A Pilot, Dose Escalating Study on VLX103 in Moderate Alcoholic Steatohepatitis
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|ClinicalTrials.gov Identifier: NCT03201159|
Recruitment Status : Withdrawn (Drug manufacturer ceased operations)
First Posted : June 28, 2017
Last Update Posted : May 30, 2018
The study drug (VLX103) is being developed for the treatment of Alcoholic Steatohepatitis and other liver diseases. Alcoholic Steatohepatitis is an inflammatory (associated with irritation, swelling and cell damage) disease that affects the liver. It is associated with heavy and chronic intake of alcohol and presence of fat in the liver. Signs and symptoms often include fever, yellowing of the skin, nausea and impairment of liver function.
The main objective of this study is to evaluate the safety, pharmacodynamics (what the drug does to the body) and pharmacokinetics (how the drug is handled by the human body, like absorption and elimination) of increasing doses of VLX103 in subjects with moderate Alcoholic Steatohepatitis. In other words, we will evaluate how your body tolerates VLX103 at a specific dose and the effects that this VLX103 dose has on your liver and your body in general. The secondary objectives of this study are to evaluate if VLX103 has the potential to treat Alcoholic Steatohepatitis patients, to determine the maximum dose that can be tolerated, and to measure the levels of VLX103 in your blood at different time points during the study.
VLX103 is an experimental drug. Experimental means that the drug has not been approved by the Food and Drug Administration (FDA) for the treatment of Alcoholic Steatohepatitis. The active ingredient in VLX103, pentamidine, is approved for treating parasitic (microorganisms) infections. Pentamidine is currently approved and marketed in about 20 countries, including the United States, for use by injection (administered by a syringe) and by inhalation (administered by a nebulizer) for other health conditions. However, VLX103 is the first oral form of pentamidine being developed, and is administered by mouth as an oral tablet.
|Condition or disease||Intervention/treatment||Phase|
|Hepatic Steatosis||Drug: VLX103||Phase 1|
This is an open label, multiple cohorts, dose escalation Phase Ib study, in which up to 3 doses of VLX103 will be assessed for safety, pharmacodynamics and pharmacokinetics in well defined moderate ASH patients cohorts receiving increasing doses of VLX103. The overall study design is characteristic for early phase, first in patient clinical evaluation of safety and pharmacodynamics, especially when prudent dose escalation is recommended. A maximum of 18 moderate ASH patients will be enrolled and treated in at least 4 clinical sites throughout the US. The open label nature of the study design will allow to efficiently monitor the safety of VLX103 throughout the trial, and taking rapid decisions about dosing adjustments (dose reduction or discontinuation within each dosing cohort, for each patient).
After an adequate screening period (Day -7 to -1), all eligible patients of the first dosing cohort will receive the initial, low dose of VLX103 150 mg per day (QD) for 14 consecutive days. Subjects will be evaluated only for safety, pharmacodynamics and pharmacokinetics during this period. Pre-established safety criteria will be used to decide upon dose escalation, for each subject. If patients tolerate well VLX103 at 150 mg QD , a second cohort will then receive a 300 mg QD regimen for 14 days. At the end of this period, safety, pharmacodynamics and pharmacokinetics will be assessed as well. The next dose will be 450 mg QD for 14 days, with the same monitoring process. Long term safety will also be assessed, at all 3 doses, at Day 30 and 90 post treatment initiation.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||This is a dose escalating Phase Ib study, in which up to 3 doses of VLX103 will be assessed for safety, pharmacodynamics and pharmacokinetics in separate patient cohorts receiving sequentially increasing doses of VLX103. A maximum of 18 well-defined moderate ASH patients will be enrolled and treated in the study, i.e. 6 per dosing cohort.|
|Masking:||None (Open Label)|
|Official Title:||A Pilot, Exploratory Dose Escalating Study on the Safety, Pharmacodynamics and Preliminary Efficacy of VLX103 in the Treatment of Moderate Alcoholic Steatohepatitis|
|Actual Study Start Date :||June 25, 2017|
|Actual Primary Completion Date :||February 27, 2018|
|Actual Study Completion Date :||February 27, 2018|
Experimental: VLX103 150mg
In the first group, 150 mg dosing cohort, one VLX103 tablet will be administered daily for 14 days.
Other Name: Pentamidine Isethionate
Experimental: VLX103 300mg
In the second group, 300 mg dosing cohort, two VLX103 tablets will be administered daily for 14 days.
Other Name: Pentamidine Isethionate
Experimental: VLX103 450mg
In the third group, 450 mg dosing cohort, three VLX103 tablets will be administered daily for 14 days.
Other Name: Pentamidine Isethionate
- Frequencies of subjects experiencing at least one adverse event will be displayed by body system and preferred term according to MedDRA terminology [ Time Frame: 90 days ]Summary tables will present the number of subjects observed with adverse events and cooresponding percentages. The incidence of adverse events will be summarized by treatment group.
- Distribution of laboratory measures over time will be prepared [ Time Frame: 90 days ]Listing and summary tables will be prepared for laboratory measures and will be structured to allow review of data by test as the dose is increased
- Preliminary efficacy of VLX103 in the target patient population [ Time Frame: 7 days and 14 days ]Efficacy as measured by changes in MELD score and serum bilirubin
- Maximum Tolerated Dose of VLX103 in moderate ASH patients [ Time Frame: 14 days ]determined as the highest safe dose reached according to pre-established safety criteria in the majority of patients
- To establish further the hepatoselectivity of VLX103 following up to 14 days of repeated oral administration, through the assessment of systemic drug exposure (serum levels) at selected time points. [ Time Frame: 14 days ]assessed by systemic drug levels at selected time points Hepatoselectivity; demonstrated as non significant or absent serum VLX103 levels at Days 7,and 14 and measurable drug concentrations in the liver tissue (if specimens are available).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03201159
|United States, Massachusetts|
|UMass Medical School|
|Worcester, Massachusetts, United States, 01605|
|Principal Investigator:||Gyongyi Szabo, MD, PhD||UMass Medical School|