Study of Obeticholic Acid（OCA） Combination With Ursodeoxycholic Acid (UDCA) in Patients With Primay Biliary Cirrhosis (PBC)

A Multi-center, Randomized, Double-blind Trail Evaluating the Efficacy and Safety of Combination of Obecholic Acid and UDCA Compared With UDCA Monotherapy in PBC Patients With an Inadequate Response to UDCA .

Obecholic acid is a modified bile acid and Farnesoid X receptor (FXR) agonist. FXR is a key regulator of bile acid synthesis and transport. Bile acids are used by the body to help with digestion. Conventional therapy with obecholic acid will improve liver function of patients with PBC.

Study Overview

• Status: Recruiting
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Drug: Placebo; Drug: Obeticholic Acid Tablets; Drug: UDCA

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Junqi Niu, Professor; Phone Number: 13756661205; Email: junqiniu@aliyun.com

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130000
      • Recruiting
      • The First Hospital of Jilin University
      • Contact: Junqi Niu; Phone Number: 13756661205; Email: junqiniu@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female aged 18 to 75 years.

2. Meet at least 2 of the following 3 PBC diagnoses:

   1. Patients had elevated alkaline phosphatase for at least 3 months before enrolment.
   2. AMA positive (titer ≥1:40), or if AMA negative, PBC specific antibodies (anti- GP210 and/or anti-SP100 and/or AMA-M2) are required.
   3. Liver biopsy suggested PBC 48 weeks before enrollment.
3. ALP > 1.67× ULN before enrollment.
4. Taking UDCA with stable dose for at least 3 months before enrollment.

Exclusion Criteria:

1. Merging with other virus infected.
2. With other existing liver disease or a history of liver disease.
3. With clinical complications of PBC or clinically significant hepatic decompensation.
4. Child-pugh grade B or C.
5. Creatinine (Cr) ≥ 1.5×ULN and serum creatinine clearance rate < 60mL/min; [Calculation formula: Cr:(140-age)×weight(kg) /0.818 × Scr (μmol/L)，female Cr=Cr × 0.85].
6. ALT or AST>5×ULN;Tbil > 2×ULN.
7. Patients with a history of severe pruritus 2 months before enrollment.
8. The presence of clinically relevant arrhythmias or associated history that may affect survival during the study period.
9. With diseases that may cause nonhepatic ALP increases (e.g., Paget's disease) or which may diminish life expectancy to < 2 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OCA Tablets 5-10 mg; OCA 5 mg once daily in combination with UDCA for 24 weeks and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period.	Drug: Obeticholic Acid Tablets; Obeticholic Acid：Once a day (QD) by mouth (PO).; Drug: UDCA; UDCA：continue prestudy dose
Placebo Comparator: Placebo; Placebo once daily in combination with UDCA for 48 weeks.	Drug: Placebo; Placebo; Drug: UDCA; UDCA：continue prestudy dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of PBC patients reaching the compound endpoint after 48 weeks of treatment (Compound endpoint: alkaline phosphatase (ALP) < 1.67× Upper Limit of Normal(ULN), ALP decrease by at least 15% , and total bilirubin ≤ ULN )	Compound endpoint: ALP < 1.67× ULN, ALP decrease by at least 15% , and total bilirubin ≤ ULN	up to 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of PBC patients reaching the compound endpoint after 4 weeks, 12 weeks, 24 weeks and 36 weeks of treatment (Compound endpoint: ALP < 1.67× ULN, ALP decrease by at least 15% , and total bilirubin ≤ ULN )	Compound endpoint: ALP < 1.67× ULN, ALP decrease by at least 15% , and total bilirubin ≤ ULN	up to 36 weeks
Rate of change of liver function indicators from baseline	Liver function: ALP (alkaline phosphatase ), ALT (Alaninetransaminase), AST(aspartate transaminase), GGT( γ-glutamyl transpeptadase ), TBA (total bile acid) and Tbil (total bilirubin)	up to 48 weeks

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2021
• Primary Completion (Anticipated): September 20, 2023
• Study Completion (Anticipated): September 20, 2023

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 9, 2021

Study Record Updates

• Last Update Posted (Actual): July 26, 2021
• Last Update Submitted That Met QC Criteria: July 23, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: ABDS-CS-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No