AZD2693 for Non-alcoholic Steatohepatitis with Fibrosis

(FORTUNA Trial)

Recruiting at 167 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Disqualifiers: Liver disease, Cirrhosis, Renal disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

220 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called AZD2693, which is given as an injection under the skin. It is aimed at adults with a specific liver condition and a certain genetic marker. The goal is to see if it can reduce liver damage and improve liver function.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What makes the drug AZD2693 unique for treating non-alcoholic steatohepatitis (NASH) with fibrosis?

AZD2693 is a novel treatment option for NASH with fibrosis, a condition for which there are currently no approved drugs. This makes it a potentially groundbreaking therapy in addressing a significant unmet medical need. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults aged 18-75 with non-cirrhotic non-alcoholic steatohepatitis (NASH) with fibrosis, who carry the PNPLA3 148M risk allele. They must have a liver biopsy showing NASH and fibrosis stage F2 or F3. Excluded are those with other liver diseases, severe kidney disease, abnormal blood counts or certain elevated liver enzymes.

Inclusion Criteria

I carry the PNPLA3 gene variant linked to liver disease.

I have NASH with moderate to severe liver damage.

Exclusion Criteria

I have a liver condition not caused by alcohol or viruses.

I have a history of severe liver disease.

My kidney function is low, with an eGFR under 40.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD2693 or placebo via subcutaneous injection

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• AZD2693
• Placebo

Trial Overview The study tests AZD2693's effectiveness and safety in treating NASH with fibrosis among carriers of the PNPLA3 risk allele. Participants will receive either AZD2693 or a placebo through subcutaneous injections to compare outcomes between the two groups.

Participant Groups

Group I: AZD2693 dose 2 Experimental Treatment 1 Intervention

Participants will receive AZD2693 dose 2

Group II: AZD2693 dose 1 Experimental Treatment 1 Intervention

Participants will receive AZD2693 dose 1

Group III: Placebo Placebo Group 1 Intervention

Participants in this arm will receive placebo

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

AstraZeneca K.K.

Collaborator

Trials

2

Recruited

650+

Findings from Research

In a study of 187 participants with nonalcoholic steatohepatitis (NASH) receiving placebo treatment, 20% showed a significant reduction in liver fat content (PDFF) after 12 weeks, highlighting a notable 'placebo effect' that can impact trial outcomes.

The analysis revealed an average decrease of 2.3 units in absolute PDFF values after 24 weeks of placebo treatment, suggesting that future clinical trials should account for this effect when calculating sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Nedrud, MA., Chaudhry, M., Middleton, MS., et al.[2023]

Out of 49 therapeutic options investigated for nonalcoholic steatohepatitis (NASH), only six showed potential for conditional FDA approval based on histological surrogate endpoints, with obeticholic acid being the only therapy to demonstrate significant fibrosis improvement in a phase 3 trial.

Several other treatments, including cenicriviroc, liraglutide, semaglutide, and resmetirom, showed promising results in earlier phase studies, but more research is needed to confirm their efficacy and safety in preventing NASH progression to cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Horizon scanning of therapeutic modalities for nonalcoholic steatohepatitis. Patikorn, C., Veettil, SK., Phisalprapa, P., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical trial: Effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy-confirmed nonalcoholic steatohepatitis. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients With Nonalcoholic Steatohepatitis. [2021]

5. Mexico pubmed.ncbi.nlm.nih.gov

Horizon scanning of therapeutic modalities for nonalcoholic steatohepatitis. [2022]