AZD2693 for Non-alcoholic Steatohepatitis with Fibrosis

(FORTUNA Trial)

No longer recruiting at 202 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, AZD2693, to determine its effectiveness for people with non-alcoholic steatohepatitis (NASH), a liver condition causing fat buildup and inflammation, who also have fibrosis (a type of liver scarring). The trial compares AZD2693 to a placebo (a harmless substance with no medical effect) to assess its safety and efficacy. It targets individuals with a specific genetic marker (PNPLA3 148M risk allele) linked to NASH and diagnosed with liver scarring but not cirrhosis (severe liver damage). Those diagnosed with NASH and possessing this genetic marker may be suitable for the study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in NASH treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AZD2693 is generally safe for humans. Studies have examined its safety and how the body processes it. These studies indicate that the treatment specifically targets the liver.

No serious safety issues have been reported so far. Most side effects have been mild and manageable, such as minor reactions at the injection site. This suggests that AZD2693 could be a safe option for those considering joining the trial. However, as this is a Phase 2 trial, further research is needed to fully understand the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AZD2693 for treating non-alcoholic steatohepatitis (NASH) with fibrosis because it offers a novel approach compared to existing treatments. Most current therapies focus on lifestyle changes and some medications that target metabolic risk factors. However, AZD2693 stands out as it specifically targets and modulates the underlying liver inflammation and fibrosis processes in NASH. This unique mechanism of action could potentially halt or even reverse liver damage more effectively than existing options, sparking interest in its potential to significantly improve patient outcomes.

What evidence suggests that AZD2693 could be an effective treatment for non-alcoholic steatohepatitis with fibrosis?

Research has shown that AZD2693, which participants in this trial may receive, may help treat non-alcoholic steatohepatitis (NASH) with fibrosis. In earlier studies, AZD2693 successfully lowered the activity of a gene called PNPLA3 in human liver cells and mice. This gene is linked to increased liver fat and damage in NASH. AZD2693 was generally well tolerated, meaning it did not cause serious side effects. These findings suggest that AZD2693 could help slow down or reverse liver damage in people with NASH who have a specific version of the PNPLA3 gene. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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 have NASH with moderate to severe liver damage.

I carry the PNPLA3 gene variant linked to liver disease.

Exclusion Criteria

Confirmed platelet count outside the normal range

INR > 1.3

ALP > 1.5 × ULN

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05809934

NCT05809934 | A Study to Evaluate AZD2693 in ... A Randomised, Double-blind, Placebo-controlled, Multi-centre Phase 2b Study to Evaluate the Efficacy, Safety and Tolerability of AZD2693 in Participants ...

2. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7830C00004

A study to evaluate AZD2693 in participants who are ... A study to evaluate the efficacy, safety and tolerability of AZD2693 given by subcutaneous injection in adult participants with non-cirrhotic non-alcoholic ...

3. clinicaltrial.be clinicaltrial.be/en/details/264609?per_page=100&only_recruiting=0&only_eligible=0

A Study to Evaluate AZD2693 in Participants Who Are Carri... A study to evaluate the efficacy, safety and tolerability of AZD2693 given by subcutaneous injection in adult participants with non-cirrhotic non-alcoholic ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39798707/

AZD2693, a PNPLA3 antisense oligonucleotide, for the ... Results: AZD2693 potently reduced PNPLA3 expression in human hepatocytes and livers of mice. Clinically, AZD2693 was generally well tolerated (no adverse events ...

5. clinicaltrials.eu clinicaltrials.eu/inn/azd2693-sodium/

Azd2693 Sodium – Application in Therapy and Current ... The condition targeted by AZD2693 SODIUM is specifically non-cirrhotic NASH with fibrosis, meaning the liver damage has not yet progressed to cirrhosis.

6. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7830C00002/

A Study to Assess Safety, Tolerability, PK and PD of ... This study is intended to investigate the safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD2693, following subcutaneous (SC) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0168827825000030

AZD2693, a PNPLA3 antisense oligonucleotide, for the ... AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics.