A Multicenter, Randomized, Controlled Trial of Prednisone Combined with Ursodeoxycholic Acid in the Treatment of Primary Biliary Cholangitis with Moderate to Severe Interface Hepatitis Characteristics

Phase 2

• Conditions: Primary Biliary Cholangitis (PBC)
• Interventions: Drug: Prednisone; Drug: UDCA (Ursodeoxycholic acid)

• Registration Number: NCT06591468
• Lead Sponsor: Han Ying

Brief Summary

About 1/3 of patients with primary biliary cholangitis (PBC) exhibit moderate to severe interface hepatitis, and this group of patients have poor response to UDCA treatment. However, as it is not yet sufficient to diagnose autoimmune hepatitis or overlap syndrome, it is difficult to initiate immunosuppressive therapy such as steroids according to current guidelines. The aim of this study is to explore whether PBC patients with moderate to severe interfacial inflammation can benefit from UDCA combined with prednisone therapy, and its treatment safety.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-07
• Study First Submitted QC: 2024-09-07
• Study First Posted: 2024-09-19
• Study Start: 2024-10-30
• Last Update Submitted: 2024-12-23
• Last Update Posted: 2024-12-27
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 244

Inclusion Criteria

1. Voluntarily joining the group, able to understand and sign an informed consent form;
2. 18 years old ≤ age ≤ 75 years old;
3. The diagnosis of primary biliary cholangitis follows the AASLD international diagnostic and treatment guidelines (meeting two of the following three criteria: AMA or gp210, sp100 positive; Elevated serum ALP levels; Pathological manifestations include non suppurative cholangitis and destruction of the interlobular bile duct;
4. Liver histology suggests moderate to severe interfacial hepatitis (moderate,<50% portal or fibrous septa destruction, severe,>50% portal or fibrous septa destruction) with serum ALT<5 * ULN, serum IgG<2 * ULN, and negative serum anti smooth muscle antibodies;
5. Not receiving UDCA, hormone or other immunosuppressive therapy before enrollment;
6. ALP>1.67 * ULN.

Exclusion Criteria

• History or presence of other concomitant liver diseases.
• ALT or AST > 5×ULN, TBIL > 3×ULN.
• If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating.
• Allergic to fenofibrate or ursodeoxycholic acid.
• Taking hepatotoxic drugs (e.g., dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) for more than 2 weeks within 6 months, and long-term hormonal users.
• Recurrent variceal bleeding, poorly controlled hepatic encephalopathy or refractory ascites.
• Patients with a history of severe cardiac, cerebrovascular, renal, respiratory disease or functional failure, and psychiatric disorders (including those due to alcohol and drug abuse).
• Creatinine >1.5×ULN and creatinine clearance <60 ml/min.
• Currently using statins (such as pravastatin, fluvastatin, and simvastatin), other fibrates (such as gemfibrozil and bezafibrate), and drugs structurally similar to fenofibrate (like ketoprofen).
• Planned to receive an organ transplant or an organ transplant recipient.
• Needing Liver transplantation within 1 year according to the Mayo Rick score.
• Any other condition(s) that would compromise the safety of the subject or compromise

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prednisone	UDCA (Ursodeoxycholic acid)	Combination therapy of UDCA (13-15 mg/kg/day) and prednisone. Prednisone 30-40 mg/day, at 7am in the morning, gradually reduced after 1 month (5mg every 7-14 days) to 5-10 mg for maintenance treatment
UDCA	UDCA (Ursodeoxycholic acid)	UDCA (13-15 mg/kg/day)
Prednisone	Prednisone	Combination therapy of UDCA (13-15 mg/kg/day) and prednisone. Prednisone 30-40 mg/day, at 7am in the morning, gradually reduced after 1 month (5mg every 7-14 days) to 5-10 mg for maintenance treatment

Primary Outcome Measures

Name	Time	Method
Percentage of patients with biochemical response	1 year	Alkaline Phosphatase \< 1.67\*ULN

Secondary Outcome Measures

Name	Time	Method
Assessment of the pruritus and fatigue	1, 3, 6, 9, and 12 months	Change From Baseline in Fatigue and Pruritus as Assessed by Visual Analogue Scale (VAS) Total Score for Fatigue and Pruritus. (0-10, higher scires mean a worse outcome)
Survival without transplantation and hepatic impairment	1 year	Occurrence of ascites, variceal bleeding, hepatic encephalopathy, liver-transplantation, or death.

Trial Locations

Locations (1)

Xijing hospital; 🇨🇳 Xi'an, Shaanxi, China