AZD4831 for NASH with Fibrosis

(COSMOS Trial)

No longer recruiting at 63 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Weight loss drugs, Vitamin E, Corticosteroids, others

Disqualifiers: Alcoholic liver disease, Viral hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of AZD4831, an experimental drug, for individuals with NASH (a liver disease causing fat buildup) and fibrosis (scarring of the liver). Participants will receive either AZD4831 or a placebo (a pill with no active drug) to compare the effects. The study helps researchers gather information to develop treatments, even though participants may not experience direct benefits. It suits those diagnosed with NASH through a liver biopsy and who have elevated liver enzyme levels. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to potential advancements in NASH treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you've recently used certain drugs for weight loss, high doses of vitamin E, or specific therapies linked to liver conditions. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that AZD4831 is likely to be safe for humans?

Previous studies found that AZD4831 was generally well tolerated, with most participants experiencing no serious side effects. Research has shown no new safety concerns. Participants took AZD4831 daily for 12 weeks, and researchers closely monitored their health. While this does not guarantee safety for everyone, these findings suggest AZD4831 is safe enough for further testing in people with NASH, a liver condition that causes damage and scarring. Joining clinical trials helps researchers learn more about the treatment and improve it for future patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NASH?

Unlike the standard treatments for NASH with fibrosis, which often include lifestyle changes and medications like vitamin E or pioglitazone, AZD4831 works differently by targeting a specific enzyme called myeloperoxidase (MPO). This enzyme is involved in inflammation and fibrosis, key factors in the progression of NASH. Researchers are excited about AZD4831 because it offers a novel approach that could directly address the underlying causes of the condition, potentially leading to better outcomes for patients. By inhibiting MPO, AZD4831 might reduce liver inflammation and slow fibrosis more effectively than existing treatments.

What evidence suggests that AZD4831 might be an effective treatment for NASH?

Research has shown that AZD4831, which participants in this trial may receive, might help treat NASH, a liver condition that causes damage and scarring. An earlier study demonstrated that AZD4831 reduced the activity of an enzyme called MPO by 69%. MPO is linked to inflammation, and lowering its activity might help reduce liver damage. Although participants in the current trial are not expected to see direct benefits, these findings suggest that AZD4831 could potentially be effective in treating NASH. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-75 with Non-alcoholic Steatohepatitis (NASH) and liver fibrosis, confirmed by biopsy, can join this trial. They should have a history of increased liver enzymes but no other liver diseases or recent use of weight loss drugs or treatments that could affect the fatty liver.

Inclusion Criteria

- NAS ≥ 4 with a score of ≥ 1 for each component: steatosis, lobular inflammation and ballooning

My liver condition was confirmed as NASH by a biopsy within the last year.

- Presence of fibrosis F1, F2-F3

Exclusion Criteria

I have been taking a high dose of vitamin E for the last 6 months.

I have used medications like steroids or methotrexate in the last 6 months.

I have a liver condition not caused by NASH.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive once daily dosing of AZD4831 or placebo for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AZD4831
• Placebo

Trial Overview The study is testing AZD4831 against a placebo to see its effects on NASH with fibrosis. Participants will be randomly assigned to either the drug or placebo for 12 weeks and monitored for an additional 4 weeks after treatment ends.

How Is the Trial Designed?

Group I: AZD4831 Experimental Treatment 1 Intervention

AZD4831

Group II: Placebo Placebo Group 1 Intervention

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

Published Research Related to This Trial

Obeticholic acid (OCA) has shown both safety and efficacy in treating nonalcoholic steatohepatitis (NASH) in phase 3 trials, leading to a new drug application for its approval, which could significantly impact treatment options for this condition.

Elafibranor, on the other hand, did not demonstrate efficacy in its phase 3 trial but is undergoing further assessment, highlighting the ongoing need for effective therapies as the prevalence of NASH increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies for the treatment of nonalcoholic steatohepatitis: A systematic review. Guirguis, E., Grace, Y., Bolson, A., et al.[2021]

In a systematic review of 10 studies involving patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), treatment with 4 mg saroglitazar significantly reduced liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST), indicating improved liver function.

Saroglitazar also led to significant improvements in liver stiffness and metabolic parameters such as glycated hemoglobin, total cholesterol, and triglycerides, suggesting it is an effective and safe treatment option for managing NAFLD and NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Bandyopadhyay, S., Samajdar, SS., Das, S.[2023]

Statins, particularly atorvastatin, have shown promising results in improving liver health and reducing cardiovascular disease (CVD) risk in patients with non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), based on analyses of over 11,000 participants from randomized controlled trials.

Statin treatment not only improves liver enzyme levels and liver imaging results but also significantly reduces CVD morbidity and mortality, with statin-treated NAFLD/NASH patients experiencing a 50% reduction in CVD events compared to those with normal liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statins: An Under-Appreciated Asset for the Prevention and the Treatment of NAFLD or NASH and the Related Cardiovascular Risk. Athyros, VG., Boutari, C., Stavropoulos, K., et al.[2022]

Obeticholic acid (OCA), an FXR agonist, has shown significant improvement in hepatic fibrosis for patients with NASH stage 2/3 in a phase 3 trial, although it has side effects like itching and increased LDL cholesterol.

Several other treatments, including selonsertib and emricasan, were discontinued due to lack of efficacy, while new agents and combination therapies are being explored in ongoing phase 3 trials, indicating a continued search for effective NASH treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and new pharmacotherapy options for non-alcoholic steatohepatitis. Sumida, Y., Yoneda, M., Ogawa, Y., et al.[2022]

Citations

1. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-azd4831-for-adults-with-non-cirrhotic-non-alcoholic-steatohepatitis-nash-with-fibrosis/

Study on the Safety and Effects of AZD4831 for Adults ... This study investigates the safety and effects of AZD4831 in adults suffering from Non-Cirrhotic Non-Alcoholic Steatohepatitis (NASH) with ...

2. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/AZN/pressreleases/33329872/astrazenecas-nash-study-completes-market-implications-of-azd4831/

AstraZeneca's NASH Study Completes: Market Implications ... The study aimed to assess the safety and effectiveness of AZD4831 in treating NASH with fibrosis, a condition with significant unmet medical ...

3. withpower.com withpower.com/trial/phase-2-non-alcoholic-fatty-liver-disease-9-2022-7cc3d

AZD4831 for NASH with Fibrosis (COSMOS Trial) This trial is testing a new drug called AZD4831 to see if it can help people with a liver condition known as NASH, which causes liver damage and scarring.

4. astrazeneca.com astrazeneca.com/media-centre/medical-releases/astrazenecas-investigational-mpo-inhibitor-azd4831-shows-promise-in-patients-with-heart-failure-and-a-preserved-ejection-fraction.html

AstraZeneca's investigational MPO inhibitor AZD4831 ... Findings from a planned interim analysis of the SATELLITE trial showed a 69% (95% CI: 36.3, 85.0) reduction in MPO activity in the AZD4831 group ...

5. clinicaltrials.eu clinicaltrials.eu/inn/azd4831/

Azd4831 – Application in Therapy and Current Clinical ... The main outcomes being measured in AZD4831 clinical trials include ... This clinical trial is focused on studying Non-Alcoholic Steatohepatitis (NASH) ...

6. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D6581C00001

A Study in Participants with Non-cirrhotic NASH with Fibrosis All participants will be treated once daily with AZD4831 or placebo for 12 weeks. The safety, tolerability, and pharmacodynamics will be evaluated at 12 weeks.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05638737

NCT05638737 | A Study in Participants With Non-cirrhotic ... All participants will be treated once daily with AZD4831 or placebo for 12 weeks. The safety, tolerability, and pharmacodynamics will be evaluated at 12 weeks.