Obeticholic Acid Versus Placebo, in Combination with Ursodeoxycholic Acid in Patients with Primary Biliary Cirrhosis

NCT06715319 | Completed Phase 3 DMC

• 1 other identifier: FDZJ-OCA-202011
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase III, randomized, double-blind, multicentre study assessing the efficacy and safety of obecholic acid and Ursodeoxycholic Acid(UDCA) compared with placebo and UDCA in treating of primary biliary cirrhosis (PBC) in adults with an inadequate response to UDCA.

Conditions

PBC

Outcome Measures

Primary Outcomes (1)

• Composite Endpoint Alkaline Phosphatase (ALP) And Total Bilirubin

  Composite Endpoint : Percentage of participants at Month 12 with ALP \< 1.67 x upper limit of normal (ULN) and total bilirubin ≤ ULN and ALP decrease of ≥ 15% from baseline.

  up to 6 months

Secondary Outcomes (8)

• Percentage of PBC patients reaching the composite endpoint after 12 weeks, 36 weeks and 48 weeks of treatment

  up to 12 months

• Absolute change and percentage change of ALP from baseline to Month 3, 6, 9 and 12

  up to 12 months

• Absolute change and percentage change of total bilirubin from baseline to Month 3, 6, 9 and 12

  up to 12 months

• Absolute change and percentage change of direct bilirubin from baseline to Month 3, 6, 9 and 12

  up to 12 months

• Absolute change and percentage change of alanine transaminase(ALT) from baseline to Month 3, 6, 9 and 12

  up to 12 months

Study Arms (2)

OCA and UDCA

EXPERIMENTAL

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: OCA; Drug: UDCA

Placebo and UDCA

PLACEBO COMPARATOR

Placebo once daily. Subjects receiving UDCA continued taking UDCA throughout the trial.

Drug: UDCA; Drug: Placebo

Interventions

OCA DRUG

OCA 5 mg once daily in combination with UDCA for 12 weeks and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period.

Also known as: Obeticholic Acid

OCA and UDCA

UDCA DRUG

13\~15 mg/kg/day

OCA and UDCA; Placebo and UDCA

Placebo DRUG

Once a day (QD) by mouth (PO)

Placebo and UDCA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• At least 1 of the following qualifying biochemistry values: ① ALP ≥ 1.67x ULN；② Total bilirubin \> ULN but \< 2x ULN；
• Taking UDCA for at least 6 months (stable dose for ≥ 2 months) prior to the first dose；
• Patients of childbearing potential must agree to take contraception during the study and for 1 month after the last day of treatment;
• Patients capable of giving written informed consent.

You may not qualify if:

• History or presence of other concomitant liver diseases including:
• Hepatitis C virus (HCV) infection; participants with active hepatitis B (HBV) infection will be excluded, however, participants who have seroconverted (hepatitis B surface antigen \[Hbs Ag\] and hepatitis B e antigen \[Hbe Ag\] negative) may be included after consultation with the medical monitor.
• Primary sclerosing cholangitis (PSC) Alcoholic liver disease Definite autoimmune liver disease or overlap hepatitis Nonalcoholic steatohepatitis (NASH) Gilbert's Syndrome (due to interpretability of bilirubin levels)Child-pugh grade B or C
• Presence of clinical complications of PBC or clinically significant hepatic decompensation, including:
• History of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥ 15 Portal hypertension with complications, including: known gastric or large esophageal varices, poorly controlled or diuretic resistant ascites, history of variceal bleeds or related therapeutic or prophylactic interventions (for example, beta blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt \[TIPS\]), or hepatic encephalopathy Cirrhosis with 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/deciliter dL) (178 micromoles \[µmol\])/liter \[L\])
• Participants with severe pruritus or those requiring systemic treatment for pruritus (for example, with bile acid sequestrants \[BAS\] or rifampicin) within 2 months prior to the first dose
• Patients who took obeticholic acid within 3 months prior to the first dose
• Administration of the following drugs within 1 month prior to the first dose: azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline, bicyclol and with S.chinensis ingredients; fenofibrate or other fibrates; budesonide and other systemic corticosteroids; hepatotoxic drugs (including α-methyldopa, sodium valproate, isoniazid, nitrofurantoin, etc.);
• Administration of the following drugs within 2 months prior to the first dose: antibodies or immunotherapy against interleukins or other cytokines or chemokines.
• ALT≥ 10 × ULN with/or ALT≥ 10 × ULN;
• Direct bilirubin\>3×ULN;
• Serum creatinine (Cr) ≥ 1.5 × ULN and serum creatinine clearance \< 60 mL/min;
• History or presence of clinically concerning cardiac arrhythmias likely to affect survival during the trial, or prolongation of Screening (pretreatment) QT or QTc interval;
• Women who are pregnant or lactating;
• Known history of human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

• Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

MeSH Terms

Interventions

obeticholic acid

Study Officials

• Junqi Niu

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: December 4, 2024
• Study Start: October 9, 2021
• Primary Completion: October 16, 2023
• Study Completion: April 29, 2024
• Last Updated: December 4, 2024

Record last verified: 2024-11

Locations

CN (1)