Trial Outcomes & Findings for Study to Evaluate the Effects of Two Doses of Seladelpar (MBX-8025) in Subjects With Primary Biliary Cirrhosis (PBC) (NCT NCT02609048)

NCT ID: NCT02609048

Last Updated: 2025-02-25

Results Overview

Baseline for AP level was defined as the mean between assessments at Visit 1 (Week -4 to Week 0) and Visit 2 (Week 0).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

Baseline

Results posted on

2025-02-25

Participant Flow

Participants were enrolled at study sites in Canada, Germany, the United Kingdom, and the United States.

70 participants were screened.

Participant milestones

Participant milestones
Measure	Seladelpar 200 mg Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a placebo-to-match (PTM) seladelpar capsule, orally, once daily for 12 weeks.	Placebo Participants received 2 PTM seladelpar capsules, orally, once daily for 12 weeks.
Overall Study STARTED	13	14	14
Overall Study COMPLETED	2	4	4
Overall Study NOT COMPLETED	11	10	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Seladelpar 200 mg Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a placebo-to-match (PTM) seladelpar capsule, orally, once daily for 12 weeks.	Placebo Participants received 2 PTM seladelpar capsules, orally, once daily for 12 weeks.
Overall Study Adverse Event	3	0	0
Overall Study Randomized but never treated	1	1	1
Overall Study Withdrawal of informed consent	1	0	0
Overall Study Reason not specified	6	9	9

Baseline Characteristics

For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline

Population: The modified intent-to-treat (mITT) Analysis Set was defined as any randomized participant who received at least 1 dose of medication and had at least 1 on-treatment AP evaluation.

Baseline for AP level was defined as the mean between assessments at Visit 1 (Week -4 to Week 0) and Visit 2 (Week 0).

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Baseline Alkaline Phosphatase (AP) Levels	248.3 units per liter (U/L) Standard Deviation 88.69	311.6 units per liter (U/L) Standard Deviation 94.83	232.8 units per liter (U/L) Standard Deviation 72.51

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percent change in AP serum levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by last observation carried forward (LOCF). Baseline for AP level was defined as the mean between assessments at Visit 1 (Week -4 to Week 0) and Visit 2 (Week 0).

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Alkaline Phosphatase (AP) Levels	-62.83 percent change in AP levels Standard Error 4.312	-53.21 percent change in AP levels Standard Error 3.961	-1.84 percent change in AP levels Standard Error 4.020

SECONDARY outcome

Timeframe: Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Participants were defined as responders for the composite endpoint of AP and total bilirubin if their AP level was \<1.67 × upper limit of normal (ULN) and had decreased at least 15% from their Baseline level and their total bilirubin value was within the normal range \[0.1-1.1 milligrams/deciliter (mg/dL)\].

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percentage of Participants With Response as Determined by Composite Endpoint of Alkaline Phosphatase and Total Bilirubin	100 percentage of participants	69.2 percentage of participants	8.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in AST levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for AST level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Aspartate Aminotransferase (AST)	232.69 percent change in AST levels Standard Error 77.409	130.81 percent change in AST levels Standard Error 66.933	-2.02 percent change in AST levels Standard Error 69.364

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT analysis set were analyzed.

Percentage change in ALT levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for ALT level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Alanine Aminotransferase (ALT)	181.11 percent change in ALT levels Standard Error 77.864	111.83 percent change in ALT levels Standard Error 68.061	-4.67 percent change in ALT levels Standard Error 69.632

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in GGT levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for GGT level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Gamma-glutamyl Transferase (GGT)	-47.17 percent change in GGT levels Standard Error 9.084	-42.60 percent change in GGT levels Standard Error 7.796	-1.83 percent change in GGT levels Standard Error 7.889

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in 5'Nucleotidase levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for 5NT level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in 5'Nucleotidase (5NT)	-34.35 percent change in 5'Nucleotidase levels Standard Error 8.446	-24.92 percent change in 5'Nucleotidase levels Standard Error 7.148	-0.08 percent change in 5'Nucleotidase levels Standard Error 7.305

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in total bilirubin levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for total bilirubin level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Total Bilirubin	1.40 percent change in total bilirubin levels Standard Error 6.384	-16.79 percent change in total bilirubin levels Standard Error 5.586	-4.79 percent change in total bilirubin levels Standard Error 5.793

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in conjugated bilirubin levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for conjugated bilirubin level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Conjugated Bilirubin	42.30 percent change in conjugated bilirubin Standard Error 10.213	2.00 percent change in conjugated bilirubin Standard Error 8.932	10.84 percent change in conjugated bilirubin Standard Error 9.296

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in unconjugated bilirubin levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for unconjugated bilirubin level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Unconjugated Bilirubin	-11.86 percent change in unconjugated bilirubin Standard Error 6.197	-23.04 percent change in unconjugated bilirubin Standard Error 5.431	-8.89 percent change in unconjugated bilirubin Standard Error 5.620

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in bone-specific AP levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for bone-specific level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Bone-specific AP Levels	-50.39 percent change in bone-specific AP level Standard Error 4.837	-39.09 percent change in bone-specific AP level Standard Error 4.355	-4.43 percent change in bone-specific AP level Standard Error 4.544

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in TG levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for TG level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Triglycerides (TG)	-7.11 percent change in TG levels Standard Error 9.415	-30.27 percent change in TG levels Standard Error 8.243	7.04 percent change in TG levels Standard Error 8.617

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in TC levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for TC level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Total Cholesterol (TC)	-16.43 percent change in TC levels Standard Error 3.250	-8.44 percent change in TC levels Standard Error 2.774	-0.32 percent change in TC levels Standard Error 2.905

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in HDL-C levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for HDL-C level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C)	-13.06 percent change in HDL-C levels Standard Error 4.326	3.44 percent change in HDL-C levels Standard Error 3.747	4.33 percent change in HDL-C levels Standard Error 3.884

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set were analyzed.

Percentage change in LDL-C levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for LDL-C level was defined as the last non-missing assessments prior to or on the date of the first study dose.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)	-17.63 percent change in LDL-C levels Standard Error 4.372	-12.83 percent change in LDL-C levels Standard Error 3.763	-2.78 percent change in LDL-C levels Standard Error 3.958

SECONDARY outcome

Timeframe: Week 12

Population: Participants in the mITT Analysis Set with available data were analyzed. Only participants who did not meet the criteria for response at Baseline were included in the analysis. Baseline for published PBC response criteria (Paris I) was defined as the last non-missing assessments prior to or on the date of the first study dose.

Published criteria for response to treatment in PBC included Paris I criteria. For Paris I, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 3x ULN and AST ≤ 2x ULN and Total Bilirubin ≤ 1 mg/dL. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=2 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=4 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=2 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris I)	2 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Participants in the mITT Analysis Set with available data were analyzed. Only participants who did not meet the criteria for response at Baseline were included in the analysis. Baseline for published PBC response criteria (Paris II) was defined as the last non-missing assessments prior to or on the date of the first study dose.

Published criteria for response to treatment in PBC included Paris II criteria. For Paris II, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 1.5x ULN and AST ≤ 1.5x ULN and Total Bilirubin ≤ 1 mg/dL. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=8 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=9 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris II)	5 Participants	8 Participants	9 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Participants in the mITT Analysis Set with available data were analyzed. Only participants who did not meet the criteria for response at Baseline were included in the analysis. Baseline for published PBC response criteria (Toronto I) was defined as the last non-missing assessments prior to or on the date of the first study dose.

Published criteria for response to treatment in PBC included Toronto I criteria. For Toronto I, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 1.67x ULN. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=4 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=11 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=8 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto I)	0 Participants	3 Participants	7 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Participants in the mITT Analysis Set with available data were analyzed. Only participants who did not meet the criteria for response at Baseline were included in the analysis. Baseline for published PBC response criteria (Toronto II) was defined as the last non-missing assessments prior to or on the date of the first study dose.

Published criteria for response to treatment in PBC included Toronto II criteria. For Toronto II, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 1.76x ULN. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=4 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=11 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=9 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto II)	0 Participants	2 Participants	7 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Participants in the mITT Analysis Set with available data were analyzed.

The UK-PBC Risk Score was used to estimate the risk that a PBC participant would develop liver failure that would require liver transplantation within 5, 10 or 15 years from diagnosis. The UK-PBC Risk Score calculation was adapted based on the AP assessment, transaminases (refers to the ALT, where available, otherwise the AST assessment) and total bilirubin assessment respectively at end of treatment divided by its upper limits of the corresponding normal ranges; "albumin" and "platelet" refer to the baseline values of these parameters divided by their corresponding lower limits of normal ranges. Missing assessments at end of treatment was imputed by last observation carried forward (LOCF). The UK-PBC risk scores for 5, 10 and 15 years was calculated for each treatment group

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=12 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score UK-PBC Risk Score by 5 years	1.3642 percentage risk Standard Deviation 0.95452	1.8530 percentage risk Standard Deviation 2.32301	3.1102 percentage risk Standard Deviation 5.1892
United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score UK-PBC Risk Score by 10 years	3.9796 percentage risk Standard Deviation 2.74081	5.2712 percentage risk Standard Deviation 6.31842	8.3004 percentage risk Standard Deviation 12.51699
United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score UK-PBC Risk Score by 15 years	6.4392 percentage risk Standard Deviation 4.36737	8.3379 percentage risk Standard Deviation 9.57184	12.4804 percentage risk Standard Deviation 17.05244

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set with available data were analyzed.

The 5-D itch scale was used to for the multidimensional quantification of pruritus over time. It assessed five aspects of itching: degree, duration, direction, disability, and distribution.The 5-D itch Scale is a measure of itching that has been validated in patients with chronic pruritus to detect changes over time. A 5-D itch scale score typically ranges from 5 to 25 with a higher score indicating greater itch severity, where 5 represents no pruritus (itching) and 25 represents the most severe pruritus; Each dimension is scored separately, and the scores are added together to get a total 5-D itch score. Higher scores indicate worsening of itching. The total 5-D itch Scale score change from Baseline was calculated. Baseline for 5-D itch scale was defined as the last non-missing assessments prior to or on the date of the first study dose. Missing assessments at end of treatment was imputed by LOCF.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=10 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=11 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Change From Baseline in 5-Dimension (5-D) Itch Scale Score	-0.9 score on a scale Standard Error 1.31	0.5 score on a scale Standard Error 1.15	0.2 score on a scale Standard Error 1.25

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set with available data were analyzed.

VAS was used to measure pruritis in participants with PBC. Participants placed a mark representing their level of itching since the previous measurement on a 100-mm VAS with 0 indicating no itching and 100 mm indicating the worst possible itching. Higher scores indicated worsening of itching The change from Baseline was presented by treatment group. Baseline for VAS score was defined as the last non-missing assessments prior to or on the date of the first study dose. Missing assessments at end of treatment was imputed by LOCF.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=9 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=12 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=12 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Change From Baseline in Pruritus Visual Analog Scale (VAS) Score	0.9 score on a scale Standard Error 7.54	-0.7 score on a scale Standard Error 6.35	8.3 score on a scale Standard Error 6.42

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Participants in the mITT Analysis Set with available data were analyzed.

The PBC-40 questionnaire was used to evaluate health-related quality of life measures, specifically fatigue. The PBC-40 questionnaire is a disease-specific tool developed to specifically measure the psychometric profile of PBC patients. It consists of 40 items divided into the six domains relevant to PBC including Cognitive, Social, EmotionalFunction, Fatigue, Itch, and Other Symptoms/General Questions. Items are scored from 1 to 5 and individual items scores are summed to give a total domain score. PBC 40 QoL domain score ranges are:Cognitive (6-30), Emotional Function (3-15),Fatigue (11-55), Itch (3-15),Social (10-50),Symptoms (7-35).Higher scores represent high impact and lower scores low impact of PBC on quality of life.The change and percentage change from Baseline for individual domain score at end of treatment were reported. Baseline for PBC-40 questionnaire was the last non-missing assessments prior to or on the date of the first study dose.Missing assessments imputed by LOCF.

Outcome measures

Outcome measures
Measure	Seladelpar 200 mg n=7 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=11 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=10 Participants Participants received 2 placebo to match (PTM) seladelpar capsules, orally, once daily for 12 weeks.
Change From Baseline in PBC-40 Quality of Life Questionnaire Cognitive Domain Score	2.6 score on a scale Standard Error 0.96	0.9 score on a scale Standard Error 0.76	-0.8 score on a scale Standard Error 0.80
Change From Baseline in PBC-40 Quality of Life Questionnaire Emotional Function Domain Score	0.4 score on a scale Standard Error 0.73	0.4 score on a scale Standard Error 0.58	0.0 score on a scale Standard Error 0.62
Change From Baseline in PBC-40 Quality of Life Questionnaire Fatigue Domain Score	-0.3 score on a scale Standard Error 1.50	2.3 score on a scale Standard Error 1.20	-1.9 score on a scale Standard Error 1.26
Change From Baseline in PBC-40 Quality of Life Questionnaire Itch Domain Score	-0.6 score on a scale Standard Error 0.81	0.3 score on a scale Standard Error 0.65	-0.4 score on a scale Standard Error 0.67
Change From Baseline in PBC-40 Quality of Life Questionnaire Symptoms Domain Score	1.1 score on a scale Standard Error 0.76	0.9 score on a scale Standard Error 0.62	-1.5 score on a scale Standard Error 0.64
Change From Baseline in PBC-40 Quality of Life Questionnaire Social Domain Score	3.2 score on a scale Standard Error 1.32	0.3 score on a scale Standard Error 1.06	-0.5 score on a scale Standard Error 1.09

Adverse Events

Seladelpar 200 mg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Seladelpar 50 mg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Seladelpar 200 mg n=12 Participants Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks.	Seladelpar 50 mg n=13 Participants Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks.	Placebo n=13 Participants Participants received 2 PTM seladelpar capsules, orally, once daily for 12 weeks.	Total n=38 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=12 Participants	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=38 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=12 Participants	12 Participants n=13 Participants	12 Participants n=13 Participants	33 Participants n=38 Participants
Age, Categorical >=65 years	3 Participants n=12 Participants	1 Participants n=13 Participants	1 Participants n=13 Participants	5 Participants n=38 Participants
Age, Continuous	57 years STANDARD_DEVIATION 11.4 • n=12 Participants	54 years STANDARD_DEVIATION 7.4 • n=13 Participants	55 years STANDARD_DEVIATION 10.1 • n=13 Participants	55 years STANDARD_DEVIATION 9.5 • n=38 Participants
Sex: Female, Male Female	12 Participants n=12 Participants	12 Participants n=13 Participants	12 Participants n=13 Participants	36 Participants n=38 Participants
Sex: Female, Male Male	0 Participants n=12 Participants	1 Participants n=13 Participants	1 Participants n=13 Participants	2 Participants n=38 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=12 Participants	1 Participants n=13 Participants	0 Participants n=13 Participants	1 Participants n=38 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=12 Participants	12 Participants n=13 Participants	13 Participants n=13 Participants	37 Participants n=38 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=38 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=13 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=37 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.
Race (NIH/OMB) Asian	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=13 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=37 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=13 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=37 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.
Race (NIH/OMB) Black or African American	2 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=13 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	2 Participants n=37 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.
Race (NIH/OMB) White	10 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	12 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	13 Participants n=13 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	35 Participants n=37 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.
Race (NIH/OMB) More than one race	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=13 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=37 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=12 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=13 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.	0 Participants n=37 Participants • For Race, data was not collected for 1 participant in the Seladelpar 50 mg group.
Region of Enrollment United States	6 Participants n=12 Participants	5 Participants n=13 Participants	6 Participants n=13 Participants	17 Participants n=38 Participants
Region of Enrollment United Kingdom	2 Participants n=12 Participants	4 Participants n=13 Participants	3 Participants n=13 Participants	9 Participants n=38 Participants
Region of Enrollment Germany	3 Participants n=12 Participants	2 Participants n=13 Participants	3 Participants n=13 Participants	8 Participants n=38 Participants
Region of Enrollment Canada	1 Participants n=12 Participants	2 Participants n=13 Participants	1 Participants n=13 Participants	4 Participants n=38 Participants