Clinical trial NCT06750276: A Study to Evaluate the Safety, Tolerability, PK, and PD Effects of AZD2389 in Participants With Liver Fibrosis and Compensated Cirrhosis.
Official title: A Phase 2a, Randomised, Single-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics and Explore the Pharmacodynamic Effects of AZD2389 in Participants With Liver Fibrosis and Compensated Cirrhosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Liver Fibrosis
Hepatic Cirrhosis
Keywords: Liver Fibrosis
Hepatic Cirrhosis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-12-27
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The total duration of study participation for each participant in Cohorts A and B will be approximately 63 days (9 weeks) and will include an up to 28-day screening period, a 28-day treatment period, and a follow-up visit seven days following completion of treatment.

Assessments will be conducted as described in the SoA.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure the safety, tolerability, and the way the body absorbs, distributes, and metabolises AZD2389 as compared to placebo in participants with liver fibrosis and compensated cirrhosis. The study will also examine how the drug acts on the body

Detailed description: Study details include:

The study duration will be up to 63 days (9 weeks).

* 1 or 2 screening visits (up to 28 days before treatment)
* 28 days of treatment including 5 clinic visits
* Week 1: 24-hour in-clinic stay (Day 1)
* Week 2: Outpatient clinic visit (Day 7)
* Week 3: Outpatient clinic visit (Day 14)
* Week 4: Telephone visit (Day 21)
* Week 5: 24 to 48-hour in-clinic stay (Day 28)
* Week 6: Follow-up visit (Day 35) Disclosure Statement: The study consists of two cohorts, each with a parallel-group design and two arms, with participants blinded to treatment allocation.

Number of Participants:

The study will randomise approximately 36 participants in total. Cohort A: Approximately 75 participants with presumed MASH/NASH with fibrosis will be screened such that approximately 18 participants will be randomised. Twelve participants will be randomised to receive AZD2389 and 6 participants will receive placebo. Cohort B: Approximately 75 participants with SLD with advanced fibrosis including compensated cirrhosis will be screened such that approximately 18 participants will be randomised. Twelve participants will be randomised to receive AZD2389 and 6 participants will receive placebo

Eligibility criteria: Key inclusions:

* Males/females aged ≥ 18 years
* Indications: Presumed MASH (cohort A) or other steatotic liver disease (cohort B) with fibrosis
* No significant change in weight over the last 6 months
* Barrier contraceptives use by males
* Capable of informed consent
* Judged to be suitable for study by investigator

Key exclusions:

* A condition that could put the participant at risk, influence the participant's ability to participate in the trial, interfere with evaluation of the study intervention or affect the interpretation of the results
* Other causes of liver disease which are not the principal inclusion criteria for each cohort
* Significant elevations in liver blood tests or platelets \<140 x10\^9/L
* Decompensated liver disease, hepatobiliary cancer or listing for liver transplantation
* Bleeding disorders or major bleeding risk
* HIV infection or hepatitis B infection
* Clinically significant cardiovascular (e.g. severe ischaemic heart disease, severe heart failure or cardiac dysrhythmia) or cerebrovascular disease within the past 3 months
* Stage 2 hypertension
* eGFR \<60ml/min/1.73m2
* Clinically significant gastrointestinal disease which can affect the interpretation of pharmacokinetic, safety, and tolerability data
* Skin disorders or ongoing wound healing
* Psychiatric disorders which may negatively affect participation in the trial.
* Females of childbearing potential

Primary outcomes:
measure: Reported quantity and severity of adverse events (AEs) following oral administration of AZD2389
timeFrame: Up to and including day 35 (from pre-screening to follow-up visit)
measure: Number of participants with observed changes in blood pressure against baseline mmHg value
timeFrame: Up to and including Day 35 (from pre-screening to follow-up visit)
measure: Number of participants with observed changes in heart rate (BPM) against baseline value
timeFrame: Up to and including day 35 (from pre-screening to follow-up visit)
measure: Number of participants with observed changes in Sp02 oxygen values against baseline measurement
timeFrame: Up to and including day 35 (from pre-screening to follow-up visit)
measure: Number of participants with observed changes in body temperature against baseline value
timeFrame: Up to and including day 35 (from pre-screening to follow-up visit)
measure: Number of participants with observed changes in respiratory rate against baseline value
timeFrame: Up to and including day 35 (from pre-screening to follow-up visit)
measure: Number of participants with identified abnormalities in results of 12-lead safety electrocardiograms (ECG)
timeFrame: Up to and including day 35 (from pre-screening to follow-up visit)
measure: Number of participants with changes in physical baseline values identified during physical examinations
timeFrame: Up to and including day 35 (from pre-screening to follow-up visit)
measure: Number of participants with abnormal laboratory test results detected in blood samples
timeFrame: Up to and including day 35 (from pre-screening to follow-up visit)
measure: Number of participants with abnormal laboratory results detected in urine samples
timeFrame: Up to and including day 35 (from pre-screening to follow-up visit)
measure: Number of participants with visible changes (against baseline observations) to the condition of abdominal organs as identified by FibroScan imaging
timeFrame: Up to and including Day 35 (from pre-screening to follow-up visit)
Secondary outcomes:
measure: To evaluate the effect of AZD2389 on plasma FAP activity following oral administration of AZD2389 in participants with CLD and hepatic fibrosis
timeFrame: From Day 1 to Day 35
measure: Maximum Plasma Concentration (Cmax) detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Time to Maximum Concentration (Tmax) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Area Under the Concentration-time Curve to the Last Measurable Concentration (AUClasta) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Terminal Half-life (t1/2λz) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Apparent Volume of Distribution (Vz/F) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Apparent Clearance (CL/F) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Temporal Change Parameter (TCP) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Cmax Accumulation Ratio (Rac Cmax) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: AUC Accumulation Ratio (Rac AUC) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Renal Clearance (CLR) as detected in blood sample
timeFrame: From Day 1 to Day 35
measure: Amount of Drug Excreted in Urine (Ae) as detected in urine sample
timeFrame: From Day 1 to Day 35
measure: Fraction of Drug Excreted in Urine (Fe) as detected in urine sample
timeFrame: From Day 1 to Day 35
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Rialto
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Morehead City
country: United States
facility: Research Site
state: North Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: San Juan
country: Puerto Rico
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
References: