A Study to Evaluate AZD2693 in Participants Who Are Carriers of the PNPLA3 148M Risk Allele With Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis (FORTUNA)

AstraZeneca

Status and phase: Active, not recruiting; Phase 2

Conditions: Nonalcoholic Steatohepatitis

Treatments: Other: Placebo; Drug: AZD2693

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT05809934

2022-001629-65 (EudraCT Number)

D7830C00004

Details and patient eligibility

About

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

Enrollment: 175 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).
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   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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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175 participants in 3 patient groups, including a placebo group

AZD2693 dose 1

Experimental group

Description:

Participants will receive AZD2693 dose 1

Treatment:

Drug: AZD2693

AZD2693 dose 2

Experimental group

Description:

Participants will receive AZD2693 dose 2

Treatment:

Drug: AZD2693

Placebo

Placebo Comparator group

Description:

Participants in this arm will receive placebo

Treatment:

Other: Placebo