Nonalcoholic Steatohepatitis
Conditions
Keywords
Nonalcoholic Steatohepatitis, NASH, fatty liver disease, Non alcoholic fatty liver, liver fibrosis, PNPLA3 148M Risk Allele, Non Cirrhotic
Brief summary
A Study to Evaluate the Efficacy, Safety and Tolerability of AZD2693 given by subcutaneous injection in adult participants with non-cirrhotic non-alcoholic steatohepatitis with fibrosis and who are carriers of the PNPLA3 148M Risk Allele
Interventions
DRUGAZD2693
AZD2693 solution SC once per month
OTHERPlacebo
Sodium chloride 0.9% solution SC once per month
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention model description
Randomised, Double-blind, Placebo-controlled, Multi-centre Phase 2b Study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria : Participants are eligible to be included in the study only if all the following criteria apply: Age 1. Participant must be 18 to 75 years of age (inclusive) at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. Participants who are carriers for the PNPLA3 rs738409 148M risk allele. 3. Participants with histological evidence of NASH based on central pathologist evaluation of a liver biopsy obtained up to 6 months before randomisation, or during screening, fulfilling both criteria: 1. Definitive NASH with NAS ≥ 4 with ≥ 1 in each component (ie, steatosis, lobular inflammation, and ballooning). <!-- --> 1. Presence of fibrosis stage F2 or F3 according to the NASH CRN fibrosis staging system based on central pathologist evaluation. Key
Exclusion criteria
: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Liver disease of other aetiologies (eg, alcoholic steatohepatitis; drug-induced, viral or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha-1 antitrypsin deficiency; Wilson's disease) 2. History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding. 3. Historical persistent or pre-existing renal disease marked by eGFR \< 40 mL/min/1.73 m2 (as defined by Kidney Disease Improving Global Outcomes guidelines). 4. Confirmed platelet count outside the normal range at the screening visit. 5. Any of the following confirmed at the screening visit: 1. ALT \> 5.0 × ULN 2. TBL \> 1.5 mg/dL (TBL \> 1.5 mg/dL is allowed if conjugated bilirubin is \< 1.5 × ULN) 3. INR \> 1.3 4. ALP \> 1.5 × ULN (unless the ALP elevation is not from hepatic origin as determined by a bone-specific ALP)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving NASH resolution without worsening of fibrosis based on histology after 52 weeks treatment | after 52 weeks | To assess the effect of AZD2693 versus placebo on histological resolution of NASH in participants with non-cirrhotic NASH with fibrosis and PNPLA3 risk allele carriers after 52 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with ≥ 2-point improvement from baseline in NAS based on biopsy after 52 weeks treatment | after 52 weeks | To assess the effect of AZD2693 versus placebo on ≥ 2-point improvement in NAS |
| Proportion of participants with improvement in fibrosis by at least one stage based on biopsy after 52 weeks treatment | after 52 weeks | To assess the effect of AZD2693 versus placebo on improvement in fibrosis by at least one stage |
| Proportion of participants with at least one stage of liver fibrosis improvement with no worsening of NASH based on biopsy after 52 weeks treatment | after 52 weeks | To assess the effects of AZD2693 versus placebo on histological fibrosis improvement |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal laboratory test results | 64 weeks | Haematology, urinalysis, clinical chemistry and eGFR |
| Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal clinical test results | 64 weeks | Vital signs and electrocardiogram (ECG) assessments |
Countries
Argentina, Brazil, Chile, China, Colombia, Germany, Hong Kong, India, Italy, Japan, Malaysia, Mexico, Peru, Philippines, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United States, Vietnam
Outcome results
None listed