A Clinical Trial of ALE.F02 in Patients With Advanced Liver Fibrosis and/or With Mild Cirrhosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate how a human body processes ALE.F02 (pharmacokinetics profile) in patients with impaired liver function.

Official Title
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A Double-Blind Placebo-Controlled Randomised Phase 1b Study of the Pharmacokinetics of ALE.F02 in Patients With Advanced Liver Fibrosis and/or With Mild Cirrhosis

Conditions
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Advanced Liver Fibrosis, Liver Cirrhosis

Intervention / Treatment
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* Drug: ALE.F02
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 130.0 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Twenty-eight patients will receive 3 doses of ALE.F02 or matching placebo, administered once every second week as a continuous intravenous (IV) infusion over 1 hour, to a total of 3 doses per patient at the same dose level. The 3 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 (high dose) (8:2).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALE.F02<br>Patients will receive 3 doses of ALE.F02 administered once every second week as a continuous intravenous (IV) infusion to a total of 3 doses. | Drug: ALE.F02<br>* Continuous intravenous (IV) infusion over 1 hour administered once every second week to a total of 3 doses.<br>|
| Placebo Comparator: Placebo<br>Patients will receive 3 doses of matching placebo administered once every second week as a continuous intravenous (IV) infusion to a total of 3 doses. | Drug: Placebo<br>* Continuous intravenous (IV) infusion over 1 hour administered once every second week to a total of 3 doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) profile of ALE.F02 in patients with advanced liver fibrosis and/or with mild cirrhosis using noncompartmental analysis. | Maximum Serum Concentration [Cmax] | Baseline to Day 14 and Day 29 to Day 43 | 
| Pharmacokinetics (PK) profile of ALE.F02 in patients with advanced liver fibrosis and/or with mild cirrhosis using noncompartmental analysis. | Time of Maximum Serum Concentration [Tmax] | Baseline to Day 14 and Day 29 to Day 43 | 
| Pharmacokinetics (PK) profile of ALE.F02 in patients with advanced liver fibrosis and/or with mild cirrhosis using noncompartmental analysis. | Area under the serum concentration versus time curve [AUC0-tau, AUC0-inf] | Baseline to Day 14 and Day 29 to Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target engagement (TE) profile of ALE.F02 in patients with advanced liver fibrosis and/or with mild cirrhosis. | Relative change (%) of serum levels of CD44 between baseline and the EOT. | Baseline to Day 72 | 
| Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of ALE.F02 in patients with advanced liver fibrosis and/or with mild cirrhosis. | Incidence of Treatment-Emergent Adverse Events assessed by CTCAE v5.0 criteria Incidence of Serious Adverse Events assessed by CTCAE v5.0 criteria | Baseline to Day 72 | 
| Pharmacodynamic (PD) profile of ALE.F02 in patients with advanced liver fibrosis and/or with mild cirrhosis. | 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. | Baseline to Day 72 |