Chronic Hepatitis CPhase 2NCT02971033
Ezetimibe as a Safe and Efficacious Treatment for Chronic Hepatitis C
A Phase 2 study testing 20mg ezetimibe and 40mg ezetimibe in people with Chronic Hepatitis C, run by VA Office of Research and Development at 1 site in United States.
Trial summary
To address the need for more affordable hepatitis C virus (HCV) antivirals with high barriers to viral resistance and strategies to shorten the current treatment duration, the goal is to develop affordable therapeutic regimens to prevent HCV entry/spread and test the efficacy of those inhibitors for treating HCV… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- 20mg ezetimibe and 40mg ezetimibe
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Apr 2018to 31 Mar 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Males/females 18 - 70 yrs of age
- Serum HCV RNA >2,000 IU/ml
- Hepatitis C genotype 1
- Other causes of chronic liver disease excluded by appropriate clinical, laboratory, or histologic evaluation
- The following hematological criteria must be met:
- Hemoglobin > 12 g/dl
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- Absolute neutrophil count (ANC) > 1.0x109 /L
- Platelets 150 x 108 /L (i.e normal)
- Serum creatinine <1.5 times the upper limit of normal (ULN) at screening.
- Fasting blood sugar normal for non-diabetics or hemoglobin A1C < 8.5% with diabetes
- Women of childbearing potential must have a negative pregnancy test prior to receiving treatment. Sexually active women must take adequate precautions to prevent pregnancy during the study. Pregnancy tests will be done at the final clinic visits and every 4 weeks
- Patient provides written informed consent
Who cannot join
- Evidence of liver disease other than HCV:
- Antinuclear antibodies (ANA) >1:160
- Active alcoholic liver disease.
- Hepatitis B surface antigen positive
- Hemochromatosis
- Wilson disease
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- Alpha-1-antitrypsin deficiency
- Recent hepatotoxic drug exposure
- Cirrhosis with complications of portal hypertension including esophageal varices (> grade 1 by endoscopy), ascites, or hepatic encephalopathy, or bilirubin >2.0 mg/dl
- Patients with advanced fibrosis (defined herein as decompensated cirrhosis, FIB4 > 2.5, platelet count <150 x 103/uL, clinical or radiographic evidence of cirrhosis)
- Extrahepatic manifestations of liver disease or HIV co-infection
- Use of fibric acid, Fenofibrate or cholestyramine
- Active substance abuse including, but not limited to alcohol or i.v./inhaled drugs
- Use of chemotherapy or systemic steroid therapy within 30 days prior to enrollment
- Pregnancy, females who are breast feeding, or females of child bearing potential who are not using adequate birth control measures
- History of a medical condition that could interfere with participation or completion of the protocol
- Organ transplant recipient
- History of hypersensitivity to ezetimibe
Trial locations and contacts
1 site in 1 country.
United States1 site
Edward Hines Jr. VA Hospital, Hines, IL
Hines, Illinois, 60141-5000
About this study
To address the need for more affordable hepatitis C virus (HCV) antivirals with high barriers to viral resistance and strategies to shorten the current treatment duration, the goal is to develop affordable therapeutic regimens to prevent HCV entry/spread and test the efficacy of those inhibitors for treating HCV infection. The investigators recently discovered that a major cholesterol uptake receptor is required for HCV entry into hepatocytes and that there is already an FDA-approved drug that inhibits cholesterol uptake by this receptor. Importantly the same drug also potently blocks HCV entry in human liver cells both in cell culture and in a small animal model. Further, looking back at people who were previously treated for HCV infection, the investigators found treatment response to be better (i.e. larger viral log reduction) in patients who happened to be taking ezetimibe (EZE). Hence, the objective of this study is to assess whether the FDA-approved drug (ezetimibe) is useful for the treatment of chronic HCV. The investigators predict that when administered as monotherapy ezetimibe will reduce HCV viremia perhaps allowing for viral clearance and that when included in combination treatment regimens that EZE will increase HCV decline resulting in faster viral clearance (i.e. shorter/cheaper direct-acting antiviral [DAA] therapy). To test these hypotheses, the investigators will execute the following aims: (1) Assess the efficacy of EZE monotherapy in chronically HCV infected and predict time to cure; (2) Assess the efficacy of EZE as an adjunct therapy in chronically HCV infected patients undergoing currently approved HCV DAA treatment.
Read the detailed description
To address the need for more affordable HCV antivirals with high barriers to viral resistance and/or strategies to shorten the current treatment duration, the goal is to develop affordable therapeutic regimens to prevent HCV entry/spread and test the efficacy of those inhibitors for treating HCV infection. The investigators recently discovered that the Niemann-Pick C1 Like-1 (NPC1L1) cellular cholesterol uptake receptor is required for HCV entry into hepatocytes and that ezetimibe, an FDA-approved drug that inhibits NPC1L1-mediated cholesterol uptake potently blocks HCV entry in human hepatoma cells and human hepatocytes transplanted into urokinase-type plasminogen activator-severe combined immunodeficiency (uPA-SCID) mice. Further, retrospective analysis of the National VA database using multivariable logistic regression models to control for age, sex, race, alcohol use, drug use, and other co-morbidities, the investigators found HCV prevalence to be lower (p <.001) and interferon/ribavirin (IFN/RBV) treatment response to be better (i.e. larger viral log reduction) in patients taking ezetimibe. Hence, the specific objective of this application is to assess the efficacy of EZE for the treatment of chronic HCV. Based on preliminary in vitro, in vivo, clinical retrospective data and HCV/DAA modeling, the investigators hypothesize that when administered as monotherapy EZE will reduce HCV viremia perhaps allowing for viral clearance and that when included in combination treatment regimens that EZE will augment 2nd phase HCV decline resulting in faster viral clearance (i.e. shorter/cheaper DAA therapy). To test these hypotheses, the investigators will execute the following aims: (1) Assess the efficacy of EZE monotherapy in chronically HCV infected and predict time to cure; (2) Assess the efficacy of EZE as an adjunct therapy in chronically HCV infected patients undergoing currently approved HCV DAA treatment.
- Conditions
- Chronic Hepatitis C
- Being tested
- 20mg ezetimibe, Placebo, 40mg ezetimibe
- Keywords
- hepatitis C virus, antiviral treatment, viral entry inhibitor, mathematical modeling
- Medical subject headings
- Hepatitis C, Chronic, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
20mg ezetimibeDrug
Also called 20mg Zetia
Participants assigned to this intervention will receive 20mg per day of ezetimibe for 12 weeks.
PlaceboDrug
Participants assigned to this intervention will receive placebo every day for 12 weeks
40mg ezetimibeDrug
Also called 40mg Zetia
Participants assigned to this intervention will receive 40mg per day of ezetimibe for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | placebo Receives: Drug: Placebo |
| 20mg/day ezetimibe | Experimental | 20mg/day ezetimibe Receives: Drug: 20mg ezetimibe |
| 40mg/day ezetimibe | Experimental | 40mg/day ezetimibe Receives: Drug: 40mg ezetimibe |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Viral Load
Participants will have their HCV-RNA measured in international unit per milliliter at baseline and 8 weeks. HCV RNA international unit per milliliter ranges from 0 to infinity, with higher levels indicating HCV positivity. The change in international unit per milliliter will be compared among the three intervention groups (i.e., placebo or control cohort, those assigned to 20mg ezetimibe per day, and 40mg ezetimibe per day). Change is calculated based on 8 weeks minus baseline (0 weeks).
Measured: 0 weeks, 8 weeks
Second Phase Slope
HCV declines in a biphasic manner under HCV treatment. Here we are measuring the slope (i.e., rate) at which HCV is declining during the second slower phase of viral decline.
Measured: 3 days through 4 weeks
Secondary outcomes (1)
Change in Alanine Aminotransferase (ALT)
Participants will have their ALT levels measured in units per liter (U/L) at baseline and 8 weeks. ALT ranges from 0 to infinity with higher levels of ALT indicating hepatocyte death. The change in ALT levels will be compared among the three intervention groups (i.e., placebo or control cohort, those assigned to 20mg ezetimibe per day, and 40mg ezetimibe per day).
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2016 (estimated)
- Study start16 Apr 2018
- Primary completion31 Mar 2021
- Study completion31 Mar 2021
Why it stopped: Study Funding ended
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Susan L. Uprichard, PhD, Principal investigator, Edward Hines Jr. VA Hospital, Hines, IL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02971033
- Sponsor's protocol ID
- INFA-015-16S
- Status last verified
- May 2022
- First submitted
- 21 Oct 2016
- Last updated
- 6 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ezetimibe as a Safe and Efficacious Treatment for Chronic Hepatitis C
- ClinicalTrials.gov ID
- NCT02971033
- Acronym / sponsor ID
- INFA-015-16S
- Conditions
- Chronic Hepatitis C
- Keywords
- hepatitis C virus, antiviral treatment, viral entry inhibitor, mathematical modeling
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study Funding ended
- Enrolment
- 2 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 16 Apr 2018 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 31 Mar 2021 (actual)
- First posted
- 22 Nov 2016 (estimated)
- Results
- Posted 6 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To address the need for more affordable hepatitis C virus (HCV) antivirals with high barriers to viral resistance and strategies to shorten the current treatment duration, the goal is to develop affordable therapeutic regimens to prevent HCV entry/spread and test the efficacy of those inhibitors for treating HCV infection. The investigators recently discovered that a major cholesterol uptake receptor is required for HCV entry into hepatocytes and that there is already an FDA-approved drug that inhibits cholesterol uptake by this receptor. Importantly the same drug also potently blocks HCV entry in human liver cells both in cell culture and in a small animal model. Further, looking back at people who were previously treated for HCV infection, the investigators found treatment response to be better (i.e. larger viral log reduction) in patients who happened to be taking ezetimibe (EZE). Hence, the objective of this study is to assess whether the FDA-approved drug (ezetimibe) is useful for the treatment of chronic HCV. The investigators predict that when administered as monotherapy ezetimibe will reduce HCV viremia perhaps allowing for viral clearance and that when included in combination treatment regimens that EZE will increase HCV decline resulting in faster viral clearance (i.e. shorter/cheaper direct-acting antiviral [DAA] therapy). To test these hypotheses, the investigators will execute the following aims: (1) Assess the efficacy of EZE monotherapy in chronically HCV infected and predict time to cure; (2) Assess the efficacy of EZE as an adjunct therapy in chronically HCV infected patients undergoing currently approved HCV DAA treatment.
Detailed description
To address the need for more affordable HCV antivirals with high barriers to viral resistance and/or strategies to shorten the current treatment duration, the goal is to develop affordable therapeutic regimens to prevent HCV entry/spread and test the efficacy of those inhibitors for treating HCV infection. The investigators recently discovered that the Niemann-Pick C1 Like-1 (NPC1L1) cellular cholesterol uptake receptor is required for HCV entry into hepatocytes and that ezetimibe, an FDA-approved drug that inhibits NPC1L1-mediated cholesterol uptake potently blocks HCV entry in human hepatoma cells and human hepatocytes transplanted into urokinase-type plasminogen activator-severe combined immunodeficiency (uPA-SCID) mice. Further, retrospective analysis of the National VA database using multivariable logistic regression models to control for age, sex, race, alcohol use, drug use, and other co-morbidities, the investigators found HCV prevalence to be lower (p <.001) and interferon/ribavirin (IFN/RBV) treatment response to be better (i.e. larger viral log reduction) in patients taking ezetimibe. Hence, the specific objective of this application is to assess the efficacy of EZE for the treatment of chronic HCV. Based on preliminary in vitro, in vivo, clinical retrospective data and HCV/DAA modeling, the investigators hypothesize that when administered as monotherapy EZE will reduce HCV viremia perhaps allowing for viral clearance and that when included in combination treatment regimens that EZE will augment 2nd phase HCV decline resulting in faster viral clearance (i.e. shorter/cheaper DAA therapy). To test these hypotheses, the investigators will execute the following aims: (1) Assess the efficacy of EZE monotherapy in chronically HCV infected and predict time to cure; (2) Assess the efficacy of EZE as an adjunct therapy in chronically HCV infected patients undergoing currently approved HCV DAA treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: Placeboplacebo |
| 20mg/day ezetimibe | Experimental | Drug: 20mg ezetimibe20mg/day ezetimibe |
| 40mg/day ezetimibe | Experimental | Drug: 40mg ezetimibe40mg/day ezetimibe |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Males/females 18 - 70 yrs of age
- Serum HCV RNA >2,000 IU/ml
- Hepatitis C genotype 1
- Other causes of chronic liver disease excluded by appropriate clinical, laboratory, or histologic evaluation
- The following hematological criteria must be met:
Key exclusion criteria (18 listed)
- Evidence of liver disease other than HCV:
- Patients with advanced fibrosis (defined herein as decompensated cirrhosis, FIB4 > 2.5, platelet count <150 x 103/uL, clinical or radiographic evidence of cirrhosis)
- Extrahepatic manifestations of liver disease or HIV co-infection
- Use of fibric acid, Fenofibrate or cholestyramine
- Active substance abuse including, but not limited to alcohol or i.v./inhaled drugs
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 |
|---|---|---|
| 20mg ezetimibeAlso: 20mg ZetiaParticipants assigned to this intervention will receive 20mg per day of ezetimibe for 12 weeks. | Drug | 20mg/day ezetimibe |
| PlaceboParticipants assigned to this intervention will receive placebo every day for 12 weeks | Drug | placebo |
| 40mg ezetimibeAlso: 40mg ZetiaParticipants assigned to this intervention will receive 40mg per day of ezetimibe for 12 weeks. | Drug | 40mg/day ezetimibe |
Primary outcome
Change in Viral Load
Time frame: 0 weeks, 8 weeks
Participants will have their HCV-RNA measured in international unit per milliliter at baseline and 8 weeks. HCV RNA international unit per milliliter ranges from 0 to infinity, with higher levels indicating HCV positivity. The change in international unit per milliliter will be compared among the three intervention groups (i.e., placebo or control cohort, those assigned to 20mg ezetimibe per day, and 40mg ezetimibe per day). Change is calculated based on 8 weeks minus baseline (0 weeks).
Second Phase Slope
Time frame: 3 days through 4 weeks
HCV declines in a biphasic manner under HCV treatment. Here we are measuring the slope (i.e., rate) at which HCV is declining during the second slower phase of viral decline.
1 secondary outcome
Change in Alanine Aminotransferase (ALT)
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Susan L. Uprichard, PhD principal investigator
Edward Hines Jr. VA Hospital, Hines, IL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 20mg ezetimibe and 40mg ezetimibe in people with Chronic Hepatitis C, run by VA Office of Research and Development 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 12 inclusion and 18 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: stopped early, as of the sponsor's last update on 6 Jun 2022. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Viral Load (time frame: 0 weeks, 8 weeks). 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 6 Jun 2022.