Trial Outcomes & Findings for A Trial of Setanaxib in Patients With Primary Biliary Cholangitis (PBC) and Liver Stiffness (NCT NCT05014672)

A Trial of Setanaxib in Patients With Primary Biliary Cholangitis (PBC) and Liver Stiffness

Change in ALP at Week 24 Compared to Baseline, ratio of week 24 value to baseline value.

The Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7b measures the severity of fatigue since waking. There are 7 questions, each scored between 1 and 5, with a total score between 7 to 35. A higher score indicates worse fatigue. This raw score is converted to a T score (a standardized score with a mean of 50 and a SD of 10).

The Patient's Global Impression of Severity (PGIS)-Fatigue is a global index where subjects are asked to rate the severity of fatigue on a 5-point scale within the past 7 days, with choices of 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe. Higher scores indicate a worse assessment for fatigue.

The Patient's Global Impression of Change (PGIC)-Fatigue is a 7-point scale reflecting a subject's rating of overall improvement where subjects are asked to rate their overall improvement with fatigue with 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Worse, 6=Much worse, 7=Very much worse. Higher scores indicate a worse outcome for change in fatigue.

PBC-40 fatigue domain includes 11 item questions, items scores range from 1 to 5. The individual item scores are summed to obtain a total domain score (Range for fatigue domain: 11 to 55), high scores represent high impact and low scores indicate low impact of PBC on the quality of life.

Change in liver stiffness at Week 24 compared to Screening, as assessed by transient elastography (FibroScan®)

WI-NRS is a daily patient-reported measure of itch intensity using an 11-point scale where 0=no itch and 10=worst itching imaginable. The WI-NRS score is calculated by averaging the daily WI-NRS scores before the visit date (inclusive). Higher scores indicate worse functioning for pruritus on the WI-NRS.

Pruritus was assessed by answering 3 questions on the PBC-40 Itch domain from 1 to 5, which was also summed to obtain a total domain score (range 3 to 15). A high score represents a high impact, and a low score indicates low impact of pruritus on the quality of life.

PGIS-Pruritus is a global index where subjects are asked to rate the severity of pruritus on a 5-point scale within the past 7 days, with choices of 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe. Higher scores indicate a worse assessment for pruritus.

The PGIC-Pruritus is a 7-point scale reflecting a subject's rating of overall improvement where subjects are asked to rate their overall improvement with fatigue with 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Worse, 6=Much worse, 7=Very much worse. Higher scores indicate a worse outcome for change in pruritus.

Changes in markers of cholestasis as assessed by proportion of patients at Week 24 with: * ALP reduction to \<1.67×ULN and total bilirubin ≤1×ULN and a ≥15% or ≥30% or ≥40% or ≥70% ALP reduction from Baseline, respectively * ALP reduction to \<1.5×ULN and total bilirubin ≤1×ULN and a ≥40% ALP reduction from Baseline * ALP \<1×ULN and total bilirubin ≤1×ULN * Total bilirubin \<0.6×ULN

Change in ALP at Week 24 Compared to Baseline, ratio of week 24 value to baseline value. Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment\*visit, and log(baseline)\*visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.

The Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7b measures the severity of fatigue since waking. There are 7 questions, each scored between 1 and 5, with a total score between 7 to 35. A higher score indicates worse fatigue. This raw score is converted to a T score (a standardized score with a mean of 50 and a SD of 10). Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment\*visit, and log(baseline)\*visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.

PBC-40 fatigue domain includes 11 item questions, items scores range from 1 to 5. The individual item scores are summed to obtain a total domain score (Range for fatigue domain: 11 to 55), high scores represent high impact and low scores indicate low impact of PBC on the quality of life. Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment\*visit, and log(baseline)\*visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.

Change in liver stiffness at Week 24 compared to Screening, as assessed by transient elastography (FibroScan®). Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment\*visit, and log(baseline)\*visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.