Study of AZD2389 Safety, Tolerability, and Pharmacodynamics in Adults With Steatotic Liver Disease and Advanced Fibrosis

Официальное название

A Phase IIa, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AZD2389 in Adult Participants With Steatotic Liver Disease and Advanced Fibrosis (BRAVO)

Обзор

The purpose of this study is to evaluate the safety, tolerability, and pharmacodynamic effects of AZD2389 in adult participants with steatotic liver disease (SLD) and advanced fibrosis.

Подробное описание

Study details include:

* The study duration will be approximately 32 weeks, including screening duration of 4 weeks, the treatment duration of up to 24 weeks, and follow-up period of 4 weeks. * The visit frequency will be approximately every 4 weeks except from Visit 2 to Visit 4, which is every 2 weeks.

Disclosure Statement:

This is a parallel group treatment study that is blinded to the participants and investigators.

Number of Participants:

Approximately 230 participants with SLD and advanced fibrosis will be screened such that approximately 104 participants will be randomised. Approximately 52 participants will be randomised to receive AZD2389 and approximately 52 participants will receive placebo.

Note: 'Screened' means a participant's, or their legally authorised representative's, agreement to participate in a clinical study following completion of the informed consent process.

Study Arms and Duration:

Arm A will include 52 participants with SLD and advanced fibrosis who will receive oral AZD2389 for 24 weeks. Arm B will include 52 participants with SLD and advanced fibrosis who will receive oral placebo for 24 weeks.

Вмешательства

• Препарат AZD2389
  potent, selective, first-in-class, small molecule oral inhibitor of FAP and is being developed for the treatment of CLDs with advanced hepatic fibrosis including cirrhosis.
• Другое Placebo
  Oral administration

Первичные конечные точки

• Absolute change in Enhanced Liver Fibrosis (ELF) score from baseline to week 24 [Срок оценки: 24 weeks]
• Reported quantity and severity of adverse events (AEs) [Срок оценки: Up to and including Day 197]
• Number of participants with observed changes in blood pressure against baseline mmHg value [Срок оценки: Up to and including Day 197]
• Number of participants with identified abnormalities in results of 12-lead safety electrocardiograms (ECG) [Срок оценки: Up to and including Day 197]
• Number of participants with abnormal laboratory results detected in urine samples [Срок оценки: Up to and including Day 197]
• Number of participants with observed changes in heart rate (BPM) against baseline value [Срок оценки: Up to and including Day 197]
• Number of participants with observed changes in Sp02 oxygen values against baseline measurement [Срок оценки: Up to and including Day 197]
• Number of participants with observed changes in body temperature against baseline value [Срок оценки: Up to and including Day 197]
• Number of participants with observed changes in respiratory rate against baseline value [Срок оценки: Up to and including Day 197]
• Number of participants with abnormal laboratory test results detected in blood samples [Срок оценки: Up to and including Day 197]

Вторичные конечные точки (5)

• Absolute change in Procollagen Type III N-terminal Propeptide (ProC3) from baseline to week 24 [Срок оценки: 24 weeks]
• Absolute change in Liver Stiffness Measurement (LSM) from baseline to week 24 [Срок оценки: 24 weeks]
• Absolute change in Controlled Attenuation Parameter (CAP) from baseline to week 24 [Срок оценки: 24 weeks]
• Percentage change in Procollagen Type III N-terminal Propeptide (ProC3) from baseline to week 24 [Срок оценки: 24 weeks]
• Percentage change in Liver Stiffness Measurement (LSM) from baseline to week 24 [Срок оценки: 24 weeks]

Критерии участия

Критерии включения

• Males/females aged 18 or over
• A diagnosis of SLD with advanced fibrosis
• No significant change in weight over the last 6 months
• Contraceptive us by participants or participants partners
• Capable of giving informed consent
• Judged by the investigator to be suitable for study

Критерии исключения

• Portal hypertension (LSM >25 kPa or 20-25 kPa with platelets <150×10⁹/L), decompensated liver disease, Child-Pugh >A6, MELD >12, other chronic liver diseases, prior/planned liver transplant, or malignant liver tumors.
• Positive viral infections, including HIV or hepatitis B, or hepatitis C unless HCV RNA-negative ≥12 weeks after treatment.
• Alcohol intake above protocol thresholds, or positive screen for drugs of abuse.
• Significant metabolic, cardiovascular, or GI disorders, including T1DM or insulin-treated T2DM, uncontrolled hypertension, recent major cardiac/cerebrovascular events, severe heart failure, serious arrhythmias, significant pancreatic disease, or major GI surgery.
• History of psychosis, bipolar disorder, recent major depression, or suicide attempt/ideation within 1 year.
• Bleeding risk or wound-healing concerns, including coagulation disorders, major bleeding history, active wounds or recent major surgery, or severe dermatologic immune conditions.
• Prohibited medications or hypersensitivities, including moderate/strong CYP3A4 or BCRP/OAT3 inhibitors/inducers, anticoagulants/antiplatelets (except aspirin ≤81 mg/day), or hypersensitivity to DPP4 inhibitors.
• Other protocol-defined exclusions, including significant abnormal labs (e.g., worsening ALT/AST), recent participation in another IMP study, or investigator judgment of unsuitability.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 20 центров

• Research Site — Chandler
• Research Site — Tucson
• Research Site — Jupiter
• Research Site — Miami
• Research Site — Port Orange
• Research Site — Kansas City
• Research Site — St Louis
• Research Site — Las Vegas
• … и ещё 12 центров

Идентификаторы

NCT: NCT07610837 · D7930C00008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗