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A Study in Participants With Non-cirrhotic NASH With Fibrosis

Phase 2
Completed
Conditions
Non-Cirrhotic Non-alcoholic Steatohepatitis With Fibrosis
Interventions
Other: Placebo
Registration Number
NCT05638737
Lead Sponsor
AstraZeneca
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
122
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AZD4831AZD4831AZD4831
PlaceboPlaceboPlacebo
Primary Outcome Measures
NameTimeMethod
Change from baseline and over placebo to Week 12 - ALT12 weeks

ALT change from baseline and over placebo to Week 12

Secondary Outcome Measures
NameTimeMethod
Change from baseline over placebo to Week 12 - Pro-C312 weeks

Pro-C3 change from baseline and over placebo to Week 12

Plasma concentration of AZD4831 (Ctrough)12 weeks

Plasma concentration of AZD4831 (Ctrough)

Trial Locations

Locations (1)

Research Site

🇸🇪

Uppsala, Sweden

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