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)

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ClinicalTrials.gov Identifier: NCT05809934

Recruitment Status : Recruiting

First Posted : April 12, 2023

Last Update Posted : April 12, 2024

See Contacts and Locations

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborator:

AstraZeneca K.K.

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

February 23, 2023

First Posted Date ^ICMJE

April 12, 2023

Last Update Posted Date

April 12, 2024

Actual Study Start Date ^ICMJE

March 15, 2023

Estimated Primary Completion Date

November 7, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Proportion of participants achieving NASH resolution without worsening of fibrosis based on histology after 52 weeks treatment [ Time Frame: 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

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

Proportion of participants with at least one stage of liver fibrosis improvement with no worsening of NASH based on biopsy after 52 weeks treatment [ Time Frame: after 52 weeks ]
To assess the effects of AZD2693 versus placebo on histological fibrosis improvement
Proportion of participants with ≥ 2-point improvement from baseline in NAS based on biopsy after 52 weeks treatment [ Time Frame: 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 [ Time Frame: after 52 weeks ]
To assess the effect of AZD2693 versus placebo on improvement in fibrosis by at least one stage

Original Secondary Outcome Measures ^ICMJE

Proportion of participants with at least one stage of liver fibrosis improvement with no worsening of NASH based on biopsy after 52 weeks treatment [ Time Frame: after 52 weeks ]
To assess the effects of AZD2693 versus placebo on histological fibrosis improvement in participants who are carriers of the PNPLA3 risk allele
Proportion of participants with ≥ 2-point improvement from baseline in NAS based on biopsy after 52 weeks treatment [ Time Frame: after 52 weeks ]
To assess the effect of AZD2693 versus placebo on ≥ 2-point improvement in NASH in participants who are carriers of the PNPLA3 risk allele
Proportion of participants with improvement in fibrosis by at least one stage based on biopsy after 52 weeks treatment [ Time Frame: after 52 weeks ]
To assess the effect of AZD2693 versus placebo on improvement in fibrosis by at least one stage in participant who are carriers of the PNPLA3 risk allele

Current Other Pre-specified Outcome Measures

Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal laboratory test results [ Time Frame: 64 weeks ]
Haematology, urinalysis, clinical chemistry and eGFR
Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal clinical test results [ Time Frame: 64 weeks ]
Vital signs and electrocardiogram (ECG) assessments

Original Other Pre-specified Outcome Measures

Same as current

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

A Randomised, Double-blind, Placebo-controlled, Multi-centre Phase 2b Study to Evaluate the Efficacy, Safety and Tolerability of AZD2693 in Participants With Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) With Fibrosis Who Are Carriers of the PNPLA3 rs738409 148M Risk Allele

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

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomised, Double-blind, Placebo-controlled, Multi-centre Phase 2b Study

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose: Treatment

Condition ^ICMJE

Nonalcoholic Steatohepatitis

Intervention ^ICMJE

Drug: AZD2693
AZD2693 solution SC once per month
Other: Placebo
Sodium chloride 0.9% solution SC once per month

Study Arms ^ICMJE

Experimental: AZD2693 dose 1
Participants will receive AZD2693 dose 1

Intervention: Drug: AZD2693
Experimental: AZD2693 dose 2
Participants will receive AZD2693 dose 2

Intervention: Drug: AZD2693
Placebo Comparator: Placebo
Participants in this arm will receive placebo

Intervention: Other: Placebo

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

180

Original Estimated Enrollment ^ICMJE

232

Estimated Study Completion Date ^ICMJE

November 7, 2025

Estimated Primary Completion Date

November 7, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Key Inclusion Criteria :

Participants are eligible to be included in the study only if all the following criteria apply:

Age

Participant must be 18 to 75 years of age (inclusive) at the time of signing the informed consent.

Type of Participant and Disease Characteristics
Participants who are carriers for the PNPLA3 rs738409 148M risk allele.
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

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)
History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding.
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).
Confirmed platelet count outside the normal range at the screening visit.
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)

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 75 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Listed Location Countries ^ICMJE

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, Vietnam

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT05809934

Other Study ID Numbers ^ICMJE

D7830C00004
2022-001629-65 ( EudraCT Number )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
Time Frame:	AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria:	When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home