Study of AZD2389 Safety, Tolerability, and Pharmacodynamics in Adults With Steatotic Liver Disease and Advanced Fibrosis (BRAVO)
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)
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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
Contacts et emplacements
Coordonnées de l'étude
- Nom: AstraZeneca Clinical Study Information Center
- Numéro de téléphone: 1-877-240-9479
- E-mail: information.center@astrazeneca.com
Lieux d'étude
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San Juan, Porto Rico, 00927
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- Research Site
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Arizona
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Chandler, Arizona, États-Unis, 85224
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Tucson, Arizona, États-Unis, 85712
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California
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Fresno, California, États-Unis, 93720
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Florida
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Jupiter, Florida, États-Unis, 33458
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Miami, Florida, États-Unis, 33122
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Port Orange, Florida, États-Unis, 32127
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Missouri
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Kansas City, Missouri, États-Unis, 64131
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St Louis, Missouri, États-Unis, 63123
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Nevada
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Las Vegas, Nevada, États-Unis, 89106
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North Carolina
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Morehead City, North Carolina, États-Unis, 28557
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Raleigh, North Carolina, États-Unis, 27607
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Ohio
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Westlake, Ohio, États-Unis, 44145
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Oklahoma
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Yukon, Oklahoma, États-Unis, 73099
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Tennessee
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Clarksville, Tennessee, États-Unis, 37040
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Texas
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Austin, Texas, États-Unis, 78757
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Denison, Texas, États-Unis, 75020
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Georgetown, Texas, États-Unis, 78626
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Houston, Texas, États-Unis, 77004
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Houston, Texas, États-Unis, 77079
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San Antonio, Texas, États-Unis, 78215
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San Antonio, Texas, États-Unis, 78222
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Key Inclusion Criteria:
- 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
Key Exclusion Criteria:
- 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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: Arm A
Doses of AZD2389 to be administered orally. |
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.
Autres noms:
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Comparateur placebo: Arm B
Doses of placebo to be administered orally. |
Oral administration |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Absolute change in Enhanced Liver Fibrosis (ELF) score from baseline to week 24
Délai: 24 weeks
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To evaluate the effects of AZD2389 versus placebo on improvement in ELF score. Lowered ELF scores would suggest better outcome. Note: ELF is not bounded, i.e. there are no minimum and maximum values |
24 weeks
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Reported quantity and severity of adverse events (AEs)
Délai: Up to and including Day 197
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To assess the safety and tolerability of AZD2389 in participants with SLD and advanced fibrosis |
Up to and including Day 197
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Number of participants with observed changes in blood pressure against baseline mmHg value
Délai: Up to and including Day 197
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Assess blood pressure level (with systolic and diastolic pressure) in mmHg |
Up to and including Day 197
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Number of participants with identified abnormalities in results of 12-lead safety electrocardiograms (ECG)
Délai: Up to and including Day 197
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12-lead safety ECG (PR interval, QRS complex, ST interval, T wave) |
Up to and including Day 197
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Number of participants with abnormal laboratory results detected in urine samples
Délai: Up to and including Day 197
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Urinalysis - Paper chromatography |
Up to and including Day 197
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Number of participants with observed changes in heart rate (BPM) against baseline value
Délai: Up to and including Day 197
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Pulse rate measured in beats per minute (BPM) |
Up to and including Day 197
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Number of participants with observed changes in Sp02 oxygen values against baseline measurement
Délai: Up to and including Day 197
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Sp02 oxygen saturations measured by percentage |
Up to and including Day 197
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Number of participants with observed changes in body temperature against baseline value
Délai: Up to and including Day 197
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Body temperature measured in degrees Celsius |
Up to and including Day 197
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Number of participants with observed changes in respiratory rate against baseline value
Délai: Up to and including Day 197
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Respiratory rate measured in respirations per minute |
Up to and including Day 197
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Number of participants with abnormal laboratory test results detected in blood samples
Délai: Up to and including Day 197
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Hematology - Platelets (x10^9/L) |
Up to and including Day 197
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Number of participants with abnormal laboratory test results detected in blood samples
Délai: Up to and including Day 197
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Coagulation - INR |
Up to and including Day 197
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Number of participants with abnormal laboratory test results detected in blood samples
Délai: Up to and including Day 197
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Clinical Chemistry - ALT (U/L) |
Up to and including Day 197
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Number of participants with abnormal laboratory test results detected in blood samples
Délai: Up to and including Day 197
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Fibrinolysis - D-dimer (ng/mL fibrinogen-equivalent units) |
Up to and including Day 197
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Number of participants with abnormal laboratory test results detected in blood samples
Délai: Up to and including Day 197
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Clinical Chemistry - AST (U/L) |
Up to and including Day 197
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Number of participants with abnormal laboratory test results detected in blood samples
Délai: Up to and including Day 197
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Clinical Chemistry - ALP (U/L) |
Up to and including Day 197
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Absolute change in Procollagen Type III N-terminal Propeptide (ProC3) from baseline to week 24
Délai: 24 weeks
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To assess the effects of AZD2389 versus placebo on improvement in ProC3 |
24 weeks
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Absolute change in Liver Stiffness Measurement (LSM) from baseline to week 24
Délai: 24 weeks
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To assess the effects of AZD2389 versus placebo on improvement in LSM measured by Vibration-controlled transient elastography (VCTE) |
24 weeks
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Absolute change in Controlled Attenuation Parameter (CAP) from baseline to week 24
Délai: 24 weeks
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To assess the effects of AZD2389 versus placebo on improvement in CAP |
24 weeks
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Percentage change in Procollagen Type III N-terminal Propeptide (ProC3) from baseline to week 24
Délai: 24 weeks
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To assess the effects of AZD2389 versus placebo on improvement in ProC3 |
24 weeks
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Percentage change in Liver Stiffness Measurement (LSM) from baseline to week 24
Délai: 24 weeks
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To assess the effects of AZD2389 versus placebo on improvement in LSM measured by Vibration-controlled transient elastography (VCTE) |
24 weeks
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Collaborateurs et enquêteurs
Parrainer
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- D7930C00008
Plan pour les données individuelles des participants (IPD)
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Délai de partage IPD
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