A Multiple Dose Study in Participants with Severe Alcohol-Associated Hepatitis to Assess the Safety and the Way the Body Absorbs, Distributes, and Eliminates the drug SZN-043.
- Conditions
- Severe Alcohol-Associated HepatitisOral and Gastrointestinal - Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
- Registration Number
- ACTRN12624000194561
- Lead Sponsor
- Surrozen Operating, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 18
1. 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. BMI between 18.0 and 36.0 kg/m2, inclusive, at Screening.
3. A clinical diagnosis of AH that is anticipated to require inpatient care for a period to encompass at a minimum the first dose of study drug based on typical serum chemistry (as determined by local laboratory) meeting all of the following parameters:
a. Onset of jaundice within prior 8 weeks;
b. History of heavy alcohol abuse: >40 (female) or 60 (male) g alcohol/day for greater than or equal to 6 months;
c. Consumed alcohol within 8 weeks before study entry;
d. AST >50, AST/ALT >1.5, and both values are: <400 IU/L, and
e. Serum total bilirubin >3.0 mg/dL.
4. MELD score of 21 to 30, inclusive.
5. Willing to use acceptable methods of contraception or not physically able to conceive or impregnate others.
1. Previous receipt of antibody or biologic therapy 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
4. Recent start of liver toxic medications
5. Have a portosystemic shunt or scheduled for transjugular intrahepatic portosystemic shunt placement or highly likely to receive a liver transplant during the study.
6. Dependent upon inotropic support (including selepressin or terlipressin) or ventilatory or vasopressor support.
7. Organ failure (as defined by hepatic encephalopathy >stage 3) or requires renal replacement therapy or creatinine >2.5 mg/dL (or 221 mmol/L).
8. Uncontrolled hyperthyroidism, history of Paget's disease, osteomalacia, or fracture within 4 weeks of Screening.
9. Uncontrolled bacterial infections, as determined by the investigator's judgment 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, evidence of recurrence of certain skin cancers, or under investigation for a malignancy.
13. Gastrointestinal (GI) bleeding within 2 days of Screening requiring transfusion of more than 3 units of blood.
14. Grade 3 or higher encephalopathy by West Haven Criteria.
15. Acute kidney injury defined as an increase in serum creatinine (sCr) greater than or equal to 0.3 mg/dL within 48 h or increase in sCr greater than or equal to 50% from baseline known or presumed
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 non-prescribed opiates.
24. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study.
25. Planning to donate sperm (male) or ovum (female) within 90 days after the last dose of study drug.
26. Current use of anticoagulants that affect prothrombin time or international normalised ratio (INR).
27. Eligibility: All participants where HepQuant SHUNT test kit use is specified:
a. Extensive resection of large segments of small intestine (short gut) or severe
gastroparesis; On either a non-selective beta blocker or an angiotensin-converting
enzyme inhibitor or angiotensin II receptor blockers who are unwilling or unable
to delay taking their normal dose the morning of the HepQuant SHUNT test;
b. Allergy to any ingredient in the formulations or components in the HepQuant Lab
Developed kit.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method