Advanced Liver Fibrosis, Liver Cirrhosis
Conditions
Brief summary
The purpose of this study is to evaluate how a human body processes ALE.F02 (pharmacokinetics profile) in patients with impaired liver function.
Interventions
DRUGALE.F02
Continuous intravenous (IV) infusion administered once every second week to a total of 3 doses.
DRUGPlacebo
Continuous intravenous (IV) infusion administered once every second week to a total of 3 doses.
Sponsors
Alentis Therapeutics AG
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Thirty-eight patients will receive 3 doses of ALE.F02 or matching placebo, administered once every second week as a continuous intravenous (IV) infusion to a total of 3 doses per patient at the same dose level. The 4 cohorts are enrolled in a staggered sequence and escalated upon review and approval of a Safety Review Committee: Cohort 1 (low dose) (4:2 active:placebo), Cohort 2 (intermediate dose) (8:4), Cohort 3 (intermediate dose) (8:2), Cohort 4 (high dose) (8:2).
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Principal Inclusion Criteria: * Outpatients between 18 and 80 years * Have been diagnosed with advanced liver fibrosis or mild cirrhosis attributable to NASH, ALD, or following a sustained virological response to treatment for hepatitis C * Have an ELF Score of at least 9.5 but no more than 13 * Have stable hepatic impairment, defined as no clinically significant change in disease status, and no previous liver cirrhosis decompensation episodes * Body weight within the range of 50.0 kg to 140.0 kg * Clinical frailty score \<6 Principal
Exclusion criteria
* Child-Pugh score ≥7, as determined at screening * MELD score ≥12, as determined at screening * Estimated glomerular filtration rate \<60 mL/min per the CKD-EPI creatinine-cystatin C equation * Current or history of HCC * Be suffering from or have symptoms of an acute or chronic infection * Have active hepatitis C infection * Other causes of liver disease including, but not limited to, hepatitis B, autoimmune disorders drug-induced hepatotoxicity, Wilson's disease, iron overload, and alpha-1-antitryspin deficiency, based on medical history review. * Is a woman of childbearing potential
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) profile of ALE.F02 in patients with advanced liver fibrosis and/or with mild cirrhosis using noncompartmental analysis. | Baseline to Day 14 and Day 29 to Day 72 | Maximum Serum Concentration \[Cmax\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of ALE.F02 in patients with advanced liver fibrosis and/or with mild cirrhosis. | Baseline to Day 72 | Incidence of Treatment-Emergent Adverse Events assessed by CTCAE v5.0 criteria Incidence of Serious Adverse Events assessed by CTCAE v5.0 criteria |
| Pharmacodynamic (PD) profile of ALE.F02 in patients with advanced liver fibrosis and/or with mild cirrhosis. | Baseline to Day 72 | Relative change (%) of serum levels of PRO-C3 between baseline and the EOT. Relative change (%) of serum levels of tissue inhibitor of matrix metalloproteinase \[TIMP1\] between baseline and the EOT. Relative change (%) of serum levels of hyaluronic acid between baseline and the EOT. Relative change (%) of serum levels of procollagen III amino-terminal peptide \[PIIINP\] between baseline and the EOT. |
Countries
Germany, Romania, Slovakia, United States
Outcome results
None listed