Trial Outcomes & Findings for Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC) (NCT NCT04526665)

Results Overview

Cholestasis response was defined as alkaline phosphatase (ALP) \< 1.67 x upper limit of normal (ULN) and total bilirubin (TB) \<= ULN and ALP decrease from baseline \>= 15% at Week 52 and based on the composite strategy imputing non-response for participants who experienced intercurrent events (ICEs) (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

161 participants

Primary outcome timeframe

At Week 52

Results posted on

2026-02-03

Participant Flow

This Phase III, double-blind (DB), placebo-controlled study followed by an open-label long-term extension (LTE) was conducted in participants with primary biliary cholangitis (PBC) at 82 sites in 14 countries (Argentina, Belgium, Brazil, Canada, Chile, France, Germany, Italy, South Africa, Spain, Switzerland, Turkey, United Kingdom, and United States). First participant was recruited on 24 September 2020 and data cut-off (DCO) date was 01 June 2023.

This study consisted of a 2- to 12-week screening period, a 52- to 104-week DB period consisting of a 52-week common DB period followed by a variable DB period of up to 52 weeks in duration; a 4- to 5-year LTE period; and a 4-week safety follow-up period after the last dose of study treatment. A total of 161 participants were randomized in 2:1 ratio to receive once daily elafibranor or placebo. Results are presented up to DCO of 01 June 2023.

Participant milestones

Participant milestones
Measure	Elafibranor 80 mg Participants received elafibranor 80 milligrams (mg) orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Overall Study STARTED	108	53
Overall Study COMPLETED	94	46
Overall Study NOT COMPLETED	14	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Elafibranor 80 mg Participants received elafibranor 80 milligrams (mg) orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Overall Study Withdrawal by Subject	6	3
Overall Study Adverse Event	4	1
Overall Study Physician Decision	2	2
Overall Study Death	2	0
Overall Study Other	0	1

Baseline Characteristics

Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Elafibranor 80 mg n=108 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).	Total n=161 Participants Total of all reporting groups
Age, Continuous	57.5 Years STANDARD_DEVIATION 8.4 • n=13 Participants	56.4 Years STANDARD_DEVIATION 9.3 • n=15 Participants	57.1 Years STANDARD_DEVIATION 8.7 • n=28 Participants
Sex: Female, Male Female	102 Participants n=13 Participants	52 Participants n=15 Participants	154 Participants n=28 Participants
Sex: Female, Male Male	6 Participants n=13 Participants	1 Participants n=15 Participants	7 Participants n=28 Participants
Race/Ethnicity, Customized White	101 Participants n=13 Participants	46 Participants n=15 Participants	147 Participants n=28 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=13 Participants	0 Participants n=15 Participants	2 Participants n=28 Participants
Race/Ethnicity, Customized Asian	1 Participants n=13 Participants	3 Participants n=15 Participants	4 Participants n=28 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=13 Participants	1 Participants n=15 Participants	1 Participants n=28 Participants
Race/Ethnicity, Customized Other	3 Participants n=13 Participants	2 Participants n=15 Participants	5 Participants n=28 Participants
Race/Ethnicity, Customized Not Reported	1 Participants n=13 Participants	1 Participants n=15 Participants	2 Participants n=28 Participants

PRIMARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants.

Cholestasis response was defined as alkaline phosphatase (ALP) \< 1.67 x upper limit of normal (ULN) and total bilirubin (TB) \<= ULN and ALP decrease from baseline \>= 15% at Week 52 and based on the composite strategy imputing non-response for participants who experienced intercurrent events (ICEs) (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=108 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response to Treatment Based on Cholestasis Response at Week 52	50.9 Percentage of participants Interval 41.6 to 60.2	3.8 Percentage of participants Interval 1.0 to 12.8

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants.

Response to treatment based on normalization of ALP at Week 52 was defined as percentage of participants with ALP =\<1.0× ULN and based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=108 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Key Secondary Endpoint: Percentage of Participants With Response to Treatment Based on ALP Normalization at Week 52	14.8 Percentage of participants Interval 9.3 to 22.7	0 Percentage of participants Interval 0.0 to 6.8

SECONDARY outcome

Timeframe: Baseline (up to 14 days pre-dose) and Week 52

Population: The Pruritus ITT population included all participants from the ITT analysis set with baseline PBC Worst Itch NRS score ≥4. Only those participants with data collected at Week 52 are reported.

The PBC Worst Itch NRS is a simple, self-administered patient reported outcome (PRO) questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake).

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=44 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=22 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Key Secondary Endpoint: Change From Baseline in Pruritus Based on PBC Worst Itch Numeric Rating Scale (NRS) Score in Participants With Baseline PBC Worst Itch NRS Score ≥4 to Week 52	-1.930 Scores on a scale Interval -2.602 to -1.258	-1.146 Scores on a scale Interval -2.143 to -0.15

SECONDARY outcome

Timeframe: Baseline (up to 14 days pre-dose) and Week 24

Population: The Pruritus ITT population included all participants from the ITT analysis set with baseline PBC Worst Itch NRS score ≥4. Only those participants with data collected at Week 24 are reported.

The PBC Worst Itch NRS is a simple, self-administered PRO questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake).

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=44 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=22 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Key Secondary Endpoint: Change From Baseline in Pruritus Based on PBC Worst Itch NRS Score in Participants With Baseline PBC Worst Itch NRS Score ≥4 to Week 24	-1.598 Scores on a scale Interval -2.246 to -0.951	-1.255 Scores on a scale Interval -2.201 to -0.309

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Weeks 4, 13, 26, 39 and 52

Population: The ITT population included all randomized participants. Only those participants with data collected at specified timepoints are reported.

Blood samples were collected at specified timepoints for assessment of ALP. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=104 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=48 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in ALP at Weeks 4, 13, 26, 39 and 52 Week 39	-134.7 Units per Liter (U/L) Standard Deviation 89.8	-20.0 Units per Liter (U/L) Standard Deviation 90.1
Change From Baseline in ALP at Weeks 4, 13, 26, 39 and 52 Week 52	-117.7 Units per Liter (U/L) Standard Deviation 96.5	-8.8 Units per Liter (U/L) Standard Deviation 91.2
Change From Baseline in ALP at Weeks 4, 13, 26, 39 and 52 Week 4	-116.4 Units per Liter (U/L) Standard Deviation 63.1	-14.3 Units per Liter (U/L) Standard Deviation 92.6
Change From Baseline in ALP at Weeks 4, 13, 26, 39 and 52 Week 13	-131.8 Units per Liter (U/L) Standard Deviation 74.6	-19.1 Units per Liter (U/L) Standard Deviation 78.3
Change From Baseline in ALP at Weeks 4, 13, 26, 39 and 52 Week 26	-126.2 Units per Liter (U/L) Standard Deviation 85.5	-6.0 Units per Liter (U/L) Standard Deviation 75.6

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

ALP response was defined as ALP decrease from baseline \>= 10%; ALP decrease from baseline \>= 20% and ALP decrease from baseline \>= 40% at Week 52 and based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=106 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With ALP Response From Baseline at Week 52 ALP response >= 10% decrease from baseline	75.5 Percentage of participants	22.6 Percentage of participants
Percentage of Participants With ALP Response From Baseline at Week 52 ALP response >= 20% decrease from baseline	69.8 Percentage of participants	5.7 Percentage of participants
Percentage of Participants With ALP Response From Baseline at Week 52 ALP response >= 40% decrease from baseline	54.7 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Response to treatment was according to ALP \< 1.5x ULN, ALP decrease from baseline \>= 40% and TB =\<ULN at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=106 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response to Treatment According to ALP < 1.5x ULN, ALP Decrease From Baseline >= 40% and TB =<ULN at Week 52	37.7 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Response to treatment was according to ALP \< 3x ULN, AST \< 2x ULN and TB =\< 1 mg/dL (Paris I) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=106 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response to Treatment According to ALP < 3x ULN, Aspartate Aminotransferase (AST) < 2x ULN and TB =< 1 Milligrams Per Deciliter (mg/dL) (Paris I) at Week 52	68.9 Percentage of participants	47.2 Percentage of participants

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Response to treatment was according to ALP =\< 1.5x ULN, AST =\< 1.5x ULN and TB =\< 1 mg/dL (Paris II) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=107 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response to Treatment According to ALP =< 1.5x ULN, AST =< 1.5x ULN and TB =< 1 mg/dL (Paris II) at Week 52	43.0 Percentage of participants	5.7 Percentage of participants

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Response to treatment was according to TB decrease of 15% change from baseline at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=105 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response to Treatment According to TB Decrease of 15% Change From Baseline at Week 52	31.4 Percentage of participants	22.6 Percentage of participants

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Response to treatment was according to TB (TB =\< ULN) and/or albumin (ALB \>= LLN) (Rotterdam) at week 52. Participant was considered as responder at Week 52 only if total bilirubin and albumin were normal. The endpoint was analyzed in participants with abnormal total bilirubin (TB \> ULN) or albumin (ALB \< LLN) at baseline. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=4 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=2 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response to Treatment According to Normalization of TB (TB =< ULN) and/or Albumin (ALB >= Lower Limit of Normal [LLN]) (Rotterdam) at Week 52 TB (TB =< ULN)	25.0 Percentage of participants	50.0 Percentage of participants

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Response to treatment was according to TB ≤0.6 x ULN at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=105 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response to Treatment According to TB ≤0.6 x ULN at Week 52	74.3 Percentage of participants	77.4 Percentage of participants

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Response to treatment was according to ALP ≤1.67 x ULN and TB ≤1 mg/dL (Momah/ Lindor) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=106 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response to Treatment According to ALP ≤1.67 x ULN and TB ≤1 mg/dL (Momah/ Lindor) at Week 52	51.9 Percentage of participants	9.4 Percentage of participants

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Response to treatment was according to no worsening of TB, which was defined as level of TB \<ULN or no increase from baseline of more than 0.1 x ULN at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=105 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response to Treatment According to no Worsening of TB at Week 52	85.7 Percentage of participants	83.0 Percentage of participants

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Response to treatment according to complete biochemical response which was defined as \<= ULN values of ALP, TB, AST, ALT and ALB, and international normalized ratio (INR) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=107 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response to Treatment According to Complete Biochemical Response at Week 52	9.3 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

The UK-PBC risk score was defined by the mean percentage risk that a PBC participant treated with UDCA would develop liver failure requiring liver transplantation in 5, 10, and 15 years from diagnosis. It is calculated from the following equation at week 52 as follows: UK-PBC score = 0.0287854\*(alpEPxULN-1.722136304) - 0.0422873\*(\[{altastEP x ULN/10}\^-1\] - 8.675729006) + 1.4199 \* (LN(bilEPxULN /10)+2.709607778) - 1.960303\*(alb x LLN -1.17673001)-0.4161954\*(plt x LLN -1.873564875). The survival S(t) for any given participants was then calculated by S(t) = S0(t) exp(UK-PBC score). Here, alpEP x ULN=ALP /Upper Level Normal ALP at the timepoint, altastEPxULN=(ALT, AST or TA) /upper level normal of the value at the timepoint, bilEP x ULN=bilirubin /upper level normal bilirubin at the timepoint, alb x LLN=alb /alb lower level normal at baseline and plt x LLN=plt/plt lower level normal at baseline. Lower UK-PBC score predicts lower risk and better prognosis.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=93 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=47 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
PBC 5-, 10- and 15-year Risk Scores Based on United Kingdom (UK)-PBC Score at Week 52 UK PBC 5-year risk score	0.0102 Scores on a scale Standard Deviation 0.0126	0.0146 Scores on a scale Standard Deviation 0.0264
PBC 5-, 10- and 15-year Risk Scores Based on United Kingdom (UK)-PBC Score at Week 52 UK PBC 10-year risk score	0.0330 Scores on a scale Standard Deviation 0.0393	0.0454 Scores on a scale Standard Deviation 0.0731
PBC 5-, 10- and 15-year Risk Scores Based on United Kingdom (UK)-PBC Score at Week 52 UK PBC 15-year risk score	0.0593 Scores on a scale Standard Deviation 0.0670	0.0786 Scores on a scale Standard Deviation 0.1109

SECONDARY outcome

Timeframe: At Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported

The GLOBE score was a validated risk assessment tool providing an estimate of transplant-free survival for participants with PBC. It was developed by the Global PBC Study Group using Cox regression model on over 4,000 participants with PBC. It is calculated from the following equation at week 52 as follows: GLOBE score = 0.044378 \* age at start of ursodeoxycholic acid (UDCA) therapy + 0.93982 \* LN (TB x ULN) + 0.335648 \* LN (ALP x ULN) - 2.266708 \* ALB x LLN - 0.002581 \* platelet count per 10\^9/L) + 1.216865; where TB x ULN = bilirubin/ULN at the timepoint, ALP x ULN = ALP/ULN at the timepoint, ALB x LLN = ALB/LLN at the timepoint, platelet count per 10\^9/L = platelet count per 10\^9/L at the timepoint. The Lower GLOBE PBC score predicts lower risk and better prognosis.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=92 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=45 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Global PBC Study Group (GLOBE) Score at Week 52	-1.03 Scores on a scale Standard Deviation 0.70	-0.62 Scores on a scale Standard Deviation 0.83

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 for each parameter are reported.

Hepatobiliary injury and liver function were assessed as measured by AST, ALT, GGT, 5'-NT, and fractionated ALP (hepatic) (H1 and H2). Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=94 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=47 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Hepatobiliary Injury and Liver Function as Assessed by AST, ALT, Gamma-glutamyl Transferase (GGT), 5 Prime Nucleotidase (5'-NT), and Fractionated ALP (Hepatic) (H1 and H2) at Week 52 AST	-2.5 U/L Standard Deviation 17.8	-4.3 U/L Standard Deviation 24.3
Change From Baseline in Hepatobiliary Injury and Liver Function as Assessed by AST, ALT, Gamma-glutamyl Transferase (GGT), 5 Prime Nucleotidase (5'-NT), and Fractionated ALP (Hepatic) (H1 and H2) at Week 52 ALT	-9.7 U/L Standard Deviation 22.1	-6.3 U/L Standard Deviation 26.3
Change From Baseline in Hepatobiliary Injury and Liver Function as Assessed by AST, ALT, Gamma-glutamyl Transferase (GGT), 5 Prime Nucleotidase (5'-NT), and Fractionated ALP (Hepatic) (H1 and H2) at Week 52 GGT	-44.0 U/L Standard Deviation 95.6	-17.3 U/L Standard Deviation 112.7
Change From Baseline in Hepatobiliary Injury and Liver Function as Assessed by AST, ALT, Gamma-glutamyl Transferase (GGT), 5 Prime Nucleotidase (5'-NT), and Fractionated ALP (Hepatic) (H1 and H2) at Week 52 5'-NT	-3.63 U/L Standard Deviation 5.40	-2.09 U/L Standard Deviation 10.52
Change From Baseline in Hepatobiliary Injury and Liver Function as Assessed by AST, ALT, Gamma-glutamyl Transferase (GGT), 5 Prime Nucleotidase (5'-NT), and Fractionated ALP (Hepatic) (H1 and H2) at Week 52 Hepatic ALP H1	-107.68 U/L Standard Deviation 77.17	-32.20 U/L Standard Deviation 71.42
Change From Baseline in Hepatobiliary Injury and Liver Function as Assessed by AST, ALT, Gamma-glutamyl Transferase (GGT), 5 Prime Nucleotidase (5'-NT), and Fractionated ALP (Hepatic) (H1 and H2) at Week 52 Hepatic ALP H2	-11.76 U/L Standard Deviation 14.67	-5.20 U/L Standard Deviation 54.83

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 for each parameter are reported.

Hepatobiliary injury and liver function were assessed as measured by total and conjugated bilirubin. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=93 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=47 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by Total and Conjugated Bilirubin at Week 52 Total Bilirubin	-0.67 Micromoles per liter (μmol/L) Standard Deviation 3.18	0.87 Micromoles per liter (μmol/L) Standard Deviation 4.29
Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by Total and Conjugated Bilirubin at Week 52 Conjugated bilirubin	-0.09 Micromoles per liter (μmol/L) Standard Deviation 1.98	0.61 Micromoles per liter (μmol/L) Standard Deviation 2.41

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Hepatobiliary injury and liver function were assessed as measured by albumin. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=94 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=47 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by Albumin at Week 52	1.0 Grams per liter (g/L) Standard Deviation 2.8	-1.2 Grams per liter (g/L) Standard Deviation 2.7

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Hepatobiliary injury and liver function were assessed as measured by INR. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=95 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=46 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by INR at Week 52	0.028 Ratio Standard Deviation 0.148	0.035 Ratio Standard Deviation 0.131

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Biomarkers of inflammation were assessed as measured by hsCRP. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=93 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=47 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Biomarkers of Inflammation as Measured by High-sensitivity C-reactive Protein (hsCRP) at Week 52	-1.38 mg/L Standard Deviation 6.53	0.22 mg/L Standard Deviation 2.64

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 for each parameter are reported.

Biomarkers of inflammation were assessed as measured by fibrinogen and haptoglobin. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=93 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=47 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Biomarkers of Inflammation as Measured by Fibrinogen and Haptoglobin at Week 52 Fibrinogen	-1.002 g/L Standard Deviation 1.303	-0.776 g/L Standard Deviation 1.265
Change From Baseline in Biomarkers of Inflammation as Measured by Fibrinogen and Haptoglobin at Week 52 Haptoglobin	-0.185 g/L Standard Deviation 0.407	0.023 g/L Standard Deviation 0.302

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Biomarkers of inflammation were assessed as measured by TNF-alpha. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=81 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=39 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Biomarkers of Inflammation as Measured by Tumor Necrosis Factor Alpha at Week 52	-3.346 Picograms per milliliter (pg/mL) Standard Deviation 15.442	-0.224 Picograms per milliliter (pg/mL) Standard Deviation 0.921

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 for each parameter are reported.

Immune response was assessed as measured by IgG and IgM. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=95 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=46 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Immune Response as Measured by Immunoglobulin (Ig)G and IgM at Week 52 IgG	-0.423 g/L Standard Deviation 1.591	0.298 g/L Standard Deviation 1.159
Change From Baseline in Immune Response as Measured by Immunoglobulin (Ig)G and IgM at Week 52 IgM	-0.606 g/L Standard Deviation 0.907	0.017 g/L Standard Deviation 0.762

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 for each parameter are reported.

Biomarkers and non-invasive measures of hepatic fibrosis were assessed as measured by ELF: hyaluronic acid \[HA\], type 2 procollagen peptide \[PIINP\], tissue inhibitor of metalloproteinases-1\[TIMP-1\]) and PAI-1. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=89 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=44 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Enhanced Liver Fibrosis (ELF) and Plasminogen Activator Inhibitor-1 (PAI-1) at Week 52 HA	7.93 Micrograms per liter (mcg/L) Standard Deviation 80.35	16.36 Micrograms per liter (mcg/L) Standard Deviation 48.60
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Enhanced Liver Fibrosis (ELF) and Plasminogen Activator Inhibitor-1 (PAI-1) at Week 52 PIINP	-2.79 Micrograms per liter (mcg/L) Standard Deviation 32.55	-5.60 Micrograms per liter (mcg/L) Standard Deviation 20.03
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Enhanced Liver Fibrosis (ELF) and Plasminogen Activator Inhibitor-1 (PAI-1) at Week 52 TIMP-1	-3.03 Micrograms per liter (mcg/L) Standard Deviation 51.06	23.26 Micrograms per liter (mcg/L) Standard Deviation 65.03
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Enhanced Liver Fibrosis (ELF) and Plasminogen Activator Inhibitor-1 (PAI-1) at Week 52 PAI-1	0.053 Micrograms per liter (mcg/L) Standard Deviation 3.032	0.785 Micrograms per liter (mcg/L) Standard Deviation 7.028

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 for each parameter are reported.

Biomarkers and non-invasive measures of hepatic fibrosis were assessed as measured by CK-18 (M30 and M65). Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=83 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=42 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Cytokeratin-18 (CK-18) at Week 52 CK-18 M30	-70.71 Picomoles per liter (pmol/L) Standard Deviation 444.31	-5.39 Picomoles per liter (pmol/L) Standard Deviation 334.22
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Cytokeratin-18 (CK-18) at Week 52 CK-18 M65	-50.02 Picomoles per liter (pmol/L) Standard Deviation 246.28	-83.73 Picomoles per liter (pmol/L) Standard Deviation 481.30

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Biomarkers and non-invasive measures of hepatic fibrosis were assessed as measured by TGF-beta. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=8 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=6 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Transforming Growth Factor Beta (TGF-beta) at Week 52	713.074 pg/mL Standard Deviation 6553.956	-6172.360 pg/mL Standard Deviation 3279.127

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

FibroScan® TE device (Echosens, Paris, France) is a non-invasive technique used to measure liver stiffness, which correlated with fibrosis. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=90 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=44 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Liver Stiffness Measured by Transient Elastography (TE) at Week 52	-0.16 Kilopascal (kPa) Standard Deviation 3.70	0.35 Kilopascal (kPa) Standard Deviation 6.39

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 for each parameter are reported.

Blood samples were collected at specified timepoints for assessment of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol and triglycerides (TG). Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=95 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=47 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Lipid Parameters at Week 52 Total cholesterol	-0.532 Millimoles per liter (mmol/L) Standard Deviation 0.910	-0.318 Millimoles per liter (mmol/L) Standard Deviation 1.144
Change From Baseline in Lipid Parameters at Week 52 LDL cholesterol	-0.428 Millimoles per liter (mmol/L) Standard Deviation 0.730	-0.274 Millimoles per liter (mmol/L) Standard Deviation 1.086
Change From Baseline in Lipid Parameters at Week 52 HDL cholesterol	0.011 Millimoles per liter (mmol/L) Standard Deviation 0.364	-0.056 Millimoles per liter (mmol/L) Standard Deviation 0.399
Change From Baseline in Lipid Parameters at Week 52 VLDL cholesterol	-0.118 Millimoles per liter (mmol/L) Standard Deviation 0.159	0.015 Millimoles per liter (mmol/L) Standard Deviation 0.156
Change From Baseline in Lipid Parameters at Week 52 TG	-0.268 Millimoles per liter (mmol/L) Standard Deviation 0.370	0.031 Millimoles per liter (mmol/L) Standard Deviation 0.343

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Blood samples were collected at specified timepoints for assessment of FPG. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=90 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=42 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52	-0.267 mmol/L Standard Deviation 0.861	0.086 mmol/L Standard Deviation 0.381

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 for each parameter are reported.

Blood samples were collected at specified timepoints for assessment bile acids and biomarkers of bile acid synthesis. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=65 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=38 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Chenodeoxycholic acid	0.177 µmol/L Standard Deviation 0.807	0.100 µmol/L Standard Deviation 0.527
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Cholic acid	0.156 µmol/L Standard Deviation 0.656	0.027 µmol/L Standard Deviation 0.337
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Deoxycholic acid	-0.027 µmol/L Standard Deviation 0.288	-0.039 µmol/L Standard Deviation 0.360
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Glycochenodeoxycholic acid	-0.564 µmol/L Standard Deviation 3.310	0.581 µmol/L Standard Deviation 4.408
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Glycocholic acid	-0.370 µmol/L Standard Deviation 2.422	2.253 µmol/L Standard Deviation 12.291
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Glycodeoxycholic acid	-0.516 µmol/L Standard Deviation 1.247	-0.266 µmol/L Standard Deviation 2.688
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Glycolithocholic acid	-0.0234 µmol/L Standard Deviation 0.0762	-0.0187 µmol/L Standard Deviation 0.1768
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Lithocholic acid	-0.010 µmol/L Standard Deviation 0.047	-0.003 µmol/L Standard Deviation 0.047
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Taurochenodeoxycholic acid	-0.085 µmol/L Standard Deviation 2.495	0.857 µmol/L Standard Deviation 3.048
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Taurocholic acid	0.070 µmol/L Standard Deviation 2.059	1.127 µmol/L Standard Deviation 4.380
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Taurodeoxycholic acid	-0.0828 µmol/L Standard Deviation 0.4412	-0.0343 µmol/L Standard Deviation 0.3683
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52 Taurolithocholic acid	-0.0098 µmol/L Standard Deviation 0.0424	-0.0082 µmol/L Standard Deviation 0.0684

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Blood samples were collected at specified timepoints for assessment of bile acids and biomarkers of bile acid synthesis as measured by C4. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=61 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=30 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline at Week 52 in Bile Acids and Biomarkers of Bile Acid Synthesis as Measured by 7 Alpha-hydroxy-4-cholesten-3-one (C4) at Week 52	-7.288 mcg/L Standard Deviation 16.779	-4.044 mcg/L Standard Deviation 12.995

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Blood samples were collected at specified timepoints for assessment bile acids and biomarkers of bile acid synthesis as measured by Fibroblast Growth Factor 19. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=73 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=36 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis as Measured Fibroblast Growth Factor 19 at Week 52	-12.89 pg/mL Standard Deviation 80.24	54.54 pg/mL Standard Deviation 343.47

SECONDARY outcome

Timeframe: Baseline (up to 14 days pre-dose) and at Week 24 and Week 52

Population: The Pruritus ITT population included all participants from the ITT analysis set with baseline PBC Worst Itch NRS score ≥4. Only those participants with data collected at Weeks 24 and 52 are reported.

The PBC Worst Itch NRS is a simple, self-administered PRO questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Response to PBC Worst Itch NRS was according to clinically meaningful change at least 30% reduction; one point, two points or three points decrease in score from baseline in participants with a baseline NRS score ≥4. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake).

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=39 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=21 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52 Week 24: 30% reduction from baseline	43.6 Percentage of participants	28.6 Percentage of participants
Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52 Week 52: 30% reduction from baseline	55.6 Percentage of participants	33.3 Percentage of participants
Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52 Week 24: One-point decrease from baseline	53.8 Percentage of participants	42.9 Percentage of participants
Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52 Week 52: One-point decrease from baseline	61.1 Percentage of participants	38.9 Percentage of participants
Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52 Week 24: Two-point decrease from baseline	38.5 Percentage of participants	28.6 Percentage of participants
Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52 Week 52: Two-point decrease from baseline	47.2 Percentage of participants	33.3 Percentage of participants
Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52 Week 24: Three-point decrease from baseline	28.2 Percentage of participants	19.0 Percentage of participants
Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52 Week 52: Three-point decrease from baseline	41.7 Percentage of participants	33.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (up to 14 days pre-dose) and at Week 24 and Week 54

Population: The Pruritus ITT population included all participants from the ITT analysis set with baseline PBC Worst Itch NRS score ≥4.. Only those participants with data collected at Week 24 and Week 54 are reported.

The PBC Worst Itch NRS is a simple, self-administered PRO questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake). A worsening of Pruritus was defined by a positive change from baseline in PBC Worst Itch NRS score greater than 2 at week 24 and 52.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=93 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=51 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With no Worsening of Pruritus as Measured by the PBC Worst Itch NRS Score at Weeks 24 and 52 Week 24	89.2 Percentage of participants	86.3 Percentage of participants
Percentage of Participants With no Worsening of Pruritus as Measured by the PBC Worst Itch NRS Score at Weeks 24 and 52 Week 52	76.7 Percentage of participants	82.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

The 5-D Itch scale is a questionnaire that has been validated in several different diseases. It assesses symptoms in terms of 5 domains: duration: score range 1 (less than 6 hours) to 5 (all day); degree: score range 1 (not present) to 5 (unbearable); duration: score range 1 (less than 6 hours) and 5 (all day); direction: score range 1(completely resolved) and 5 (getting worse); disability: score range 1 (never affects or not applicable) and 5 (delays falling asleep and frequently wakes up at night or always affects this activity) and distribution: where the question was to mark where itching is present in body parts over the last two weeks. Participants rated their symptoms over preceding 2-week period on a 1 to 5 scale, with 5 being the most affected. The 5-D Itch total score ranged between 5 (no pruritus) and 25 (most severe pruritus). Higher scores indicated worse outcomes. Baseline= last non-missing value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=95 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=46 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in 5-D Itch at Week 52	-1.9 Scores on a scale Interval -2.6 to -1.3	-0.6 Scores on a scale Interval -1.6 to 0.3

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

The PROMIS Fatigue Short Form 7a consists of seven items that measure both the experience of fatigue and the interference of fatigue on daily activities over the past week. Participants completed the PROMIS Fatigue Short Form 7a and answered following questions on a scale from 1 (never) to 5 (always) : "How often did you feel tired"; "How often did you experience extreme exhaustion"; "How often did you run out of energy"; "How often did your fatigue limit you at work"; "How often were you too tired to think clearly"; "How often were you too tired to take a bath or shower" and 'How often did you have enough energy to exercise strenuously". T-score values include mean of 50 and standard deviation of 10. The PROMIS Fatigue T-score ranged from 29.4 (best) to 83.2 (worst). Higher scores indicated worse outcomes. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=95 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=46 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a at Week 52	-2.45 T-score Interval -3.84 to -1.07	-1.23 T-score Interval -3.22 to 0.77

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

The ESS is a short, self-administered questionnaire that consists of 8 questions asking to rate how likely it is to fall asleep in everyday situations (each question can be scored from 0 to 3 points; '0' indicates no chance of dozing and '3' indicates high chance of dozing). It provides a total score which has been shown to relate to the participant's level of daytime sleepiness (total score range 0 \[no sleepiness\] to 24 points \[significant sleepiness\]). The total score is the sum of all item scores and ranged from 0 (best) to 24 (worst). Higher scores indicated more chances of sleepiness. Participants were asked to complete the ESS with regard to the level of sleepiness they experienced over approximately the past 7 days. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=95 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=46 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 52	-0.3 Scores on a scale Interval -1.1 to 0.5	-0.5 Scores on a scale Interval -1.7 to 0.6

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

PBC-40 assess symptoms across 6 domains:symptoms,itch,fatigue,cognitive,emotional and social. Participants responded on verbal response scale,depending on section options range from 'never'/'not at all'/'strongly disagree' to 'always'/'very much'/'strongly agree'.5 items (3/3 in itch domain and 2/10 in social domain)also included a 'does not apply' option.Domains:Symptoms(7 questions)score range 7-35,Itch(3 questions)score range 3-15,Fatigue(11 questions)score range 11-55,Cognitive(6 questions)score range 6-30,Emotional(3 questions)score range 3-15,Social(10 questions)score range 10-50.Score for each domain was provided(total score was not calculated),with each verbal response scale correlating to score of 1-5 per item(0-5 on items with a 'does not apply' option);5=most affected.Individual item scores are summed to give total domain score.Higher scores=worse outcomes.PBC-40 had 4-week recall period.Baseline=last non-missing value on or before first dose of randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=95 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=46 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in PBC-40 at Week 52 Emotional	-0.8 Scores on a scale Interval -1.2 to -0.3	-0.6 Scores on a scale Interval -1.2 to 0.1
Change From Baseline in PBC-40 at Week 52 Symptoms	0.2 Scores on a scale Interval -0.5 to 0.8	-0.9 Scores on a scale Interval -1.8 to 0.1
Change From Baseline in PBC-40 at Week 52 Itch	-1.4 Scores on a scale Interval -1.8 to -0.9	-0.2 Scores on a scale Interval -0.9 to 0.5
Change From Baseline in PBC-40 at Week 52 Fatigue	-1.5 Scores on a scale Interval -2.7 to -0.2	-1.2 Scores on a scale Interval -3.0 to 0.7
Change From Baseline in PBC-40 at Week 52 Cognitive	-0.6 Scores on a scale Interval -1.4 to 0.2	-0.7 Scores on a scale Interval -1.8 to 0.4
Change From Baseline in PBC-40 at Week 52 Social	-1.1 Scores on a scale Interval -2.3 to 0.1	-0.4 Scores on a scale Interval -2.1 to 1.3

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

The EQ-5D-5L is a 6-item, standardized questionnaire that assesses mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and overall health state. The visual analog scale (VAS) of EQ-5D-5L questionnaire is numbered from 0 (worst) to 100 (best). Higher scores indicated better outcomes. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=94 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=46 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Health Utility as Measured by the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) at Week 52	2.5 Scores on a scale Interval 0.0 to 4.9	1.6 Scores on a scale Interval -1.9 to 5.0

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 for each parameter are reported.

DEXA scanning (hip and lumbar) was performed in participants to assess bone mineral density (femoral neck, lumbar and total hip). T-scores were calculated based on actual measured bone density value. The T-score compared a participant's bone density against that of a healthy 30-year-old adult. T-scores were used to determine primary osteoporosis, which exists on its own without any other cause and were divided into 3 categories: low risk, medium risk, and high risk (osteoporosis). T-scores measure the number of minerals in a participant's bone. A participant's level of bone loss was compared to that of a typical, healthy 30-year-old adult. A score ≥-1.0 indicates low risk, medium risk is a score between-2.5 and -1.0, and a high risk/osteoporosis is a score ≤-2.5. A positive change in T-score indicates an improvement in bone mineral density. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=64 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=27 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in T-Scores for Bone Mineral Density Assessed by Dual-energy X-ray Absorptiometry (DEXA) Scanning at Week 52 Femoral Neck Bone Mineral Density T-score	-0.016 T-score Standard Deviation 0.402	-0.111 T-score Standard Deviation 0.533
Change From Baseline in T-Scores for Bone Mineral Density Assessed by Dual-energy X-ray Absorptiometry (DEXA) Scanning at Week 52 Lumbar Bone Mineral Density T-score	-0.006 T-score Standard Deviation 0.487	-0.022 T-score Standard Deviation 0.405
Change From Baseline in T-Scores for Bone Mineral Density Assessed by Dual-energy X-ray Absorptiometry (DEXA) Scanning at Week 52 Total Hip Bone Mineral Density T-score	0.039 T-score Standard Deviation 0.529	-0.371 T-score Standard Deviation 0.618

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Blood samples were collected at specified timepoints for assessment of serum markers of bone turnover, CTX. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=81 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=32 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Serum Markers of Bone Turnover Carboxy Terminal Crosslinked Telopeptides of Type 1 Collagen [CTX] at Week 52	36.5 pg/mL Standard Deviation 212.6	44.5 pg/mL Standard Deviation 129.7

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 52

Population: The ITT population included all randomized participants. Only those participants with data collected at Week 52 are reported.

Blood samples were collected at specified timepoints for assessment of serum markers of bone turnover, P1NP. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=81 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=32 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Change From Baseline in Serum Markers of Bone Turnover Type 1 Procollagen Peptide [P1NP]) at Week 52	-2.79 mcg/L Standard Deviation 32.55	-5.60 mcg/L Standard Deviation 20.03

SECONDARY outcome

Timeframe: From Day 1 up to Week 52

Population: The ITT population included all randomized participants.

Onset of clinical outcomes were described as a composite endpoint composed of the following: model for end stage liver disease sodium (MELD-Na) \>14 for participants with baseline MELD-Na \<12; liver transplant; uncontrolled ascites requiring treatment; hospitalization for new onset or recurrence of any including, variceal bleed, hepatic encephalopathy defined as West-Haven score of 2 or more and spontaneous bacterial peritonitis; and death.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=108 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Percentage of Participants With Onset of Clinical Outcomes Uncontrolled ascites requiring treatment	0.9 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Onset of Clinical Outcomes Hospitalization for new onset or recurrence of variceal bleed	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Onset of Clinical Outcomes Meld-Na > 14 while baseline Meld-Na < 12	0.9 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Onset of Clinical Outcomes Liver transplant	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Onset of Clinical Outcomes Hospitalization for new onset or recurrence of Hepatic encephalopathy	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Onset of Clinical Outcomes Hospitalization for new onset or recurrence of Spontaneous bacterial peritonitis	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Onset of Clinical Outcomes Death	0.9 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: TEAEs were collected from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days.

Population: Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.

An AE was any untoward medical occurrence in a participant or clinical investigation participant who was administered an investigational product, and which does not necessarily have a causal relationship with treatment. A TEAE was defined as any AE with onset during TEAE assessment period, or any event started prior to first dose of treatment and worsened or became serious during the TEAE assessment period. An SAE was any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect. An AESI was an AE that might not be serious but was of special importance to a particular treatment or class.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=108 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 Participants Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) TEAEs	104 Participants	48 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) TESAEs	11 Participants	7 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) AESIs	32 Participants	14 Participants

SECONDARY outcome

Timeframe: Week 4: pre-dose, 0.5 hour, 1.5 hours, between 2-3 hours, 4 hours and 6 hours post-dose

Population: Pharmacokinetics Analysis Set included all participants who were administered at least one dose of elafibranor and have at least one post-dose PK sample. Only those participants with data collected at specified timepoints are reported.

Blood samples were collected at specified timepoints to evaluate plasma concentration of Elafibranor and its metabolite GFT1007.

Outcome measures

Outcome measures
Measure	Elafibranor 80 mg n=103 Participants Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Plasma Concentrations of Elafibranor and GFT1007 Elafibranor: Week 4: Pre-dose	92.7 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 52.9	—
Plasma Concentrations of Elafibranor and GFT1007 Elafibranor: Week 4: 0.5 hour post-dose	408.2 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 104.1	—
Plasma Concentrations of Elafibranor and GFT1007 Elafibranor: Week 4: 1.5 hours post-dose	281.7 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 66.1	—
Plasma Concentrations of Elafibranor and GFT1007 Elafibranor: Week 4: between 2-3 hours post-dose	182.0 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 67.8	—
Plasma Concentrations of Elafibranor and GFT1007 Elafibranor: Week 4: 4 hours post-dose	127.7 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 52.7	—
Plasma Concentrations of Elafibranor and GFT1007 Elafibranor: Week 4: 6 hours post-dose	117.1 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 53.5	—
Plasma Concentrations of Elafibranor and GFT1007 GFT1007: Week 4: Pre-dose	77.3 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 85.6	—
Plasma Concentrations of Elafibranor and GFT1007 GFT1007: Week 4: 0.5 hour post-dose	894.6 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 150.0	—
Plasma Concentrations of Elafibranor and GFT1007 GFT1007: Week 4: 1.5 hours post-dose	1707.2 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 52.1	—
Plasma Concentrations of Elafibranor and GFT1007 GFT1007: Week 4: between 2-3 hours post-dose	1160.8 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 53.9	—
Plasma Concentrations of Elafibranor and GFT1007 GFT1007: Week 4: 4 hours post-dose	655.8 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 54.7	—
Plasma Concentrations of Elafibranor and GFT1007 GFT1007: Week 4: 6 hours post-dose	375.7 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 65.9	—

Adverse Events

Elafibranor 80 mg

Serious events: 11 serious events

Other events: 103 other events

Deaths: 2 deaths

Placebo

Serious events: 7 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Ipsen

Phone: see email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Elafibranor 80 mg n=108 participants at risk Participants received elafibranor 80 mg orally once daily before breakfast during the DB period (maximum observed exposure= 104 weeks).	Placebo n=53 participants at risk Participants received placebo matched to elafibranor orally once daily before breakfast during the DB period (maximum observed exposure= 106 weeks).
Gastrointestinal disorders Abdominal pain upper	7.4% 8/108 • Number of events 10 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	5.7% 3/53 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Gastrointestinal disorders Constipation	8.3% 9/108 • Number of events 11 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	1.9% 1/53 • Number of events 1 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Gastrointestinal disorders Diarrhoea	11.1% 12/108 • Number of events 13 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	9.4% 5/53 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Gastrointestinal disorders Dyspepsia	3.7% 4/108 • Number of events 4 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	5.7% 3/53 • Number of events 3 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Gastrointestinal disorders Gastrooesophageal reflux disease	6.5% 7/108 • Number of events 7 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	1.9% 1/53 • Number of events 1 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Gastrointestinal disorders Nausea	11.1% 12/108 • Number of events 13 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	5.7% 3/53 • Number of events 3 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Gastrointestinal disorders Vomiting	11.1% 12/108 • Number of events 15 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	1.9% 1/53 • Number of events 1 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
General disorders Fatigue	9.3% 10/108 • Number of events 10 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	13.2% 7/53 • Number of events 8 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
General disorders Pain	0.00% 0/108 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	5.7% 3/53 • Number of events 3 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Infections and infestations COVID-19	28.7% 31/108 • Number of events 31 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	35.8% 19/53 • Number of events 19 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Infections and infestations Upper respiratory tract infection	6.5% 7/108 • Number of events 8 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	3.8% 2/53 • Number of events 2 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Infections and infestations Urinary tract infection	11.1% 12/108 • Number of events 16 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	17.0% 9/53 • Number of events 10 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Metabolism and nutrition disorders Abnormal weight gain	19.4% 21/108 • Number of events 21 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	18.9% 10/53 • Number of events 11 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 9/108 • Number of events 12 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	3.8% 2/53 • Number of events 2 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Musculoskeletal and connective tissue disorders Back pain	3.7% 4/108 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	11.3% 6/53 • Number of events 6 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Musculoskeletal and connective tissue disorders Muscle spasms	2.8% 3/108 • Number of events 3 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	5.7% 3/53 • Number of events 4 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Musculoskeletal and connective tissue disorders Pain in extremity	2.8% 3/108 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	5.7% 3/53 • Number of events 4 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Nervous system disorders Headache	8.3% 9/108 • Number of events 9 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	11.3% 6/53 • Number of events 6 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Skin and subcutaneous tissue disorders Pruritus	20.4% 22/108 • Number of events 26 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	26.4% 14/53 • Number of events 14 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.
Vascular disorders Hypertension	3.7% 4/108 • Number of events 4 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.	5.7% 3/53 • Number of events 3 • Treatment-emergent adverse events (TEAEs) were reported from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days. Safety analysis set included all participants who were administered at least one dose of DB study drug irrespective of the treatment received.