FEGATO-01: A Clinical Trial of ALE.F02 in Patients With Advanced Liver Fibrosis and/or With Mild Cirrhosis

Sponsor

Alentis Therapeutics AG (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05939947

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

11.3

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Liver Fibrosis Liver Cirrhosis	Drug: ALE.F02 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Thirty-four 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) (8:4 active:placebo), Cohort 2 (intermediate dose) (8:4), Cohort 3 (high dose) (8:2).Thirty-four 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) (8:4 active:placebo), Cohort 2 (intermediate dose) (8:4), Cohort 3 (high dose) (8:2).

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Double-blind

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALE.F02 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 Continuous intravenous (IV) infusion over 1 hour administered once every second week to a total of 3 doses.
Placebo Comparator: Placebo 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 Continuous intravenous (IV) infusion over 1 hour administered once every second week to a total of 3 doses.

Arm

Intervention/Treatment

Experimental: ALE.F02

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

Continuous intravenous (IV) infusion over 1 hour administered once every second week to a total of 3 doses.

Placebo Comparator: Placebo

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

Continuous intravenous (IV) infusion over 1 hour administered once every second week to a total of 3 doses.

Outcome Measures

Primary Outcome Measures

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 43]
Maximum Serum Concentration [Cmax]
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 43]
Time of Maximum Serum Concentration [Tmax]
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 43]
Area under the serum concentration versus time curve [AUC0-tau, AUC0-inf]

Secondary Outcome Measures

Target engagement (TE) 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 CD44 between baseline and the EOT.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Principal Inclusion Criteria:

Outpatients between 18 and 70 years
Have been diagnosed with advanced liver fibrosis or mild cirrhosis attributable to NASH or following a sustained virological response to treatment for hepatitis C
Have an ELF Score of at least 9.8 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 <7

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
Other causes of liver disease including, but not limited to, alcoholic liver disease, hepatitis B, autoimmune disorders
Is a woman of childbearing potential

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	APEX GmbH	Munich	Germany	81241
2	ARENSIA Exploratory Medicine S.R.L.	Bucharest	Romania	011665
3	Summit Clinical Research	Bratislava	Slovakia	851 05

Sponsors and Collaborators

Alentis Therapeutics AG

Investigators

Study Director: Luigi Manenti, MD, Alentis Therapeutics AG

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Alentis Therapeutics AG

ClinicalTrials.gov Identifier:

NCT05939947

Other Study ID Numbers:

ALE.F02.02

First Posted:

Jul 11, 2023

Last Update Posted:

Jul 11, 2023

Last Verified:

Jul 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Liver Cirrhosis

Fibrosis

Study Results

No Results Posted as of Jul 11, 2023