Clinical trial NCT04278820: A Study of TQA3526 in the Treatment of Primary Biliary Cirrhosis (PBC)
Official title: A Phase IIa, Randomized, Double-blind, Placebo-controlled Study of TQA3526 in the Treatment of Naive or Previously Treated PBC Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Primary Biliary Cirrhosis
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-02-20
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Alkaline phosphatase (ALP)
timeFrame: Baseline up to 24w
Secondary outcomes:
measure: Liver function：ALP (excluding 12W/24W), ALT, AST, GGT, TBA and Tbil
timeFrame: Baseline up to 2, 4, 8, 12, 14, 16, 20, 24 weeks
measure: Fasting lipid：LDL-C、HDL-C、TG and TC
timeFrame: Baseline up to 2, 4, 8, 12, 14, 16, 20, 24 weeks
measure: Cmax
timeFrame: predose, Weeks 2, 4, 8, 12, 14, 16, 20, 24 : 0, 1.5, 3.5 hours following drug administration
measure: tmax
timeFrame: predose, Weeks 2, 4, 8, 12, 14, 16, 20, 24 : 0, 1.5, 3.5 hours following drug administration
measure: AUC0-∞
timeFrame: predose, Weeks 2, 4, 8, 12, 14, 16, 20, 24 : 0, 1.5, 3.5 hours following drug administration
measure: pharmacodynamics
timeFrame: Baseline up to 2, 4, 8, 12, 14, 16, 20, 24 weeks
measure: safety and tolerability: incidence of treatment emergent adverse events and serious treatment emergent adverse events
timeFrame: Baseline up to 2, 4, 8, 12, 14, 16, 20, 24 weeks
Other outcomes:
Locations:
city: Changchun
country: China
facility: The first hospital of Jilin University
state: Jilin
Study officials:
References: