Non-cirrhotic non-alcoholic steatohepatitis with fibrosis MedDRA version: 24.1 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Product Name: AZD2693
Product Code: [AZD2693]
Pharmaceutical Form: Solution for injection/infusion
Current Sponsor code: AZD2693 Sodium
Concentration unit: mg/ml milligram(s)/millilitre
Concentration
Sponsors
ASTRAZENECA AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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, who have either homozygous or heterozygous G/G or G/C genotypes. 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: (a) Definitive NASH with NAS = 4 with = 1 in each component (ie, steatosis, lobular inflammation, and ballooning). (b) Presence of fibrosis stage F2 or F3 according to the NASH CRN fibrosis staging system based on central pathologist evaluation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 286 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: 1 History of liver transplant or current placement on a liver transplant list. 2 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) 3 History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding. 4 Historical persistent or pre-existing renal disease marked by eGFR 5.0 × ULN (b) TBL > 1.5 mg/dL (TBL > 1.5 mg/dL is allowed if conjugated bilirubin is 1.3 (d) 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 |
|---|---|
| Main Objective: To assess the effect of AZD2693 versus placebo on histological resolution of NASH in participants with non-cirrhotic NASH with fibrosis (and homozygous for the PNPLA3 rs738409 148M risk allele) after 52 weeks;Secondary Objective: 1. To assess the effects of AZD2693 to placebo on histological fibrosis improvement in participants homozygous for the PNPLA3 rs738409 148M risk allele 2. To assess the effect of AZD2693 versus placebo on = 2-point improvement in NAS in participants homozygous for the PNPLA3 rs738409 148M risk allele 3. To assess the effect of AZD2693 versus placebo on improvement in fibrosis by at least one stage in participants homozygous for the PNPLA3 rs738409 148M risk allele 4. To assess the effect of AZD2693 versus placebo on circulating biomarkers of fibrosis and fibrogenesis in participants homozygous for the PNPLA3 rs738409 148M risk allele 5. To assess safety and tolerability of AZD2693 compared with placebo in participants with non-cirrhotic NASH with fibrosis and carriers of PNPLA3 rs738409 148M risk allele;Primary end point(s): The primary objective is to demonstrate superiority of AZD2693 compared to placebo on the resolution of NASH with no worsening of fibrosis after Week 52 in patients homozygous for the PNPLA3 rs738409 148M risk allele. To support the primary objective, the primary endpoint is - The resolution of NASH without any worsening of fibrosis (yes/no). - The resolution of NASH is defined as a ballooning score of 0, inflammation score of 0 to 1 and steatosis score of any degree (from 0 to 3), as assessed by NASH CRN/NAS score. - Worsening of fibrosis is defined as an increase in the NASH CRN fibrosis score;Timepoint(s) of evaluation of this end point: Week 52 of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For patients homozygous for the PNPLA3 rs738409 148M risk allele, secondary endpoints are: • At least one stage of liver fibrosis improvement with no worsening of NASH (yes/no) after 52 weeks (worsening defined as an increase of at least one stage of either lobular inflammation or hepatocyte ballooning according to NASH CRN criteria) • Proportion of patients with improvement in fibrosis by at least one stage based on biopsy after Week 52 • = 2-point improvement in NAS in patients homozygous for the PNPLA3 rs738409 148M risk allele after 52 weeks;Timepoint(s) of evaluation of this end point: Week 52 of treatment | — |
Countries
Argentina, Brazil, Chile, China, Colombia, Germany, Hong Kong, India, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Peru, Philippines, Portugal, Singapore, Spain, Taiwan, Thailand, Turkey, United States, Viet Nam
Contacts
Public ContactClinical Study Information Center
Astrazeneca
Outcome results
None listed