Clinical trial NCT05809934: A Study to Evaluate AZD2693 in Participants Who Are Carriers of the PNPLA3 148M Risk Allele With Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis
Official title: A Randomised, Double-blind, Placebo-controlled, Multi-centre Phase 2b Study to Evaluate the Efficacy, Safety and Tolerability of AZD2693 in Participants With Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) With Fibrosis Who Are Carriers of the PNPLA3 rs738409 148M Risk Allele
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis
Keywords: Nonalcoholic Steatohepatitis
NASH
fatty liver disease
Non alcoholic fatty liver
liver fibrosis
PNPLA3 148M Risk Allele
Non Cirrhotic
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-04-12
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, Double-blind, Placebo-controlled, Multi-centre Phase 2b Study
Primary purpose: TREATMENT

Brief summary: A Study to Evaluate the Efficacy, Safety and Tolerability of AZD2693 given by subcutaneous injection in adult participants with non-cirrhotic non-alcoholic steatohepatitis with fibrosis and who are carriers of the PNPLA3 148M Risk Allele


Eligibility criteria: Key Inclusion Criteria :

Participants are eligible to be included in the study only if all the following criteria apply:

Age

1. Participant must be 18 to 75 years of age (inclusive) at the time of signing the informed consent.

   Type of Participant and Disease Characteristics
2. Participants who are carriers for the PNPLA3 rs738409 148M risk allele.
3. Participants with histological evidence of NASH based on central pathologist evaluation of a liver biopsy obtained up to 6 months before randomisation, or during screening, fulfilling both criteria:

   1. Definitive NASH with NAS ≥ 4 with ≥ 1 in each component (ie, steatosis, lobular inflammation, and ballooning).

   <!-- -->

   1. Presence of fibrosis stage F2 or F3 according to the NASH CRN fibrosis staging system based on central pathologist evaluation.

Key Exclusion Criteria :

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

1. Liver disease of other aetiologies (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 cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding.
3. Historical persistent or pre-existing renal disease marked by eGFR \< 40 mL/min/1.73 m2 (as defined by Kidney Disease Improving Global Outcomes guidelines).
4. Confirmed platelet count outside the normal range at the screening visit.
5. Any of the following confirmed at the screening visit:

   1. ALT \> 5.0 × ULN
   2. TBL \> 1.5 mg/dL (TBL \> 1.5 mg/dL is allowed if conjugated bilirubin is \< 1.5 × ULN)
   3. INR \> 1.3
   4. ALP \> 1.5 × ULN (unless the ALP elevation is not from hepatic origin as determined by a bone-specific ALP)

Primary outcomes:
measure: Proportion of participants achieving NASH resolution without worsening of fibrosis based on histology after 52 weeks treatment
timeFrame: after 52 weeks
Secondary outcomes:
measure: Proportion of participants with at least one stage of liver fibrosis improvement with no worsening of NASH based on biopsy after 52 weeks treatment
timeFrame: after 52 weeks
measure: Proportion of participants with ≥ 2-point improvement from baseline in NAS based on biopsy after 52 weeks treatment
timeFrame: after 52 weeks
measure: Proportion of participants with improvement in fibrosis by at least one stage based on biopsy after 52 weeks treatment
timeFrame: after 52 weeks
Other outcomes:
measure: Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal laboratory test results
timeFrame: 64 weeks
measure: Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal clinical test results
timeFrame: 64 weeks
Locations:
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Peoria
country: United States
facility: Research Site
state: Arizona
city: Surprise
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Gardena
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: Lancaster
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Montclair
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Rialto
country: United States
facility: Research Site
state: California
city: Santa Ana
country: United States
facility: Research Site
state: California
city: Boca Raton
country: United States
facility: Research Site
state: Florida
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Port Orange
country: United States
facility: Research Site
state: Florida
city: Winter Park
country: United States
facility: Research Site
state: Florida
city: Marietta
country: United States
facility: Research Site
state: Georgia
city: Topeka
country: United States
facility: Research Site
state: Kansas
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Westlake
country: United States
facility: Research Site
state: Ohio
city: Chickasha
country: United States
facility: Research Site
state: Oklahoma
city: Hershey
country: United States
facility: Research Site
state: Pennsylvania
city: Summerville
country: United States
facility: Research Site
state: South Carolina
city: Cordova
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Brownsville
country: United States
facility: Research Site
state: Texas
city: Denison
country: United States
facility: Research Site
state: Texas
city: Edinburg
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Red Oak
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Sugar Land
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
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: Cordoba
country: Argentina
facility: Research Site
city: Florencio Varela
country: Argentina
facility: Research Site
city: La Plata
country: Argentina
facility: Research Site
city: Mar del Plata
country: Argentina
facility: Research Site
city: Botucatu
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: Sao Jose Do Rio Preto
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Valdivia
country: Chile
facility: Research Site
city: Baotou
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Liaocheng
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Xuzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Zhenjiang
country: China
facility: Research Site
city: Cartagena
country: Colombia
facility: Research Site
city: Konstanz
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Hyderabad
country: India
facility: Research Site
city: Jaipur
country: India
facility: Research Site
city: Jaipur
country: India
facility: Research Site
city: Punjab
country: India
facility: Research Site
city: Surat
country: India
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Fukui-shi
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Gifu-shi
country: Japan
facility: Research Site
city: Kagoshima-shi
country: Japan
facility: Research Site
city: Kawasaki-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Kure-shi
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Minato-ku
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Oita-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Omura-shi
country: Japan
facility: Research Site
city: Osaka
country: Japan
facility: Research Site
city: Saga-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Takasaki-shi
country: Japan
facility: Research Site
city: Tsu-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Jung-gu
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Kota Kinabalu
country: Malaysia
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Pulau Pinang
country: Malaysia
facility: Research Site
city: Seremban
country: Malaysia
facility: Research Site
city: Acapulco
country: Mexico
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: Torreon
country: Mexico
facility: Research Site
city: Veracruz
country: Mexico
facility: Research Site
city: Xalapa
country: Mexico
facility: Research Site
city: Chorrillos
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Cebu
country: Philippines
facility: Research Site
city: Puerto Princesa City
country: Philippines
facility: Research Site
city: Roxas City
country: Philippines
facility: Research Site
city: San Fernando
country: Philippines
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: A Coruña
country: Spain
facility: Research Site
city: Almeria
country: Spain
facility: Research Site
city: Lérida
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Bursa
country: Turkey
facility: Research Site
city: Eskisehir
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Rize
country: Turkey
facility: Research Site
city: Ho Chi Minh City
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
References: