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History of Changes for Study: 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 (FORTUNA)
Latest version (submitted April 11, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 30, 2023 None (earliest Version on record)
2 April 26, 2023 Contacts/Locations and Study Status
3 May 26, 2023 Contacts/Locations and Study Status
4 September 20, 2023 Contacts/Locations, Study Status, Outcome Measures and Study Design
5 September 28, 2023 Contacts/Locations and Study Status
6 October 26, 2023 Contacts/Locations and Study Status
7 December 12, 2023 Contacts/Locations and Study Status
8 January 11, 2024 Contacts/Locations and Study Status
9 February 12, 2024 Contacts/Locations and Study Status
10 March 13, 2024 Contacts/Locations and Study Status
11 April 11, 2024 Contacts/Locations and Study Status
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Study NCT05809934
Submitted Date:  March 30, 2023 (v1)

Open or close this module Study Identification
Unique Protocol ID: D7830C00004
Brief Title: A Study to Evaluate AZD2693 in Participants Who Are Carriers of the PNPLA3 148M Risk Allele With Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis (FORTUNA)
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
Secondary IDs: 2022-001629-65 [EudraCT Number]
Open or close this module Study Status
Record Verification: March 2023
Overall Status: Recruiting
Study Start: March 15, 2023
Primary Completion: November 7, 2025 [Anticipated]
Study Completion: November 7, 2025 [Anticipated]
First Submitted: February 23, 2023
First Submitted that
Met QC Criteria:
March 30, 2023
First Posted: April 12, 2023 [Actual]
Last Update Submitted that
Met QC Criteria:
March 30, 2023
Last Update Posted: April 12, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: AstraZeneca
Responsible Party: Sponsor
Collaborators: AstraZeneca K.K.
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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
Detailed Description:
Open or close this module Conditions
Conditions: Nonalcoholic Steatohepatitis
Keywords: Nonalcoholic Steatohepatitis
NASH
fatty liver disease
Non alcoholic fatty liver
liver fibrosis
PNPLA3 148M Risk Allele
Non Cirrhotic
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Randomised, Double-blind, Placebo-controlled, Multi-centre Phase 2b Study
Number of Arms: 3
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 232 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: AZD2693 dose 1
Participants will receive AZD2693 dose 1
Drug: AZD2693
AZD2693 solution SC once per month
Experimental: AZD2693 dose 2
Participants will receive AZD2693 dose 2
Drug: AZD2693
AZD2693 solution SC once per month
Placebo Comparator: Placebo
Participants in this arm will receive placebo
Placebo
Sodium chloride 0.9% solution SC once per month
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Proportion of participants achieving NASH resolution without worsening of fibrosis based on histology after 52 weeks treatment
[ Time Frame: after 52 weeks ]

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
Secondary Outcome Measures:
1. Proportion of participants with at least one stage of liver fibrosis improvement with no worsening of NASH based on biopsy after 52 weeks treatment
[ Time Frame: after 52 weeks ]

To assess the effects of AZD2693 versus placebo on histological fibrosis improvement in participants who are carriers of the PNPLA3 risk allele
2. Proportion of participants with ≥ 2-point improvement from baseline in NAS based on biopsy after 52 weeks treatment
[ Time Frame: after 52 weeks ]

To assess the effect of AZD2693 versus placebo on ≥ 2-point improvement in NASH in participants who are carriers of the PNPLA3 risk allele
3. Proportion of participants with improvement in fibrosis by at least one stage based on biopsy after 52 weeks treatment
[ Time Frame: after 52 weeks ]

To assess the effect of AZD2693 versus placebo on improvement in fibrosis by at least one stage in participant who are carriers of the PNPLA3 risk allele
Other Outcome Measures:
1. Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal laboratory test results
[ Time Frame: 64 weeks ]

Haematology, urinalysis, clinical chemistry and eGFR
2. Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal clinical test results
[ Time Frame: 64 weeks ]

Vital signs and electrocardiogram (ECG) assessments
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 75 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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)
Open or close this module Contacts/Locations
Central Contact Person: AstraZeneca Clinical Study Information Center
Telephone: 1-877-240-9479
Email: information.center@astrazeneca.com
Locations: Argentina
Research Site
[Not yet recruiting]
Caba, Argentina, C1119ACN
Research Site
[Not yet recruiting]
Ciudad de Buenos Aires, Argentina, 1280
Research Site
[Not yet recruiting]
Cordoba, Argentina, X5014PQC
Research Site
[Not yet recruiting]
Cordoba, Argentina, X5016
Research Site
[Not yet recruiting]
La Plata, Argentina, 1900
Research Site
[Not yet recruiting]
Ramos Mejía, Argentina, B1704ETD
Brazil
Research Site
[Not yet recruiting]
Botucatu, Brazil, 18618-687
Research Site
[Not yet recruiting]
Porto Alegre, Brazil, 90035-000
Research Site
[Not yet recruiting]
Porto Alegre, Brazil, 90035-903
Research Site
[Not yet recruiting]
Rio de Janeiro, Brazil, 21941-913
Research Site
[Not yet recruiting]
Salvador, Brazil, 40110-160
Research Site
[Not yet recruiting]
Sao Jose Do Rio Preto, Brazil, 15090-000
Research Site
[Not yet recruiting]
Sao Paulo, Brazil, 05403-000
Research Site
[Not yet recruiting]
Sao Paulo, Brazil, 05652-900
Chile
Research Site
[Not yet recruiting]
La Serena, Chile, 1781094
Research Site
[Not yet recruiting]
Santiago, Chile, 7620157
Research Site
[Withdrawn]
Santiago, Chile, 8330336
Research Site
[Not yet recruiting]
Santiago, Chile
Research Site
[Not yet recruiting]
Valdivia, Chile, 5110683
China
Research Site
[Not yet recruiting]
Chengdu, China, 610072
Research Site
[Not yet recruiting]
Xi'an, China, 710061
Colombia
Research Site
[Not yet recruiting]
Armenia, Colombia, 630004
Research Site
[Not yet recruiting]
Cartagena, Colombia, 130013
Germany
Research Site
[Not yet recruiting]
Konstanz, Germany, 78464
Research Site
[Not yet recruiting]
Mainz, Germany, 55131
Research Site
[Not yet recruiting]
Mannheim, Germany, 68167
Hong Kong
Research Site
[Not yet recruiting]
Hong Kong, Hong Kong
Research Site
[Not yet recruiting]
Shatin, Hong Kong
India
Research Site
[Not yet recruiting]
Belagavi, India, 590010
Research Site
[Not yet recruiting]
Chandigarh, India, 160012
Research Site
[Not yet recruiting]
Gurugram, India, 122001
Research Site
[Not yet recruiting]
Hyderabad, India, 500072
Research Site
[Not yet recruiting]
Jaipur, India, 302001
Research Site
[Not yet recruiting]
Jaipur, India, 302018
Research Site
[Not yet recruiting]
Jodhpur, India, 342005
Research Site
[Not yet recruiting]
Nagpur, India, 440010
Research Site
[Not yet recruiting]
Punjab, India, 160062
Italy
Research Site
[Not yet recruiting]
Milano, Italy, 20122
Research Site
[Not yet recruiting]
Palermo, Italy, 90127
Research Site
[Not yet recruiting]
Roma, Italy, 00128
Research Site
[Not yet recruiting]
Rome, Italy, 00168
Research Site
[Not yet recruiting]
Torino, Italy, 10126
Japan
Research Site
[Not yet recruiting]
Bunkyo-ku, Japan, 113-8655
Research Site
[Not yet recruiting]
Fukui-shi, Japan, 918-8503
Research Site
[Withdrawn]
Fukuoka-Shi, Japan, 812-8582
Research Site
[Not yet recruiting]
Fukuoka-shi, Japan, 810-0065
Research Site
[Recruiting]
Gifu-shi, Japan, 500-8513
Research Site
[Not yet recruiting]
Kagoshima-shi, Japan, 890-8520
Research Site
[Not yet recruiting]
Kawasaki-shi, Japan, 216-8511
Research Site
[Not yet recruiting]
Kobe-shi, Japan, 650-0017
Research Site
[Withdrawn]
Kobe-shi, Japan, 650-0047
Research Site
[Not yet recruiting]
Kumamoto-shi, Japan, 860-8556
Research Site
[Not yet recruiting]
Kurume-shi, Japan, 830-0011
Research Site
[Not yet recruiting]
Kyoto-shi, Japan, 602-8566
Research Site
[Withdrawn]
Meguro-ku, Japan, 152-8902
Research Site
[Not yet recruiting]
Minato-ku, Japan, 105-8470
Research Site
[Withdrawn]
Nagakute-shi, Japan, 480-1195
Research Site
[Recruiting]
Nagoya-shi, Japan, 460-0001
Research Site
[Withdrawn]
Ogaki-shi, Japan, 503-8502
Research Site
[Not yet recruiting]
Oita-shi, Japan, 870-0837
Research Site
[Not yet recruiting]
Okayama-shi, Japan, 700-8505
Research Site
[Not yet recruiting]
Omura-shi, Japan, 856-8562
Research Site
[Not yet recruiting]
Osaka, Japan, 545-8586
Research Site
[Not yet recruiting]
Saga-shi, Japan, 849-8501
Research Site
[Not yet recruiting]
Shinjuku-ku, Japan, 160-0023
Research Site
[Not yet recruiting]
Shinjuku-ku, Japan, 160-8582
Research Site
[Not yet recruiting]
Shinjuku-ku, Japan, 162-8655
Research Site
[Withdrawn]
Suita-shi, Japan, 564-0013
Research Site
[Not yet recruiting]
Takasaki-shi, Japan, 370-0829
Research Site
[Not yet recruiting]
Tsu-shi, Japan, 514-8507
Research Site
[Not yet recruiting]
Wako-shi, Japan, 351-0102
Research Site
[Not yet recruiting]
Yokohama-shi, Japan, 236-0004
Research Site
[Not yet recruiting]
Yokohama-shi, Japan, 245-8575
Korea, Republic of
Research Site
[Not yet recruiting]
Jung-gu, Korea, Republic of, 41944
Research Site
[Not yet recruiting]
Seoul, Korea, Republic of, 03080
Research Site
[Not yet recruiting]
Seoul, Korea, Republic of, 03722
Research Site
[Not yet recruiting]
Seoul, Korea, Republic of, 04763
Research Site
[Not yet recruiting]
Seoul, Korea, Republic of, 6351
Malaysia
Research Site
[Not yet recruiting]
Kota Kinabalu, Malaysia, 88586
Research Site
[Not yet recruiting]
Kuala Lumpur, Malaysia, 56000
Research Site
[Not yet recruiting]
Kuala Lumpur, Malaysia, 59100
Research Site
[Not yet recruiting]
Pulau Pinang, Malaysia, 10450
Mexico
Research Site
[Not yet recruiting]
Ciudad de Mexico, Mexico, 06700
Research Site
[Not yet recruiting]
Guadalajara, Mexico, 44670
Research Site
[Not yet recruiting]
Mexico City, Mexico, 03330
Research Site
[Not yet recruiting]
Mexico D.F., Mexico, 014080
Philippines
Research Site
[Not yet recruiting]
Cebu, Philippines, 6000
Research Site
[Not yet recruiting]
Puerto Princesa City, Philippines, 5300
Research Site
[Not yet recruiting]
Roxas City, Philippines, 5800
Research Site
[Not yet recruiting]
San Fernando, Philippines, 2000
Portugal
Research Site
[Not yet recruiting]
Lisboa, Portugal, 1250-189
Research Site
[Not yet recruiting]
Vila Real, Portugal, 5000-508
Singapore
Research Site
[Not yet recruiting]
Singapore, Singapore, 119074
Research Site
[Not yet recruiting]
Singapore, Singapore, 169608
Research Site
[Not yet recruiting]
Singapore, Singapore, 308433
Spain
Research Site
[Not yet recruiting]
A Coruña, Spain, 15006
Research Site
[Not yet recruiting]
Almeria, Spain, 4009
Research Site
[Not yet recruiting]
Lérida, Spain, 25198
Research Site
[Not yet recruiting]
Malaga, Spain, 29010
Research Site
[Not yet recruiting]
Zaragoza, Spain, 50009
Taiwan
Research Site
[Not yet recruiting]
Kaohsiung, Taiwan, 80756
Research Site
[Not yet recruiting]
Tainan City, Taiwan, 70403
Research Site
[Not yet recruiting]
Taipei, Taiwan, 10002
Research Site
[Not yet recruiting]
Taipei, Taiwan, 112
Research Site
[Not yet recruiting]
Taoyuan, Taiwan, 333
Thailand
Research Site
[Not yet recruiting]
Bangkok, Thailand, 10330
Research Site
[Not yet recruiting]
Bangkok, Thailand, 10400
Research Site
[Not yet recruiting]
Bangkok, Thailand, 10700
Research Site
[Not yet recruiting]
Hat Yai, Thailand, 90110
Research Site
[Not yet recruiting]
Khon Kaen, Thailand, 40002
Turkey
Research Site
[Not yet recruiting]
Adana, Turkey, 01060
Research Site
[Not yet recruiting]
Antalya, Turkey, 07059
Research Site
[Not yet recruiting]
Bursa, Turkey, 16059
Research Site
[Not yet recruiting]
Eskisehir, Turkey, 26480
Research Site
[Not yet recruiting]
Izmir, Turkey, 35340
Research Site
[Not yet recruiting]
Rize, Turkey, 530020
Vietnam
Research Site
[Not yet recruiting]
Ho Chi Minh, Vietnam, 700000
Research Site
[Withdrawn]
Ho Chi Minh, Vietnam, 70000
Open or close this module IPDSharing
Plan to Share IPD: Yes

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Supporting Information:
Study Protocol
Statistical Analysis Plan (SAP)
Time Frame:
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria:
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Open or close this module References
Citations:
Links:
Available IPD/Information:

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