Efficacy and Safety of Obeticholic Acid in the Treatment of Primary Biliary Cholangitis

A Randomized, Double-blind, Multicenter, Placebo-controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of Obeticholic Acid in Patients With Primary Biliary Cholangitis

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 (primary biliary cholangitis)PBC.

The main objectives of the study were to assess the effects of Obeticholic Acid (OCA) on serum alkaline phosphatase (ALP) and total bilirubin, together as a composite endpoint and on safety in participants with PBC.

Study Overview

• Status: Recruiting
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Obeticholic Acid Tablets（OCA）; Drug: UDCA; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100050
    • Recruiting
    • Beijing Friendship Hospital
    • Contact: ChunXiu Yang; Phone Number: 010-63138628; Email: chunxiuyang@sina.com
    • Principal Investigator: Hong You
    • Principal Investigator: Jidong Jia

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 and ≤75 years；
2. Definite PBC diagnosis, as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors: ① Indicators reflecting cholestasis such as elevated ALP；② Positive antimitochondrial antibody (AMA) or AMA-M2, or positive PBC-specific antibody (anti-GP210 and/or anti-SP100) if AMA negative；③ Liver biopsy consistent with PBC；
3. At least 1 of the following qualifying biochemistry values: ① ALP ≥ 1.67x ULN ；② Total bilirubin > ULN but < 2x ULN；
4. Taking UDCA for at least 6 months (stable dose for ≥ 3 months) prior to Day 0, or unable to tolerate UDCA (no UDCA for ≥ 3 months) prior to Day 0；
5. Understand the study, comply with the study protocol, and voluntarily sign the informed consent form.

Exclusion Criteria:

1. Patients who took obeticholic acid within 3 months prior to Day 0;
2. Known hypersensitivity to obeticholic acid, ursodeoxycholic acid;
3. History or presence of other concomitant liver diseases;
4. Cirrhosis-related complications or end-stage liver disease manifestations;
5. Serum creatinine (Cr) ≥ 1.5 × ULN and serum creatinine clearance < 60 mL/min;
6. Patients with severe pruritus or requiring systemic drug therapy within 2 months prior to Day 0;
7. Patients with HIV or syphilis infection;
8. Presence of diseases or physiological conditions that interfere with the absorption, distribution, metabolism or excretion of test drugs, such as inflammatory bowel disease and previous gastric bypass surgery;
9. Presence of diseases that may cause non-hepatogenic ALP elevation, or diseases that may lead to a life expectancy of less than 2 years;
10. Administration of the following drugs within 6 months prior to Day 0: azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; fenofibrate or other fibrates; budesonide and other systemic corticosteroids; hepatotoxic drugs (including α-methyldopa, sodium valproate, isoniazid, nitrofurantoin, etc.);
11. Administration of the following drugs within 12 months prior to Day 0: antibodies or immunotherapy against interleukins or other cytokines or chemokines;
12. Patients with serious cardiovascular system, digestive system, respiratory system, urinary system, nervous system, mental illness, immunodeficiency disease, and judge by investigators that they are not suitable for participating in the trial;
13. Other conditions that are not considered appropriate by the investigator.

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 5 mg titrated to 10 mg ± UDCA; OCA 5 mg once daily for 3 months and then titrating up to 10 mg based on tolerability and response. Subjects receiving UDCA continued taking UDCA throughout the trial. If the subjects could not tolerate UDCA, they were not treated with UDCA.	Drug: Obeticholic Acid Tablets（OCA）; Obeticholic Acid：Once a day (QD) by mouth (PO).; Drug: UDCA; UDCA：13~15 mg/kg/day
Placebo Comparator: Placebo ± UDCA; Placebo once daily. Subjects receiving UDCA continued taking UDCA throughout the trial. If the subjects could not tolerate UDCA, they were not treated with UDCA.	Drug: UDCA; UDCA：13~15 mg/kg/day; Drug: Placebo; Placebo：Once a day (QD) by mouth (PO).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of PBC patients reaching the compound endpoint after 12 months of treatment (Compound endpoint: alkaline phosphatase (ALP) < 1.67× Upper Limit of Normal(ULN), and ALP decrease ≥ 15% from baseline, and total bilirubin ≤ ULN )	Compound endpoint: ALP < 1.67× ULN, and ALP decrease ≥ 15% from baseline, and total bilirubin ≤ ULN	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change and percentage change of ALP, total bilirubin, direct bilirubin, ALT, AST and GGT from baseline to Month 3, 6, 9 and 12	Blood samples were evaluated for ALP, total bilirubin, direct bilirubin, ALT, AST and GGT levels. Absolute change and percentage change of ALP, total bilirubin, direct bilirubin, ALT, AST and GGT from baseline to Month 3, 6, 9 and 12 are presented.	up to 12 months
Quality of life for PBC measure (PBC-40) score percentage change from baseline to Month 3, 6, 9 and 12	PBC-40 score was evaluated at certain visits. PBC-40 score percentage change from baseline to Month 3, 6, 9 and 12 is presented.	up to 12 months

Collaborators and Investigators

• Sponsor: Nanjing Chia-tai Tianqing Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: July 4, 2022
• First Submitted That Met QC Criteria: July 7, 2022
• First Posted (Actual): July 11, 2022

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: ABDSP2021-III

Drug and device information, study documents

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