A Phase IIa Study to assess Safety, Tolerability, and Pharmacodynamics of AZD4831 in Adult Participants with Non-cirrhotic NASH with Fibrosis
- Registration Number
- CTIS2022-500594-13-00
- Lead Sponsor
- Astrazeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 94
Participant must be = 18 to = 75 years of age at the time of signing the informed consent., Participants with histologically confirmed NASH as diagnosed by liver biopsy within 12 months of provision of written informed consent fulfilling all of the following histological criteria and in accordance with the NASH CRN NAFLD Activity Score (NAS). (a) NAS =4 with a score of at least 1 in each of the 3 histological components (ie, steatosis, lobular inflammation, and ballooning) (b) Presence of fibrosis stage F1, F2, or F3 Participants without a historical biopsy that meets the above histological criteria should be willing to undergo a liver biopsy at screening, result of which subsequently fulfills the criteria., Hemoglobin A1c = 9.5% (inclusive) at Visit 1 if T2DM present, managed by a stable medication (ie, no major dose adjustments in prior 3 months to randomization)., One increased serum ALT measurement (ALT > ULN) at screening, and historical local serum ALT level (> ULN [41 U/L for men and 31 U/L for women] but < 300 U/L) on = 1 occasion in the 6 months prior to screening, Participants with or without diabetes. If participants are on GLP-1 receptor agonists, SGLT2 inhibitors, or pioglitazone, the medication has to be stable for at least 6 months prior to randomization., Stable weight for at least 3 months prior to randomization. Stable weight is defined as = 5% change., Male and/or female. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. (a) Criterion not applicable to this CSP version. (b) Criterion not applicable to this CSP version. (c) Female participants: ? Female participants must not be pregnant or lactating. ? Females of childbearing potential who are sexually active with a non-sterilized male partner must agree to use an acceptable method of birth control, from enrolment throughout the study and until at least 4 weeks after last dose of study intervention. Acceptable methods of contraception include birth control pills, injections, implants or patches, intrauterine devices, and tubal ligation/occlusion. The following are not acceptable methods of contraception: periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea. Female condom and male condom should not be used together., Capable of giving signed informed consent as described in Appendix D 3, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol (including use of sample for genetic testing where allowed)., Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative.
History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the study intervention, put the participant at risk, influence the participant’s ability to participate or affect the interpretation of the results of the study., History of malignant neoplasms within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer., Prolonged QT interval (Fridericia-corrected QT interval > 470 ms) on ECG at screening (Visit 1), known congenital long QT syndrome, or family history of cardiac sudden death at age < 40 years., History or ongoing drug allergies or hypersensitivity reactions to drugs (including but not limited to rash, angioedema, acute urticaria)., Participants with hyperthyroidism, uncontrolled hypothyroidism, or any clinically significant thyroid disease as judged by the investigator. Patients with TSH = ULN should be excluded., History of psychosis or bipolar disorder. History of major depressive disorder within the past year with the participant being clinically unstable, or any history of suicide attempt or history of suicidal ideation within the past year at the discretion of the investigator., Participants with a positive SARS-CoV-2 infection test at screening (Visit 1), if clinically indicated, based on investigator discretion., Participants with a significant COVID-19 illness within 6 months of enrollment: (a) Participants with a diagnosis of COVID-19 pneumonia based on radiological assessment. (b) Participants with diagnosis of COVID-19 with significant findings from pulmonary imaging tests. (c) Participants with a diagnosis of COVID-19 requiring hospitalization and/or oxygen supplementation therapy., History of excessive alcohol consumption, defined as an average weekly intake of > 21 drinks/week (294 g/week) for males or > 14 drinks/week (196 g/week) for females. One drink is equivalent to 14 g alcohol., Evidence of alcohol dependence as assessed by the AUDIT questionnaire at screening (Appendix B). Participants with an AUDIT questionnaire score to 13 or more in women and 15 or more in men will be excluded., Positive screen for drugs of abuse at screening or admission to the study site prior to the administration of the study intervention. Note: participants who test positive for drugs (ie, opioids) that are prescribed for appropriate medical use are eligible to participate in the study., Any positive results for HIV infection or positive results for hepatitis B surface antigen or hepatitis B core antibody or hepatitis C antibody test., Recent (within 3 months of randomization) use of drugs approved for weight loss (eg, orlistat, bupropion/naltrexone, phentermine-topiramate, phentermine, lorcaserin), as well as those drugs used off-label., Participants planning to make significant lifestyle changes to their diet or exercise regimen during the conduct of the study., Criterion not applicable to this CSP version., High dose vitamin E (> 400 IU) unless on a stable dose within 6 months of screening., Participation in another clinical study with an IP administered in the last 3 months or 5 half-lives of the therapy (whichever is longer) at the time 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, amiodaro
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method