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FORTUNA: A Study to Evaluate AZD2693 in Participants Who Are Carriers of the PNPLA3 148M Risk Allele With Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05809934
Collaborator
AstraZeneca K.K. (Other)
232
Enrollment
118
Locations
3
Arms
31.8
Anticipated Duration (Months)
2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
232 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomised, Double-blind, Placebo-controlled, Multi-centre Phase 2b StudyRandomised, Double-blind, Placebo-controlled, Multi-centre Phase 2b Study
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 15, 2023
Anticipated Primary Completion Date :
Nov 7, 2025
Anticipated Study Completion Date :
Nov 7, 2025

Arms and Interventions

Arm Intervention/Treatment
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

Other: Placebo
Sodium chloride 0.9% solution SC once per month

Outcome Measures

Primary Outcome Measures

  1. Proportion of participants achieving NASH resolution without worsening of fibrosis based on histology after 52 weeks treatment [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 [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 [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 [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 [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 [64 weeks]

    Vital signs and electrocardiogram (ECG) assessments

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  1. Participants who are carriers for the PNPLA3 rs738409 148M risk allele.

  2. 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:

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

  4. 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:

  6. ALT > 5.0 × ULN

  7. TBL > 1.5 mg/dL (TBL > 1.5 mg/dL is allowed if conjugated bilirubin is < 1.5 × ULN)

  8. INR > 1.3

  9. ALP > 1.5 × ULN (unless the ALP elevation is not from hepatic origin as determined by a bone-specific ALP)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Caba Argentina C1119ACN
2 Research Site Ciudad de Buenos Aires Argentina 1280
3 Research Site Cordoba Argentina X5014PQC
4 Research Site Cordoba Argentina X5016
5 Research Site La Plata Argentina 1900
6 Research Site Ramos Mejía Argentina B1704ETD
7 Research Site Botucatu Brazil 18618-687
8 Research Site Porto Alegre Brazil 90035-000
9 Research Site Porto Alegre Brazil 90035-903
10 Research Site Rio de Janeiro Brazil 21941-913
11 Research Site Salvador Brazil 40110-160
12 Research Site Sao Jose Do Rio Preto Brazil 15090-000
13 Research Site Sao Paulo Brazil 05403-000
14 Research Site Sao Paulo Brazil 05652-900
15 Research Site La Serena Chile 1781094
16 Research Site Santiago Chile 7620157
17 Research Site Santiago Chile 8330336
18 Research Site Santiago Chile
19 Research Site Valdivia Chile 5110683
20 Research Site Chengdu China 610072
21 Research Site Xi'an China 710061
22 Research Site Armenia Colombia 630004
23 Research Site Cartagena Colombia 130013
24 Research Site Konstanz Germany 78464
25 Research Site Mainz Germany 55131
26 Research Site Mannheim Germany 68167
27 Research Site Hong Kong Hong Kong
28 Research Site Shatin Hong Kong
29 Research Site Belagavi India 590010
30 Research Site Chandigarh India 160012
31 Research Site Gurugram India 122001
32 Research Site Hyderabad India 500072
33 Research Site Jaipur India 302001
34 Research Site Jaipur India 302018
35 Research Site Jodhpur India 342005
36 Research Site Nagpur India 440010
37 Research Site Punjab India 160062
38 Research Site Milano Italy 20122
39 Research Site Palermo Italy 90127
40 Research Site Roma Italy 00128
41 Research Site Rome Italy 00168
42 Research Site Torino Italy 10126
43 Research Site Bunkyo-ku Japan 113-8655
44 Research Site Fukui-shi Japan 918-8503
45 Research Site Fukuoka-shi Japan 810-0065
46 Research Site Fukuoka-Shi Japan 812-8582
47 Research Site Gifu-shi Japan 500-8513
48 Research Site Kagoshima-shi Japan 890-8520
49 Research Site Kawasaki-shi Japan 216-8511
50 Research Site Kobe-shi Japan 650-0017
51 Research Site Kobe-shi Japan 650-0047
52 Research Site Kumamoto-shi Japan 860-8556
53 Research Site Kurume-shi Japan 830-0011
54 Research Site Kyoto-shi Japan 602-8566
55 Research Site Meguro-ku Japan 152-8902
56 Research Site Minato-ku Japan 105-8470
57 Research Site Nagakute-shi Japan 480-1195
58 Research Site Nagoya-shi Japan 460-0001
59 Research Site Ogaki-shi Japan 503-8502
60 Research Site Oita-shi Japan 870-0837
61 Research Site Okayama-shi Japan 700-8505
62 Research Site Omura-shi Japan 856-8562
63 Research Site Osaka Japan 545-8586
64 Research Site Saga-shi Japan 849-8501
65 Research Site Shinjuku-ku Japan 160-0023
66 Research Site Shinjuku-ku Japan 160-8582
67 Research Site Shinjuku-ku Japan 162-8655
68 Research Site Suita-shi Japan 564-0013
69 Research Site Takasaki-shi Japan 370-0829
70 Research Site Tsu-shi Japan 514-8507
71 Research Site Wako-shi Japan 351-0102
72 Research Site Yokohama-shi Japan 236-0004
73 Research Site Yokohama-shi Japan 245-8575
74 Research Site Jung-gu Korea, Republic of 41944
75 Research Site Seoul Korea, Republic of 03080
76 Research Site Seoul Korea, Republic of 03722
77 Research Site Seoul Korea, Republic of 04763
78 Research Site Seoul Korea, Republic of 6351
79 Research Site Kota Kinabalu Malaysia 88586
80 Research Site Kuala Lumpur Malaysia 56000
81 Research Site Kuala Lumpur Malaysia 59100
82 Research Site Pulau Pinang Malaysia 10450
83 Research Site Ciudad de Mexico Mexico 06700
84 Research Site Guadalajara Mexico 44670
85 Research Site Mexico City Mexico 03330
86 Research Site Mexico D.F. Mexico 014080
87 Research Site Cebu Philippines 6000
88 Research Site Puerto Princesa City Philippines 5300
89 Research Site Roxas City Philippines 5800
90 Research Site San Fernando Philippines 2000
91 Research Site Lisboa Portugal 1250-189
92 Research Site Vila Real Portugal 5000-508
93 Research Site Singapore Singapore 119074
94 Research Site Singapore Singapore 169608
95 Research Site Singapore Singapore 308433
96 Research Site A Coruña Spain 15006
97 Research Site Almeria Spain 4009
98 Research Site Lérida Spain 25198
99 Research Site Malaga Spain 29010
100 Research Site Zaragoza Spain 50009
101 Research Site Kaohsiung Taiwan 80756
102 Research Site Tainan City Taiwan 70403
103 Research Site Taipei Taiwan 10002
104 Research Site Taipei Taiwan 112
105 Research Site Taoyuan Taiwan 333
106 Research Site Bangkok Thailand 10330
107 Research Site Bangkok Thailand 10400
108 Research Site Bangkok Thailand 10700
109 Research Site Hat Yai Thailand 90110
110 Research Site Khon Kaen Thailand 40002
111 Research Site Adana Turkey 01060
112 Research Site Antalya Turkey 07059
113 Research Site Bursa Turkey 16059
114 Research Site Eskisehir Turkey 26480
115 Research Site Izmir Turkey 35340
116 Research Site Rize Turkey 530020
117 Research Site Ho Chi Minh Vietnam 700000
118 Research Site Ho Chi Minh Vietnam 70000

Sponsors and Collaborators

  • AstraZeneca
  • AstraZeneca K.K.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT05809934
Other Study ID Numbers:
  • D7830C00004
  • 2022-001629-65
First Posted:
Apr 12, 2023
Last Update Posted:
Apr 12, 2023
Last Verified:
Mar 1, 2023
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Nonalcoholic Steatohepatitis
NASH
fatty liver disease
Non alcoholic fatty liver
liver fibrosis
PNPLA3 148M Risk Allele
Non Cirrhotic
Additional relevant MeSH terms:
Fatty Liver
Non-alcoholic Fatty Liver Disease
Fibrosis

Study Results

No Results Posted as of Apr 12, 2023