Testing a potential new treatment for patients with severe alcohol-associated hepatitis called SZN-043
- Conditions
- Severe alcohol-associated hepatitisDigestive System
- Registration Number
- ISRCTN55168173
- Lead Sponsor
- Surrozen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 18
1. Be a male or female (sex assigned at birth), 18 years of age or older AND considered to be an adult in accordance with local law
2. Have a BMI between =18.0 and =36.0 kg/m2 at Screening
3. Be willing and able to provide written informed consent
4. Have a clinical diagnosis of Alcohol-associated hepatitis (AH) that is anticipated to require inpatient care for a period to encompass at a minimum the first dose of study medication based on typical serum chemistry (as determined by local laboratory) meeting all of the following parameters:
4.1. Onset of jaundice within the prior 8 weeks
4.2. History of heavy alcohol abuse: >40 (female) or 60 (male) g alcohol/day for =6 months
4.3. Consumed alcohol within 8 weeks before study entry
4.4. AST >50, AST/ALT >1.5, and both values are: <400 IU/L, and
4.5. Serum total bilirubin >3.0 mg/dL
At the Investigator's discretion, a liver biopsy may be performed to confirm diagnosis in participants who meet criteria a-c above but where other causes of liver disease are not otherwise possible to rule out (viral, drug, autoimmune, etc)
5. MELD score of 21 to 30, inclusive
6. Acceptable methods of contraception defined in protocol Section 4.2.3 must be used from Screening until study completion. Surgically sterile males or females (Section 4.2.3) or women who are postmenopausal for =12 months do not need additional contraception methods. Postmenopausal status will be confirmed by testing follicle-stimulating hormone (FSH) levels =40 IU/L at Screening for amenorrhoeic female participants.
7. Must have the ability and willingness to attend the necessary visits to the study centre.
1. Previous receipt of antibody or biologic therapy whether licensed or investigational within the past 6 months.
2. Treatment with any experimental drug within 30 days, or within 5 half-lives (whichever is longer), before Day 0 visit (Baseline).
3. Other causes of liver disease including:
3.1. Evidence of chronic viral hepatitis (hepatitis B or C)
3.2. Biliary obstruction or cholestatic liver disease (e.g., primary biliary sclerosis, sclerosing cholangitis)
3.3. Drug-induced hepatotoxicity (e.g., acetaminophen)
3.4. Hepatocellular carcinoma
3.5. Wilson’s disease
3.6. Budd Chiari Syndrome
3.7. Metabolic dysfunction-associated steatotic liver disease
3.8. Metabolic dysfunction-associated steatohepatitis
3.9. Auto-immune hepatitis
3.10. Acute hepatitis A.
4. Introduction of a new medication with potential hepatotoxicity within 60 days of screening or any anticipated increase in dose or dose regimen of any potential hepatotoxic medication.
5. Have a portosystemic shunt or scheduled for transjugular intrahepatic portosystemic shunt placement or highly likely to receive a liver transplant during the study period.
6. Dependent upon inotropic support or ventilatory or vasopressor support.
7. Organ failure: renal replacement therapy or creatinine >2.5 mg/dL (or 221 mmol/L Uncontrolled hyperthyroidism, history of Paget's disease, osteomalacia, or fracture within 4 weeks of Screening.
9. Uncontrolled bacterial infections, after a minimum of 2 days of antibiotic therapy.
10. History of a previous severe allergic reaction with generalised urticaria, angioedema, or anaphylaxis.
11. A QT duration corrected for heart rate by Fridericia's formula (QTcF) >450 msec for males and >470 msec for females based on either single or averaged QTcF values of triplicate ECGs before study drug administration.
12. A history of malignant neoplasm, except for adequately treated non-metastatic basal or squamous cell cancers of the skin (>1 year ago) or carcinoma in situ of the uterine cervix (>3 years ago) that has been fully treated and shows no evidence of recurrence. Participants under evaluation for possible malignancy are also not eligible.
13. Gastrointestinal (GI) bleeding within 2 days of Screening requiring transfusion of more than 3 units of blood (participants with a recent upper gastrointestinal bleeding that is controlled for >48 h is allowed).
14. Grade 3 or higher encephalopathy by West Haven Criteria.
15. Acute kidney injury defined as an increase in serum creatinine (sCr) =0.3 mg/dL within 48 h or an increase in sCr =50% from baseline known or presumed (Baseline sCr: a value of sCr obtained in the previous 3 months, closest to admission; if no previous sCr value, the sCr on admission is baseline), within the prior 7 days or the requirement for renal replacement therapy.
16. Presence of portal vein thrombosis.
17. Presence of acute pancreatitis.
18. Cerebral hemorrhage, extensive retinal hemorrhage, acute myocardial infarction (within the last 6 weeks) or severe cardiac arrhythmias (not including atrial fibrillation).
19. Evidence of GI bleeding or renal failure after 7 days of treatment within 8 weeks of screening.
20. Liver imaging at screening showing any lesions (except benign lesions, i.e., hemangiomas).
21. Known infection with HIV or HIV Ab positive at screening.
22. Organ transplantation (such as liver, kidney, lung, heart, bone marrow, or stem cell etc.), other than cornea transplant.
23. Positive urine screen for amphetamines, cocaine, or opia
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The safety and tolerability of SZN-043 in participants with severe alcohol-associated hepatitis at the proposed doses, based on the frequency and severity of treatment-emergent adverse events, treatment-emergent serious adverse events, treatment-emergent laboratory, electrocardiogram (ECGs), and physical examination findings from baseline through to 90 days after receipt of treatment (safety is measured continuously)
- Secondary Outcome Measures
Name Time Method