Steatohepatitis
Conditions
Keywords
Cirrhosis
Brief summary
The purpose of this study is to measure the safety, tolerability, and PK (measurement of drug activity in the body over time) of AZD7503 injected subcutaneously, and compared to placebo, in participants with suspected NASH, a type of liver disease.
Detailed description
This is a Phase I, randomised, single-blind (in which the study centre staff including the Principal Investigator, remain blinded during the clinical conduct of a given cohort) placebo controlled, multiple ascending dose (MAD) study in male and female participants conducted at multiple centres. Each participant is expected to be in the study for approximately 24 weeks, including a screening period of up to 4 weeks, a 12-week study intervention period, and a follow-up visit at week 18 (10 weeks following the final dose). Participants will be randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Study intervention will be administered via subcutaneous injection.
Interventions
DRUGAZD7503
Each participant is expected to be in the study for approximately 24 weeks, including a screening period of up to 28 days, a 12-week study intervention period, and a follow-up visit at week 18 (10 weeks following the final dose). Participants will be randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Study intervention will be administered via subcutaneous injection.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This is a single-blind, randomised, placebo-controlled, MAD study with up to 3 study intervention cohorts that are participant- and investigator-blinded.
Intervention model description
Each participant is expected to be in the study for approximately 24 weeks, including a screening period of up to 4 weeks, a 12-week study intervention period, and a follow-up visit at week 18 (10 weeks following the final dose). Participants will be randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Study intervention will be administered via subcutaneous injection.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria 1. Biopsy-confirmed NASH diagnosis with CRN score of fibrosis stage of F1 to F3 within the previous 12 months prior to screening or history of fatty liver disease by imaging plus clinical suspicion of NASH based on history of type 2 DM for at least 5 years or overweight/obesity with BMI 25 to 40 kg/m\^2 with 2 additional metabolic syndrome components. 2. Males and females of non-child bearing potential. 3. Willing to provide written informed consent and comply with study requirements. Key
Exclusion criteria
1. Evidence of any clinical important condition which in the investigator opinion makes it undesirable for the participant to participate in the study 2. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention 3. History of liver transplant or presence or history of hepatic disease other than NASH or histological or imaging evidence of cirrhosis. 4. Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV)virus, seropositive for Hepatitis C virus (HCV) 5. History of excessive alcohol consumption 6. Uncontrolled high blood pressure 7. Any clinically important abnormalities in ECG 8. Suspected history of illicit drug abuse 9. Clinically important abnormalities in urine and blood laboratory results 10. Changes in concomitant medication within 1 month of screening 11. Received another investigational drug within 90 days of administration of study intervention in this study 12. Has received any chemical entity or investigational drug targeting HSD17B13 (eg, ARO-HSD or ALN-HSD).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with adverse events (AEs) | Up to and including week 19 (from pre-screening to follow-up visit) | AEs will be collected at all sites visits per SOA. |
| Number of subjects with serious adverse events (SAEs) | Up to and including week 18 (from pre-screening to final visit). | SAEs will be reported and collected as they occur. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma drug concentration (Cmax) | Day 1 to Day 127 | PK parameters to be collected per the SOA. |
| Area under the concentration-time curve from time 0 to infinity (AUCinf) for plasma PK | Day 1 to 127 | PK parameters to be collected per the SOA. |
| Area under the concentration-time curve over the dosing interval (AUCtau) for plasma PK | Time frame: Day 1 to 127 | PK parameters to be collected per the SOA. |
| Fraction of the dose excreted unchanged into the urine from time t1 to t2 (fe(t1-t2)) for urine PK | Day 1 and Day 57: Pre-dose and between 0-6 hours, 6-12 hours, 12-24 hours, 24-36 hours and 36-48 hours post-dose | PK parameters to be collected per the SOA. |
Countries
Puerto Rico, United States
Outcome results
None listed