A Study in Participants With Non-cirrhotic NASH With Fibrosis

NCT ID: NCT05638737

Last Updated: 2025-07-09

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-26

Study Completion Date

2024-04-04

Brief Summary

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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

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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.

Conditions

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Non-Cirrhotic Non-alcoholic Steatohepatitis With Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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AZD4831

AZD4831

Group Type EXPERIMENTAL

AZD4831

Intervention Type DRUG

AZD4831

Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo

Interventions

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AZD4831

AZD4831

Intervention Type DRUG

Placebo

Placebo

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Participant must be ≥ 18 to ≤ 75 years of age at the time of signing the informed consent.
2. 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
3. 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.

Exclusion Criteria

1. 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).
2. 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.
3. 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.
4. High dose vitamin E (\> 400 IU) unless on a stable dose within 6 months of screening.
5. 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).
6. Recent (within 6 months of screening) use of obeticholic acid or other therapy under investigation for NASH.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Chandler, Arizona, United States

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Tucson, Arizona, United States

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Chula Vista, California, United States

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Montclair, California, United States

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Orange, California, United States

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Redondo Beach, California, United States

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Stanford, California, United States

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Jacksonville, Florida, United States

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Lakeland, Florida, United States

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Lakeland, Florida, United States

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Miami, Florida, United States

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Las Vegas, Nevada, United States

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Yonkers, New York, United States

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Morehead City, North Carolina, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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CABA, , Argentina

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CABA, , Argentina

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CABA, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Mar del Plata, , Argentina

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Pilar, , Argentina

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Ramos Mejía, , Argentina

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Aarhus N, , Denmark

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Esbjerg, , Denmark

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København NV, , Denmark

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København Ø, , Denmark

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Køge, , Denmark

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Catania, , Italy

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Foggia, , Italy

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Milan, , Italy

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Milan, , Italy

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Roma, , Italy

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Roma, , Italy

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Rozzano, , Italy

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San Giovanni Rotondo, , Italy

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Torino, , Italy

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Boca del Rio, , Mexico

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Cuauhtémoc, , Mexico

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Guadalajara, , Mexico

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Guadalajara, , Mexico

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Guadalajara, , Mexico

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Mexico City, , Mexico

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Mexico City, , Mexico

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Mexico City, , Mexico

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México, , Mexico

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Monterrey, , Mexico

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Monterrey, , Mexico

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Monterrey, , Mexico

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Gjøvik, , Norway

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Grålum, , Norway

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Lørenskog, , Norway

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Oslo, , Norway

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Tromsø, , Norway

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Lisbon, , Portugal

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A Coruña, , Spain

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Lleida, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Pozuelo de Alarcón, , Spain

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Santander, , Spain

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Valencia, , Spain

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Linköping, , Sweden

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Uppsala, , Sweden

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Countries

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United States Argentina Denmark Italy Mexico Norway Portugal Spain Sweden

References

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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.

Reference Type DERIVED
PMID: 41108609 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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D6581C00001

Identifier Type: -

Identifier Source: org_study_id

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