A Study in Participants With Non-cirrhotic NASH With Fibrosis
COSMOS
A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety, Tolerability, and Pharmacodynamics of AZD4831 (Mitiperstat) in Participants With Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) With Fibrosis
1 other identifier
interventional
112
9 countries
65
Brief Summary
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Participants will be in the trial for up to 24 weeks, including a screening period lasting up to 8 weeks, a 12-week treatment period, and a 4-week safety follow-up period Participants are not expected to directly benefit from treatment during this trial. Participants will help researchers learn more about and how to develop AZD4831 to treat NASH.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2022
Shorter than P25 for phase_2
65 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 3, 2022
CompletedStudy Start
First participant enrolled
October 26, 2022
CompletedFirst Posted
Study publicly available on registry
December 6, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 4, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
April 4, 2024
CompletedResults Posted
Study results publicly available
July 9, 2025
CompletedJuly 9, 2025
July 1, 2025
1.4 years
October 3, 2022
March 24, 2025
July 8, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Relative to Baseline Alanine Aminotransferase (ALT)
ALT at 12 weeks relative to baseline. ALT is measured in Units per litre (U/L)
Measurements on Baseline, Week 2, Week 4, Week 8, Week 12 and Week 16. Change reported from Baseline to Week 12.
Secondary Outcomes (1)
Relative to Baseline Pro-C3
Measurements on Baseline, Week 4 and Week 12
Study Arms (2)
AZD4831
EXPERIMENTALAZD4831
Placebo
PLACEBO COMPARATORPlacebo
Interventions
Eligibility Criteria
You may qualify if:
- Participant must be ≥ 18 to ≤ 75 years of age at the time of signing the informed consent.
- Histological confirmed NASH per Clinical Research Network (CRN) criteria as diagnosed by liver biopsy (within 12 months prior screening, participants without historical biopsy should be willing to undergo a liver biopsy at screening) fulfilling all of the following criteria:
- NAS ≥ 4 with a score of ≥ 1 for each component: steatosis, lobular inflammation and ballooning
- Presence of fibrosis F1, F2-F3
- One increased serum ALT measurement (ALT \> ULN) at screening, and historical local serum ALT level (\> ULN \[41 U/L for men and 31 U/L for women\] but \< 300 U/L) on ≥ 1 occasion in the 6 months prior to screening.
You may not qualify if:
- Liver disease of other etiologies (eg, alcoholic steatohepatitis; drug-induced, viral, or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha 1 antitrypsin deficiency; Wilson's disease).
- History of excessive alcohol consumption, defined as an average weekly intake of \> 21 drinks/week for males or \> 14 drinks/week for females. One drink is equivalent to 14 g alcohol.
- Recent (within 3 months of randomization) use of drugs approved for weight loss (eg, orlistat, bupropion/naltrexone, phentermine-topiramate, phentermine, lorcaserin), as well as those drugs used off-label.
- High dose vitamin E (\> 400 IU) unless on a stable dose within 6 months of screening.
- Recent (within 6 months of screening) use of therapies associated with development of NAFLD (eg, systemic corticosteroids, methotrexate, tamoxifen, amiodarone, or long-term use of tetracyclines).
- Recent (within 6 months of screening) use of obeticholic acid or other therapy under investigation for NASH.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (65)
Research Site
Chandler, Arizona, 85224, United States
Research Site
Tucson, Arizona, 85712, United States
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Chula Vista, California, 91911, United States
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Montclair, California, 91763, United States
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Orange, California, 92868, United States
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Redondo Beach, California, 90277, United States
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Stanford, California, 94305, United States
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Jacksonville, Florida, 32256, United States
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Lakeland, Florida, 33803, United States
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Lakeland, Florida, 33813, United States
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Miami, Florida, 33135, United States
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Las Vegas, Nevada, 89109, United States
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Yonkers, New York, 10701, United States
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Morehead City, North Carolina, 28557, United States
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Dallas, Texas, 75230, United States
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Houston, Texas, 77090, United States
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San Antonio, Texas, 78229, United States
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CABA, C1056ABJ, Argentina
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CABA, C1119ACN, Argentina
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CABA, C1426, Argentina
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Ciudad de Buenos Aires, 1280, Argentina
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Mar del Plata, 7600, Argentina
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Pilar, 1664, Argentina
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Ramos Mejía, B1704ETD, Argentina
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Aarhus N, 8200, Denmark
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Esbjerg, 6700, Denmark
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København NV, 2400, Denmark
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København Ø, 2100, Denmark
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Køge, 4600, Denmark
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Catania, 95100, Italy
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Foggia, 71100, Italy
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Milan, 20122, Italy
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Milan, 20132, Italy
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Roma, 00128, Italy
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Roma, 00168, Italy
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Rozzano, 20089, Italy
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San Giovanni Rotondo, 71013, Italy
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Torino, 10126, Italy
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Boca del Rio, 94299, Mexico
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Cuauhtémoc, 06700, Mexico
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Guadalajara, 44210, Mexico
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Guadalajara, 44340, Mexico
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Guadalajara, 44670, Mexico
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Mexico City, 014080, Mexico
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Mexico City, 03330, Mexico
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Mexico City, 06700, Mexico
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México, 03300, Mexico
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Monterrey, 64000, Mexico
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Monterrey, 64460, Mexico
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Monterrey, 64710, Mexico
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Gjøvik, 2819, Norway
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Grålum, 1714, Norway
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Lørenskog, N-1478, Norway
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Oslo, 0456, Norway
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Tromsø, N-9038, Norway
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Lisbon, 1250-189, Portugal
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A Coruña, 15006, Spain
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Lleida, 25198, Spain
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Madrid, 28046, Spain
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Málaga, 29010, Spain
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Pozuelo de Alarcón, 28223, Spain
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Santander, 39008, Spain
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Valencia, 46014, Spain
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Linköping, 581 85, Sweden
Research Site
Uppsala, 751 85, Sweden
Related Publications (1)
Armisen J, Flor A, Eriksson J, Nelander K, Bhattacharya CS, Sunnaker M, Carter D, Trebski M, Gardmark E, Aurell M, Whatling C, Challis B, Vespasiani-Gentilucci U; COSMOS Investigators. A Phase 2a Trial of Myeloperoxidase Inhibitor Mitiperstat in Non-Cirrhotic Metabolic Dysfunction-Associated Steatohepatitis. Liver Int. 2025 Nov;45(11):e70406. doi: 10.1111/liv.70406.
PMID: 41108609DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 3, 2022
First Posted
December 6, 2022
Study Start
October 26, 2022
Primary Completion
April 4, 2024
Study Completion
April 4, 2024
Last Updated
July 9, 2025
Results First Posted
July 9, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request 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.