Non-Cirrhotic Non-alcoholic Steatohepatitis With FibrosisPhase 2COSMOSNCT05638737
A Study in Participants With Non-cirrhotic NASH With Fibrosis
A Phase 2 study testing AZD4831 in people with Non-Cirrhotic Non-alcoholic Steatohepatitis With Fibrosis, run by AstraZeneca at 65 sites in 9 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-Cirrhotic Non-alcoholic Steatohepatitis With Fibrosis
- What is being tested?
- AZD4831
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 65 sitesin 9 countries
- Study dates
- 26 Oct 2022to 4 Apr 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
65 sites in 9 countries.
65 sites in 9 countries
United States17 sites
Research Site
Chandler, Arizona, 85224
Research Site
Chula Vista, California, 91911
Research Site
Dallas, Texas, 75230
Research Site
Houston, Texas, 77090
Research Site
Jacksonville, Florida, 32256
Research Site
Lakeland, Florida, 33803
Research Site
Lakeland, Florida, 33813
Research Site
Las Vegas, Nevada, 89109
Research Site
Miami, Florida, 33135
Research Site
Montclair, California, 91763
Research Site
Morehead City, North Carolina, 28557
Research Site
Orange, California, 92868
Research Site
Redondo Beach, California, 90277
Research Site
San Antonio, Texas, 78229
Research Site
Stanford, California, 94305
Research Site
Tucson, Arizona, 85712
Research Site
Yonkers, New York, 10701
Mexico12 sites
Research Site
Boca del Rio, 94299
Research Site
Cuauhtémoc, 06700
Research Site
Guadalajara, 44210
Research Site
Guadalajara, 44340
Research Site
Guadalajara, 44670
Research Site
México, 03300
Research Site
Mexico City, 014080
Research Site
Mexico City, 03330
Research Site
Mexico City, 06700
Research Site
Monterrey, 64000
Research Site
Monterrey, 64460
Research Site
Monterrey, 64710
Italy9 sites
Research Site
Catania, 95100
Research Site
Foggia, 71100
Research Site
Milan, 20122
Research Site
Milan, 20132
Research Site
Roma, 00128
Research Site
Roma, 00168
Research Site
Rozzano, 20089
Research Site
San Giovanni Rotondo, 71013
Research Site
Torino, 10126
Argentina7 sites
Research Site
CABA, C1056ABJ
Research Site
CABA, C1119ACN
Research Site
CABA, C1426
Research Site
Ciudad de Buenos Aires, 1280
Research Site
Mar del Plata, 7600
Research Site
Pilar, 1664
Research Site
Ramos Mejía, B1704ETD
Spain7 sites
Research Site
A Coruña, 15006
Research Site
Lleida, 25198
Research Site
Madrid, 28046
Research Site
Málaga, 29010
Research Site
Pozuelo de Alarcón, 28223
Research Site
Santander, 39008
Research Site
Valencia, 46014
Denmark5 sites
Research Site
Aarhus N, 8200
Research Site
Esbjerg, 6700
Research Site
København NV, 2400
Research Site
København Ø, 2100
Research Site
Køge, 4600
Norway5 sites
Research Site
Gjøvik, 2819
Research Site
Grålum, 1714
Research Site
Lørenskog, N-1478
Research Site
Oslo, 0456
Research Site
Tromsø, N-9038
About this study
Official title: 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
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.
Read the detailed description
A randomized, double blind, placebo-controlled, parallel-group, multicenter study including a maximum of approximately 90 randomized adult participants with biopsy-proven non-cirrhotic non-alcoholic steatohepatitis (NASH) with fibrosis (NAS ≥ 4, fibrosis stages F1, F2, F3). The study will be conducted at approximately 48 sites across approximately 9 countries.
During screening, the participants will be checked for eligibility and enrolled in the study. Following a 8-week screening period, approximately 90 participants will be randomized in a 1:1 ratio to once daily dosing of AZD4831 or placebo. 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. This is the first clinical study to test AZD4831 in participants with non-cirrhotic NASH with fibrosis.
- Being tested
- AZD4831, Placebo
- Keywords
- NASH, Non-Cirrhotic, Steatohepatitis
- Medical subject headings
- Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4831Drug
AZD4831
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| AZD4831 | Experimental | AZD4831 Receives: Drug: AZD4831 |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative to Baseline Alanine Aminotransferase (ALT)
ALT at 12 weeks relative to baseline. ALT is measured in Units per litre (U/L)
Measured: 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
Pro-C3 at 12 weeks relative to baseline. Pro-C3 is measured in nanograms per milliliter (ng/mL).
Measured: Measurements on Baseline, Week 4 and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2022
- Study start26 Oct 2022
- Primary completion4 Apr 2024
- Study completion4 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Cirrhotic Non-alcoholic Steatohepatitis With FibrosisStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05638737
- Sponsor's protocol ID
- D6581C00001
- Acronym
- COSMOS
- Status last verified
- Jul 2025
- First submitted
- 3 Oct 2022
- Last updated
- 9 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 41108609
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05638737
- Acronym / sponsor ID
- COSMOS / D6581C00001
- Keywords
- NASH, Non-Cirrhotic, Steatohepatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 26 Oct 2022 (actual)
- Primary completion
- 4 Apr 2024 (actual)
- Study completion
- 4 Apr 2024 (actual)
- First posted
- 6 Dec 2022 (actual)
- Results
- Posted 9 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A randomized, double blind, placebo-controlled, parallel-group, multicenter study including a maximum of approximately 90 randomized adult participants with biopsy-proven non-cirrhotic non-alcoholic steatohepatitis (NASH) with fibrosis (NAS ≥ 4, fibrosis stages F1, F2, F3). The study will be conducted at approximately 48 sites across approximately 9 countries.
During screening, the participants will be checked for eligibility and enrolled in the study. Following a 8-week screening period, approximately 90 participants will be randomized in a 1:1 ratio to once daily dosing of AZD4831 or placebo. 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. This is the first clinical study to test AZD4831 in participants with non-cirrhotic NASH with fibrosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD4831 | Experimental | Drug: AZD4831AZD4831 |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
- 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.
Key exclusion criteria (6 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD4831AZD4831 | Drug | AZD4831 |
| PlaceboPlacebo | Other | Placebo |
Primary outcome
Relative to Baseline Alanine Aminotransferase (ALT)
Time frame: Measurements on Baseline, Week 2, Week 4, Week 8, Week 12 and Week 16. Change reported from Baseline to Week 12.
ALT at 12 weeks relative to baseline. ALT is measured in Units per litre (U/L)
1 secondary outcome
Relative to Baseline Pro-C3
Time frame: Measurements on Baseline, Week 4 and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41108609Armisen 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.
- D6581C00001-Redacted\_SAPLink provided by the sponsor.
- D6581C00001\_Redacted\_CSPLink provided by the sponsor.
- d6581C00001-Redacted\_CSR\_SynopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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RecruitingPhase 3
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NASH With Fibrosis, MASH With Fibrosis
Active, not recruitingPhase 3
A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )
NASH - Nonalcoholic Steatohepatitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
65 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD4831 in people with Non-Cirrhotic Non-alcoholic Steatohepatitis With Fibrosis, run by AstraZeneca at 65 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 65 sites in United States, Mexico, Italy, Argentina, Spain and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative to Baseline Alanine Aminotransferase (ALT) (time frame: Measurements on Baseline, Week 2, Week 4, Week 8, Week 12 and Week 16. Change reported from Baseline to Week 12.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05638737, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2025.