Trial Outcomes & Findings for A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis (NCT NCT03394924)

The trial included 68 participants from 43 sites in Australia, Canada, Europe and the United States from December 2017 to January 2020.

132 participants were screened, 64 of which were screen failures. The remaining 68 were enrolled and received trial treatment.

A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis

Percent change was calculated as \[(ALP at Week 12 - ALP at Baseline)/ALP at Baseline\] \*100. The participant was considered to have successfully achieved a 20% reduction in ALP if the result was ≤-20. The participant was considered to have successfully achieved ALP normalization if ALP was abnormal at Baseline and normal at Week 12.

An adverse event (AE) was defined as any event, side effect, or untoward medical occurrence in a subject enrolled in a clinical trial whether or not it is considered to have a causal relationship to the study drug. A TEAE was an AE that first occurred or began previous to and worsened on or after the first dose date and before the last dose date +7 days.

A SAE is any untoward medical occurrence at any dose that results in death, is a life-threatening event, requires inpatient hospitalization or prolonged hospitalization of an existing hospitalization, results in permanent or prolonged disability or incapacity, is a congenital anomaly or birth defect in the offspring of a study subjects, or is a medically important event.

An adverse event (AE) was defined as any event, side effect, or untoward medical occurrence in a subject enrolled in a clinical trial whether or not it is considered to have a causal relationship to the study drug. A TEAE was an AE that first occurred or began previous to and worsened on or after the first dose date and before the last dose date +7 days.

The data presented below was measured using least square mean change from baseline.

The ELF panel included hyaluronic acid (HA), procollagen III amino terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP 1). This endpoint also presents PRO C3 results.

APRI was calculated as (\[AST level/AST upper limit of normal\]/\[Platelet count 1\^09/L\])×100. AST is aspartate aminotransferase. The aspartate transaminase to platelet ratio index (APRI) is used to assess liver fibrosis in participants with chronic liver disease. Scores range from 0 to ≥ 2.0, with scores \< 0.5 predictive of no liver fibrosis; scores \>1.5 significant fibrosis; and scores \> 2.0 indicative of cirrhosis. A negative change from baseline indicates a decrease in fibrosis.

Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score that is calculated using formula: FIB-4 = (Age \[years\] x AST \[U/L\]) / (platelets \[10\^9/L\] x (square root of ALT \[U/L\])). A FIB-4 index of \< 1.45 indicates no or moderate fibrosis and an index of \> 3.25 indicates extensive fibrosis/cirrhosis. A positive change from Baseline indicates increased fibrosis.

For IL, both IL6 and IL1β variants were analysed. For TNF, both TNF α and TNF β (also known as lymphotoxin alpha) variants were analyzed.

The 5D-Itch scale is a multidimensional questionnaire completed by participants to quantify the magnitude of pruritus, assessed considering the past 2 weeks. Scale range is 1 to 5 covering five dimensions: duration (1=Less than 6 hrs/day to 5=All day), degree (1=Not present to 5=Unbearable), direction (1=Completely resolved to 5=Getting worse), disability (for Sleep rated as 1=Never affects sleep to 5=Delays falling asleep and frequently wakes me up at night; for Leisure/Social, Housework/Errands and Work/School rated as 1=Never affects activity to 5=Always affects activity), and distribution (assess if itching is present in 16 body locations, scored as 1=present at 0-2 locations to 5=present at 14-16 locations). Total scores (including highest disability score obtained from any of the daily activities) ranged between 5 and 25 where higher scores indicated more severe itching. Negative change scores indicate improvement from the baseline score.

An itch VAS (0-100mm) was used to record the intensity of the event. Participants drew a line on a scale corresponding to the maximum intensity of itch. Lines drawn towards the right of the line indicated greater itching and higher scores indicated more severe itching. Negative change from baseline indicates decrease in itching.

The PBC-40 is a survey measuring health related quality of life in participants with PBC. The 40 questions from the PBC-40 questionnaire are scored from 1-5, with 5 representing the highest impact and 1 the lowest impact of PBC on the quality of life. Six domains were computed from the 40 questions: symptoms (score range 7-35), itch (0-15), fatigue (11-55), cognition (6-30), social (8-50) and emotional (1-15). Higher scores indicate worse quality of life and negative change scores indicate improvement from the baseline score.

Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679.

Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679.

Metabolites of EDP-305 are EP-022571, EP-022572, and EP-022679.

FGF19 was measured in plasma. BA was measured in serum. C4 was measured in serum.

AUC0-8 is area under the biomarker concentration-time curve from time zero to 8 hours. AUC2-8 is area under the biomarker concentration-time curve from 2 hours to 8 hours. FGF19 was measured in plasma. BA was measured in serum. C4 was measured in serum.