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

Phase 3

• Conditions: Primary Biliary Cirrhosis
• Interventions: Drug: Obeticholic Acid Tablets; Drug: UDCA; Drug: Placebo

• Registration Number: NCT04956328
• Lead Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2021-07
• Study First Submitted: 2021-07-01
• Study First Submitted QC: 2021-07-08
• Study First Posted: 2021-07-09
• Study Start: 2021-07-22
• Last Update Submitted: 2021-07-23
• Last Update Posted: 2021-07-26
• Primary Completion: 2023-09-20
• Study Completion: 2023-09-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
OCA Tablets 5-10 mg	Obeticholic Acid Tablets	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.
Placebo	Placebo	Placebo once daily in combination with UDCA for 48 weeks.
Placebo	UDCA	Placebo once daily in combination with UDCA for 48 weeks.
OCA Tablets 5-10 mg	UDCA	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.

Primary Outcome Measures

Name	Time	Method
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 )	up to 48 weeks	Compound endpoint: ALP \< 1.67× ULN, ALP decrease by at least 15% , and total bilirubin ≤ ULN

Secondary Outcome Measures

Name	Time	Method
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 )	up to 36 weeks	Compound endpoint: ALP \< 1.67× ULN, ALP decrease by at least 15% , and total bilirubin ≤ ULN
Rate of change of liver function indicators from baseline	up to 48 weeks	Liver function: ALP (alkaline phosphatase ), ALT (Alaninetransaminase), AST(aspartate transaminase), GGT( γ-glutamyl transpeptadase ), TBA (total bile acid) and Tbil (total bilirubin)

Trial Locations

Locations (1)

The first hospital of Jilin University; 🇨🇳 Changchun, Jilin, China