Nonalcoholic Steatohepatitis Clinical Trial
— FORTUNAOfficial 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
| Verified date | June 2024 |
| Source | AstraZeneca |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Active, not recruiting |
| Enrollment | 175 |
| Est. completion date | October 7, 2025 |
| Est. primary completion date | October 7, 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility | 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) |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Research Site | Caba | |
| Argentina | Research Site | Caba | |
| Argentina | Research Site | Ciudad de Buenos Aires | |
| Argentina | Research Site | Cordoba | |
| Argentina | Research Site | Florencio Varela | |
| Argentina | Research Site | La Plata | |
| Argentina | Research Site | Mar del Plata | |
| Brazil | Research Site | Botucatu | |
| Brazil | Research Site | Porto Alegre | |
| Brazil | Research Site | Porto Alegre | |
| Brazil | Research Site | Salvador | |
| Brazil | Research Site | Sao Jose Do Rio Preto | |
| Brazil | Research Site | Sao Paulo | |
| Chile | Research Site | Santiago | |
| Chile | Research Site | Santiago | |
| Chile | Research Site | Valdivia | |
| China | Research Site | Baotou | |
| China | Research Site | Beijing | |
| China | Research Site | Beijing | |
| China | Research Site | Beijing | |
| China | Research Site | Chengdu | |
| China | Research Site | Fuzhou | |
| China | Research Site | Guangzhou | |
| China | Research Site | Hangzhou | |
| China | Research Site | Liaocheng | |
| China | Research Site | Nanchang | |
| China | Research Site | Qingdao | |
| China | Research Site | Shanghai | |
| China | Research Site | Shanghai | |
| China | Research Site | Shanghai | |
| China | Research Site | Shenyang | |
| China | Research Site | Taiyuan | |
| China | Research Site | Wenzhou | |
| China | Research Site | Xi'an | |
| China | Research Site | Xuzhou | |
| China | Research Site | Zhenjiang | |
| Colombia | Research Site | Cartagena | |
| Germany | Research Site | Konstanz | |
| Germany | Research Site | Magdeburg | |
| Germany | Research Site | Mainz | |
| Germany | Research Site | Münster | |
| Hong Kong | Research Site | Hong Kong | |
| Hong Kong | Research Site | Shatin | |
| India | Research Site | Hyderabad | |
| India | Research Site | Jaipur | |
| India | Research Site | Jaipur | |
| India | Research Site | Punjab | |
| India | Research Site | Surat | |
| Italy | Research Site | Milano | |
| Italy | Research Site | Palermo | |
| Italy | Research Site | Roma | |
| Italy | Research Site | Rome | |
| Italy | Research Site | Torino | |
| Japan | Research Site | Bunkyo-ku | |
| Japan | Research Site | Fukui-shi | |
| Japan | Research Site | Fukuoka-shi | |
| Japan | Research Site | Gifu-shi | |
| Japan | Research Site | Kagoshima-shi | |
| Japan | Research Site | Kawasaki-shi | |
| Japan | Research Site | Kobe-shi | |
| Japan | Research Site | Kumamoto-shi | |
| Japan | Research Site | Kure-shi | |
| Japan | Research Site | Kurume-shi | |
| Japan | Research Site | Kyoto-shi | |
| Japan | Research Site | Minato-ku | |
| Japan | Research Site | Nagoya-shi | |
| Japan | Research Site | Oita-shi | |
| Japan | Research Site | Okayama-shi | |
| Japan | Research Site | Omura-shi | |
| Japan | Research Site | Osaka | |
| Japan | Research Site | Saga-shi | |
| Japan | Research Site | Shinjuku-ku | |
| Japan | Research Site | Shinjuku-ku | |
| Japan | Research Site | Shinjuku-ku | |
| Japan | Research Site | Takasaki-shi | |
| Japan | Research Site | Tsu-shi | |
| Japan | Research Site | Yokohama-shi | |
| Japan | Research Site | Yokohama-shi | |
| Korea, Republic of | Research Site | Jung-gu | |
| Korea, Republic of | Research Site | Seoul | |
| Korea, Republic of | Research Site | Seoul | |
| Malaysia | Research Site | Kota Kinabalu | |
| Malaysia | Research Site | Kuala Lumpur | |
| Malaysia | Research Site | Kuala Lumpur | |
| Malaysia | Research Site | Pulau Pinang | |
| Malaysia | Research Site | Seremban | |
| Mexico | Research Site | Acapulco | |
| Mexico | Research Site | Ciudad de Mexico | |
| Mexico | Research Site | Guadalajara | |
| Mexico | Research Site | Guadalajara | |
| Mexico | Research Site | México | |
| Mexico | Research Site | Mexico City | |
| Mexico | Research Site | Monterrey | |
| Mexico | Research Site | Torreon | |
| Mexico | Research Site | Veracruz | |
| Mexico | Research Site | Xalapa | |
| Peru | Research Site | Chorrillos | |
| Peru | Research Site | Lima | |
| Peru | Research Site | Lima | |
| Peru | Research Site | Lima | |
| Philippines | Research Site | Cebu | |
| Philippines | Research Site | Puerto Princesa City | |
| Philippines | Research Site | Roxas City | |
| Philippines | Research Site | San Fernando | |
| Singapore | Research Site | Singapore | |
| Singapore | Research Site | Singapore | |
| Singapore | Research Site | Singapore | |
| Spain | Research Site | A Coruña | |
| Spain | Research Site | Almeria | |
| Spain | Research Site | Lérida | |
| Spain | Research Site | Malaga | |
| Spain | Research Site | Zaragoza | |
| Taiwan | Research Site | Kaohsiung | |
| Taiwan | Research Site | Tainan City | |
| Taiwan | Research Site | Taipei | |
| Taiwan | Research Site | Taipei | |
| Taiwan | Research Site | Taoyuan | |
| Thailand | Research Site | Bangkok | |
| Thailand | Research Site | Bangkok | |
| Thailand | Research Site | Bangkok | |
| Thailand | Research Site | Hat Yai | |
| Thailand | Research Site | Khon Kaen | |
| Turkey | Research Site | Adana | |
| Turkey | Research Site | Antalya | |
| Turkey | Research Site | Bursa | |
| Turkey | Research Site | Eskisehir | |
| Turkey | Research Site | Izmir | |
| Turkey | Research Site | Rize | |
| United States | Research Site | Ann Arbor | Michigan |
| United States | Research Site | Austin | Texas |
| United States | Research Site | Boca Raton | Florida |
| United States | Research Site | Brownsville | Texas |
| United States | Research Site | Buffalo | New York |
| United States | Research Site | Chandler | Arizona |
| United States | Research Site | Chickasha | Oklahoma |
| United States | Research Site | Cordova | Tennessee |
| United States | Research Site | Denison | Texas |
| United States | Research Site | Detroit | Michigan |
| United States | Research Site | Edinburg | Texas |
| United States | Research Site | Gardena | California |
| United States | Research Site | Hershey | Pennsylvania |
| United States | Research Site | Hialeah | Florida |
| United States | Research Site | Houston | Texas |
| United States | Research Site | Jacksonville | Florida |
| United States | Research Site | La Mesa | California |
| United States | Research Site | Lancaster | California |
| United States | Research Site | Las Vegas | Nevada |
| United States | Research Site | Los Angeles | California |
| United States | Research Site | Marietta | Georgia |
| United States | Research Site | Montclair | California |
| United States | Research Site | Orange | California |
| United States | Research Site | Peoria | Arizona |
| United States | Research Site | Port Orange | Florida |
| United States | Research Site | Red Oak | Texas |
| United States | Research Site | Rialto | California |
| United States | Research Site | Richmond | Virginia |
| United States | Research Site | San Antonio | Texas |
| United States | Research Site | Santa Ana | California |
| United States | Research Site | Seattle | Washington |
| United States | Research Site | Sugar Land | Texas |
| United States | Research Site | Summerville | South Carolina |
| United States | Research Site | Surprise | Arizona |
| United States | Research Site | Topeka | Kansas |
| United States | Research Site | Tucson | Arizona |
| United States | Research Site | Tucson | Arizona |
| United States | Research Site | Westlake | Ohio |
| United States | Research Site | Winter Park | Florida |
| Vietnam | Research Site | Ho Chi Minh | |
| Vietnam | Research Site | Ho Chi Minh City |
| Lead Sponsor | Collaborator |
|---|---|
| AstraZeneca | AstraZeneca K.K. |
United States, Vietnam, Argentina, Brazil, Chile, China, Colombia, Germany, Hong Kong, India, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Peru, Philippines, Singapore, Spain, Taiwan, Thailand, Turkey,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal laboratory test results | Haematology, urinalysis, clinical chemistry and eGFR | 64 weeks | |
| Other | Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal clinical test results | Vital signs and electrocardiogram (ECG) assessments | 64 weeks | |
| Primary | Proportion of participants achieving NASH resolution without worsening of fibrosis based on histology after 52 weeks treatment | To assess the effect of AZD2693 versus placebo on histological resolution of NASH in participants with non-cirrhotic NASH with fibrosis and PNPLA3 risk allele carriers after 52 weeks | after 52 weeks | |
| Secondary | Proportion of participants with at least one stage of liver fibrosis improvement with no worsening of NASH based on biopsy after 52 weeks treatment | To assess the effects of AZD2693 versus placebo on histological fibrosis improvement | after 52 weeks | |
| Secondary | Proportion of participants with = 2-point improvement from baseline in NAS based on biopsy after 52 weeks treatment | To assess the effect of AZD2693 versus placebo on = 2-point improvement in NAS | after 52 weeks | |
| Secondary | Proportion of participants with improvement in fibrosis by at least one stage based on biopsy after 52 weeks treatment | To assess the effect of AZD2693 versus placebo on improvement in fibrosis by at least one stage | after 52 weeks |
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