A Study to Assess Safety, Tolerability, PK and PD of AZD2693 in Non-alcoholic Steatohepatitis Patients

Study identifier:D7830C00002

ClinicalTrials.gov identifier:NCT04483947

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 1, Double Blind, Randomised, Placebo-Controlled, Multi-centre, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD2693 in Patients with Non-alcoholic Steatohepatitis (NASH) with Fibrosis Stage 0-3 and Carriers of the PNPLA3 148M Risk Alleles

Medical condition

Non-alcoholic steatohepatitis (NASH)

Phase

Phase 1

Healthy volunteers

Study drug

AZD2693

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 06 Nov 2020

Primary Completion Date: 18 Dec 2023

Study Completion Date: 18 Dec 2023

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2024 by AstraZeneca

Collaborators

Parexel International

Inclusion and exclusion criteria

Inclusion Criteria

For Cohorts 1 to 3:
• An MRI-PDFF ≥7% and one of the following:
- Previous liver biopsy: Acceptable if taken in the previous 3 years for fibrosis stages F0 to F2, or within the previous 1 year for stage F3; or
- Previous imaging results taken in the previous 2 years: An MRE between 2.55 kPa and 3.63 kPa, or a vibration-controlled transient elastography (VCTE) between 7.1 kPa and 11.9 kPa;
• Participants who are homozygous for rs738409 (PNPLA3 148M). Cohort 2 will enroll participants who are heterozygous for PNPLA3 148M.
For Cohort 4:
• An MRI-PDFF ≥ 7% and participant’s consent for a liver biopsy.
- Participants with suspected or confirmed Non-alcoholic fatty liver disease (NAFLD) or NASH are eligible for the Screening liver biopsy if they meet main protocol inclusion/exclusion criteria AND have any of the following:
Alanine aminotransferase > Upper Limit of Normal (ULN) but < 3 × ULN, OR
Imaging demonstrating hepatic steatosis including attenuation parameter (CAP) > 290dB/m, OR
A Magnetic resonance elastography (MRE) between 2.55 kPa and 3.63 kPa, or a vibration-controlled transient elastography (VCTE) between 7.1 kPa and 11.9 kPa.
- Histologic evidence of NAFLD or NASH with a NASH Activity Score (NAS) ≥ 3 (independent of subcategory scoring) following Screening liver biopsy.
- Participants who are homozygous for rs738409 (PNPLA3 148M).

Exclusion Criteria

• History of liver transplant, or current placement on a liver transplant list (this may be checked at the optional Pre-Screening Visit).
• History or presence of hepatic disease (with the exception of hepatic steatosis, NASH) or evidence of other known forms of known chronic liver disease such as alcoholic liver disease, hepatitis B, primary biliary cirrhosis, primary sclerotic cirrhosis, autoimmune hepatitis, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or suspected hepatocellular carcinoma (this may be checked at the optional Pre-Screening Visit).
• Histological or imaging (MRE or VCTE) evidence of cirrhosis.
• Participants with history or pre-existing renal disease, as defined below:
- estimated glomerular filtration rate < 60 mL/min/1.73 m^2 (calculated using the Chronic Kidney Disease Epidemiology Collaboration formula)
• Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding (frequent bleeding gums or nose bleeds).
• History of major bleed or high-risk of bleeding diathesis.

No locations available

Arms	Assigned Interventions
Experimental: Cohort 1 15 participants will receive AZD2693 dose 1 and 5 participants will receive placebo	Drug: AZD2693 Subcutaneous administration of AZD2693 multiple ascending doses in participants with NASH and who are carriers of the PNPLA3 148M risk allele(s). Other: Placebo Participants randomised to placebo will receive the corresponding dose volume of solution as participants receiving AZD2693 within the same cohort
Experimental: Cohort 2 15 participants will receive AZD2693 dose 2 and 5 participants will receive placebo	Drug: AZD2693 Subcutaneous administration of AZD2693 multiple ascending doses in participants with NASH and who are carriers of the PNPLA3 148M risk allele(s). Other: Placebo Participants randomised to placebo will receive the corresponding dose volume of solution as participants receiving AZD2693 within the same cohort
Experimental: Cohort 3 15 participants will receive AZD2693 dose 1 and 5 participants will receive placebo	Drug: AZD2693 Subcutaneous administration of AZD2693 multiple ascending doses in participants with NASH and who are carriers of the PNPLA3 148M risk allele(s). Other: Placebo Participants randomised to placebo will receive the corresponding dose volume of solution as participants receiving AZD2693 within the same cohort
Experimental: Cohort 4 15 participants will receive AZD2693 dose 3 and 5 participants will receive placebo	Drug: AZD2693 Subcutaneous administration of AZD2693 multiple ascending doses in participants with NASH and who are carriers of the PNPLA3 148M risk allele(s). Other: Placebo Participants randomised to placebo will receive the corresponding dose volume of solution as participants receiving AZD2693 within the same cohort

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Rohit Loomba

Director, NAFLD Research Center Director of Hepatology, Professor of Medicine Vice Chief, Division of Gastroenterology University of California at San Diego ACTRI Building, 1W202 9500 Gilman Drive La Jolla, CA, 92037-0887