None listed
Conditions
Brief summary
This is a first-in-human, two-part, Phase 1, randomised, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) escalation study in cohorts of HVs and subjects with liver cirrhosis, respectively. The study will be conducted in parts defined by design (SAD or MAD) and population and cohorts defined by dose. The primary purpose of the study is to characterise the safety and tolerability of single ascending doses and multiple ascending doses of SZN-043 in healthy volunteers (HVs).
Interventions
Part 1: Single doses of SZN-043 will be administered via intravenous injection. Each dose level will be tested within one cohort. Each patient will only be assigned one dose level. Escalating dose cohorts will be explored as low as 1mg/kg up to 10mg/kg, increments varying by tolerability and PK data. Progression between cohorts will commence based upon recommendation of the SRC based on its review of safety data after all patients in the preceding cohort have been observed for at least 14 days
Part 1: Single doses of SZN-043 will be administered via intravenous injection. Each dose level will be tested within one cohort. Each patient will only be assigned one dose level. Escalating dose cohorts will be explored as low as 1mg/kg up to 10mg/kg, increments varying by tolerability and PK data. Progression between cohorts will commence based upon recommendation of the SRC based on its review of safety data after all patients in the preceding cohort have been observed for at least 14 days after dose. All dosing is performed while patients are confined in the clinical trial unit for a period prior and after dosing. Part 2: Multiple doses (6) of SZN-043 will be administered via intravenous injection. Dosing will occur on Days 0, 14, 17, 21, 24 and 28. Part 2 may commence upon recommendation of the SRC based on its review of all safety data after a higher dose cohort in Part 1 has completed dosing, and the last participant has been observed for 14 days. Each patient will only be assigned one dose level. Dose cohorts will increase through a dose not higher in exposure than doses considered safe to progress in Part 1. Progression between cohorts will commence based upon recommendation of the SRC based on its review of safety data after all patients in the preceding cohort have been observed for at least 14 days after their last dose. All dosing is performed while patients are confined in the clinical trial unit for a period prior and after dosing.
Sponsors
Surrozen Operating, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Part 1: 1. Healthy male or female volunteers. Part 2: 1. Males or female with documented history of liver cirrhosis and a Child-Pugh score between 5 and 7, inclusive, at screening. 2. A fibroscan of equal to or greater than 6kPa. 3. MELD Score of equal to or less than 12 at Screening based on local lab results.
Exclusion criteria
Part 1 (Healthy Volunteers) 1. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study. 2. Previous receipt of antibody or biologic therapy whether licensed or investigational (immunoglobulin products, monoclonal antibodies or antibody fragments) within the past 6 months. 3. History of hyperthyroidism, Paget’s disease, osteomalacia, or fracture within 4 weeks of Screening. 4. 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 prior to study drug administration. 5. Regular excessive alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint ~240 mL of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. 6. 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. Subjects under evaluation for possible malignancy are not eligible. Part 2: Subjects with Liver Cirrhosis 1. Cirrhosis from biliary aetiology. 2. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study. 3. Previous receipt of antibody or biologic therapy whether licensed or investigational (immunoglobulin products, monoclonal antibodies or antibody fragments) within the past 6 months. 4. History of hyperthyroidism, Paget’s disease, osteomalacia, or fracture within 4 weeks of Screening. 5. Use of controlled substances (including inhaled or injected drugs), or non-prescribed use of prescription drugs within previous 12 months. 6. History of alcohol consumption within 3 months prior to Screening for subjects with cirrhosis due to alcoholic liver disease. 7 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. 8. Hepatic mass(es) evident on liver imaging (ultrasound) at Screening. 9. Previous liver transplantation. 10. Active or recent (within 14 days of Screening) gastrointestinal bleeding. 11. Subjects with portal vein thrombosis. 12. Subjects with a portosystemic shunt or scheduled for transjugular intrahepatic portosystemic shunt (TIPS) placement during the study period. 13. Requirement for renal replacement therapy. 14. Current use of anticoagulants that affect prothrombin time or international normalised ratio. 15. Extensive resection of large segments of small intestine (short gut) or severe gastroparesis.
Outcome results
None listed