A Study of TQA3526 in the Treatment of Primary Biliary Cirrhosis (PBC)

Phase 2

• Conditions: Primary Biliary Cirrhosis
• Interventions: Drug: TQA3526; Drug: Placebo to match TQA3526

• Registration Number: NCT04278820
• Lead Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Brief Summary

TQA3526 is a modified bile acid and FXR agonist. FXR is a key regulator of bile acid synthesis and transport. Bile acids are used by the body to help with digestion. It is hypothesized that regular treatment with TQA3526 will improve liver function in persons with Primary Biliary Cirrhosis (PBC).

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-12
• Study First Submitted: 2020-01-18
• Study First Submitted QC: 2020-02-18
• Last Update Submitted: 2020-02-18
• Study First Posted: 2020-02-20
• Last Update Posted: 2020-02-20
• Study Start: 2020-03-20
• Primary Completion: 2022-11-30
• Study Completion: 2022-11-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

• 1.18 and 70 years old, male or female. 2.Proven as PBC, as demonstrated by the patient presenting with at least 2 of the following 3 diagnostic factors:

  • History of increased ALP levels for at least 3 months prior to Day 0 in previously treated PBC patients，or ALP levels increased during screening in treatment naive PBC patients； ② Positive AMA titer (>1:40 titer on immunofluorescence or M2 positive by ELISA) or PBC-specific antinuclear antibodies (anti-GP210 and anti-SP100 positive)； ③ Liver biopsy consistent with PBC within 24W prior to randomization； 3.ALP value between 1.67 and 10 × ULN; 4.Taking ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for ≥ 3 months) prior to Day 0, or unable to tolerate UDCA (no UDCA for ≥ 3 months) prior to Day 0.

Exclusion Criteria

• 1.Has other virus infected ; 2.History or presence of other concomitant liver diseases； 3.Presence of clinical complications of PBC or clinically significant hepatic decompensation； 4.Child-pugh grade B or C in patients with cirrhosis； 5.Creatinine (Cr) ≥1.5 times the upper limit of normal value and serum creatinine clearance rate <60mL/min； 6.ALT or AST>5×ULN；TBil>3×ULN； 7.Patients with a history of severe pruritus within 2 months prior to day 0; 8.History or presence of clinically concerning cardiac arrhythmias, the duration of the study may affect survival; 9.Presence of any other disease or condition that is interfering with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the intestine; 10.Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease) or which may diminish life expectancy to < 2 years.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Titration group	TQA3526	-
Titration group	Placebo to match TQA3526	-
Extension group	Placebo to match TQA3526	-
Climbing group	Placebo to match TQA3526	-
Extension group	TQA3526	-
Climbing group	TQA3526	-

Primary Outcome Measures

Name	Time	Method
Alkaline phosphatase (ALP)	Baseline up to 24w	The reduction of ALP level from baseline to 24 weeks.

Secondary Outcome Measures

Name	Time	Method
Liver function：ALP (excluding 12W/24W), ALT, AST, GGT, TBA and Tbil	Baseline up to 2, 4, 8, 12, 14, 16, 20, 24 weeks	The reduction of ALP , ALT, AST, GGT, TBA and Tbil from baseline to each time point.
Fasting lipid：LDL-C、HDL-C、TG and TC	Baseline up to 2, 4, 8, 12, 14, 16, 20, 24 weeks	The rate of change of LDL-C、HDL-C、TG and TC from baseline to each time point.
safety and tolerability: incidence of treatment emergent adverse events and serious treatment emergent adverse events	Baseline up to 2, 4, 8, 12, 14, 16, 20, 24 weeks	Evaluate safety and tolerability as assessed by the incidence of treatment emergent adverse events and serious treatment emergent adverse events comparing TQA3526 to placebo.
AUC0-∞	predose, Weeks 2, 4, 8, 12, 14, 16, 20, 24 : 0, 1.5, 3.5 hours following drug administration	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity
pharmacodynamics	Baseline up to 2, 4, 8, 12, 14, 16, 20, 24 weeks	The rate of change of FGF-19、C4、IgG and IgM from baseline to each time point.
tmax	predose, Weeks 2, 4, 8, 12, 14, 16, 20, 24 : 0, 1.5, 3.5 hours following drug administration	Time from dosing to maximum concentration
Cmax	predose, Weeks 2, 4, 8, 12, 14, 16, 20, 24 : 0, 1.5, 3.5 hours following drug administration	Maximum concentration of the analyte in plasma.

Trial Locations

Locations (1)

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