Primary Biliary Cholangitis (PBC) MedDRA version: 20.1 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis System Organ Class: 100000004871
Conditions
Sponsors
Enanta Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. An informed consent document must be signed and dated by the subject 2. Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive 3. Male or female with a diagnosis of PBC by at least two of the following criteria: • History of ALP above ULN for at least 6 months • Positive Anti-Mitochondrial Antibodies (AMA) titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay [ELISA] or positive PBC-specific antinuclear antibodies [PBC- ANAb]) • Documented liver biopsy result consistent with PBC (with no cirrhosis) 4. For subjects with no documented liver biopsy performed within 2 years, subjects must undergo a transient elastography (Fibroscan) showing liver stiffness ULN but 35 mIU/mL). 9. All male participants who have not had a vasectomy must use effective contraception from Day -1 to 90 days after their last dose of study drug. Effective contraception is defined as a condom and spermicide for the male, or condom and at least one of the following for a female partner: • Intrauterine device • Oral, injectable, implantable, transdermal, or intravaginal hormonal contraceptive • Be of non-childbearing potential 10. Male subjects must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drug 11. Screening body mass index (BMI) of =18 kg/m2 12. Subject must be willing and able to adhere to the assessments, visit schedule, prohibitions and restrictions, as described in this protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 19
Exclusion criteria
Exclusion criteria: 1. Laboratory Screening Results: • AST >5 × ULN • ALT >5 × ULN • Patients with Gilbert’s syndrome will not be allowed due to interpretability of bilirubin levels • Total white blood cells (WBC) 1.2 • Serum creatinine >2 mg/dL or creatinine clearance 2 mg/dL (178 µmol/L) 15. Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B and C, esophageal varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed) 16. Patients with a history of severe pruritus requiring current or prior systemic treatment (e.g., with BAS or rifampicin) 17. Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease) 18. Any condition possibly affecting drug absorption (eg, gastrectomy <3 years prior to Screening. NOTE: Subjects who have undergone gastric surgeries known to not affect drug absorption such as gastric band or gastric sleeve will be allowed if they are stable for at least 1 year prior to Screening. 19. History of regular alcohol consumption exceeding 14 drinks/week for females and 21 drinks/week for males within 6 months of Screening. One drink is defined as 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) 20. Participation in a clinical trial within 30 days prior to study drug administration 21. Clinically significant electrocardiogram (ECG) abnormalities or QTcF greater than 450 ms for males and 470 ms for females at either Screening or Baseline, or any prior history of QT abnormality 22. Use of CYP3A4 and P-gp indu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of EDP-305 on alkaline phosphatase (ALP) levels. ;Secondary Objective: • To evaluate the safety and tolerability of EDP-305 • To evaluate the effect of EDP-305 on bilirubin levels • To evaluate the effects of EDP-305 on other markers of liver function • To evaluate the effects of EDP-305 on non-invasive markers of liver fibrosis • To evaluate the effects of EDP-305 on inflammatory markers • To evaluate the effects of EDP-305 on lipids • To evaluate the effects of EDP-305 on pruritus • To evaluate the effects of EDP-305 on Quality of Life (QoL) • To evaluate the pharmacokinetics (PK) of EDP-305 and metabolites in plasma • To evaluate the pharmacodynamics (PD) of EDP-305;Primary end point(s): Proportion of subjects with at least 20% reduction in ALP from pretreatment value or normalization of ALP at Week 12 ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Frequency of adverse events (AEs), serious AEs, and AEs leading to discontinuation through Week 12 • Bilirubin (Total, Conjugated, Unconjugated) decline from Baseline at Week 12 • Change from Baseline in Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST), Gamma-Glutamyl transferase (GGT) at Week 12 • Change from Baseline of noninvasive liver fibrosis markers (Enhanced Liver Fibrosis [ELF] panel, PRO C3, AST to Platelet Ratio Index [APRI] and fibrosis-4 [FIB-4]) at Week 12 • Change from Baseline in fibrinogen, CRP, IL6, IL1ß, TNF-a, TNF-ß , alpha2 macroglobulin and haptoglobin levels at Week 12 • Change from Baseline in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 • Change from Baseline in 5D-itch scale and Visual Analog Score (VAS) at Week 12 • Change from Baseline in PBC-40 Quality of Life (QoL) at Week 12 • Pharmacokinetic parameters of EDP-305 (and metabolites): Cmax, Tmax, and AUClast. • Pharmacodynamic parameters of EDP-305: FGF19, C4 and Bile Acid (BA) at Week 12;Timepoint(s) of evaluation of this end point: Week 12 | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactNathalie Adda
Enanta Pharmaceuticals, Inc.
Outcome results
None listed