Clinical trial NCT05638737: A Study in Participants With Non-cirrhotic NASH With Fibrosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Cirrhotic Non-alcoholic Steatohepatitis With Fibrosis
Keywords: NASH
Non-Cirrhotic
Steatohepatitis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-12-06
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline and over placebo to Week 12 - ALT
timeFrame: 12 weeks
Secondary outcomes:
measure: Change from baseline over placebo to Week 12 - Pro-C3
timeFrame: 12 weeks
measure: Plasma concentration of AZD4831 (Ctrough)
timeFrame: 12 weeks
Other outcomes:
measure: Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal clinical test results
timeFrame: 12 weeks
measure: Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal laboratory test results
timeFrame: 12 weeks
Locations:
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Montclair
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Lakeland
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Yonkers
country: United States
facility: Research Site
state: New York
city: Caba
country: Argentina
facility: Research Site
city: Caba
country: Argentina
facility: Research Site
city: Caba
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aires
country: Argentina
facility: Research Site
city: Mar del Plata
country: Argentina
facility: Research Site
city: Ramos Mejía
country: Argentina
facility: Research Site
city: Aarhus N
country: Denmark
facility: Research Site
city: Esbjerg
country: Denmark
facility: Research Site
city: Koge
country: Denmark
facility: Research Site
city: København NV
country: Denmark
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Foggia
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: San Giovanni Rotondo
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Ciudad de Mexico
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: México
country: Mexico
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: Tromsø
country: Norway
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: La Coruña
country: Spain
facility: Research Site
city: Lérida
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Pozuelo de Alarcon
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
Study officials:
References: