COSMOS: A Study in Participants With Non-cirrhotic NASH With Fibrosis

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05638737

Collaborator

(none)

Enrollment

Locations

Arms

19.2

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Participants will be in the trial for up to 22 weeks, including a screening period lasting up to 6 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.

Condition or Disease	Intervention/Treatment	Phase
Non-Cirrhotic Non-alcoholic Steatohepatitis With Fibrosis	Drug: AZD4831 Other: Placebo	Phase 2

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 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 6-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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AZD4831 in Participants With Noncirrhotic Non-alcoholic Steatohepatitis (NASH) With Fibrosis

Actual Study Start Date :

Oct 26, 2022

Anticipated Primary Completion Date :

May 31, 2024

Anticipated Study Completion Date :

May 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD4831 AZD4831	Drug: AZD4831 AZD4831
Placebo Comparator: Placebo Placebo	Other: Placebo Placebo

Arm

Intervention/Treatment

Experimental: AZD4831

AZD4831

Drug: AZD4831

AZD4831

Placebo Comparator: Placebo

Placebo

Other: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

Change from baseline and over placebo to Week 12 - ALT [12 weeks]
ALT change from baseline and over placebo to Week 12

Secondary Outcome Measures

Change from baseline over placebo to Week 12 - Pro-C3 [12 weeks]
Pro-C3 change from baseline and over placebo to Week 12
Plasma concentration of AZD4831 (Ctrough) [12 weeks]
Plasma concentration of AZD4831 (Ctrough)

Other Outcome Measures

Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal clinical test results [12 weeks]
Maculopapular rash grade 3, Vital signs and clinical chemistry
Number of participants with Adverse Events/Serious Adverse Events (AEs/SAEs) and abnormal laboratory test results [12 weeks]
Haematology, urinalysis, electrocardiogram (ECG) assessments and eGFR

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant must be ≥ 18 to ≤ 75 years of age at the time of signing the informed consent.
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 F2-F3

Increased serum ALT level (> ULN but < 300 U/L) at screening.
Stable weight for the last 3 months prior screening. Stable weight is defined as ≤ 5% change.
Male and/or female of non-childbearing potential. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

Any positive results for HIV infection or positive results for hepatitis B surface antigen or hepatitis C antibody test.
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).
History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding.
Prior or planned liver transplantation.
Clinically significant cardiovascular or cerebrovascular disease within the past 3 months, including but not limited to, myocardial infarction, acute coronary syndrome, unstable angina pectoris, transient ischemic attack, or stroke, or participants who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening.
Clinically significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper gastrointestinal tract (including bariatric surgery) that may affect gastric emptying or could affect the interpretation of the safety and tolerability data.
History or ongoing allergy/hypersensitivity reactions to drugs (including but not limited to rash, angioedema, acute urticaria).
Participants with hyperthyroidism, uncontrolled hypothyroidism (including but not limited to TSH ≥ 10 mIU/mL), or any clinically significant thyroid disease as judged by the investigator.
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.
Evidence of alcohol dependence as assessed by the AUDIT questionnaire at screening.
Recent (within 3 months of screening) use of drugs approved for weight loss (eg, orlistat, bupropion/naltrexone, phentermine-topiramate, phentermine, lorcaserin), as well as those drugs used off-label.
High dose vitamin E (> 400 IU) unless on a stable dose within 6 months of screening.
Participation in a clinical study testing anti-obesity medications within 12 months of screening.
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).
Recent (within 6 months of screening) use of obeticholic acid or other therapy under investigation for NASH.
Abnormal laboratory values including any of the following:
AST or ALT > 5 × UL.
ALP ≥ 1.5 × ULN, unless not of hepatic origin.
Impaired renal function defined as estimated glomerular filtration rate ≤ 30 mL/minute/1.73 m2 at screening (estimated according to chronic kidney disease epidemiology collaboration).
Albumin < 35 g/L.
International normalized ratio > 1.3.
TBL > 25 μmol/L in the absence of known Gilbert's disease.
Platelets < 100,000/mm3.
MELD score ≥ 12.
Any other clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results as judged by the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Chandler	Arizona	United States	85224
2	Research Site	Tucson	Arizona	United States	85712
3	Research Site	Chula Vista	California	United States	91911
4	Research Site	Montclair	California	United States	91763
5	Research Site	Orange	California	United States	92868
6	Research Site	Redondo Beach	California	United States	90277
7	Research Site	Stanford	California	United States	94305
8	Research Site	Lakeland	Florida	United States	33813
9	Research Site	Miami	Florida	United States	33125
10	Research Site	Yonkers	New York	United States	10701
11	Research Site	San Antonio	Texas	United States	78229
12	Research Site	Caba		Argentina	C1056ABJ
13	Research Site	Caba		Argentina	C1119ACN
14	Research Site	Caba		Argentina	C1426
15	Research Site	Ciudad de Buenos Aires		Argentina	1280
16	Research Site	Mar del Plata		Argentina	7600
17	Research Site	Ramos Mejía		Argentina	B1704ETD
18	Research Site	Aarhus N		Denmark	8200
19	Research Site	Esbjerg		Denmark	6700
20	Research Site	Koge		Denmark	4600
21	Research Site	København NV		Denmark	2400
22	Research Site	Foggia		Italy	71100
23	Research Site	Milano		Italy	20132
24	Research Site	Milan		Italy	20122
25	Research Site	Roma		Italy	00128
26	Research Site	Rome		Italy	00168
27	Research Site	Rozzano		Italy	20089
28	Research Site	San Giovanni Rotondo		Italy	71013
29	Research Site	Torino		Italy	10126
30	Research Site	Ciudad de Mexico		Mexico	06700
31	Research Site	Guadalajara		Mexico	44210
32	Research Site	Guadalajara		Mexico	44340
33	Research Site	Monterrey		Mexico	64000
34	Research Site	México		Mexico	03300
35	Research Site	Grålum		Norway	1714
36	Research Site	Lørenskog		Norway	N-1478
37	Research Site	Oslo		Norway	0456
38	Research Site	Tromsø		Norway	N-9038
39	Research Site	Lisboa		Portugal	1250-189
40	Research Site	La Coruña		Spain	15006
41	Research Site	Málaga		Spain	29010
42	Research Site	Pozuelo de Alarcon		Spain	28223
43	Research Site	Santander		Spain	39008
44	Research Site	Valencia		Spain	46014
45	Research Site	Linköping		Sweden	581 85
46	Research Site	Uppsala		Sweden	751 85