A Phase 2 clinical study evaluating safety and efficacy of EDP-305 in Subjects with Primary Biliary Cholangitis (PBC) without adequate response or intolerance to Ursodeoxycholic Acid (UDCA).
- Conditions
- Primary Biliary Cholangitis (PBC)MedDRA version: 20.1Level: LLTClassification code 10036680Term: Primary biliary cirrhosisSystem Organ Class: 100000004871Therapeutic area: Body processes [G] - Immune system processes [G12]
- Registration Number
- EUCTR2017-003528-62-DE
- Lead Sponsor
- Enanta Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 119
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 <14.0 kPA
5.Must be on a stable dose of UDCA12-20 mg/kg/day for at least 6 months prior to Screening or intolerant of UDCA in the opinion of the Investigator (no UDCA for at least 12 weeks prior to Screening)
6.Alkaline Phosphatase (ALP) =1.67 × ULN and/or total bilirubin >ULN but <2 × ULN (<2.4 mg/dL)
7.Subjects must have Screening laboratory values for Hepatitis B surface antigen (HBsAg), anti-HCV antibodies and HCV RNA negative, and Human Immunodeficiency Virus (HIV) 1 and 2 antibodies (Ab) as seronegative. NOTE: Subjects previously infected by chronic hepatitis C and treated with direct acting antivirals (DAAs) with sustained virologic response (SVR) for at least 3 years will be allowed.
8.Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP-305. Effective methods of contraception are defined as:
•a condom for the male partner and at least one of the following for the female participant:
oIntrauterine device
oOral, injectable, implantable, transdermal, or intravaginal hormonal contraceptive
Note: The above does not apply to female subjects of non-childbearing potential (ie, physiologically incapable of becoming pregnant) defined as:
-has had a complete hysterectomy greater than or equal to 3 months prior to dosing or
-has had a bilateral oophorectomy (ovariectomy) or
-has had a bilateral tubal ligation or fallopian tube inserts or
-is postmenopausal (a demonstration of a total cessation of menses for =1 year with an FSH level of >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
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) <3000 cells/mm3
•Absolute neutrophil count (ANC) <1500 cells/mm3
•Platelet count <140,000/mm3
•Prothrombin time (international normalized ratio, INR) >1.2
•Serum creatinine >2 mg/dL or creatinine clearance <60 mL/min (based on Cockroft-Gault Method)
2.Suspected to have relevant nonalcoholic fatty liver disease (NAFLD) as based on the judgment of the Investigator at Screening
3.Known history of alpha-1-Antitrypsin deficiency
4.Use of immunosuppressants known to have an effect on the liver of patients with PBC (eg, colchicine, methotrexate, or azathioprine) in the 3 months preceding Screening.
5.Current use of fibrates, including fenofibrates. NOTE: Subjects who discontinued fibrates for at least 3 months before Screening can participate
6.Use of an experimental treatment for PBC within the past 6 months
7.Prior use and/or concomitant treatment with obeticholic acid (OCA)
8.Use of experimental or unapproved drugs within 1 year of Screening
9.Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Principal Investigator (PI)
10.Pregnant or nursing females
11.Recipients of liver or other organ transplantation or anticipated need for orthotropic organ transplantation in one year as determined by a Model for End-Stage Liver Disease (MELD) Score =15
12.Co-existing liver or biliary diseases, such as primary sclerosing cholangitis, choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis (NASH), acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cirrhosis, cholangiocarcinoma diagnosed or suspected liver cancers
13.Cirrhosis with or without complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma
14.Hepatorenal syndrome (type I or II) or Screening serum creatinine >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 <br>•To evaluate the effect of EDP-305 on bilirubin levels<br>•To evaluate the effects of EDP-305 on other markers of liver function<br>•To evaluate the effects of EDP-305 on non-invasive markers of liver fibrosis<br>•To evaluate the effects of EDP-305 on inflammatory markers<br>•To evaluate the effects of EDP-305 on lipids <br>•To evaluate the effects of EDP-305 on pruritus <br>•To evaluate the effects of EDP-305 on Quality of Life (QoL)<br>•To evaluate the pharmacokinetics (PK) of EDP-305 and metabolites in plasma<br>•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 Outcome Measures
Name Time Method