AZD4831 for NASH with Fibrosis

(COSMOS Trial)

Recruiting at 44 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

122 Participants Needed

Trial Summary

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.

How is the drug AZD4831 different from other treatments for NASH with fibrosis?

AZD4831 is a novel treatment option for NASH with fibrosis, addressing the unmet need for effective anti-fibrotic therapies. Unlike existing treatments, which have limitations and side effects, AZD4831 offers a new approach, potentially changing the treatment landscape for this condition. ^{1 2 3 4 5}

What is the purpose of this 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. The study involves adults who have been diagnosed with NASH but do not have cirrhosis. Researchers hope that AZD4831 will reduce liver inflammation and scarring.

Eligibility Criteria

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

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

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

- 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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

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

Emerging therapies for the treatment of nonalcoholic steatohepatitis: A systematic review. [2021]

2. France 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. [2023]

3. United Arab Emirates 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Current and new pharmacotherapy options for non-alcoholic steatohepatitis. [2022]

5. 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]