Hepatic SteatosisPhase 1NCT03201159
A Pilot, Dose Escalating Study on VLX103 in Moderate Alcoholic Steatohepatitis
A Phase 1 study testing VLX103 in people with Hepatic Steatosis, run by Gyongyi Szabo at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatic Steatosis
- What is being tested?
- VLX103
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jun 2017to 27 Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligible subjects must meet all of the following inclusion criteria:
- Male and non pregnant female subjects; female subjects must use 2 reliable methods of contraception
- 18-70 years
- BMI less than 30 mg/kg2
- Established diagnosis of Alcoholic Steatohepatitis (ASH), based on at least 2 of the following signs and symptoms should be present: nausea, jaundice, anorexia, right upper quadrant abdominal pain, leukocytosis or hepatomegaly AND
- Elevation of total bilirubin > 3 mg/dL AND
Show all 10Show fewer
- Liver biopsy showing ASH OR ultrasound of liver showing increased echogenicity OR CT scan showing decreased attenuation of liver compared to spleen OR MRI showing fatty liver (decreased signaling intensity on T1 weighted images) History of chronic alcohol consumption, i.e. more than 50 g/day for a minimum of 6 months and at least 2 months before enrolment
- AST/ALT ratio greater than 1.5
- MELD score between 12 and 19
- Signature of a dated Informed Consent Form (ICF) indicating that the subject has been informed of all the relevant aspects of the trial prior to enrolment Willingness and ability to comply with scheduled visits and trial procedures
Who cannot join
- Eligible subjects must not meet any of the following exclusion criteria:
- Liver disease caused by other etiologies than alcohol (except Hepatitis C and hemochromatosis)
- Baseline ALT ≥ 200 IU/L
- Baseline AST ≥ 500 IU/L
- Signs of systemic infection: fever > 38°C and positive blood or ascites cultures on appropriate antibiotic therapy for ≥ 3 days within 3 days of inclusion
- Presence of portosystemic encephalopathy at enrolment
Show all 20Show fewer
- Presence of cancer at enrolment
- Presence of uncontrolled diabetes, defined as Hb1Ac ≥ 8.5
- History of clinically significant hypoglycaemia, with fasting blood glucose < 3 mmol/L within 3 months prior to enrolment
- Presence of clinically significant renal impairment, defined as serum creatinine ≥ 2.0 x ULN
- Hypotension with BP < 80/50 mm Hg after volume repletion
- Current or recent (2 years) history or presence of pancreatitis
- History of Long QT Syndrome or any significant risk factor for clinically meaningful QT prolongation and Torsades de Pointe.
- History of significant gastrointestinal surgery that may interfere with the absorption of VLX103
- Previous treatment with corticosteroids or other immunosuppressive drugs including specific anti-TNF alpha therapy and calcineurin inhibitors within the previous 3 months. Inhaled steroids for asthma are acceptable as long as their use has not been initiated less than 10 days prior to enrolment and their dosing regimen remain stable during the study
- Concomitant therapy with probiotics, oral neomycin or polymyxin B, rifaximin or other investigational agents or participation in another clinical trial within 3 months of signature of ICF
- Previous use of pentamidine with treatment discontinuation of less than 12 months prior to study enrolment
- History of allergy or hypersensitivity to pentamidine
- Pregnancy or breastfeeding. All female subjects of childbearing potential must have a negative urine pregnancy test prior to first dose of study medication. Breastfeeding is prohibited during the study.
- Severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgement of the investigator, excess risk associated with trial participation of study drug administration, or which in the judgement of the investigator, would make the subject inappropriate for entry into this trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
UMass Medical School
Worcester, Massachusetts, 01605
About this study
Official title: A Pilot, Exploratory Dose Escalating Study on the Safety, Pharmacodynamics and Preliminary Efficacy of VLX103 in the Treatment of Moderate Alcoholic Steatohepatitis
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.
Read the detailed description
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.
- Conditions
- Hepatic Steatosis
- Being tested
- VLX103
- Keywords
- ASH
- Medical subject headings
- Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VLX103Drug
Also called Pentamidine Isethionate
150mg tablets
| Study group | Role | What they receive |
|---|---|---|
| VLX103 150mg | Experimental | In the first group, 150 mg dosing cohort, one VLX103 tablet will be administered daily for 14 days. Receives: Drug: VLX103 |
| VLX103 300mg | Experimental | In the second group, 300 mg dosing cohort, two VLX103 tablets will be administered daily for 14 days. Receives: Drug: VLX103 |
| VLX103 450mg | Experimental | In the third group, 450 mg dosing cohort, three VLX103 tablets will be administered daily for 14 days. Receives: Drug: VLX103 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequencies of subjects experiencing at least one adverse event will be displayed by body system and preferred term according to MedDRA terminology
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.
Measured: 90 days
Distribution of laboratory measures over time will be prepared
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
Measured: 90 days
Secondary outcomes (3)
Preliminary efficacy of VLX103 in the target patient population
Efficacy as measured by changes in MELD score and serum bilirubin
Measured: 7 days and 14 days
Maximum Tolerated Dose of VLX103 in moderate ASH patients
determined as the highest safe dose reached according to pre-established safety criteria in the majority of patients
Measured: 14 days
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.
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).
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2017
- Study start25 Jun 2017
- Primary completion27 Feb 2018
- Study completion27 Feb 2018
Why it stopped: Drug manufacturer ceased operations
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic SteatosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gyongyi Szabo
- Sponsor type
- University, hospital or other
- Collaborators
- The Cleveland Clinic, University of Texas Southwestern Medical Center, University of Louisville, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor-investigator, Gyongyi Szabo, University of Massachusetts, Worcester
- Investigators
- Gyongyi Szabo, MD, PhD, Principal investigator, UMass Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03201159
- Sponsor's protocol ID
- H00011711
- Other IDs
- VLX103-ASH-16-01, U01AA021893
- Status last verified
- May 2018
- First submitted
- 24 Mar 2017
- Last updated
- 30 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be filtered through Data Coordinating Center
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot, Exploratory Dose Escalating Study on the Safety, Pharmacodynamics and Preliminary Efficacy of VLX103 in the Treatment of Moderate Alcoholic Steatohepatitis
- ClinicalTrials.gov ID
- NCT03201159
- Acronym / sponsor ID
- H00011711
- Conditions
- Hepatic Steatosis
- Keywords
- ASH
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Drug manufacturer ceased operations
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Gyongyi SzaboUniversity, hospital or other
- Collaborators
- The Cleveland Clinic, University of Texas Southwestern Medical Center, University of Louisville, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 25 Jun 2017 (actual)
- Primary completion
- 27 Feb 2018 (actual)
- Study completion
- 27 Feb 2018 (actual)
- First posted
- 28 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| VLX103 150mg | Experimental | Drug: VLX103In the first group, 150 mg dosing cohort, one VLX103 tablet will be administered daily for 14 days. |
| VLX103 300mg | Experimental | Drug: VLX103In the second group, 300 mg dosing cohort, two VLX103 tablets will be administered daily for 14 days. |
| VLX103 450mg | Experimental | Drug: VLX103In the third group, 450 mg dosing cohort, three VLX103 tablets will be administered daily for 14 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male and non pregnant female subjects; female subjects must use 2 reliable methods of contraception
- 18-70 years
- BMI less than 30 mg/kg2
- Established diagnosis of Alcoholic Steatohepatitis (ASH), based on at least 2 of the following signs and symptoms should be present: nausea, jaundice, anorexia, right upper quadrant abdominal pain, leukocytosis or hepatomegaly AND
- Elevation of total bilirubin > 3 mg/dL AND
Key exclusion criteria (20 listed)
- Liver disease caused by other etiologies than alcohol (except Hepatitis C and hemochromatosis)
- Baseline ALT ≥ 200 IU/L
- Baseline AST ≥ 500 IU/L
- Signs of systemic infection: fever > 38°C and positive blood or ascites cultures on appropriate antibiotic therapy for ≥ 3 days within 3 days of inclusion
- Presence of portosystemic encephalopathy at enrolment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VLX103Also: Pentamidine Isethionate150mg tablets | Drug | VLX103 150mg, VLX103 300mg, VLX103 450mg |
Primary outcome
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
3 secondary outcomes
Preliminary efficacy of VLX103 in the target patient population
Time frame: 7 days and 14 days
Maximum Tolerated Dose of VLX103 in moderate ASH patients
Time frame: 14 days
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2018.
- Individual participant dataSharing planned: Yes. Data will be filtered through Data Coordinating Center
Related trials for Hepatic Steatosis
Not yet recruiting
Personalized Dietary Feedback to Reduce Hepatic Steatosis in Patients With MASLD
MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease), MetALD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
Active, not recruitingObservational study
Assessment of the Prevalence of Steatotic Liver Disease Associated With Metabolic Dysfunction in Patients With Heterozygous Familial Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia
Not yet recruitingPhase 2
The Effects of Glucagon on Hepatic Metabolism in People With Type 2 Diabetes After Caloric Restriction
Type2diabetes
RecruitingPhase 2
Non-Alcoholic Fatty Liver Disease, the HEpatic Response to Oral Glucose, and the Effect of Semaglutide (NAFLD HEROES)
Non-Alcoholic Steatohepatitis, Non-Alcoholic Fatty Liver Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gyongyi Szabo, MD, PhD principal investigator
UMass Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VLX103 in people with Hepatic Steatosis, run by Gyongyi Szabo at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 30 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2018.