 20 April 2020 
 
GENFIT 
 
Page 83 of 83 
 
Abbreviation 
Definition 
VLDL-C 
Very low-density lipoprotein 
WBC 
White blood cells 
WHO 
World Health Organization 
WHODD 
World Health Organization Drug Dictionary 
WMA 
World Medical Association 
WOCBP 
Woman of childbearing potential 
 


Si g nat ure Pa ge f or G F T 5 0 5 E- 2 1 8- 1- 0 0 7 5 5 v 1. 0
Si g nat ure Pa ge f or G F T 5 0 5 E- 2 1 8- 1- 0 0 7 5 5 v 1. 0
Reas o n f or si g ni n g: A p pr o ve d
Na me:
R ole: 
Date o
A pr- 2 0 2 0 0 6: 4 8: 2 7
G M T + 0 0 0 0
G F T 5 0 5 E- 2 1 8- 1 _ Pr ot oc ol _ V 4. 0 _ 2 0 A pr 2 0 2 0 | G F T 5 0 5 E- 2 1 8- 1- 0 0 7 5 5 | 1. 0
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SAP_001.pdf: 
 
Genfit 
Parc Eurasanté 
885, avenue Eugène Avinée 
59120 LOOS 
France 
 
 
 
 
 
An Open Label, Randomized, Multicenter Study to Assess the Pharmacokinetic and 
Pharmacodynamic Profile and the Safety and Tolerability of Two Dose Levels of 
Elafibranor (80 mg and 120 mg) in Children and Adolescents, 8 to 17 Years of Age, 
with Nonalcoholic Steatohepatitis (NASH) 
 
 
Phase 2a Study 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
 
 
 
 
 
 
 
Product:  
Elafibranor (GFT505) 
 
Study No:  
GFT505E-218-1 
 
Date:  
20 August 2020 
 
Version:  
Final 2.0 
 
Reference: 
INF - SOP STAT 007 - Version 4.0_Statistical Analysis Plan 
 
 
 
 
 
 
 
 


G F T 5 0 5 E- 2 1 8- 1
G e nfit
i nf er e nti al
S T A TI S TI C A L  A N A L Y SI S  P L A N  A P P R O V A L  F O R M
S P O N S O R:  G e nfit
S T U D Y  N U M B E R:  G F T 5 0 5- 2 1 8- 1
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wit h  N o n al c o h oli c  St e at o h e p atiti s  ( N A S H)
S T U D Y  P A R T:  Fi n al
V E R SI O N:  Fi n al  2. 0  - 2 0  A u g u st  2 0 2 0
A ut h or
N a m e:  
 Si g n at ur e  
F u n cti o n:  
R e vi e w er  I nf er e nti al
N a m e:  
 
Si g n at ur e
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R e vi e w er s  S p o n s or
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F u n cti o n:  
D at e
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F u n cti o n:  
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2 0  A u g u st  2 0 2 0,  Fi n al 2. 0
i nf er e nti al
2
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D at e: 2 0 2 0. 0 8. 2 1 1 7: 0 8: 4 9 + 0 2' 0 0'
Di git all y si g n e d b y
 
 
D at e: 2 0 2 0. 0 8. 2 1 1 7: 1 1: 3 0 + 0 2' 0 0'
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


G F T 5 0 5 E -2 1 8 -1  
G e nfit  
 
2 0 A u g u st 2 0 2 0, Fi n al 2. 0  
 
3  
 
 
 
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V er si o n  
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A ut h or  
D e s cri pti o n  
0. 1  
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1. 0  
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2. 0  
2 0 A u g u st 2 0 2 0  
 
I m pl e m e nt ati o n of c o m m e nt s o n v er si o n Fi n al 
1. 0  
 
 
P P D
P P D
P P D
P P D


GFT505E-218-1 
Genfit 
 
20 August 2020, Final 2.0 
 
4 
 
 
 
Table of Contents 
 
TABLE OF CONTENTS ............................................................................................. 4 
LIST OF TABLES ...................................................................................................... 8 
LIST OF FIGURES..................................................................................................... 8 
LIST OF ABBREVIATIONS ....................................................................................... 9 
1. 
INTRODUCTION ............................................................................................. 11 
1.1 
Objectives of the Study ....................................................................... 11 
1.1.1 
Primary Objective ................................................................... 11 
1.1.2 
Secondary Objectives ............................................................. 11 
1.1.3 
Safety Secondary Objectives ................................................. 11 
1.1.4 
Exploratory objectives ............................................................ 11 
1.2 
Study Design ....................................................................................... 11 
1.2.1 
Experimental Design .............................................................. 11 
1.2.2 
Study Duration ........................................................................ 12 
1.2.3 
Number of Patients ................................................................. 12 
1.3 
Study Parameters ............................................................................... 13 
1.3.1 
Primary Endpoint .................................................................... 13 
1.3.2 
Secondary Efficacy Endpoints ................................................ 13 
1.3.3 
Safety Parameters .................................................................. 13 
1.3.4 
Exploratory parameters .......................................................... 13 
1.3.5 
Compliance ............................................................................ 13 
1.4 
Flow Chart ........................................................................................... 14 
1.5 
Protocol Amendments ......................................................................... 19 
1.6 
Treatment ............................................................................................ 19 
2. 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED 
ANALYSES ..................................................................................................... 20 
2.1 
Protocol Amendments ......................................................................... 20 
2.2 
Changes in the Statistical Analysis Plan ............................................. 20 
3. 
STATISTICAL CONSIDERATIONS ................................................................ 21 
4. 
STUDY PATIENTS .......................................................................................... 22 
4.1 
Disposition of Patients ......................................................................... 22 
4.2 
Protocol Deviations ............................................................................. 23 
4.3 
Data Sets Analyzed ............................................................................. 23 
4.3.1 
All Enrolled Patients ............................................................... 23 
4.3.2 
All Included Patients ............................................................... 23 
4.3.3 
Pharmacokinetic Population(s) ............................................... 23 
4.3.4 
Intent-To-Treat (ITT) Population ............................................. 24 
4.3.5 
Safety Population ................................................................... 24 
4.4 
Dose Switch During the Study ............................................................. 24 
5. 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ............... 25 
5.1.1 
Demographic Characteristics ................................................. 25 
5.1.2 
NASH Diagnosis ..................................................................... 26 
5.1.3 
Alcohol Use Disorders Identification Test (AUDIT) ................. 26 
5.1.4 
Medical and Surgical History .................................................. 26 
5.2 
Prior Medications ................................................................................ 26 


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5.3 
Prior Procedures ................................................................................. 27 
5.4 
Laboratory Screen Tests ..................................................................... 27 
6. 
TREATMENT COMPLIANCE .......................................................................... 29 
7. 
EFFICACY EVALUATION ............................................................................... 30 
7.1.1 
Primary Efficacy Analysis ....................................................... 30 
7.1.2 
Secondary Efficacy Analyses ................................................. 30 
7.1.3 
Statistical / Analytical Issues .................................................. 32 
7.1.3.1 
Adjustments for Covariates ............................... 32 
7.1.3.2 
Handling of Dropouts or Missing Data ............... 32 
7.1.3.3 
Interim Analyses and Data Monitoring ............... 32 
7.1.3.4 
Multicenter Studies ............................................ 32 
7.1.3.5 
Multiple Comparison/Multiplicity ........................ 32 
7.1.3.6 
Use of an ‘Efficacy’ Subset of Patients .............. 32 
7.1.3.7 
Active-Control Studies Intended to Show 
Equivalence ....................................................... 32 
7.1.3.8 
Examination of Subgroups ................................ 32 
7.1.4 
Tabulation of Individual Response Data ................................. 32 
7.1.5 
Drug Dose, Drug Concentration and Relationships to 
Response ............................................................................... 32 
7.1.6 
Drug-Drug and Drug-Disease Interactions ............................. 32 
8. 
PHARMACOKINETIC EVALUATION ............................................................. 33 
9. 
SAFETY EVALUATION .................................................................................. 34 
9.1 
Exposure, Study and Treatment Durations ......................................... 34 
9.2 
Adverse Events ................................................................................... 34 
9.2.1 
Summary of AEs ..................................................................... 34 
9.2.2 
Display of Adverse Events ...................................................... 36 
9.2.2.1 
Adverse Events ................................................. 36 
9.2.2.2 
Treatment Emergent AEs .................................. 36 
9.2.2.3 
Treatment Emergent AEs Related to Study 
Treatment .......................................................... 36 
9.2.2.4 
Treatment Emergent AEs Related to Study 
Procedures ........................................................ 36 
9.2.2.5 
Treatment Emergent AEs by Maximum 
Event Severity ................................................... 36 
9.2.2.6 
Serious AEs ....................................................... 36 
9.2.2.7 
Serious Treatment Emergent AEs ..................... 37 
9.2.2.8 
Serious Treatment Emergent AEs Related to 
Study Treatment ................................................ 37 
9.2.2.9 
Serious Treatment Emergent AEs Related to 
Study Procedures .............................................. 37 
9.2.2.10 
Serious Treatment Emergent AEs by 
Maximum Event Severity ................................... 37 
9.2.2.11 
AEs Leading to Treatment Withdrawal .............. 37 
9.2.2.12 
Treatment Emergent AEs Leading to 
Treatment Withdrawal ....................................... 37 
9.2.2.13 
AEs Leading to Study Withdrawal ..................... 37 
9.2.2.14 
Treatment Emergent AEs Leading to Study 
Withdrawal ......................................................... 38 


GFT505E-218-1 
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9.2.2.15 
Fatal AEs ........................................................... 38 
9.2.2.16 
Fatal Treatment Emergent AEs ......................... 38 
9.2.3 
Analysis of Adverse Events .................................................... 38 
9.2.4 
AEs Listings ............................................................................ 38 
9.2.5 
Adverse Events of Special Interest ......................................... 38 
9.3 
Deaths, Other Serious AEs and Other Significant AEs ....................... 39 
9.3.1 
Listings of Deaths, Other Serious AEs and Other 
Significant AEs ....................................................................... 39 
9.3.2 
Narratives of Deaths, Other Serious AEs and Other 
Significant AEs ....................................................................... 39 
9.4 
Clinical Laboratory Evaluation ............................................................. 39 
9.4.1 
Listings of Individual Laboratory Measurements..................... 40 
9.4.2 
Evaluation of Each Laboratory Parameter .............................. 40 
9.5 
Vital Signs, Physical Findings and Other Observations Related to 
Safety .................................................................................................. 41 
9.5.1 
Vital Signs .............................................................................. 41 
9.5.2 
Other Observations Related to Safety .................................... 42 
9.5.2.1 
Physical Examination ........................................ 42 
9.5.2.2 
Electrocardiogram ............................................. 42 
9.6 
Concomitant Medications .................................................................... 43 
9.7 
Concomitant Procedures ..................................................................... 43 
9.8 
Collection of PK Blood Samples .......................................................... 44 
10. TABLES, FIGURES AND GRAPHS REFERRED TO BUT NOT 
INCLUDED IN THE TEXT ............................................................................... 45 
10.1 
General Remarks about Tables .......................................................... 45 
10.2 
Demographic Data Summary and Figures .......................................... 45 
10.2.1 Study Patients ........................................................................ 45 
10.2.2 Demographics and Patient Characteristics ............................. 46 
10.2.3 Treatment Compliance ........................................................... 47 
10.3 
Efficacy Data Summary Figures and Tables ....................................... 47 
10.3.1 Secondary Efficacy Variables ................................................. 47 
10.4 
Safety Data Summary Figures and Tables ......................................... 48 
10.4.1 Exposure, Study and Treatment Durations ............................. 48 
10.4.2 Displays of Adverse Events .................................................... 48 
10.4.2.1 
Summary of Adverse Events ............................. 48 
10.4.2.2 
Display of Adverse Events ................................. 49 
10.4.3 Listings of Deaths, Other Serious and Significant Adverse 
Events .................................................................................... 51 
10.4.4 Narratives of Deaths, Other Serious and Significant 
Adverse Events ...................................................................... 52 
10.4.5 Abnormal Laboratory Value Listing......................................... 52 
10.4.6 Display of Laboratory Data ..................................................... 52 
10.4.7 Vital Signs, Physical Findings and Other Observations 
Related to Safety .................................................................... 52 
10.4.8 Concomitant Medications ....................................................... 53 
10.4.9 Concomitant Procedures ........................................................ 53 
11. DOCUMENTATION OF STATISTICAL METHODS ........................................ 54 
11.1 
Missing and Partially Known Dates ..................................................... 54 
11.2 
Demographics and Other Baseline Characteristics ............................. 54 


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11.3 
Medications ......................................................................................... 54 
11.4 
Treatment Compliance ........................................................................ 55 
11.5 
Efficacy Variables ................................................................................ 56 
11.6 
Exposure and Durations ...................................................................... 57 
11.7 
Adverse Events ................................................................................... 57 
11.8 
Laboratory Data .................................................................................. 59 
11.8.1 Laboratory Evaluation ............................................................. 59 
11.8.2 Reference Ranges .................................................................. 60 
12. PATIENT DATA LISTINGS ............................................................................. 61 
12.1 
General Remarks about Listings ......................................................... 61 
12.2 
Disposition of Patients ......................................................................... 61 
12.3 
Protocol Deviations ............................................................................. 61 
12.4 
Patients Excluded from Efficacy Analysis ........................................... 61 
12.5 
Demographic Data .............................................................................. 61 
12.6 
Compliance and/or Drug Concentration Data ..................................... 62 
12.7 
Individual Efficacy Response Data ...................................................... 62 
12.8 
Adverse Event Listings ........................................................................ 62 
12.9 
Listing of Individual Laboratory Measurements ................................... 62 
12.10 Vital signs, Physical Findings and Other Observations Related to 
Safety .................................................................................................. 62 
12.11 Concomitant Medications and Procedures .......................................... 62 
12.12 Collection of PK Blood Samples .......................................................... 63 
13. APPENDIX ...................................................................................................... 64 
14. ATTACHEMENTS ........................................................................................... 70 
 
 
 


GFT505E-218-1 
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8 
 
 
 
List of Tables 
 
Table 1 
Study General Assessment Schedule ................................................. 14 
Table 2 
Study Biological Schedule ................................................................... 15 
Table 3 
Assessment of Treatment Emergent Adverse Events ......................... 58 
Table 4 
Data for Computation of BMI Z-score .................................................. 64 
 
 
List of Figures 
 
Figure 1 
Study Schematic ................................................................................. 17 
 


GFT505E-218-1 
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20 August 2020, Final 2.0 
 
9 
 
 
 
List of Abbreviations 
 
 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
ALP 
ALkaline Phosphatase 
ALT 
ALanine amino Transferase 
AMA 
Antimitochondrial Assay 
ApoAI 
Apolipoprotein A-I 
ApoB 
Apolipoprotein B 
AST 
ASpartate Transaminase 
BMI 
Body Mass Index 
CI 
Confidence Interval 
CPK 
Creatinine Phosphokinase 
CV 
Coefficient of Variation 
DBP 
Diastolic Blood Pressure 
DRM 
Data Review Meeting 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
eGFR 
Estimated Glomerular Filtration Rate 
EOS 
End Of Study 
EOT 
End Of Treatment 
FFA 
Fatty Free Acids 
GGT 
Gamma-Glutamyl Transferase 
HAV 
Hepatitis A Virus 
HbA1c 
Hemoglobin A1C 
HB 
Hepatitis B 
HCV 
Hepatitis C Virus 
HDL 
High-Density Lipoprotein 
HDL-C 
High-Density Lipoprotein Cholesterol 
HEV 
Hepatitis E virus 
HIV 
Human Immunodeficiency Virus 
HOMA-IR 
HOmeostatic Model Assessment for Insulin Resistance 
HRQOL 
Health-Related Quality of Life 


GFT505E-218-1 
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20 August 2020, Final 2.0 
 
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ICH 
International Conference on Harmonisation 
INR 
International Normalized Ratio 
ITT 
Intent-To-Treat  
LDL-C 
Low-Density Lipoprotein Cholesterol 
LLN 
Lower Limit of Normality 
LLT 
Lower Level Term 
MedDRA 
Medical Dictionary for Regulatory Activities 
N 
Number 
NASH 
NonAlcoholic SteatoHepatitis 
NCA 
Non-Compartmental Analysis 
PD 
PharmacoDynamic 
PedsQLTM 
Pediatric Quality of Life 
PK 
PharmacoKinetic 
PT 
Prothrombin Time 
PT 
Preferred Term 
Q1 
25th percentile 
Q3 
75th percentile 
RBC 
Red Blood Cells 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic Blood Pressure 
SD 
Standard Deviation 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event 
TG 
Triglycerides 
TSH 
Thyroid Stimulation Hormone 
ULN 
Upper Limit of Normality 
VLDL-C 
Very Low-Density Lipoprotein 
WBC 
White Blood Cells 
WHODD 
WHO Drug Dictionary 
WHO-DRUG 
World Health Organisation-Drug reference list 


G F T 5 0 5 E -2 1 8 -1  
 
2 0 A u g u st 2 0 2 0, Fi n al 2. 0  
 
1 1  
 
 
 
1.  
IN T R O D U C TI O N  
 
T hi s St ati sti c al A n al y si s Pl a n ( S A P) o utli n e s a n d d e s cri b e s t h e st ati sti c al a n al y s e s of 
b a s eli n e , 
effi c a c y a n d 
s af et y  d at a 
c oll e ct e d 
d uri n g t h e 
c o ur s e 
of 
st u d y  
G F T 5 0 5 E -2 1 8 -1 .  
 
P h ar m a c o Ki n eti c  ( P K) a n al y s e s will b e d e s cri b e d i n t h e P K S A P . 
 
1. 1  
O bj e cti v e s of t h e St u d y  
 
1. 1. 1  
Pri m ar y O bj e cti v e  
 
•  T o a s s e s s t h e p h ar m a c o ki n eti c s of el afi br a n or a n d it s a cti v e 
m et a b olit e 
G F T 1 0 0 7, f oll o wi n g o n c e d ail y or al a d mi ni str ati o n of t w o d o s e l e v el s of 
el afi br a n or ( 8 0 m g a n d 1 2 0 m g) t o c hil dr e n a n d a d ol e s c e nt s, 8 t o 1 7 y e ar s of 
a g e.  
 
1. 1. 2  
S e c o n d ar y O bj e cti v e s  
  
•  T o 
a s s e s s c h a n g e s i n s er u m 
al a ni n e a mi n otr a n sf er a s e ( A L T), 
a s p art at e 
a mi n otr a n sf er a s e ( A S T), g a m m a -gl ut a m yl tr a n sf er a s e ( G G T), a n d al k ali n e 
p h o s p h at a s e ( A L P) a n d ot h er li v er m ar k er s , 
•  T o a s s e s s c h a n g e s i n 
m ar k er s of gl u c o s e h o m e o st a si s ( h o m e o st ati c 
m o d el 
a s s e s s m e nt f or i n s uli n r e si st a n c e ( H O M A-I R) a n d f a sti n g i n s uli n), 
•  T o a s s e s s c h a n g e s i n s er u m li pi d p ar a m et er s,  
•  T o a s s e s s c h a n g e s i n b o d y w ei g ht a n d B o d y M a s s I n d e x ( B MI) Z -s c or e,  
•  T o a s s e s s c h a n g e s  i n w ai st cir c u mf er e n c e, 
•  T o a s s e s s c h a n g e s i n i nfl a m m at or y m ar k er s , 
•  T o a s s e s s t h e c h a n g e i n p e di atri c q u ali ty of lif e ( P e d s Q L T M ) s c or e a s c o m pl et e d 
b y t h e c hil d/ a d ol e s c e nt a n d t h e p ar e nt/l e g al g u ar di a n . 
 
1. 1. 3  
S af et y S e c o n d ar y O bj e cti v e s  
 
•  T o a s s e s s t h e s af et y a n d t ol er a bilit y pr ofil e of t w o d o s e l e v el s of el afi br a n or ( 8 0 
m g a n d 1 2 0 m g) i n c hil dr e n a n d a d ol e s c e nt s, 8 t o 1 7 y e ar s of a g e.  
 
1. 1. 4  
E x pl or at or y o bj e cti v e s  
 
•  
 
 
 
1. 2  
St u d y D e si g n  
 
1. 2. 1  
E x p eri m e nt al D e si g n  
 
•  D e si g n:  O p e n -l a b el, r a n d o mi z e d, m ulti c e nt er , s e q u e nti al c o h ort  st u d y ,  
C CI


GFT505E-218-1 
 
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12 
 
 
 
• Centers: Two planned centers in the United States, 
• Cohorts: A total of 20 patients will be enrolled across the two cohorts: 
o Cohort 1: ≥12 to ≤17 years of age. A total of approximately 12 patients will be 
randomized in this cohort, 
o Cohort 2: ≥8 to ≤11 years of age. A total of approximately 8 patients will be 
randomized in this cohort. Enrollment in this cohort will not start until 80% of 
the patients in cohort 1 have been evaluated through Visit 4 by the Data 
Safety Monitoring Board (DSMB). 
• Study groups: Patients will be randomized 1:1 to receive either dose: 
o 80 mg once daily for 12 weeks (n=10 patients), 
o 120 mg once daily for 12 weeks (n=10 patients). 
• Stratification: Patients will also be stratified: 
o by age (Group 1: 8 to 11 years of age (approximately 8 patients) and Group 
2: 12 to 17 years of age (approximately 12 patients), 
o and according to fibrosis severity (stratum 1: fibrosis stage 0 to 1 and stratum 
2: fibrosis stage 2 to 3).  
o At least 4 patients ≥12 to ≤17 years of age and at least 2 patients ≥8 to ≤11 
years of age with fibrosis stage 2 or 3 will be enrolled. 
• Treatment: Daily dose of elafibranor for 12 weeks, 
• Blinding: not applicable (open-label study), 
• Data collection: Case Report Form (eCRF). 
 
1.2.2 
Study Duration 
 
Each patient will participate in the study for up to approximately 20 weeks (screening 
through final follow-up visit). 
 
1.2.3 
Number of Patients 
 
The primary objective of this study is to characterize individual PK parameters in 
children and adolescents 8 to 17 years of age (inclusive), by collecting rich PK 
samples to support non-compartmental analysis (NCA). Inter-patient variability of PK 
parameters in adults was low to moderate (coefficient of variation [CV]% ranged from 
23.3% to 68.3%). Assuming a similar degree of variability in pediatric population, a 
sample size of 20 patients is set to target a 95% CI [confidence interval] within 60% 
and 140% of the geometric mean estimates of clearance and volume of distribution 
for elafibranor with at least 80% power (Wang, 2012). Additionally, 20 patients 
should be sufficient to evaluate the safety and tolerability and explore the 
responsiveness (efficacy) of once daily oral dosing of 80 mg and 120 mg of 
elafibranor for up to 12 weeks. 


G F T 5 0 5 E -2 1 8 -1  
 
2 0 A u g u st 2 0 2 0, Fi n al 2. 0  
 
1 3  
 
 
 
1. 3  
St u d y P ar a m et er s  
 
1. 3. 1  
Pri m ar y E n d p oi nt  
 
•  Pl a s m a  c o n c e ntr ati o n s of el afi br a n or a n d it s a cti v e m et a b olit e G F T 1 0 0 7.  
 
1. 3. 2  
S e c o n d ar y Effi c a c y E n d p oi nt s  
 
•  C h a n g e fr o m b a s eli n e i n s er u m A L T, A S T, G G T, A L P a n d ot h er li v er m ar k er s , 
•  C h a n g e fr o m b a s eli n e i n gl u c o s e h o m e o st a si s m a k er s ( fa sti n g pl a s m a gl u c o s e , 
H O M A -I R a n d f a sti n g i n s uli n),  
•  C h a n g e fr o m b a s eli n e  i n s er u m li pi d p ar a m et er s, 
•  C h a n g e fr o m b a s eli n e  i n b o d y w ei g ht a n d B MI Z-s c or e,  
•  C h a n g e fr o m b a s eli n e i n w ai st cir c u mf er e n c e , 
•  C h a n g e fr o m b a s eli n e i n i nfl a m m at or y m ar k er s ,  
•  C h a n g e f r o m b a s eli n e i n P e d s Q L T M  s c or e s . 
 
1. 3. 3  
S af et y P ar a m et er s  
 
•  I n ci d e n c e a n d s e v erit y of tr e at m e nt e m er g e nt a d v er s e e v e nt s ( T E A E s) a n d t h eir 
r el ati o n s hi p t o st u d y dr u g,  
•  I n ci d e n c e of cli ni c all y 
m e a ni n gf ul c h a n g e s fr o m b a s eli n e i n s af et y l a b or at or y 
p ar a m et er s, p h y si c al e x a mi n ati o n, e l e ctr o c ar di o gr a m (E C G ) a n d vit al si g n s.  
 
1. 3. 4  
E x pl or at or y p ar a m et er s  
 
•  
 
 
 
1. 3. 5  
C o m pli a n c e  
 
Fr o m Vi sit 1 a n d at e a c h s u b s e q u e nt vi sit w hil e t h e p ati e nt i s b ei n g tr e at e d wit h 
st u d y dr u g u p t o t h e E n d of Tr e at m e nt ( E O T ) vi sit, t h e p ati e nt will b e i n str u ct e d t o 
bri n g b a c k all u s e d a n d u n u s e d c art o n s a n d w all et s c o nt ai ni n g bli st er s.  C o m pli a n c e 
will b e c h e c k e d b y t h e I n v e sti g at or or t h eir d e si g n e e d uri n g t h o s e vi sit s a n d r e c or d e d 
i n t h e e C R F.  If tr e at m e nt i s i nt err u pt e d, w h at e v er t h e c a u s e, d ur ati o n a n d r e a s o n f or 
t h e i nt err u pti o n s h o ul d b e  d o c u m e nt e d i n t h e d o si n g di ar y a n d o n t h e s o ur c e 
d o c u m e nt ati o n . 
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GFT505E-218-1 
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1.4 
Flow Chart 
 
Table 1 
Study General Assessment Schedule 
 
 
 
Screening Period 
Treatment Period 
Follow-up 
Period 
Visit 
SV1 
SV2 
V1 
V2 
V3 
V4 
V5 
V6/End of 
Treatment1 
V7/End of Study 
 
Week 
-4 to -1 
-1 week 
0 
2 
4 
4 
8 
12 
16 
Visit Day with Permitted Margin 
-28 to -7 
-5 (±2 days) 
1 
15 (±2 
days)  
29 (±2 
days)  
Day 30 
57 (±2 
days) 
85 (±2 days)  
113 (±2 days) 
Obtain informed consent / assent  
x 
 
 
 
 
 
 
 
 
Medical history / demographics 
x 
 
 
 
 
 
 
 
 
Check inclusion / exclusion 
criteria 
x 
 
x 
 
 
 
 
 
 
Life Style Modifications (diet and 
exercise recommendations) 
 
Physical examination  
x 
 
x 
x 
x 
 
x 
x 
x 
Vital signs, height and weight 
measurement (calculation of BMI 
Z-score) 
x 
 
x 
x 
x 
 
x 
x 
x 
Waist circumference 
x 
 
x 
x 
x 
 
x 
x 
x 
12-Lead Electrocardiogram  
 
 
x 
 
 
 
 
x 
 
Pediatric Quality of Life (PedsQL™) 
 
 
x 
 
 
 
 
x 
 
Lab evaluation (see table “study 
biological assessment schedule”) 
x 
 
x 
x 
x 
 
x 
x 
x 
PK blood sampling  
 
 
x2 
 
x2 
x2 
 
 x2 
 
Phone call to the patient 
 
x 
 
 
 
 
 
 
 
Randomization 
 
 
x 
 
 
 
 
 
 
Review prior/concomitant 
medication 
x 
 
x 
x 
x 
 
x 
x 
x 
Adverse events 
 
Study Drug Dispensing  
 
 
x 
 
x 
 
x 
 
 


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15 
 
 
 
 
 
Screening Period 
Treatment Period 
Follow-up 
Period 
Visit 
SV1 
SV2 
V1 
V2 
V3 
V4 
V5 
V6/End of 
Treatment1 
V7/End of Study 
 
Week 
-4 to -1 
-1 week 
0 
2 
4 
4 
8 
12 
16 
Study Drug Dosing 
 
 
Daily3 
 
 
Compliance Check  
(pill count and dosing diary) 
 
 
 
x 
x 
 
x 
x 
 
 
Table 2 
Study Biological Schedule 
 
 
Screening period 
Treatment Period 
Follow-up 
period 
Visit 
SV1 
V1 
V2 
V3 
V4 
V5 
V6/EOT1 
V7/EOS 
Week 
(-4 to -1) 
0 
2 
4 
4 
8 
12 
16 
Visit Day with Permitted Margin 
-28 to -7 
1 
15 ± 2 days  
29 ± 2 days  
29 
57 ± 2 days 
85 ±2 days  
113 ± 2 days 
Labs – Hematology and Coagulation Parameters 
haemoglobin, haematocrit, RBC, WBC, differential count, platelet count, 
reticulocytes count, prothrombin time (PT) and international normalized 
ratio (INR) 
x 
x 
x 
x 
 
x 
x 
x 
Labs – Urinary Pregnancy tests4 
x 
x 
x 
x 
 
x 
x 
x 
Labs – Serology 
HIV, HAV, HBs and HEV serology 
x 
 
 
 
 
 
 
 
Labs – other parameters for eligibility assessment5 
Antimitochondrial Antibody (AMA), Alpha-1-Antitrypsin Phenotype, 
Ceruloplasmin, Ferritin, Transferrin Saturation (Serum Iron , Total Iron 
Binding Capacity) 
x5 
 
 
 
 
 
 
 
Labs – Biochemistry 
 
 
 
 
 
 
 
 
creatinine, creatinine clearance (eGFR), total protein, albumin, electrolytes 
(sodium, potassium, chloride, calcium), uric acid, urea, CPK, AST, ALT, 
GGT, alkaline phosphatase, total and conjugated bilirubin, hsCRP, fasting 
plasma glucose, fasting insulin, HOMA-IR, fructosamine, C-peptide, FFA, 
HbA1c, TSH, Cystatin C, eGFR from Cystatin C 
x 
x 
x 
x 
 
x 
x 
x 
Labs – Lipids 
 
 
 
 
 
 
 
 
Total Cholesterol, Non HDL-C, HDL-C, TG, calculated VLDL-C, ApoAI, 
ApoB, LDL-C 
x 
x 
x 
x 
 
x 
x 
x 


GFT505E-218-1 
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20 August 2020, Final 2.0 
 
16 
 
 
 
 
 
Screening period 
Treatment Period 
Follow-up 
period 
Visit 
SV1 
V1 
V2 
V3 
V4 
V5 
V6/EOT1 
V7/EOS 
Week 
(-4 to -1) 
0 
2 
4 
4 
8 
12 
16 
Visit Day with Permitted Margin 
-28 to -7 
1 
15 ± 2 days  
29 ± 2 days  
29 
57 ± 2 days 
85 ±2 days  
113 ± 2 days 
Inflammatory markers 
fibrinogen, haptoglobin, TNF-, IL-6, PAI-1   
 
x 
 
x 
 
x 
x 
x 
Liver markers: 
CK18 (M65 & M30), adiponectin, ferritin, FGF19 & FGF21, 2 
macroglobulin, hyaluronic acid, PIIINP, TIMP-1 
 
x 
 
x 
 
x 
x 
x 
Urinalysis  
α1 microglobulin, β-NAG, N-Gal, albumin, creatinine, microscopic analysis6  
 
x 
 
x 
 
x 
x 
x 
Labs – Urinalysis (dipstick) 
Specific gravity, pH, protein, glucose, ketones, bilirubin, urobilinogen, blood, 
nitrite, leukocytes 
 
x 
 
x 
 
x 
x 
x 
Labs – Additional samples 
x 
x 
 
 
 
 
x 
 
Blood Volume Collected Each Visit 
30.3 mL 
33 mL 
17.3 mL 
37.5 mL 
1 mL 
29.5 mL 
32 mL 
29.5 mL 
Total Volume of Blood Collected Over the Study Period: 210.1 mL 
1: If patient prematurely discontinues, EOT visit procedures must be performed and patient will be encouraged to return for EOS one month later. 
2: PK sample collected on Day 1 To (prior to first dose), Day 29, T0 (trough), 0.5 hour (±2 minutes), 1 hour (±2 minutes), 1.5 hour (±2 minutes), 2 hours (±5 minutes), 4 hours (±5 minutes), 6 hours (±10 
minutes), and 8 hours (±10 minutes) post dose, Day 30, 24 hours (±10 minutes) after the dose administered the previous day, and Day 85 24 hours (±10 minutes) after the dose administered the previous day. 
3: From V1 to V5 the study dosing occurs at site during the visit. 
4:  Females of childbearing potential (FOCBP) only. 
5: Parameters to be analyzed at SV1 only if not screened in the past for these tests (with available results in source documentation). 
6: Microscopic analysis is performed centrally in case urinalysis dipstick is abnormal. 
 
 
 
 


GFT505E-218-1 
Genfit 
 
20 August 2020, Final 2.0 
 
17 
 
 
 
Figure 1 
Study Schematic 
 
A: Enrollment 
 
 
 
 
 
 
 
 
 
 


GFT505E-218-1 
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20 August 2020, Final 2.0 
 
18 
 
 
 
 
B: Visit  Schedule     
 


GFT505E-218-1 
 
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1.5 
Protocol Amendments 
 
• Protocol v1.0 dated 04 January 2019  
• Protocol v2.0 dated 24 September 2019  
• Protocol v3.0 dated 21 February 2020  
 
1.6 
Treatment 
 
Patients will receive either 80 mg or 120 mg of elafibranor once daily by the oral 
route for 12 weeks. 
 
 


GFT505E-218-1 
 
20 August 2020, Final 2.0 
 
20 
 
 
 
2. 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSES 
 
2.1 
Protocol Amendments 
 
Description of amendments to the clinical study protocol which may have impacted 
the statistical analyses: 
 
Not applicable. 
 
2.2 
Changes in the Statistical Analysis Plan 
 
The following change was made in the SAP before database lock with regards to the 
analyses as compared to the analyses planned in protocol version V3.0: 
• Addition of a listing describing Adverse Event of Special Interest (AESI). 
 


GFT505E-218-1 
 
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21 
 
 
 
3. 
STATISTICAL CONSIDERATIONS 
 
Statistical analyses will be performed using the SAS® software (SAS Institute, Cary, 
NC, USA) version 9.4. 
 
Continuous data will be summarized using the number of observations, mean, 
standard deviation (SD), median, 25% (Q1) and 75% (Q3) percentiles, minimum and 
maximum. 
 
The same number of decimal places as in the raw data will be presented when 
reporting median, minimum, maximum, Q1 and Q3, 1 more decimal place than in the 
raw data will be presented when reporting mean and SD. 
 
Dichotomous and categorical data will be presented in tables along with the number 
and percentages of patients by category. 
 
No statistical test will be performed. All analyses will be descriptive. 


GFT505E-218-1 
 
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22 
 
 
 
4. 
STUDY PATIENTS 
 
4.1 
Disposition of Patients 
 
The following descriptions will be performed either on all enrolled patients (See 
Section 4.3.1 for definition) or on all included patients (See Section 4.3.2 for 
definition) globally, by dose group (80 mg vs 120 mg), by age group (8 to 11 years vs 
12 to 17 years) and by fibrosis severity (stage 0-1 vs stage 2-3), unless specified 
otherwise: 
• Disposition of patients (See Table 14.1.1.1.1 by dose group, Table 14.1.1.1.2 by 
age group and Table 14.1.1.1.3 by fibrosis severity) on all enrolled patients: 
Screened patients, Included patients, Randomized patients, Randomized and 
treated patients, Treated patients, Patients who completed the study. 
• Patients screen failed and Reason for screen failures (See Table 14.1.1.2) on all 
enrolled patients. 
• Patients not randomized and Reason for non randomized patients (See Table 
14.1.1.3) on all included patients. 
• Patients not treated and Reason for non treated patients (See Table 14.1.1.4 by 
dose group) on all included patients. 
• Patients prematurely withdrawn from the study and Reason for premature 
withdrawal (See Table 14.1.1.5.1 by dose group, Table 14.1.1.5.2 by age group 
and Table 14.1.1.5.3 by fibrosis severity) on all included patients. 
• Patient disposition by visit (See Table 14.1.1.6.1 by dose group, Table 14.1.1.6.2 
by age group and Table 14.1.1.6.3 by fibrosis severity) on all included patients: 
number of patients by visit. 
• Patients with major protocol deviations throughout the study (See Table 
14.1.2.1.1 by dose group, Table 14.1.2.1.2 by age group and Table 14.1.2.1.3 by 
fibrosis severity) on all included patients: number and percentage of patients with 
at least one major protocol deviation by category (See Section 4.2 for more 
details). 
• Patients with minor protocol deviations throughout the study (See Table 14.1.2.2 
by dose group) on all included patients: number and percentage of patients with 
at least one minor protocol deviation by category (See Section 4.2 for more 
details). 
• Analysis sets (See Table 14.1.3.1.1 by dose group, Table 14.1.3.1.2 by age 
group and Table 14.1.3.1.3 by fibrosis severity) on all included patients: number 
and percentage of patients in the PK population(s), in the Intent-To-Treat (ITT) 
population and in the Safety population (See Section 4.3.3, Section 4.3.4 and 
Section 4.3.5, respectively). 
• Exclusion from analysis sets (See Table 14.1.3.2.1 by dose group, Table 
14.1.3.2.2 by age group and Table 14.1.3.2.3 by fibrosis severity): number and 
percentage of patients excluded from the PK population(s), from the ITT 
population and from the Safety population (See Section 4.3.3, Section 4.3.4 and 
Section Error! Reference source not found., respectively). Reasons why 
patients have been excluded from analysis sets will also be described. 


GFT505E-218-1 
 
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23 
 
 
 
The following data will be listed: 
• Patients’ final status in the study in Listing 16.2.1.1, 
• Study withdrawals in Listing 16.2.1.2, including the specification of other reason 
for withdrawal, 
• Visit dates in Listing 16.2.1.3, 
• Inclusion criteria not respected in Listing 16.2.1.4, 
• Exclusion criteria not respected in Listing 16.2.1.5, 
• Randomization data in Listing 16.2.1.6, 
• Analysis data sets in Listing 16.2.1.7, 
• Reason for exclusion from analysis data sets in Listing 16.2.1.8. 
 
These listings will be sorted by patient number. 
 
4.2 
Protocol Deviations 
 
All protocol deviations will be identified and declared major or minor at a data review 
meeting (DRM) that will occur before the lock of the database of the study. The list of 
major and minor protocol deviations will be finalized during the meeting. 
 
Major protocol deviations will be listed by patient in Listing 16.2.2.1 and minor 
protocol deviations will be listed by patient in Listing 16.2.2.2. The listings will include 
all deviation descriptions and the coded category of deviation. They will be sorted by 
patient and deviation category. Patients without any protocol deviation will not be 
included in the listings. 
 
4.3 
Data Sets Analyzed 
 
The following sets of population will be used for the statistical analyses and patient 
individual data listings: all enrolled patients, all included patients, the PK 
Population(s), the ITT population and the Safety Population. 
 
4.3.1 
All Enrolled Patients 
 
All enrolled patients will include all patients who signed their informed consent form, 
i.e. all screened patients (including screen failures). This set will be used for patient 
disposition summaries and patient individual data listings. 
 
4.3.2 
All Included Patients 
 
All included patients will comprise all enrolled patients who were included in the 
study. This set will be used for patient disposition summaries. 
 
4.3.3 
Pharmacokinetic Population(s) 
 
See PK SAP. 
 


GFT505E-218-1 
 
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24 
 
 
 
4.3.4 
Intent-To-Treat (ITT) Population  
 
The ITT population will comprise all included patients who were randomized and who 
received at least one dose of study drug. This set will be used for statistical analyses 
of baseline and efficacy data. 
 
Analyses on the ITT population will be performed according to the randomization 
dose group regardless of the dose actually received. 
 
4.3.5 
Safety Population 
 
The Safety population will comprise all included patients who received at least one 
dose of study drug and have at least one post-baseline safety assessment. This set 
will be used for statistical analyses of safety data. 
 
In case the Safety population differs significantly from the ITT population, selected 
baseline data may be described on this population in addition to being described on 
the ITT population. 
 
Analyses on the Safety population will be performed according to the dose actually 
received. 
 
4.4 
Dose Switch During the Study 
 
In the unlikely event of a patient receiving an incorrect treatment kit at any time 
during the study which would result in a switch of dose (i.e., switch to a dose group 
different from the one of the kit received at Day 1), the patient will be analyzed as 
planned in the dose group corresponding to the kit received at Day 1. All efficacy 
data will be analyzed in the ITT population. Safety data, compliance and exposure 
data will be analyzed up to the timepoint when the switch occurred. Data collected 
after the switch will be considered as missing. The corresponding values will be 
flagged in the patient individual data listings with the indication of the dose group to 
which the patient was switched. 
 
 
 
 
 


GFT505E-218-1 
 
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25 
 
 
 
5. 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS 
 
Demographics and baseline characteristics will be evaluated using the following 
assessments (the list of parameters is detailed in the next sections): 
• Demographic characteristics at Screening, 
• NASH Diagnosis at Screening, 
• Alcohol Use Disorders Identification Test (AUDIT) at Screening, 
• Laboratory screen tests: 
o Serology at Screening, 
o Other parameters for eligibility assessment at Screening, 
o Urine Pregnancy test at Screening, 
• Medical and surgical history, 
• Prior medications, 
• Prior Procedures. 
 
Depending on the assessment, data will be either listed in patient individual data 
listings or descriptive statistics of baseline data will be presented (See statistical 
considerations in Section 3Error! Reference source not found.). 
 
Unless specified otherwise, descriptive statistics will be presented on the ITT 
population globally, by dose group (80 mg vs 120 mg), by age group (8 to 11 years 
vs 12 to 17 years) and by fibrosis severity (stage 0-1 vs stage 2-3). 
 
Height, Weight, BMI z-score, waist circumference, physical examination, vital signs, 
12-lead ECG, Pediatric Quality of Life (PedsQL™) and laboratory data collected at 
screening and/or Day 1 and at post-baseline visits will be described with the efficacy 
and safety criteria in Section 7.1.2, Section 9.4 and in Section 9.5. 
 
5.1.1 
Demographic Characteristics 
 
Baseline data for demographic characteristics will correspond to those collected at 
Screening. Descriptive statistics will be presented (See Table 14.1.4.1.1 by dose 
group, Table 14.1.4.1.2 by age group and Table 14.1.4.1.3 by fibrosis severity) for: 
• Sex (Male; Female), 
• Age as continuous and categorical variable (8 to 11 years and 12 to 17 years; See 
Section 11.2 for computation of age),  
• Race (American Indian or Alaska Native; Native Hawaiian or other Pacific 
Islander; Asian; White; Black or African American; Other),  
• Ethnicity (Hispanic, Latino or Spanish origin; Not Hispanic, Latino or Spanish 
origin; Unknown; Not Reported). 
 
Listing 16.2.4.1 will list demographic data for all enrolled patients, including “Assent 
date”, “Mother / legal guardian informed consent date” (or not applicable), “Father / 


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legal guardian informed consent date” (or not applicable). The specification of other 
race will also be displayed. The listing will be sorted by patient number. 
 
5.1.2 
NASH Diagnosis 
 
The following data collected at Screening for NASH diagnosis will be described (See 
Table 14.1.4.2.1 by dose group, Table 14.1.4.2.2 by age group and Table 14.1.4.2.3 
by fibrosis severity): 
• NASH type (Type 1; Type 2; Undetermined), 
• Fibrosis stage (Stage 0; Stage 1; Stage 2; Stage 3). 
 
Listing 16.2.4.2 will list data collected for NASH diagnosis including the date of liver 
biopsy confirming the diagnosis for all enrolled patients. 
 
5.1.3 
Alcohol Use Disorders Identification Test (AUDIT) 
 
Alcohol screening was performed at Screening using the AUDIT questionnaire. The 
following data will be described (See Table 14.1.4.3.1 by dose group, Table 
14.1.4.3.2 by age group and Table 14.1.4.3.3 by fibrosis severity): 
• Collection method (Interview in English; Interview with a translator), 
• Overall score. 
 
AUDIT data will be listed in Listing 16.2.4.3 for all enrolled patients. 
 
5.1.4 
Medical and Surgical History 
 
Medical and surgical history data recorded at screening visit will be coded using the 
MedDRA dictionary version 23.0. All data will be summarized (See Table 14.1.4.4.1 
by dose group, Table 14.1.4.4.2 by age group and Table 14.1.4.4.3 by fibrosis 
severity) by Primary System Organ Class (SOC) and Preferred Term (PT). 
 
The tables will be sorted by descending frequency of SOC, and, within each SOC, by 
descending frequency of PT in all patients. 
 
Medical and surgical history data will be listed in Listing 16.2.4.4 for all enrolled 
patients. Start date, whether the condition is ongoing and/or treated and stop date (if 
applicable) will also be displayed. The listing will be sorted by patient number, start 
date, Primary SOC and PT. 
 
5.2 
Prior Medications 
 
Prior medications ended before (<) the first study treatment intake will be coded 
using the World Health Organization (WHO) Drug Dictionary (WHODD) version of 
March 2020 (B3 format) (See Section 11.3 for more details). 
 
The number and percentage of patients taking prior medications will be summarized 
(See Table 14.1.4.5.1 by dose group, Table 14.1.4.5.2 by age group and Table 
14.1.4.5.3 by fibrosis severity) overall and by Anatomical Therapeutic Chemical 


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Classification (ATC) Therapeutic Subgroup (ATC level 2), Chemical Subgroup (ATC 
level 4) and WHO Drug Name. 
 
The tables will be sorted by descending frequency of ATC Therapeutic Subgroup, 
and, within each ATC Therapeutic Subgroup, by descending frequency of ATC 
Chemical Subgroup, and, within each ATC Chemical Subgroup, by descending 
frequency of Who Drug Name in all patients. 
 
Prior medications will be listed in Listing 16.2.4.5 for all enrolled patients. The listing 
will be sorted by patient number, medication start date and stop date, ATC 
Therapeutic Subgroup, ATC Chemical Subgroup and WHO Drug Name. Indication 
(Adverse Event; Medical History; Other specification), dose, frequency (Daily; Twice 
per day; 3 times per day; 4 times per day; Every other day; Every week; Every 
month; Once; As needed; Intermittent; Continuous; Per year; Unknown; Other 
specification), unit (mg; g; ug; ml; tablet; capsule; puff; drop; application; IU; Other 
specification; Not applicable; Unknown), route (Oral; Topical; Subcutaneous; 
Intramuscular; Intravenous; Sublingual; Inhalation; Epidural; Rectal; Ophthalmic; 
Intraocular; Other specification; Unknown) will also be displayed. 
 
In case non-pharmacological treatments are reported, a specific listing will be 
provided for these treatments. 
 
5.3 
Prior Procedures 
 
Prior procedures ended before (<) the first study treatment intake will be coded using 
the MedDRA dictionary version 23.0. All data will be summarized (See Table 
14.1.4.6.1 by dose group, Table 14.1.4.6.2 by age group and Table 14.1.4.6.3 by 
fibrosis severity) by Primary System Organ Class (SOC) and Preferred Term (PT). 
 
The tables will be sorted by descending frequency of SOC, and, within each SOC, by 
descending frequency of PT in all patients. 
 
Prior procedures will be listed in Listing 16.2.4.6 for all enrolled patients. Start date, 
whether the procedure is ongoing and stop date (if applicable) will also be displayed. 
The listing will be sorted by patient number, start date, Primary SOC and PT. 
 
5.4 
Laboratory Screen Tests 
 
Data collected at Screening for laboratory screen tests will only be listed in patient 
individual data listings for all enrolled patients: 
• Listing 16.2.4.7.1 will list serology parameters (Human Immunodeficiency Virus 
(HIV), Hepatitis A Virus (HAV), Hepatitis B (HBs), Hepatitis C Virus (HCV) and 
Hepatitis E virus (HEV)),  
• Listing 16.2.4.7.2 will list other laboratory parameters for eligibility assessment 
(Antimitochondrial 
Antibody 
(AMA), 
Alpha-1-Antitrypsin 
Phenotype, 
Ceruloplasmin, Ferritin, Transferrin Saturation (Serum Iron, Total Iron Binding 
Capacity)), 


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• Listing 16.2.4.7.3 will list for women only, the data on urine pregnancy test (test 
performed ? Yes No; Date of urine pregnancy test; Result: Positive; Negative) at 
Screening. This listing will additionally present the results of urine pregnancy tests 
collected at Day 1, Day 15, Day 29, Day 57, Day 85 (EOT) and Day 113 (EOS). 
 
The listings will be sorted by patient number and visit (when applicable). 


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6. 
TREATMENT COMPLIANCE 
 
The compliance of study treatment will be summarized (See Table 14.1.5.1 by dose 
group, Table 14.1.5.2 by age group and Table 14.1.5.3 by fibrosis severity) for the 
Safety population both as a continuous and categorical variables (< 80%, 80% to 
120%, > 120%) by visit (Day 29 and Day 85) and overall. 
 
The details on treatment compliance definition and computation can be found in 
Section 11.4. 
 
Data on treatment compliance, including kit and study treatment dispensation data, 
number of tablets taken, number of tablets returned and kit replacement information 
(if applicable), will be listed in Listing 16.2.5.1 for all enrolled patients. 
 
 
 


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7. 
EFFICACY EVALUATION 
 
7.1.1 
Primary Efficacy Analysis 
 
Not applicable. 
 
7.1.2 
Secondary Efficacy Analyses 
 
Values at visits and changes from baseline corresponding to secondary efficacy 
endpoints will be described by visit on the ITT population by dose group, by age 
group, by fibrosis severity and overall. 
 
Baseline value will be defined as the last measurement before the first intake of 
treatment including unscheduled/retest that could have been performed. Depending 
on endpoints, Screening and/or Day 1 data will be taken into account to obtain the 
baseline value: 
• Change from baseline in serum ALT, AST, GGT, ALP and other liver markers 
(CK18 (M65 & M30), adiponectin, ferritin, FGF19 & FGF21, α2 macroglobulin, 
hyaluronic acid, PIIINP, TIMP-1): 
o Visits: baseline, Day 15 (except other liver markers), Day 29, Day 57, Day 85 
(EOT), Day 113 (EOS), 
o Baseline: Last measurement before first intake of treatment taking including 
Screening and Day 1. 
• Change from baseline in glucose homeostasis makers (Fasting plasma glucose, 
HOMA-IR and fasting insulin): 
o Visits: baseline, Day 15, Day 29, Day 57, Day 85 (EOT), Day 113 (EOS), 
o Baseline: Last measurement before first intake of treatment including 
Screening and Day 1. 
• Change from baseline in serum lipid parameters (Total Cholesterol, Non High-
density lipoprotein cholesterol (HDL-C), HDL‑C, TG (Triglycerides), calculated 
VLDL-C (Very low-density lipoprotein), Apolipoprotein A-I (ApoAI), Apolipoprotein 
B (ApoB), Low-density lipoprotein cholesterol (LDL-C)): 
o Visits: baseline, Day 15, Day 29, Day 57, Day 85 (EOT), Day 113 (EOS), 
o Baseline: Last measurement before first intake of treatment including 
Screening and Day 1. 
• Change from baseline in body weight and BMI Z-score: 
o Visits: baseline, Day 15, Day 29, Day 57, Day 85 (EOT), Day 113 (EOS), 
o Baseline: Last measurement before first intake of treatment including 
Screening and Day 1. 
 
• Change from baseline in waist circumference: 
o Visits: baseline, Day 15, Day 29, Day 57, Day 85 (EOT), Day 113 (EOS), 


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o Baseline: Last measurement before first intake of treatment including 
Screening and Day 1. 
 
• Change from baseline in inflammatory markers (fibrinogen, haptoglobin, TNF-α, 
IL-6, PAI-1): 
o Visits: baseline, Day 29, Day 57, Day 85 (EOT), Day 113 (EOS), 
o Baseline: Last measurement before first intake of treatment including Day 1. 
 
• 
Change from baseline in PedsQLTM scores: 
o Visits: baseline, Day 85 (EOT), 
o Baseline: Last measurement before first intake of treatment including Day 1. 
 
Analyses of Secondary endpoints will be presented in the tables below: 
 
Endpoint 
Tables 
By dose 
group and 
overall 
By age 
group and 
overall 
By fibrosis 
severity and 
overall 
Change from baseline in serum ALT, AST, 
GGT and ALP (absolute and relative 
changes) 
14.2.2.1.1 
14.2.2.1.2 
14.2.2.1.3 
Change from baseline in other liver 
markers (absolute changes) 
14.2.2.2.1 
14.2.2.2.2 
14.2.2.2.3 
Change from baseline in glucose 
homeostasis makers (absolute changes) 
14.2.2.3.1 
14.2.2.3.2 
14.2.2.3.3 
Change from baseline in serum lipid 
parameters (absolute changes) 
14.2.2.4.1 
14.2.2.4.2 
14.2.2.4.3 
Change from baseline in height (cm), body 
weight (kg) and BMI Z-score (absolute 
changes) 
14.2.2.5.1 
14.2.2.5.2 
14.2.2.5.3 
Change from baseline in waist 
circumference (absolute changes) 
14.2.2.6.1 
14.2.2.6.2 
14.2.2.6.3 
Change from baseline in inflammatory 
markers (absolute changes) 
14.2.2.7.1 
14.2.2.7.2 
14.2.2.7.3 
Change from baseline in PedsQLTM scores 
(absolute changes) 
14.2.2.8.1 
14.2.2.8.2 
14.2.2.8.3 
 
Details of the computation of BMI Z-score and PedsQLTM score can be found in 
Section 11.5. 
 
Where applicable, results will be presented in Standard International (SI) units. 
 
Date for secondary efficacy endpoints will be listed for each included patient in 
Listings 16.2.6.1 to 16.2.6.7 (see Section 12.7 for details). 
 


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Additionally, data collected on changes in patients’ lifestyle diet at post baseline 
visits will be listed in Listing 16.2.6.8. 
 
7.1.3 
Statistical / Analytical Issues 
 
7.1.3.1 Adjustments for Covariates 
 
Not applicable. Analyses will only be descriptive. 
 
7.1.3.2 Handling of Dropouts or Missing Data 
 
No replacement of missing values (including those of drop outs) will be performed. 
 
7.1.3.3 Interim Analyses and Data Monitoring 
 
No interim analysis is planned. 
 
7.1.3.4 Multicenter Studies 
 
No analysis by center is planned. 
 
7.1.3.5 Multiple Comparison/Multiplicity 
 
Not applicable. 
 
7.1.3.6 Use of an ‘Efficacy’ Subset of Patients 
 
Not applicable. 
 
7.1.3.7 Active-Control Studies Intended to Show Equivalence 
 
Not applicable. 
 
7.1.3.8 Examination of Subgroups 
 
No subgroup analysis is planned. 
 
7.1.4 
Tabulation of Individual Response Data 
 
Date for secondary efficacy endpoints will be listed for each included patient in 
Listings 16.2.6.1 to 16.2.6.7 (see Section 12.7 for details). 
 
7.1.5 
Drug Dose, Drug Concentration and Relationships to Response 
 
Not applicable. 
 
7.1.6 
Drug-Drug and Drug-Disease Interactions 
 
Not applicable. 
 


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8. 
PHARMACOKINETIC EVALUATION 
 
See PK SAP. 
 


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9. 
SAFETY EVALUATION 
 
All safety parameters will be analyzed on the Safety population by dose group, by 
age group and overall. Individual data will be presented in listings for all included 
patients. 
 
9.1 
Exposure, Study and Treatment Durations 
 
The study duration (days), treatment duration (days) and duration of exposure to 
study treatment (days) will be summarized (See Table 14.3.1.1 by dose group and 
Table 14.3.1.2 by age group). The definitions of study duration, treatment duration 
and duration of exposure can be found in Section 11.6. 
 
Data on study duration, treatment duration and duration of exposure, including study 
treatment interruption data, will be listed in Listing 16.2.5.2 for all included patients. 
The listing will be sorted by patient number. 
 
9.2 
Adverse Events 
 
AEs will be coded using the MedDRA Dictionary version 23.0.  
 
In this study, seriousness, severity, relationship to study treatment, relationship to 
study procedures, action taken, action taken with study treatment and outcome were 
recorded for each episode of an AE. Specific information related to the definitions 
and conventions used for descriptions of AEs based on these data can be found in 
Section 11.7. 
 
Unless specified otherwise, descriptions of AEs will be performed by dose group, by 
age group, by fibrosis group and overall on the Safety Population. 
 
Also, unless specified otherwise, tables by primary SOC and PT will be sorted by 
descending frequency of SOC, and, within each SOC, by descending frequency of 
PT in all patients. 
 
9.2.1 
Summary of AEs 
 
An overview of AEs (See Table 14.3.2.1.1.1 by dose group and Table 14.3.2.1.1.2 
by age group) will be provided displaying the number of events along with the 
number and percentages of patients with at least one: 
• AE, 
• TEAE, 
• TEAE related to study treatment, 
• TEAE related to study procedures, 
• SAE, 
• Serious TEAE, 
• Serious TEAE related to study treatment, 


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• Serious TEAE related to study procedures, 
• AE leading to treatment withdrawal, 
• TEAE leading to treatment withdrawal, 
• AE leading to study withdrawal, 
• TEAE leading to study withdrawal, 
• Fatal AE, 
• Fatal TEAE, 
• AESI. 
 
A summary of AEs (See Table 14.3.2.1.2.1 by dose group and Table 14.3.2.1.2.2 by 
age group) displaying the number of AEs along with the number and percentage of 
patients with at least one AE will be provided according to: 
• Seriousness (Serious; Not serious), 
• Relationship to study treatment (Related; Possibly related; Unlikely related; Not 
related; Not assessable), 
• Relationship to study procedures (Related; Not Related), 
• Severity (Mild; Moderate; Severe), 
• Action taken (None; Procedure required; Withdrawn from clinical trial due to AE; 
Treatment required; Hospitalisation or prolonged hospitalisation; Other), 
• Action taken with study treatment (Drug withdrawn, Drug interrupted, Dose not 
changed, Unknown, Not applicable), 
• Outcome (Recovering / Resolving; Not recovered / not resolved; Recovered / 
resolved; Recovered / resolved with sequelae; Fatal; Unknown). 
 
A summary of TEAEs (See Table 14.3.2.1.3.1 by dose group and Table 14.3.2.1.3.2 
by age group) displaying the number of TEAEs along with the number and 
percentage of patients with at least one TEAE will be provided according to: 
Seriousness, Relationship to study treatment, Relationship to study procedures, 
Severity, Action taken, Action taken with study treatment and Outcome. 
 
A summary of SAEs (See Table 14.3.2.4.1 by dose group and Table 14.3.2.4.2 by 
age group) displaying the number of SAEs along with the number and percentage of 
patients with at least one SAE will be provided according to: Relationship to study 
treatment, Relationship to study procedures, Severity, Action taken, Action taken 
with study treatment and Outcome, and additionally according to: 
• Seriousness criteria (Death; Initial or prolonged hospitalisation; Life threatening; 
Congenital anomaly or birth defect; Persistent or significant disability/incapacity; 
Medically important event not covered by other serious criteria). 
 
The number and percentage of patients will be presented according to the number of 
AEs (1, 2 or 3 or more AEs: See Table 14.3.2.1.2.3 by dose group and Table 
14.3.2.1.2.4 by age group), the number of TEAEs (1, 2 or 3 or more TEAEs: See 
Table 14.3.2.1.3.3 by dose group and Table 14.3.2.1.3.4 by age group) and the 


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number of SAEs (1, 2 or 3 or more SAEs: See Table 14.3.2.1.4.3 by dose group and 
Table 14.3.2.1.4.4 by age group). 
 
9.2.2 
Display of Adverse Events 
 
9.2.2.1 Adverse Events 
 
The number of AEs along with the number and percentage of patients with at least 
one AE will be presented (See Table 14.3.2.2.1.1 by dose group and Table 
14.3.2.2.1.2 by age group) according to Primary SOC and PT. 
 
9.2.2.2 Treatment Emergent AEs 
 
The number of TEAEs along with the number and percentage of patients with at 
least one TEAE will be presented (See Table 14.3.2.2.2.1 by dose group and Table 
14.3.2.2.2.2 by age group) according to Primary SOC and PT. 
 
9.2.2.3 Treatment Emergent AEs Related to Study Treatment 
 
The number of TEAEs related to the study treatment along with the number and 
percentage of patients with at least one TEAE related to study treatment will be 
presented (See Table 14.3.2.2.3.1 by dose group and Table 14.3.2.2.3.2 by age 
group) according to Primary SOC and PT. 
 
9.2.2.4 Treatment Emergent AEs Related to Study Procedures 
 
The number of TEAEs related to the study procedures along with the number and 
percentage of patients with at least one TEAE related to study treatment will be 
presented (See Table 14.3.2.2.4.1 by dose group and Table 14.3.2.2.4.2 by age 
group) according to Primary SOC and PT. 
 
9.2.2.5 Treatment Emergent AEs by Maximum Event Severity 
 
The number of TEAEs along with the number and percentage of patients with at 
least one TEAE will be presented (See Table 14.3.2.2.5.1 by dose group and Table 
14.3.2.2.5.2 by age group) according to Primary SOC, PT and maximum event 
severity (when available). 
 
The tables will be sorted by descending frequency of SOC, and, within each SOC, by 
descending frequency of PT for all severities combined in all patients. 
 
9.2.2.6 Serious AEs 
 
The number of SAEs along with the number and percentage of patients with at least 
one SAE will be presented (See Table 14.3.2.2.6.1 by dose group and Table 
14.3.2.2.6.2 by age group) according to Primary SOC and PT. 
 
 
 


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9.2.2.7 Serious Treatment Emergent AEs 
 
The number of serious TEAEs along with the number and percentage of patients 
with at least one serious TEAE will be presented (See Table 14.3.2.2.7.1 by dose 
group and Table 14.3.2.2.7.2 by age group) according to Primary SOC and PT. 
 
9.2.2.8 Serious Treatment Emergent AEs Related to Study Treatment 
 
The number of serious TEAEs related to the study treatment along with the number 
and percentage of patients with at least one serious TEAE related to the study 
treatment will be presented (See Table 14.3.2.2.8.1 by dose group and Table 
14.3.2.2.8.2 by age group) according to Primary SOC and PT. 
 
9.2.2.9 Serious Treatment Emergent AEs Related to Study Procedures 
 
The number of serious TEAEs related to the study procedures along with the number 
and percentage of patients with at least one serious TEAE related to the study 
procedures will be presented (See Table 14.3.2.2.9.1 by dose group and Table 
14.3.2.2.9.2 by age group) according to Primary SOC and PT. 
 
9.2.2.10 
Serious Treatment Emergent AEs by Maximum Event Severity 
 
The number of serious TEAEs along with the number and percentage of patients 
with at least one serious TEAE will be presented (See Table 14.3.2.2.10.1 by dose 
group and Table 14.3.2.2.10.2 by age group) according to Primary SOC, PT and 
maximum event severity (when available). 
 
The tables will be sorted by descending frequency of SOC, and, within each SOC, by 
descending frequency of PT for all severities combined in all patients. 
 
9.2.2.11 
AEs Leading to Treatment Withdrawal 
 
The number of AEs leading to treatment withdrawal along with the number and 
percentage of patients with at least one AE leading to treatment withdrawal will be 
presented (See Table 14.3.2.2.11.1 by dose group and Table 14.3.2.2.11.2 by age 
group) according to Primary SOC and PT. 
 
9.2.2.12 Treatment Emergent AEs Leading to Treatment Withdrawal 
 
The number of TEAEs leading to treatment withdrawal along with the number and 
percentage of patients with at least one TEAE leading to treatment withdrawal will be 
presented (See Table 14.3.2.2.12.1 by dose group and Table 14.3.2.2.12.2 by age 
group) according to Primary SOC and PT. 
 
9.2.2.13 
AEs Leading to Study Withdrawal 
 
The number of AEs leading to study withdrawal along with the number and 
percentage of patients with at least one AE leading to study withdrawal will be 
presented (See Table 14.3.2.2.13.1 by dose group and Table 14.3.2.2.13.2 by age 
group) according to Primary SOC and PT. 


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9.2.2.14 Treatment Emergent AEs Leading to Study Withdrawal 
 
The number of TEAEs leading to study withdrawal along with the number and 
percentage of patients with at least one TEAE leading to study withdrawal will be 
presented (See Table 14.3.2.2.14.1 by dose group and Table 14.3.2.2.14.2 by age 
group) according to Primary SOC and PT. 
 
9.2.2.15 Fatal AEs 
 
The number of fatal AEs along with the number and percentage of patients with at 
least one fatal AE will be presented (See Table 14.3.2.2.15.1 by dose group and 
Table 14.3.2.2.15.2 by age group) according to Primary SOC and PT. 
 
9.2.2.16 Fatal Treatment Emergent AEs 
 
The number of fatal TEAEs along with the number and percentage of patients with at 
least one fatal TEAE will be presented (See Table 14.3.2.2.16.1 by dose group and 
Table 14.3.2.2.16.2 by age group) according to Primary SOC and PT. 
 
9.2.3 
Analysis of Adverse Events 
 
Not applicable. 
 
9.2.4 
AEs Listings 
 
AEs will be listed in Listing 16.2.7.1 for all included patients. This listing will present a 
complete description of all episodes of AEs including SOC, PT and other MedDRA 
terms as well as investigator description, episode number, start date and time, end 
date as applicable, time to onset since treatment intake as applicable (days), 
duration (days), severity, seriousness, relationship to study treatment, relationship to 
study procedures, action taken, action taken with study treatment and outcome. 
Flags will indicate which AEs are treatment emergent. 
 
The listing will be sorted by patient number, start date, end date, SOC, PT and 
investigator description. 
 
9.2.5 
Adverse Events of Special Interest 
 
AESI are TEAEs corresponding to the conceptual definition of: 
• CPK elevations of severe intensity or leading to permanent study drug 
discontinuation 
• Muscle injury symptoms of severe intensity corresponding to:  
o Muscle pain or Myalgia 
o Muscle spasms or Tremor 
o Muscle weakness 
• Transaminases elevations from baseline of severe intensity or leading to 
permanent study drug discontinuation 


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• Liver injury events of severe intensity corresponding to:  
o Hepatic impairment 
o Hepatic failure  
• Gastrointestinal symptoms of severe intensity corresponding to: 
o Abdominal pain 
o Constipation 
o Diarrhea 
o Nausea 
o Vomiting 
o Acute cholecystis 
o Acute pancreatitis 
• Fatigue and Asthenia of severe intensity 
• Serum creatinine elevations of severe intensity or leading to permanent study 
drug discontinuation 
• Renal injury events of moderate or severe intensity corresponding to: 
o Renal failure 
o Renal impairment 
o Renal colic 
 
All of the above categories will be identified via a list of MedDRA queries of PT 
codes.  
 
All AESIs will be listed with the SOC and the PT in Listing 16.2.7.2. The listing will be 
sorted as described above for Listing 16.2.7.1. 
 
9.3 
Deaths, Other Serious AEs and Other Significant AEs 
 
9.3.1 
Listings of Deaths, Other Serious AEs and Other Significant AEs 
 
Deaths, if any, SAEs and other significant AEs, i.e. AEs leading to treatment 
withdrawal and AEs leading to study withdrawal, will be listed (See Table 14.3.3.1, 
Table 14.3.3.2, Table 14.3.3.3 and Table 14.3.3.4, respectively). 
 
The listings will be sorted as described above for Listing 16.2.7.1. 
 
9.3.2 
Narratives of Deaths, Other Serious AEs and Other Significant AEs 
 
Not applicable. 
 
9.4 
Clinical Laboratory Evaluation 
 
General remarks concerning laboratory data can be found in Section 11.8. 
 
 
 


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9.4.1 
Listings of Individual Laboratory Measurements 
 
All laboratory data will be listed for all included patients by patient number, 
parameter and visit in Listing 16.2.8.1 for hematology and coagulation parameters, 
Listing 16.2.8.2 for biochemistry parameters and Listing 16.2.8.3 for urinalysis 
parameters. 
 
In case of retest, a flag will indicate which assessment was retained for the analysis. 
Where applicable, values outside the laboratory reference ranges will also be 
flagged and presented along with assessments of clinically significant values by the 
investigator. Date of sampling or reason why samples were not collected will be 
displayed. Where applicable, specifications reported in open text fields for “Other” 
categories will also be displayed. 
 
The listings will be sorted by patient number and visit. 
 
9.4.2 
Evaluation of Each Laboratory Parameter 
 
Unless specified otherwise, descriptive statistics of laboratory parameters will be 
presented by dose group, by age group, by fibrosis severity and overall on the Safety 
Population. 
 
Continuous descriptive statistics of laboratory data will be presented by parameter 
and visit (baseline, Day 15, Day 29, Day 57, Day 85 (EOT), Day 113 (EOS)) (See 
Table 14.3.4.1.1 by dose group and Table 14.3.4.1.2 by age group for hematology 
and coagulation parameters; See Table 14.3.4.2.1 by dose group and Table 
14.3.4.2.2 by age group for biochemistry parameters; See Section 11.8.1 for the list 
of parameters). 
 
Descriptive statistics at post-baseline visits of absolute changes from baseline in 
laboratory parameters as well as number and percentage of patients by category 
according to reference range (< lower limit of normality (LLN); Normal, i.e. ≥ LLN and 
≤ upper limit of normality (ULN); > ULN and < 3 ULN; ≥ 3 ULN and < 5 ULN; ≥ 5 
ULN) will also be presented in the tables. Relative changes from baseline will 
additionally be presented in the tables for ALP, GGT, AST and ALT. 
 
Shift tables showing each individual patient's Baseline values by category according 
to reference range (see above categories) versus values by category according to 
reference range at Day 85 (EOT) will be provided (See Table 14.3.4.3.1 by dose 
group and Table 14.3.4.3.2 by age group for hematology and coagulation 
parameters; See Table 14.3.4.4.1 by dose group and Table 14.3.4.4.2 by age group 
for biochemistry parameters; See Section 11.8.1 for the list of parameters). 
 
Descriptive statistics at baseline and post-baseline visits (baseline, Day 15, Day 29, 
Day 57, Day 85 (EOT), Day 113 (EOS)) of urinalysis parameters (See Section 11.8.1 
for the list of parameters) will be presented (See Table 14.3.4.5.1 by dose group and 
Table 14.3.4.5.2 by age group for urinalysis parameters. 
 
Continuous descriptive statistics of urinalysis (dipstick) parameters (Specific Gravity, 
pH and Urobilinogen) will be presented by parameter and visit (baseline, Day 29, 


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Day 57, Day 85 (EOT), Day 113 (EOS)) (See Table 14.3.4.6.1 by dose group and 
Table 14.3.4.6.2 by age group for urinalysis (dipstick) parameters). Descriptive 
statistics at post-baseline visits of absolute changes from baseline in urinalysis 
(dipstick) parameters (Specific Gravity, pH and Urobilinogen) as well as number and 
percentage of patients by category according to reference range (< lower limit of 
normality (LLN); Normal, i.e. ≥ LLN and ≤ upper limit of normality (ULN); > ULN) will 
also be presented in the tables. 
 
Furthermore, number and percentage of patients by category (Positive; Negative) at 
baseline and post-baseline visits of urinalysis (dipstick) parameters (Protein, 
Glucose, Ketones, Bilirubin, Blood, Nitrites, Leukocytes) will also be presented in the 
tables. 
 
Baseline value will be defined as the last measurement, including Screening and  
Day 1 taking into account unscheduled assessments/retests that could have been 
performed, before the first intake of treatment. 
 
9.5 
Vital Signs, Physical Findings and Other Observations Related to 
Safety 
 
9.5.1 
Vital Signs 
 
Unless specified otherwise, descriptive statistics of vital sign parameters will be 
presented by dose group, by age group, by fibrosis severity and overall on the Safety 
Population. 
 
Continuous descriptive statistics for vital signs (Systolic blood pressure (mmHg), 
Diastolic blood pressure (mmHg), Heart rate (beats/min)) after 5 minutes rest in the 
seating position will be presented by parameter and visit (baseline, Day 15, Day 29, 
Day 57, Day 85 (EOT), Day 113 (EOS)) (See Table 14.3.5.1.1 by dose group and 
Table 14.3.5.1.2 by age group). 
 
Descriptive statistics at baseline and post-baseline visits of changes from baseline in 
vital sign parameters as well as the number and percentage of patients by out of 
range significance category (Not Clinically Significant; Clinically Significant) will also 
be presented in the tables. 
 
Baseline value will be defined as the last measurement, including Screening and  
Day 1 taking into account unscheduled assessments that could have been 
performed, before the first intake of treatment. 
 
Vital sign data will be listed in Listing 16.2.9.1 for all included patients, including vital 
sign measurement date and time or the reason why measurement was not 
performed. The listing will be sorted by patient number, parameter and visit. 
 
 
 
 
 


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9.5.2 
Other Observations Related to Safety 
 
9.5.2.1 Physical Examination 
 
Unless specified otherwise, descriptive statistics of physical examination parameters 
will be presented by dose group, by age group, by fibrosis severity and overall on the 
Safety Population. 
 
Physical examination findings (Not Clinically Significant; Clinically Significant) were 
collected according to pre-defined body systems: General Appearance; Skin; Eyes; 
Ears; Nose; Throat; Neck and Thyroid; Lungs; Heart; Upper/lower Extremities; 
Lymph Nodes; Abdomen; Musculoskeletal System; Basic Neurological Assessment; 
Other. 
 
The number and percentage of patients with a physical examination abnormality will 
be summarized by visit (baseline, Day 15, Day 29, Day 57, Day 85 (EOT), Day 113 
(EOS)) overall and by pre-defined body system (See Table 14.3.5.2.1.1 by dose 
group and Table 14.3.5.2.1.2 by age group). Within each visit, the table will be sorted 
by descending frequency of body system in all patients. 
 
The number and percentage of patients with clinically significant abnormal physical 
examination will be presented in the same way (See Table 14.3.5.2.2.1 by dose 
group and Table 14.3.5.2.2.2 by age group). 
 
Baseline value will be defined as the last measurement, including Screening and  
Day 1 taking into account unscheduled assessments/retests that could have been 
performed, before the first intake of treatment. 
 
Physical examination data will be listed in Listing 16.2.9.2 by patient, visit and pre-
defined body system for all included patients, including physical examination date or 
the reason why physical examination was not performed. Specification of body 
system “Other” will also be displayed. The listing will be sorted by patient number. 
 
9.5.2.2 Electrocardiogram 
 
Unless specified otherwise, descriptive statistics of 12-lead ECG parameters will be 
presented by dose group, by age group, by fibrosis severity and overall on the Safety 
Population. 
 
Descriptive statistics at baseline and Day 85 (EOT) of whether the ECG was 
performed (Yes; No) and of the interpretation of the ECG (Normal; Abnormal, Not 
Clinically Significant; Abnormal, Clinically Significant) will be presented in the tables 
(See Table 14.3.5.3.1 by dose group and Table 14.3.5.3.2 by age group). 
 
Baseline value will be defined as the last measurement, including Day 1 taking into 
account unscheduled assessments that could have been performed, before the first 
intake of treatment. 
 


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12-lead ECG data will be listed in Listing 16.2.9.3 for all included patients, including 
ECG date or the reason why ECG was not performed. The listing will be sorted by 
patient number and visit. 
 
9.6 
Concomitant Medications 
 
Concomitant medications ended after or on the date (≥) of the first study treatment 
intake will be coded using the World Health Organization (WHO) Drug Dictionary 
(WHODD) version of March 2020 (B3 format) (See Section 11.3 for more details). 
 
Unless specified otherwise, concomitant medications will be described by dose 
group, by age group, by fibrosis severity and overall on the Safety Population. 
 
The number and percentage of patients taking concomitant medications will be 
summarized overall and by Anatomical Therapeutic Chemical Classification (ATC) 
Therapeutic Subgroup (ATC level 2), Chemical Subgroup (ATC level 4) and WHO 
Drug Name (See Table 14.3.6.1 by dose group and Table 14.3.6.2 by age group). 
 
The tables will be sorted by descending frequency of ATC Therapeutic Subgroup, 
and, within each ATC Therapeutic Subgroup, by descending frequency of ATC 
Chemical Subgroup, and, within each ATC Chemical Subgroup, by descending 
frequency of Who Drug Name in all patients. 
 
Concomitant medications will be listed in Listing 16.2.10.1 for all included patients. 
The listing will be sorted by patient number, medication start date and stop date, 
ATC Therapeutic Subgroup, ATC Chemical Subgroup and WHO Drug Name. 
Indication (Adverse Event; Medical History; Other specification), dose, frequency 
(Daily; Twice per day; 3 times per day; 4 times per day; Every other day; Every 
week; Every month; Once; As needed; Intermittent; Continuous; Per year; Unknown; 
Other specification), unit (mg; g; ug; ml; tablet; capsule; puff; drop; application; IU; 
Other specification; Not applicable; Unknown), route (Oral; Topical; Subcutaneous; 
Intramuscular; Intravenous; Sublingual; Inhalation; Epidural; Rectal; Ophthalmic; 
Intraocular; Other specification; Unknown) will also be displayed. 
 
In case non-pharmacological treatments are reported, a specific listing will be 
provided for these treatments. 
 
9.7 
Concomitant Procedures 
 
Concomitant procedures ended after or on the date (≥) of the first study treatment 
intake will be coded using the MedDRA dictionary version 23.0. All data will be 
summarized (See Table 14.3.7.1 by dose group and Table 14.3.7.2 by age group) by 
Primary System Organ Class (SOC) and Preferred Term (PT). 
 
The tables will be sorted by descending frequency of SOC, and, within each SOC, by 
descending frequency of PT in all patients. 
 
Concomitant procedures will be listed in Listing 16.2.10.2 for all included patients. 
Start date, whether the procedure is ongoing and stop date (if applicable) will also be 


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displayed. The listing will be sorted by patient number, start date, Primary SOC and 
PT. 
 
9.8 
Collection of PK Blood Samples 
 
Information on collection of PK blood samples reported in the eCRF will not be 
described. These data will only be listed. 
 
Data on collection of PK blood samples at visits and timepoints will be listed in 
Listing 16.2.11.1 for all included patients, including whether the sample was taken, 
the sample date and time and treatment administration first and last dates and times. 
The listing will be sorted by patient number, visit and timepoint. 
 
 


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10. 
TABLES, FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED 
IN THE TEXT 
 
10.1 
General Remarks about Tables 
 
Results presented in section 14 of ICH report will be created using SAS version 9.4. 
All table templates can be found in Attachment. This section lists all tables in the 
order in which they are expected to appear in the study report. 
 
10.2 
Demographic Data Summary and Figures 
 
10.2.1 Study Patients 
Table 14.1.1.1.1 
Disposition of Patients by Dose Group - All Enrolled Patients 
Table 14.1.1.1.2 
Disposition of Patients by Age Group - All Enrolled Patients 
Table 14.1.1.1.3 
Disposition of Patients by Fibrosis Severity - All Enrolled 
Patients 
 
Table 14.1.1.2 
Reason for Screen Failures - All Enrolled Patients 
Table 14.1.1.3 
Reason for Non Randomized Patients - All Included Patients 
Table 14.1.1.4 
Reason for Non Treated Patients by Dose Group - All Included 
Patients 
 
Table 14.1.1.5.1 
Reason for Premature Withdrawals by Dose Group - All Included 
Patients 
Table 14.1.1.5.2 
Reason for Premature Withdrawals by Age Group - All Included 
Patients 
Table 14.1.1.5.3 
Reason for Premature Withdrawals by Fibrosis Severity - All 
Included Patients 
 
Table 14.1.1.6.1 
Disposition of Patients by Visit and Dose Group - All Included 
Patients 
Table 14.1.1.6.2 
Disposition of Patients by Visit and Age Group - All Included 
Patients 
Table 14.1.1.6.3 
Disposition of Patients by Visit and Fibrosis Severity - All 
Included Patients 
 
Table 14.1.2.1.1 
Major Protocol Deviations by Dose Group - All Included Patients 
Table 14.1.2.1.2 
Major Protocol Deviations by Age Group - All Included Patients 
Table 14.1.2.1.3 
Major Protocol Deviations by Fibrosis Severity - All Included 
Patients 
 
Table 14.1.2.2 
Minor Protocol Deviations by Dose Group - All Included Patients 
 
Table 14.1.3.1.1 
Analysis Sets by Dose Group - All Included Patients 
Table 14.1.3.1.2 
Analysis Sets by Age Group - All Included Patients 


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Table 14.1.3.1.3 
Analysis Sets by Fibrosis Severity - All Included Patients 
 
Table 14.1.3.2.1 
Reasons for Exclusion From Analysis Sets by Dose Group - All 
Included Patients 
Table 14.1.3.2.2 
Reasons for Exclusion From Analysis Sets by Age Group - All 
Included Patients 
Table 14.1.3.2.3 
Reasons for Exclusion From Analysis Sets by Fibrosis Severity - 
All Included Patients 
 
10.2.2 Demographics and Patient Characteristics 
Table 14.1.4.1.1 
Demographic Characteristics at Baseline by Dose Group -
 Intent-To-Treat Population 
Table 14.1.4.1.2 
Demographic Characteristics at Baseline by Age Group - Intent-
To-Treat Population 
Table 14.1.4.1.3 
Demographic Characteristics at Baseline by Fibrosis Severity - 
Intent-To-Treat Population 
 
Table 14.1.4.2.1 
Nash Diagnosis at Baseline by Dose Group - Intent-To-Treat 
Population 
Table 14.1.4.2.2 
Nash Diagnosis at Baseline by Age Group - Intent-To-Treat 
Population 
Table 14.1.4.2.3 
Nash Diagnosis at Baseline by Fibrosis Severity - Intent-To-
Treat Population 
 
Table 14.1.4.3.1 
Alcohol Use Disorders Identification Test (AUDIT) at Baseline by 
Dose Group - Intent-To-Treat Population  
Table 14.1.4.3.2 
Alcohol Use Disorders Identification Test (AUDIT) at Baseline by 
Age Group - Intent-To-Treat Population  
Table 14.1.4.3.3 
Alcohol Use Disorders Identification Test (AUDIT) at Baseline by 
Fibrosis Severity - Intent-To-Treat Population  
 
Table 14.1.4.4.1 
Surgical and Medical History by Dose Group - Intent-To-Treat 
Population 
Table 14.1.4.4.2 
Surgical and Medical History by Age Group - Intent-To-Treat 
Population 
Table 14.1.4.4.3 
Surgical and Medical History by Fibrosis Severity - Intent-To-
Treat Population 
 
Table 14.1.4.5.1  Prior Medications by ATC Therapeutic Subgroup, Chemical 
Subgroup, WHO Drug Name and Dose Group - Intent-To-Treat 
Population 
Table 14.1.4.5.2  Prior Medications by ATC Therapeutic Subgroup, Chemical 
Subgroup, WHO Drug Name and Age Group - Intent-To-Treat 
Population 


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Table 14.1.4.5.3  Prior Medications by ATC Therapeutic Subgroup, Chemical 
Subgroup, WHO Drug Name and Fibrosis Severity - Intent-To-
Treat Population 
 
Table 14.1.4.6.1  Prior Procedures by Primary System Organ Class, Preferred 
Term and Dose Group - Intent-To-Treat Population 
Table 14.1.4.6.2  Prior Procedures by Primary System Organ Class, Preferred 
Term and Age Group - Intent-To-Treat Population 
Table 14.1.4.6.3  Prior Procedures by Primary System Organ Class, Preferred 
Term and Fibrosis Severity - Intent-To-Treat Population 
 
10.2.3 Treatment Compliance 
Table 14.1.5.1 
 Treatment Compliance by Dose Group - Safety Population 
Table 14.1.5.2 
 Treatment Compliance by Age Group - Safety Population 
Table 14.1.5.3 
 Treatment Compliance by Fibrosis Severity - Safety Population 
 
10.3 
Efficacy Data Summary Figures and Tables 
 
10.3.1 Secondary Efficacy Variables 
Table 14.2.2.1.1 
Changes from Baseline in Liver Markers by Dose Group - Intent-
To-Treat Population 
Table 14.2.2.1.2  
Changes from Baseline in Liver Markers by Age Group - Intent-
To-Treat Population 
Table 14.2.2.1.3  
Changes from Baseline in Liver Markers by Fibrosis Severity - 
Intent-To-Treat Population 
 
Table 14.2.2.2.1 
Changes from Baseline in Other Liver Markers by Dose Group - 
Intent-To-Treat Population 
Table 14.2.2.2.2  
Changes from Baseline in Other Liver Markers by Age Group - 
Intent-To-Treat Population 
Table 14.2.2.2.3  
Changes from Baseline in Other Liver Markers by Fibrosis 
Severity - Intent-To-Treat Population 
 
Table 14.2.2.3.1 
Changes from Baseline in Markers of Glucose Homeostasis by 
Dose Group - Intent-To-Treat Population 
Table 14.2.2.3.2 
Changes from Baseline in Markers of Glucose Homeostasis by 
Age Group - Intent-To-Treat Population 
Table 14.2.2.3.3 
Changes from Baseline in Markers of Glucose Homeostasis by 
Fibrosis Severity - Intent-To-Treat Population 
 
Table 14.2.2.4.1 
Changes from Baseline in Serum Lipid Parameters by Dose 
Group - Intent-To-Treat Population 
Table 14.2.2.4.2 
Changes from Baseline in Serum Lipid Parameters by Age 
Group - Intent-To-Treat Population 


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Table 14.2.2.4.3 
Changes from Baseline in Serum Lipid Parameters by Fibrosis 
Severity - Intent-To-Treat Population 
 
Table 14.2.2.5.1 
Changes from Baseline in Height, Body Weight and Body Mass 
Index Z-Score by Dose Group - Intent-To-Treat Population 
Table 14.2.2.5.2 
Changes from Baseline in Height, Body Weight and Body Mass 
Index Z-Score by Age Group - Intent-To-Treat Population 
Table 14.2.2.5.3 
Changes from Baseline in Height, Body Weight and Body Mass 
Index Z-Score by Fibrosis Severity - Intent-To-Treat Population 
 
Table 14.2.2.6.1 
Changes from Baseline in Waist Circumference by Dose Group - 
Intent-To-Treat Population 
Table 14.2.2.6.2 
Changes from Baseline in Waist Circumference by Age Group - 
Intent-To-Treat Population 
Table 14.2.2.6.3 
Changes from Baseline in Waist Circumference by Fibrosis 
Severity - Intent-To-Treat Population 
 
Table 14.2.2.7.1 
Changes from Baseline in Inflammatory Markers by Dose Group 
- Intent-To-Treat Population 
Table 14.2.2.7.2 
Changes from Baseline in Inflammatory Markers by Age Group - 
Intent-To-Treat Population 
Table 14.2.2.7.3 
Changes from Baseline in Inflammatory Markers by Fibrosis 
Severity - Intent-To-Treat Population 
 
Table 14.2.2.8.1 
Changes from Baseline in Pediatric Quality of Life (PedsQLTM) 
Scores by Dose Group - Intent-To-Treat Population 
Table 14.2.2.8.2 
Changes from Baseline in Pediatric Quality of Life (PedsQLTM) 
Scores by Age Group - Intent-To-Treat Population 
Table 14.2.2.8.3 
Changes from Baseline in Pediatric Quality of Life (PedsQLTM) 
Scores by Fibrosis Severity - Intent-To-Treat Population 
 
10.4 
Safety Data Summary Figures and Tables 
 
10.4.1 Exposure, Study and Treatment Durations 
 
Table 14.3.1.1 
Exposure, Study and Treatment Durations by Dose Group - 
Safety Population 
Table 14.3.1.2 
Exposure, Study and Treatment Durations by Age Group - 
Safety Population 
 
10.4.2 Displays of Adverse Events 
 
10.4.2.1 
Summary of Adverse Events 
 
Table 14.3.2.1.1.1 Overview of Adverse Events by Dose Group - Safety Population 


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Table 14.3.2.1.1.2 Overview of Adverse Events by Age Group - Safety Population 
 
Table 14.3.2.1.2.1 Overall Safety Summary of Adverse Events by Dose Group - 
Safety Population 
Table 14.3.2.1.2.2 Overall Safety Summary of Adverse Events by Age Group - 
Safety Population 
 
Table 14.3.2.1.2.3 Number and Percentage of Patients According to Number of 
Adverse Events by Dose Group - Safety Population 
Table 14.3.2.1.2.4 Number and Percentage of Patients According to Number of 
Adverse Events by Age Group - Safety Population 
 
Table 14.3.2.1.3.1 Overall Safety Summary of Treatment Emergent Adverse Events 
by Dose Group - Safety Population 
Table 14.3.2.1.3.2 Overall Safety Summary of Treatment Emergent Adverse Events 
by Age Group - Safety Population 
 
Table 14.3.2.1.3.3 Number and Percentage of Patients According to Number of 
Treatment Emergent Adverse Events and Dose Group - Safety 
Population 
Table 14.3.2.1.3.4 Number and Percentage of Patients According to Number of 
Treatment Emergent Adverse Events and Age Group - Safety 
Population 
 
Table 14.3.2.1.4.1 Overall Safety Summary of Serious Adverse Events by Dose 
Group - Safety Population 
Table 14.3.2.1.4.2 Overall Safety Summary of Serious Adverse Events by Age 
Group - Safety Population 
 
Table 14.3.2.1.4.3 Number and Percentage of Patients According to Number of 
Serious Adverse Events and Dose Group - Safety Population 
Table 14.3.2.1.4.4 Number and Percentage of Patients According to Number of 
Serious Adverse Events and Age Group - Safety Population 
 
10.4.2.2 
Display of Adverse Events 
 
Table 14.3.2.2.1.1 Adverse Events by Primary System Organ Class, Preferred 
Term and Dose Group - Safety Population 
Table 14.3.2.2.1.2 Adverse Events by Primary System Organ Class, Preferred 
Term and Age Group - Safety Population 
 
Table 14.3.2.2.2.1 Treatment Emergent Adverse Events by Primary System Organ 
Class, Preferred Term and Dose Group - Safety Population 
Table 14.3.2.2.2.2 Treatment Emergent Adverse Events by Primary System Organ 
Class, Preferred Term and Age Group - Safety Population 
 


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Table 14.3.2.2.3.1 Treatment Emergent Adverse Events Related to Study 
Treatment by Primary System Organ Class, Preferred Term and 
Dose Group - Safety Population 
Table 14.3.2.2.3.2 Treatment Emergent Adverse Events Related to Study 
Treatment by Primary System Organ Class, Preferred Term and 
Age Group - Safety Population 
 
Table 14.3.2.2.4.1 Treatment Emergent Adverse Events Related to Study 
Procedures by Primary System Organ Class, Preferred Term 
and Dose Group - Safety Population 
Table 14.3.2.2.4.2 Treatment Emergent Adverse Events Related to Study 
Procedures by Primary System Organ Class, Preferred Term 
and Age Group - Safety Population 
 
Table 14.3.2.2.5.1 Treatment Emergent Adverse Events by Maximum Event 
Severity, Primary System Organ Class, Preferred Term and 
Dose Group - Safety Population 
Table 14.3.2.2.5.2 Treatment Emergent Adverse Events by Maximum Event 
Severity, Primary System Organ Class, Preferred Term and Age 
Group - Safety Population 
 
Table 14.3.2.2.6.1 Serious Adverse Events by Primary System Organ Class, 
Preferred Term and Dose Group - Safety Population 
Table 14.3.2.2.6.2 Serious Adverse Events by Primary System Organ Class, 
Preferred Term and Age Group - Safety Population 
 
Table 14.3.2.2.7.1 Serious Treatment Emergent Adverse Events by Primary 
System Organ Class, Preferred Term and Dose Group - Safety 
Population 
Table 14.3.2.2.7.2 Serious Treatment Emergent Adverse Events by Primary 
System Organ Class, Preferred Term and Age Group - Safety 
Population 
Table 14.3.2.2.8.1 Serious Treatment Emergent Adverse Events Related to Study 
Treatment by Primary System Organ Class, Preferred Term and 
Dose Group - Safety Population 
Table 14.3.2.2.8.2 Serious Treatment Emergent Adverse Events Related to Study 
Treatment by Primary System Organ Class, Preferred Term and 
Age Group - Safety Population 
 
Table 14.3.2.2.9.1 Serious Treatment Emergent Adverse Events Related to Study 
Procedures by Primary System Organ Class, Preferred Term 
and Dose Group - Safety Population 
Table 14.3.2.2.9.2 Serious Treatment Emergent Adverse Events Related to Study 
Procedures by Primary System Organ Class, Preferred Term 
and Age Group - Safety Population 
 


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Table 14.3.2.2.10.1 Serious Treatment Emergent Adverse Events by Maximum 
Event Severity, Primary System Organ Class, Preferred Term 
and Dose Group - Safety Population 
Table 14.3.2.2.10.2 Serious Treatment Emergent Adverse Events by Maximum 
Event Severity, Primary System Organ Class, Preferred Term 
and Age Group - Safety Population 
 
Table 14.3.2.2.11.1 Adverse Events Leading to Treatment Withdrawal by Primary 
System Organ Class, Preferred Term and Dose Group - Safety 
Population 
Table 14.3.2.2.11.2 Adverse Events Leading to Treatment Withdrawal by Primary 
System Organ Class, Preferred Term and Age Group - Safety 
Population 
 
Table 14.3.2.2.12.1 Treatment Emergent Adverse Events Leading to Treatment 
Withdrawal by Primary System Organ Class, Preferred Term and 
Dose Group - Safety Population 
Table 14.3.2.2.12.2 Treatment Emergent Adverse Events Leading to Treatment 
Withdrawal by Primary System Organ Class, Preferred Term and 
Age Group - Safety Population 
 
Table 14.3.2.2.13.1 Adverse Events Leading to Study Withdrawal by Primary System 
Organ Class, Preferred Term and Dose Group - Safety 
Population 
Table 14.3.2.2.13.2 Adverse Events Leading to Study Withdrawal by Primary System 
Organ Class, Preferred Term and Age Group - Safety Population 
 
Table 14.3.2.2.14.1 Treatment Emergent Adverse Events Leading to Study 
Withdrawal by Primary System Organ Class, Preferred Term and 
Dose Group - Safety Population 
Table 14.3.2.2.14.2 Treatment Emergent Adverse Events Leading to Study 
Withdrawal by Primary System Organ Class, Preferred Term and 
Age Group - Safety Population 
Table 14.3.2.2.15.1 Fatal Adverse Events by Primary System Organ Class, Preferred 
Term and Dose Group - Safety Population 
Table 14.3.2.2.13.2 Fatal Adverse Events by Primary System Organ Class, Preferred 
Term and Age Group - Safety Population 
 
Table 14.3.2.2.16.1 Fatal Treatment Emergent Adverse Events by Primary System 
Organ Class, Preferred Term and Dose Group - Safety 
Population 
Table 14.3.2.2.16.2 Fatal Treatment Emergent Adverse Events by Primary System 
Organ Class, Preferred Term and Age Group - Safety Population 
 
10.4.3 Listings of Deaths, Other Serious and Significant Adverse Events 
Table 14.3.3.1  
Listing of Deaths - Safety Population 


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Table 14.3.3.2  
Listing of Serious Adverse Events - Safety Population 
Table 14.3.3.3  
Listing of Adverse Events Leading to Treatment Withdrawal - 
Safety Population 
Table 14.3.3.4  
Listing of Adverse Events Leading to Study Withdrawal - Safety 
Population 
 
10.4.4 Narratives of Deaths, Other Serious and Significant Adverse Events 
Not applicable. 
 
10.4.5 Abnormal Laboratory Value Listing 
See patient individual data Listings 16.2.8.1 and 16.2.8.2. 
 
10.4.6 Display of Laboratory Data 
Table 14.3.4.1.1 
Hematology and Coagulation Parameters by Dose Group - 
Safety Population 
Table 14.3.4.1.2 
Hematology and Coagulation Parameters by Age Group - Safety 
Population 
 
Table 14.3.4.2.1 
Biochemistry Parameters by Dose Group - Safety Population 
Table 14.3.4.2.2 
Biochemistry Parameters by Age Group - Safety Population 
 
Table 14.3.4.3.1 
Shift Table of Hematology and Coagulation Parameters by Dose 
Group - Safety Population 
Table 14.3.4.3.2 
Shift Table of Hematology and Coagulation Parameters by Age 
Group - Safety Population 
 
Table 14.3.4.4.1 
Shift Table of Biochemistry Parameters by Dose Group - Safety 
Population 
Table 14.3.4.4.2 
Shift Table of Biochemistry Parameters by Age Group - Safety 
Population 
Table 14.3.4.5.1 
Urinalysis Parameters by Dose Group - Safety Population  
Table 14.3.4.5.2 
Urinalysis Parameters by Age Group - Safety Population  
 
Table 14.3.4.6.1 
Urinalysis (Dipstick) Parameters by Dose Group - Safety 
Population  
Table 14.3.4.6.2 
Urinalysis (Dipstick) Parameters by Age Group - Safety 
Population 
 
10.4.7 Vital Signs, Physical Findings and Other Observations Related to 
Safety 
Table 14.3.5.1.1 
Vital Signs Parameters by Dose Group - Safety Population 
Table 14.3.5.1.2 
Vital Signs Parameters by Age Group - Safety Population 
 


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Table 14.3.5.2.1.1 Physical Examination Abnormalities by Dose Group - Safety 
Population 
Table 14.3.5.2.1.2 Physical Examination Abnormalities by Age Group - Safety 
Population 
 
Table 14.3.5.2.2.1 Physical Examination Clinically Significant Abnormalities by 
Dose Group - Safety Population 
Table 14.3.5.2.2.2 Physical Examination Clinically Significant Abnormalities by Age 
Group - Safety Population 
 
Table 14.3.5.3.1 
12-Lead ECG Parameters by Dose Group - Safety Population 
Table 14.3.5.3.2 
12-Lead ECG Parameters by Age Group - Safety Population 
 
10.4.8 Concomitant Medications 
 
Table 14.3.6.1 
Concomitant Medications by ATC Therapeutic Subgroup, 
Chemical Subgroup, WHO Drug Name and Dose Group - Safety 
Population 
Table 14.3.6.2 
Concomitant Medications by ATC Therapeutic Subgroup, 
Chemical Subgroup, WHO Drug Name and Age Group - Safety 
Population 
 
10.4.9 Concomitant Procedures 
 
Table 14.3.7.1 
 Concomitant Procedures by Primary System Organ Class, 
Preferred Term and Dose Group - Safety Population 
Table 14.3.7.2 
 Concomitant Procedures by Primary System Organ Class, 
Preferred Term and Age Group - Safety Population 
 
 
 


GFT505E-218-1 
 
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11. 
DOCUMENTATION OF STATISTICAL METHODS 
 
11.1 
Missing and Partially Known Dates  
 
Missing dates will not be replaced. Unless specified otherwise, partially known dates 
will be defined as follows for duration computation: 
 
• Partially known begin date: 
• If only the day is missing, it is estimated as the first day of the month or first visit 
date if the month/year are the same as the month/year of the first visit. 
• If month and day are missing, they are estimated as January 1 or first visit date 
if the year is the same as the year of the first visit. 
• The first visit date will be the date of screening (or the date of study treatment 
intake in case of treatment emergent AE duration computation). 
• Partially known end date: 
• If only the day is missing, it is estimated as the last day of the month or last visit 
date if the month/year are the same as the month/year of the last visit. 
• If month and day are missing, they are estimated as December 31 or last visit 
date if the year is the same as the year of the last visit. 
• The last visit date will be the date of Early Termination visit or End of Study 
visit. 
 
The original dates without estimation will be presented in the listings. 
 
11.2 
Demographics and Other Baseline Characteristics 
 
The following rules will be applied for the computation of age: 
 
• Age will be calculated in years using the following formula: age = (initial visit date 
– birth date) / 365.25. Date of initial visit will be taken at baseline visit. Results will 
be expressed with one decimal. 
 
11.3 
Medications 
 
Medications will be coded using the WHO Drug dictionary version of March 2020 (B3 
format). Tables and listings will be presented by Anatomical Therapeutic Chemical 
Classification (ATC) Therapeutic Subgroup (ATC level 2), Chemical Subgroup (ATC 
level 4) and WHO Drug Name. 
 
A prior medication is a medication which was ended before the first study treatment 
intake (medication end date < first study treatment intake date). A concomitant 
medication is a medication which ended after or on the date of the first study 
treatment intake (medication end date ≥ first study treatment intake date). 
 
When the end date of a medication intake is missing, the medication will be 
considered as concomitant with the study treatment. 
 


GFT505E-218-1 
 
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When start and/or end dates of a medication intake are only partially known, 
medications will be categorized as prior treatment or concomitant using the following 
rules: 
• If the partial end date is before (<) the first study treatment intake (i.e. year or year 
& month is/are before (<) the first study treatment intake date) then the medication 
is categorized as prior. 
• If the partial end date is after or on the date (≥) of the first study treatment intake 
(i.e. year or year & month is/are after or on the date (≥) of the first study treatment 
intake date) then the medication is categorized as concomitant. 
 
11.4 
Treatment Compliance 
 
• Treatment compliance (%) at a post-baseline visit will be calculated as follows: 
number of tablets taken between the previous visit and the current visit divided by 
number of tablets that should be taken between the previous visit and the current 
visit. 
With: 
o Number of tablets taken = number of tablets dispensed at the previous visit - 
number of tablets returned at the visit. For Visit 3 (Day 29), the previous visit 
when tablets were dispensed is Visit 1 (Day 1). 
o Number of tablets that should be taken = one tablet per day x theoretical 
treatment duration between the previous visit and the current visit, i.e. (date 
of current visit - date of previous visit + 1) - number of days when the tablets 
have not been taken. 
o Number of days when the tablets have not been taken, i.e., number of days 
of treatment interruption = Min(date restarted, date of current visit) - 
Max(interruption start date, date of previous visit) + 1. 
 
• The overall treatment compliance (%) will be calculated as follows: total number 
of tablets taken divided by total number of tablets that should be taken. 
With: 
o Total number of tablets taken = sum over the visits of (number of tablets 
dispensed at the previous visit - number of tablets returned at the visit). 
o Total number of tablets that should be taken = one tablet per day x 
theoretical treatment duration, i.e. (last post baseline visit date - date of Visit 
1 (Day 1) + 1) - total number of days when the tablets have not been taken. 
o Total number of days when the tablets have not been taken, i.e., total number 
of days of treatment interruption = sum over the visits of (date restarted - 
interruption start date + 1). 
 
In case one of the dates is missing or incomplete in the above computations then 
the duration (number of days) is missing. See Section 11.1 for handling partially 
known dates in case dates are only partially known. If one of the variables 
necessary to compute the patient compliance is missing, the compliance will be 
set to missing. Results will be expressed with one decimal. 
 


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11.5 
Efficacy Variables 
 
• The height and the waist circumference can be collected in two different units: 
cm and inch. All results will be presented in cms. Therefore, the conversion from 
inch to cm is the following: 
 
1 𝑖𝑛𝑐ℎ= 2.54 𝑐𝑚𝑠 
 
• The weight can be collected in two different units: kg and lb. All results will be 
presented in kgs. Therefore, the conversion from lb to kg is the following: 
 
1 𝑙𝑏= 0.453592 𝑘𝑔𝑠 
 
• The Body Mass Index - BMI (Kg/m²) of patients will be calculated using the 
following formula: 
 
 
 
 
where height is in centimeters (cm) and weight in kilograms (kg). Results will be 
expressed with one decimal. 
 
• The BMI Z-score of patients will be calculated using the following formula: 
 
𝐵𝑀𝐼 𝑍−s𝑐𝑜𝑟𝑒= [ (𝐵𝑀𝐼
𝑀)
𝐿
−1 ] / (𝐿∗𝑆) 
 
where BMI is the Body Mass Index and M, L and S are values depending on sex 
and age (month) displayed in the table in Appendix. 
 
• The child, adolescent and parent/legal guardian PedsQL™ (Version 4.0) Generic 
Core Scales is composed of 23 items comprising 4 dimensions (Physical 
Functioning, Emotional Functioning, Social Functioning, and School Functioning).  
 
The scoring of  PedsQL™ will be performed as follows: 
o Items will be reversed scored and linearly transformed to a 0-100 scale, so 
that higher scores indicate better HRQOL (Health-Related Quality of Life). To 
reverse score, transform the 0-4 scale items to 0-100 as follows: 0=100, 
1=75, 2=50, 3=25, 4=0. 
o To create Scale Scores, the mean will be computed as the sum of the items 
over the number of items answered for the corresponding dimension. If more 
than 50% of the items in the dimension are missing, the Scale Score should 
not be computed. 
o To create the Psychosocial Health Summary Score, the mean will be 
computed as the sum of the items over the number of items answered in the 
Emotional, Social, and School Functioning Scales. The Physical Health 
Summary Score is the same as the Physical Functioning Scale Score. 
height)²
 
 
(0.01
weight
 
 
BMI

=


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o To create the Total Score, the mean will be computed as the sum of all the 
items over the number of items answered on all the dimensions. 
 
11.6 
Exposure and Durations 
 
Study duration will be defined in days as: Early Termination visit date (in case of 
withdrawal from the study) or End of Study visit date minus Screening visit date plus 
1. 
 
Treatment duration will be defined in days as last treatment intake date minus first 
treatment intake date plus 1. First treatment intake date corresponds to study 
treatment administration date collected at Visit 1 (Day 1). Last treatment intake date 
corresponds to last study treatment administration date collected at EOT (in case of 
withdrawal from the study) or at Visit 6 (Day 85).  
 
Duration of exposure will be defined in days as duration of study treatment minus 
the number of days when the tablets have not been taken, i.e. study drug 
interruption: sum over the visits of (date restarted - interruption start date + 1). 
 
In case one of the dates is missing or incomplete in the above computations then the 
duration is missing. See Section 11.1 for handling partially known dates in case 
dates are only partially known. 
 
11.7 
Adverse Events 
 
All AEs will be categorized as treatment emergent or not treatment emergent as 
follows: 
• Not treatment emergent: all events which started before (<) the date of first 
study treatment intake (at least one episode with start date/time before (<) the 
first study treatment intake date/time). 
• Treatment emergent: 1) all events which started after or on the date (≥) of first 
study treatment (all episodes with start date/time after or on the date (≥) of the 
first study treatment intake date/time) or 2) all events which started before the 
date of first study treatment intake and worsened or became serious after or on 
the date of the first study treatment intake (in case of multiple episodes of the 
same event before the date of first treatment intake, the severity of the episode 
closest to the date of first treatment intake will be taken into account). 
 
In case of missing severity, the emergence of adverse events will be determined 
as showed in the table below: 
 
 


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Table 3 Assessment of Treatment Emergent Adverse Events 
Severity 
 
 
AE considered as 
Closest episode 
before the date of 
first dose intake 
Episode(s) after the 
date of first 
treatment intake 
(included) 
Missing 
Missing 
 
Emergent 
Missing 
Mild 
 
Non emergent 
Missing 
Moderate 
 
Emergent 
Missing 
Severe 
 
Emergent 
Mild  
Missing 
 
Emergent 
Moderate 
Missing 
 
Emergent 
Severe 
Missing 
 
Non emergent 
 
If a start date is missing or unknown for an episode of an adverse event and the 
end date/time is either missing or after or on the date (≥) of the first study 
treatment intake date/time, the episode will be considered as starting after or on 
the date of the first study treatment intake. 
 
When start and/or end dates of an episode of an adverse events are only partially 
known, episodes will be categorized as starting before or after/on the date of the 
first treatment intake using the following rules: 
• If the partial end date is before (<) the first study treatment intake (i.e. year or 
year & month is/are before (<) the first study treatment intake date) then the 
episode will be considered as starting before the first study treatment intake, 
• If the partial start date is after or on the date (≥) of the first study treatment 
intake (i.e. year or year & month is/are after or on the date (≥) of the first 
study treatment intake date) then the episode will be considered as starting 
after or on the date of the first study treatment intake. 
 
Seriousness, severity, relationship to the study treatment, action taken and outcome 
are recorded for each episode of an adverse event. The following rules will be 
applied for the descriptions of AEs: 
• For descriptions based on seriousness: if one episode of the AE is serious 
(whatever the time it occurs), the whole event will be considered as serious. 
• For descriptions based on severity: the worst intensity among all episodes of the 
AE during the studied period will be taken into account. 
• For descriptions based on relationship to study treatment (Yes/No): if one 
episode of the AE is Related or Possibly Related or relationship to the study 
treatment is Not assessable (after or on the date of first treatment intake), the 
whole event will be considered as related to the study treatment. 
• For descriptions based on relationship to study treatment by category: the 
whole event will be categorized according to the episode (after or on the date of 


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first treatment intake) associated with the “highest” category according to the 
following order: Not related < Unlikely related < Possibly related < Related. Not 
assessable relationship is considered as related to the study treatment. 
• For descriptions based on relationship to study procedures (Yes/No): if one 
episode of the AE is Related to the study procedures or if relationship to the 
study procedures is Not assessable (after or on the date of first treatment intake), 
the whole event will be considered as related to the study treatment. 
• For descriptions based on action taken: if one episode of the AE leads to study 
withdrawal, the whole event will be considered as leading to study withdrawal. 
Otherwise, the action taken of the AE will be the action taken of the episode 
occurring on or after the day of emergence of the AE. 
• For descriptions based on action taken with study treatment: if one episode of 
the AE leads to study treatment withdrawal, the whole event will be considered 
as leading to study treatment withdrawal. Otherwise, the action taken with study 
treatment of the AE will be the action taken of the episode occurring on or after 
the day of emergence of the AE. 
• For descriptions based on outcome: the information of the last episode of the AE 
will be taken into account. 
 
The maximum event severity is the greatest severity associated with a PT for a 
patient according to the following order: Mild < Moderate < Severe. Missing severity 
is considered as severe (except for the definition of emergence: See Table 3). 
 
The duration of an adverse event will be computed in days as the difference 
between the end date of the last episode and the start date of the first episode using 
the following formula: end date of the last episode - start date of the first episode +1 
(See Section 11.1 for handling missing and partially known dates). 
 
Time to onset since first treatment intake of a treatment emergent adverse event 
will be computed in days as the difference between the start date of the first episode 
after the first treatment intake and the date of first treatment intake using the 
following formula: start date of the first episode after the first treatment intake - date 
of first treatment intake +1 (See Section 11.1 for handling missing and partially 
known dates). 
 
11.8 
Laboratory Data 
 
11.8.1 Laboratory Evaluation 
 
Laboratory measurements that will be summarized in the report are those defined in 
the study protocol: 
• Hematology and coagulation parameters: haemoglobin, haematocrit, red 
blood cells (RBC), white blood cells (WBC), differential count, platelet count, 
reticulocytes count, prothrombin time (PT) and international normalized ratio 
(INR). 


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• Biochemistry: creatinine, creatinine clearance (eGFR), total protein, albumin, 
electrolytes (sodium, potassium, chloride, calcium), uric acid, urea, Creatinine 
Phosphokinase (CPK), AST, ALT, GGT, ALP, total and conjugated bilirubin, 
hsCRP, fasting plasma glucose, fasting insulin, HOMA-IR, fructosamine,  
C-peptide, Fatty Free Acids (FFA), Hemoglobin A1C (HbA1c), Thyroid 
Stimulation Hormone (TSH), Cystatin C, eGFR from Cystatin C. 
Note: some biochemistry parameters will be quantitively described both as 
efficacy and safety data. Safety analyses will additionally include descriptions 
according to reference range and shift tables. 
• Urinalysis: α1 microglobulin, β-NAG, N-Gal, albumin, creatinine, microscopic 
analysis6. 
• Urinalysis (dipstick): Specific gravity, pH, protein, glucose, ketones, bilirubin, 
urobilinogen, blood, nitrite, leukocytes. 
 
Results will be presented Standard International (SI) units. 
 
In case of multiple results at the baseline visit for a same laboratory parameter and a 
same patient, only the result of the reliable (i.e. analyzable) test which date is closer 
and before (<) the intake of study treatment date will be retained for analysis. 
 
In case of multiple results at follow-up visit for a same laboratory parameter and a 
same patient: 
• Only the result of the first (earlier date) analyzable test will be retained for 
descriptive analysis by visit. 
• The result of the first (earlier date) analyzable test will be retained for shift table 
by visit, unless the first test value is within range and the retest value (from 
analyzable test) is out of range, in which case the retest (later date) will be 
retained in the shift table at the corresponding visit. 
 
All laboratory tests will be presented in the data listings for each patient. 
 
11.8.2 Reference Ranges 
 
For each laboratory parameter, reference ranges used to categorize the results as 
“below lower limit of normality”, “normal” or “above upper limit of normality” will be 
those provided by the laboratories which performed the tests and that were entered 
in the database. 
 
Results expressed with symbols, like “< LLN”, i.e. below lower limit of normality, and 
“> ULN”, i.e. above upper limit of normality, will be considered for the quantitative 
analyses of laboratory parameters as LLN/2 and ULN, respectively. 
 
Original results (with symbols) as reported in the database will be displayed in the 
individual data listings. 


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12. 
PATIENT DATA LISTINGS 
 
12.1 
General Remarks about Listings 
 
Listings presented in section 16.2 of ICH report will be created with SAS version 9.4. 
In each listing, the patients will be presented by patient number and, when relevant, 
parameter, visit and timepoint.  
 
The following sections present the listings in the order in which they are planned to 
appear in the study report. 
 
12.2 
Disposition of Patients 
 
Listing 16.2.1.1  
Patients’ Final Status in the Study  
Listing 16.2.1.2  
Study Withdrawals 
Listing 16.2.1.3  
Visit Dates 
Listing 16.2.1.4  
Inclusion Criteria Not Respected 
Listing 16.2.1.5  
Exclusion Criteria Not Respected 
Listing 16.2.1.6  
Randomization Data 
Listing 16.2.1.7  
Analysis Data Sets 
Listing 16.2.1.8  
Patients Excluded From Analysis Data Sets 
 
12.3 
Protocol Deviations 
 
Listing 16.2.2.1  
Major Protocol Deviations 
Listing 16.2.2.2  
Minor Protocol Deviations 
 
12.4 
Patients Excluded from Efficacy Analysis 
 
Not applicable. 
 
12.5 
Demographic Data 
 
Listing 16.2.4.1  
Demographic Characteristics 
Listing 16.2.4.2 
NASH Diagnosis 
Listing 16.2.4.3 
Alcohol Use Disorders Identification Test (AUDIT) 
Listing 16.2.4.4  
Medical and Surgical History 
Listing 16.2.4.5  
Prior Medications 
Listing 16.2.4.6  
Prior Procedures 
Listing 16.2.4.7.1 
Serology Parameters 
Listing 16.2.4.7.2 
Other Laboratory Parameters for Eligibility Assessment 


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Listing 16.2.4.7.3 
Urine Pregnancy Tests 
 
12.6 
Compliance and/or Drug Concentration Data 
 
Listing 16.2.5.1  
Treatment Compliance 
Listing 16.2.5.2  
Exposure, Study and Treatment Durations 
 
12.7 
Individual Efficacy Response Data 
 
Listing 16.2.6.1  
Liver Markers 
Listing 16.2.6.2  
Markers of Glucose Homeostasis 
Listing 16.2.6.3  
Serum Lipid Parameters 
Listing 16.2.6.4  
Height, Body Weight and Body Mass Index Z-Score 
Listing 16.2.6.5  
Waist Circumference 
Listing 16.2.6.6  
Inflammatory markers 
Listing 16.2.6.7  
Pediatric Quality of Life (PedsQLTM) 
Listing 16.2.6.8  
Lifestyle Diet 
 
12.8 
Adverse Event Listings 
 
Listing 16.2.7.1 
Adverse Events 
Listing 16.2.7.2  
Adverse Events of Special Interest 
 
12.9 
Listing of Individual Laboratory Measurements 
 
Listing 16.2.8.1  
Hematology and Coagulation Parameters 
Listing 16.2.8.2  
Biochemistry Parameters 
Listing 16.2.8.3  
Urinalysis Parameters 
 
12.10 Vital signs, Physical Findings and Other Observations Related to 
Safety 
 
Listing 16.2.9.1  
Vital Signs Parameters 
Listing 16.2.9.2  
Physical Examination 
Listing 16.2.9.3  
12-Lead ECG Parameters 
 
12.11 Concomitant Medications and Procedures 
 
Listing 16.2.10.1 
Concomitant Medications 
Listing 16.2.10.2 
Concomitant Procedures 
 


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12.12 Collection of PK Blood Samples 
 
Listing 16.2.11.1 
Collection of PK Blood Samples 
 


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13. 
APPENDIX 
 
Table 4 
Data for Computation of BMI Z-score 
Sex 
Age (month) 
L 
M 
S 
Male 
96 
-1.4629 
15.7368 
0.09526 
Male 
97 
-1.479 
15.7606 
0.09567 
Male 
98 
-1.4947 
15.7848 
0.09609 
Male 
99 
-1.5101 
15.8094 
0.09651 
Male 
100 
-1.5252 
15.8344 
0.09693 
Male 
101 
-1.5399 
15.8597 
0.09735 
Male 
102 
-1.5542 
15.8855 
0.09778 
Male 
103 
-1.5681 
15.9116 
0.09821 
Male 
104 
-1.5817 
15.9381 
0.09864 
Male 
105 
-1.5948 
15.9651 
0.09907 
Male 
106 
-1.6076 
15.9925 
0.09951 
Male 
107 
-1.6199 
16.0205 
0.09994 
Male 
108 
-1.6318 
16.049 
0.10038 
Male 
109 
-1.6433 
16.0781 
0.10082 
Male 
110 
-1.6544 
16.1078 
0.10126 
Male 
111 
-1.6651 
16.1381 
0.1017 
Male 
112 
-1.6753 
16.1692 
0.10214 
Male 
113 
-1.6851 
16.2009 
0.10259 
Male 
114 
-1.6944 
16.2333 
0.10303 
Male 
115 
-1.7032 
16.2665 
0.10347 
Male 
116 
-1.7116 
16.3004 
0.10391 
Male 
117 
-1.7196 
16.3351 
0.10435 
Male 
118 
-1.7271 
16.3704 
0.10478 
Male 
119 
-1.7341 
16.4065 
0.10522 
Male 
120 
-1.7407 
16.4433 
0.10566 
Male 
121 
-1.7468 
16.4807 
0.10609 
Male 
122 
-1.7525 
16.5189 
0.10652 
Male 
123 
-1.7578 
16.5578 
0.10695 
Male 
124 
-1.7626 
16.5974 
0.10738 
Male 
125 
-1.767 
16.6376 
0.1078 
Male 
126 
-1.771 
16.6786 
0.10823 
Male 
127 
-1.7745 
16.7203 
0.10865 
Male 
128 
-1.7777 
16.7628 
0.10906 
Male 
129 
-1.7804 
16.8059 
0.10948 


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Sex 
Age (month) 
L 
M 
S 
Male 
130 
-1.7828 
16.8497 
0.10989 
Male 
131 
-1.7847 
16.8941 
0.1103 
Male 
132 
-1.7862 
16.9392 
0.1107 
Male 
133 
-1.7873 
16.985 
0.1111 
Male 
134 
-1.7881 
17.0314 
0.1115 
Male 
135 
-1.7884 
17.0784 
0.11189 
Male 
136 
-1.7884 
17.1262 
0.11228 
Male 
137 
-1.788 
17.1746 
0.11266 
Male 
138 
-1.7873 
17.2236 
0.11304 
Male 
139 
-1.7861 
17.2734 
0.11342 
Male 
140 
-1.7846 
17.324 
0.11379 
Male 
141 
-1.7828 
17.3752 
0.11415 
Male 
142 
-1.7806 
17.4272 
0.11451 
Male 
143 
-1.778 
17.4799 
0.11487 
Male 
144 
-1.7751 
17.5334 
0.11522 
Male 
145 
-1.7719 
17.5877 
0.11556 
Male 
146 
-1.7684 
17.6427 
0.1159 
Male 
147 
-1.7645 
17.6985 
0.11623 
Male 
148 
-1.7604 
17.7551 
0.11656 
Male 
149 
-1.7559 
17.8124 
0.11688 
Male 
150 
-1.7511 
17.8704 
0.1172 
Male 
151 
-1.7461 
17.9292 
0.11751 
Male 
152 
-1.7408 
17.9887 
0.11781 
Male 
153 
-1.7352 
18.0488 
0.11811 
Male 
154 
-1.7293 
18.1096 
0.11841 
Male 
155 
-1.7232 
18.171 
0.11869 
Male 
156 
-1.7168 
18.233 
0.11898 
Male 
157 
-1.7102 
18.2955 
0.11925 
Male 
158 
-1.7033 
18.3586 
0.11952 
Male 
159 
-1.6962 
18.4221 
0.11979 
Male 
160 
-1.6888 
18.486 
0.12005 
Male 
161 
-1.6811 
18.5502 
0.1203 
Male 
162 
-1.6732 
18.6148 
0.12055 
Male 
163 
-1.6651 
18.6795 
0.12079 
Male 
164 
-1.6568 
18.7445 
0.12102 
Male 
165 
-1.6482 
18.8095 
0.12125 
Male 
166 
-1.6394 
18.8746 
0.12148 


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Sex 
Age (month) 
L 
M 
S 
Male 
167 
-1.6304 
18.9398 
0.1217 
Male 
168 
-1.6211 
19.005 
0.12191 
Male 
169 
-1.6116 
19.0701 
0.12212 
Male 
170 
-1.602 
19.1351 
0.12233 
Male 
171 
-1.5921 
19.2 
0.12253 
Male 
172 
-1.5821 
19.2648 
0.12272 
Male 
173 
-1.5719 
19.3294 
0.12291 
Male 
174 
-1.5615 
19.3937 
0.1231 
Male 
175 
-1.551 
19.4578 
0.12328 
Male 
176 
-1.5403 
19.5217 
0.12346 
Male 
177 
-1.5294 
19.5853 
0.12363 
Male 
178 
-1.5185 
19.6486 
0.1238 
Male 
179 
-1.5074 
19.7117 
0.12396 
Male 
180 
-1.4961 
19.7744 
0.12412 
Male 
181 
-1.4848 
19.8367 
0.12428 
Male 
182 
-1.4733 
19.8987 
0.12443 
Male 
183 
-1.4617 
19.9603 
0.12458 
Male 
184 
-1.45 
20.0215 
0.12473 
Male 
185 
-1.4382 
20.0823 
0.12487 
Male 
186 
-1.4263 
20.1427 
0.12501 
Male 
187 
-1.4143 
20.2026 
0.12514 
Male 
188 
-1.4022 
20.2621 
0.12528 
Male 
189 
-1.39 
20.3211 
0.12541 
Male 
190 
-1.3777 
20.3796 
0.12554 
Male 
191 
-1.3653 
20.4376 
0.12567 
Male 
192 
-1.3529 
20.4951 
0.12579 
Male 
193 
-1.3403 
20.5521 
0.12591 
Male 
194 
-1.3277 
20.6085 
0.12603 
Male 
195 
-1.3149 
20.6644 
0.12615 
Male 
196 
-1.3021 
20.7197 
0.12627 
Male 
197 
-1.2892 
20.7745 
0.12638 
Male 
198 
-1.2762 
20.8287 
0.1265 
Male 
199 
-1.2631 
20.8824 
0.12661 
Male 
200 
-1.2499 
20.9355 
0.12672 
Male 
201 
-1.2366 
20.9881 
0.12683 
Male 
202 
-1.2233 
21.04 
0.12694 
Male 
203 
-1.2098 
21.0914 
0.12704 


GFT505E-218-1 
 
20 August 2020, Final 2.0 
 
67 
 
 
 
Sex 
Age (month) 
L 
M 
S 
Male 
204 
-1.1962 
21.1423 
0.12715 
Female 
96 
-1.388 
15.681 
0.11291 
Female 
97 
-1.3966 
15.7107 
0.11335 
Female 
98 
-1.4047 
15.7415 
0.1138 
Female 
99 
-1.4125 
15.7732 
0.11424 
Female 
100 
-1.4199 
15.8058 
0.11469 
Female 
101 
-1.427 
15.8394 
0.11513 
Female 
102 
-1.4336 
15.8738 
0.11557 
Female 
103 
-1.4398 
15.909 
0.11601 
Female 
104 
-1.4456 
15.9451 
0.11644 
Female 
105 
-1.4511 
15.9818 
0.11688 
Female 
106 
-1.4561 
16.0194 
0.11731 
Female 
107 
-1.4607 
16.0575 
0.11774 
Female 
108 
-1.465 
16.0964 
0.11816 
Female 
109 
-1.4688 
16.1358 
0.11859 
Female 
110 
-1.4723 
16.1759 
0.11901 
Female 
111 
-1.4753 
16.2166 
0.11943 
Female 
112 
-1.478 
16.258 
0.11985 
Female 
113 
-1.4803 
16.2999 
0.12026 
Female 
114 
-1.4823 
16.3425 
0.12067 
Female 
115 
-1.4838 
16.3858 
0.12108 
Female 
116 
-1.485 
16.4298 
0.12148 
Female 
117 
-1.4859 
16.4746 
0.12188 
Female 
118 
-1.4864 
16.52 
0.12228 
Female 
119 
-1.4866 
16.5663 
0.12268 
Female 
120 
-1.4864 
16.6133 
0.12307 
Female 
121 
-1.4859 
16.6612 
0.12346 
Female 
122 
-1.4851 
16.71 
0.12384 
Female 
123 
-1.4839 
16.7595 
0.12422 
Female 
124 
-1.4825 
16.81 
0.1246 
Female 
125 
-1.4807 
16.8614 
0.12497 
Female 
126 
-1.4787 
16.9136 
0.12534 
Female 
127 
-1.4763 
16.9667 
0.12571 
Female 
128 
-1.4737 
17.0208 
0.12607 
Female 
129 
-1.4708 
17.0757 
0.12643 
Female 
130 
-1.4677 
17.1316 
0.12678 
Female 
131 
-1.4642 
17.1883 
0.12713 


GFT505E-218-1 
 
20 August 2020, Final 2.0 
 
68 
 
 
 
Sex 
Age (month) 
L 
M 
S 
Female 
132 
-1.4606 
17.2459 
0.12748 
Female 
133 
-1.4567 
17.3044 
0.12782 
Female 
134 
-1.4526 
17.3637 
0.12816 
Female 
135 
-1.4482 
17.4238 
0.12849 
Female 
136 
-1.4436 
17.4847 
0.12882 
Female 
137 
-1.4389 
17.5464 
0.12914 
Female 
138 
-1.4339 
17.6088 
0.12946 
Female 
139 
-1.4288 
17.6719 
0.12978 
Female 
140 
-1.4235 
17.7357 
0.13009 
Female 
141 
-1.418 
17.8001 
0.1304 
Female 
142 
-1.4123 
17.8651 
0.1307 
Female 
143 
-1.4065 
17.9306 
0.13099 
Female 
144 
-1.4006 
17.9966 
0.13129 
Female 
145 
-1.3945 
18.063 
0.13158 
Female 
146 
-1.3883 
18.1297 
0.13186 
Female 
147 
-1.3819 
18.1967 
0.13214 
Female 
148 
-1.3755 
18.2639 
0.13241 
Female 
149 
-1.3689 
18.3312 
0.13268 
Female 
150 
-1.3621 
18.3986 
0.13295 
Female 
151 
-1.3553 
18.466 
0.13321 
Female 
152 
-1.3483 
18.5333 
0.13347 
Female 
153 
-1.3413 
18.6006 
0.13372 
Female 
154 
-1.3341 
18.6677 
0.13397 
Female 
155 
-1.3269 
18.7346 
0.13421 
Female 
156 
-1.3195 
18.8012 
0.13445 
Female 
157 
-1.3121 
18.8675 
0.13469 
Female 
158 
-1.3046 
18.9335 
0.13492 
Female 
159 
-1.297 
18.9991 
0.13514 
Female 
160 
-1.2894 
19.0642 
0.13537 
Female 
161 
-1.2816 
19.1289 
0.13559 
Female 
162 
-1.2739 
19.1931 
0.1358 
Female 
163 
-1.2661 
19.2567 
0.13601 
Female 
164 
-1.2583 
19.3197 
0.13622 
Female 
165 
-1.2504 
19.382 
0.13642 
Female 
166 
-1.2425 
19.4437 
0.13662 
Female 
167 
-1.2345 
19.5045 
0.13681 
Female 
168 
-1.2266 
19.5647 
0.137 


GFT505E-218-1 
 
20 August 2020, Final 2.0 
 
69 
 
 
 
Sex 
Age (month) 
L 
M 
S 
Female 
169 
-1.2186 
19.624 
0.13719 
Female 
170 
-1.2107 
19.6824 
0.13738 
Female 
171 
-1.2027 
19.74 
0.13756 
Female 
172 
-1.1947 
19.7966 
0.13774 
Female 
173 
-1.1867 
19.8523 
0.13791 
Female 
174 
-1.1788 
19.907 
0.13808 
Female 
175 
-1.1708 
19.9607 
0.13825 
Female 
176 
-1.1629 
20.0133 
0.13841 
Female 
177 
-1.1549 
20.0648 
0.13858 
Female 
178 
-1.147 
20.1152 
0.13873 
Female 
179 
-1.139 
20.1644 
0.13889 
Female 
180 
-1.1311 
20.2125 
0.13904 
Female 
181 
-1.1232 
20.2595 
0.1392 
Female 
182 
-1.1153 
20.3053 
0.13934 
Female 
183 
-1.1074 
20.3499 
0.13949 
Female 
184 
-1.0996 
20.3934 
0.13963 
Female 
185 
-1.0917 
20.4357 
0.13977 
Female 
186 
-1.0838 
20.4769 
0.13991 
Female 
187 
-1.076 
20.517 
0.14005 
Female 
188 
-1.0681 
20.556 
0.14018 
Female 
189 
-1.0603 
20.5938 
0.14031 
Female 
190 
-1.0525 
20.6306 
0.14044 
Female 
191 
-1.0447 
20.6663 
0.14057 
Female 
192 
-1.0368 
20.7008 
0.1407 
Female 
193 
-1.029 
20.7344 
0.14082 
Female 
194 
-1.0212 
20.7668 
0.14094 
Female 
195 
-1.0134 
20.7982 
0.14106 
Female 
196 
-1.0055 
20.8286 
0.14118 
Female 
197 
-0.9977 
20.858 
0.1413 
Female 
198 
-0.9898 
20.8863 
0.14142 
Female 
199 
-0.9819 
20.9137 
0.14153 
Female 
200 
-0.974 
20.9401 
0.14164 
Female 
201 
-0.9661 
20.9656 
0.14176 
Female 
202 
-0.9582 
20.9901 
0.14187 
Female 
203 
-0.9503 
21.0138 
0.14198 
Female 
204 
-0.9423 
21.0367 
0.14208 
Source: https://www.who.int/growthref/who2007_bmi_for_age/en/


GFT505E-218-1 
 
20 August 2020, Final 2.0 
 
70 
 
 
 
14. 
ATTACHEMENTS 
 
Table templates: See attached document “Genfit - GFT505-218-1 - SAP - Final 2.0 - 
Attachment - Tables”.