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 have the PNPLA3 rs738409 148M Genetic Marker.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

28 Apr 2023 → 29 Sep 2025

Decision date (initial)

2024-07-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509704-14-00

EudraCT number

2022-001629-65

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety, Dose response, Therapy, Pharmacogenomic, Pharmacokinetic, Pharmacogenetic

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 objectives 3

1. 1. To assess the effects of AZD2693 versus placebo on histological fibrosis improvement.
2. 2. To assess the effect of AZD2693 versus placebo on ≥ 2-point improvement in NAS.
3. 3. To assess the effect of AZD2693 versus placebo on improvement in fibrosis by at least one stage.

Conditions and MedDRA coding

Non-cirrhotic non-alcoholic steatohepatitis with fibrosis

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

Yes

IPD 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 Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Age : Participant must be 18 to 75 years of age (inclusive) at the time of signing the informed consent.
2. Type of Participant and Disease Characteristics : 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: (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

Exclusion criteria 5

1. 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. 2 History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding
3. 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. 4 Confirmed platelet count
5. 5 Any of the following confirmed at the screening visit: (a) ALT > 5.0 × ULN (b) TBL > 1.5 mg/dL (TBL > 1.5 mg/dL is allowed if conjugated bilirubin is < 1.5 × ULN) (c) INR > 1.3 (d) ALP > 1.5 × ULN (unless the ALP elevation is not from hepatic origin as determined by abone-specific ALP)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. - The resolution of NASH without any worsening of liver fibrosis (yes/no) after 52 weeks of treatment.
2. - 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.
3. - Worsening of fibrosis is defined as an increase in the NASH CRN fibrosis score.

Secondary endpoints 3

1. - 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)
2. - Improvement in fibrosis by at least one stage based on biopsy after Week 52
3. - ≥ 2-point improvement in NAS after 52 weeks

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Centre

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Centre

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications