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

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ClinicalTrials.gov Identifier: NCT03394924
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : March 21, 2018
Sponsor:
Collaborators:
Pharmaceutical Research Associates
Triangle Biostatistics
Information provided by (Responsible Party):
Enanta Pharmaceuticals

Brief Summary:
A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with primary biliary cholangitis

Condition or disease Intervention/treatment Phase
Primary Biliary Cholangitis Drug: EDP-305 Dose 1 Drug: EDP-305 Dose 2 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 119 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Dose Ranging, Randomized, Double Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis (PBC) With or Without an Inadequate Response to Ursodeoxycholic Acid (UDCA)
Actual Study Start Date : December 27, 2017
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : April 2019


Arm Intervention/treatment
Experimental: EDP-305 Dose 1
Subjects will take 2 tablets once a day orally for 12 weeks
Drug: EDP-305 Dose 1
Two tablets daily for 12 weeks

Experimental: EDP-305 Dose 2
Subjects will take 2 tablets once a day orally for 12 weeks
Drug: EDP-305 Dose 2
Two tablets daily for 12 weeks

Placebo Comparator: Placebo
Subjects will take two tablets once a day orally for 12 weeks
Drug: Placebo
Two tablets daily for 12 weeks




Primary Outcome Measures :
  1. Proportion of subjects with at least 20% reduction in ALP from pre-treatment value or normalization of ALP at Week 12 [ Time Frame: Measurement at Week 12 ]

Secondary Outcome Measures :
  1. Safety as measured by • Frequency of adverse events (AEs), serious AEs, and AEs leading to discontinuation through Week 12 [ Time Frame: Up to 12 weeks ]
  2. Change from baseline in Bilirubin [ Time Frame: Measurement at Week 12 ]
  3. Change from Baseline in Alanine aminotransferase (ALT) [ Time Frame: Measurement at Week 12 ]
  4. Change from Baseline in Aspartate aminotransferase (AST) [ Time Frame: Measurement at Week 12 ]
  5. Change from Baseline in Gamma-Glutamyl transferase (GGT) [ Time Frame: Measurement at Week 12 ]
  6. Change from Baseline of Enhanced Liver Fibrosis [ELF] panel [ Time Frame: Measurement at Week 12 ]
  7. Change from Baseline of PRO C3 [ Time Frame: Measurement at Week 12 ]
  8. Change from Baseline of AST to Platelet Ratio Index [APRI] [ Time Frame: Measurement at Week 12 ]
  9. Change from Baseline of fibrosis-4 [FIB-4]) [ Time Frame: Measurement at Week 12 ]
  10. Change from Baseline in Triglycerides (TG) [ Time Frame: Measurement at Week 12 ]
  11. Change from Baseline in Total Cholesterol (TC) [ Time Frame: Measurement at Week 12 ]
  12. Change from Baseline in High Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Measurement at Week 12 ]
  13. Change from Baseline in Low Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Measurement at Week 12 ]
  14. Change from Baseline in 5D-itch scale [ Time Frame: Measurement at Week 12 ]
  15. Change from Baseline in Visual Analog Score (VAS) [ Time Frame: Measurement at Week 12 ]
  16. Change from Baseline in PBC-40 Quality of Life (QoL) [ Time Frame: Measurement at Week 12 ]
  17. Cmax of EDP-305 [ Time Frame: Up to Week 12 ]
  18. Tmax of EDP-305 [ Time Frame: Up to Week 12 ]
  19. AUC of EDP-305 [ Time Frame: Up to Week 12 ]
  20. Change from baseline of FGF19 [ Time Frame: Up to Week 12 ]
  21. Change from baseline of C4 [ Time Frame: Up to Week 12 ]
  22. Change from baseline of Total Bile Acids [ Time Frame: Up to Week 12 ]


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • An informed consent document signed and dated by the subject.
  • Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive
  • Male or female with a diagnosis of PBC by at least two of the following criteria:

    • History of ALP above ULN for at least six 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)
  • For subjects with no documented liver biopsy performed within 2 years, subjects must undergo a transient elastography (Fibroscan) showing liver stiffness < 12.5 kPA
  • 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)
  • Alkaline Phosphatase (ALP) ≥ 1.67 × ULN and/or total bilirubin >ULN but < 2×ULN
  • Subjects must have Screening laboratory values for Hepatitis B surface antigen (HBsAg), Hepatitis C surface antigen (HCsAg) 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.
  • 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.
  • 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.
  • Male subjects must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drug
  • Screening body mass index (BMI) of 18 to 30 kg/m2 with a minimum body weight of 50 kg
  • Subject must be willing and able to adhere to the assessments, visit schedule, prohibitions and restrictions, as described in this protocol

Exclusion Criteria:

  • Laboratory Screening Results:

    • AST >5 ULN
    • ALT >5 ULN
    • Total bilirubin >1.8 mg/dL: NOTE: 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
    • Creatine kinase above upper limit of normal (ULN) except when in relation with intense exercise
    • Serum creatinine >2 mg/dL or creatinine clearance <60 mL/min (based on Cockroft-Gault Method)
  • Body mass index (BMI) >30 or suspected to have relevant nonalcoholic fatty liver disease (NAFLD) as based on the judgment of the Investigator at Screening
  • Use of colchicine, methotrexate, azathioprine, or systemic steroids in the two months preceding screening
  • Current use of fibrates, including fenofibrates and statins (eg, simvastatin). Note: Subjects who discontinued fibrates for at least 3 months before screening can participate
  • Use of an experimental treatment for PBC within the past 12 months
  • 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
  • Cirrhosis with or without complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN
  • Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 μmol/L)
  • 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)
  • Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03394924


Contacts
Contact: Nathalie Adda 617 607 0705 nadda@enanta.com

Locations
United States, California
Inland Empire Liver Foundation Recruiting
Rialto, California, United States, 92377
Contact: Zeid Kayali, MD         
Principal Investigator: Zeid Kayali, MD         
United States, Texas
American Research Corporation at the Texas Liver Institute Recruiting
San Antonio, Texas, United States, 78215
Contact: Eric J Lawitz, MD    210-253-3426      
Principal Investigator: Eric Lawitz, MD         
Sponsors and Collaborators
Enanta Pharmaceuticals
Pharmaceutical Research Associates
Triangle Biostatistics

Responsible Party: Enanta Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03394924     History of Changes
Other Study ID Numbers: EDP 305-201
First Posted: January 9, 2018    Key Record Dates
Last Update Posted: March 21, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Enanta Pharmaceuticals:
PBC
Primary Ciliary Cholangitis (PBC)

Additional relevant MeSH terms:
Cholangitis
Liver Cirrhosis, Biliary
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Cholestasis
Liver Diseases
Liver Cirrhosis
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents