Chronic Hepatitis CPhase 1NCT01678131

Evaluating Fine Needle Aspiration to Measure Hepatic Vaniprevir (MK-7009) Concentrations in Participants With Chronic Hepatitis C (MK-7009-048)

A Phase 1 study testing Vaniprevir 600 mg, Peg-IFN alfa-2b and Ribavirin in people with Chronic Hepatitis C, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Chronic Hepatitis C
What is being tested?: Vaniprevir 600 mg, Peg-IFN alfa-2b and Ribavirin
Type of treatment: Pill or oral medicine, Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: No sites listed yet
Study dates: 30 Oct 2012to 2 Sep 2013
Phase: Phase 1
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Body Mass Index (BMI) ≥18.5 kg/m^2 and ≤32.0 kg/m^2
Under evaluation for treatment of chronic hepatitis C virus (HCV)
Chronic compensated, genotype 1 HCV infection
Treatment-naïve or previously treated and tolerated at least 12 weeks of continuous licensed interferon (including pegylated interferon) and ribavirin combination therapy with at least a partial response, or previously treated with investigational products and/or vaccines, other than HCV nonstructural proteins (NS) NS3/4A protease inhibitors, either alone or in combination with other licensed therapies
Able to avoid use of anticoagulants, nonsteroidal anti-inflammatory agents and aspirin for at least seven (7) days preceding the initial liver biopsy and continuing throughout the entire study
Female participants of childbearing potential or male participants with female sexual partners of childbearing potential must agree to use two acceptable methods of birth control from 2 weeks prior to the first dose through at least 6 months after last dose of study drug, or longer if dictated by local regulation

Who cannot join

Pregnant, lactating, or intending to become pregnant or donate eggs, or intending to donate sperm
History of stroke, chronic seizures, or major neurological disorder
Did not achieve a viral response to prior treatment with licensed interferon-based therapy
Previously treated with an NS3/4A protease inhibitor (investigational or licensed)
Evidence or history of chronic hepatitis not caused by HCV infection including but not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced hepatitis or autoimmune hepatitis
Clinical or laboratory evidence of cirrhosis or other advanced liver disease

Show all 17Show fewer

Decompensated liver disease as indicated by a history of ascites, hepatic encephalopathy, or bleeding esophageal varices
Diagnosed with or suspected of having hepatocellular carcinoma
Co-infection with human immunodeficiency virus (HIV)
Positive hepatitis B surface antigen or other evidence of active hepatitis B infection
History of gastric bypass surgery or bowel resection
History of clinically significant uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
History of clinically significant neoplastic disease
Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL], wine [125 mL], or distilled spirits [25 mL]) per day
Regular user, including use of any illicit drugs, or has a history of drug (including alcohol) abuse within the last 3 months
Surgery or donation of 1 unit of blood (approximately 500 mL) or participation in another investigational study within a period of 4 weeks prior to the prestudy (screening) visit
History of multiple and/or severe allergies, or has had an anaphylactic reaction or intolerability to prescription or nonprescription drugs or food

About this study

Official title: A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-7009 in Chronic Hepatitis C Patients

This study will evaluate the technical feasibility of using fine needle aspiration (FNA) of liver tissue to obtain vaniprevir (MK-7009) liver pharmacokinetic (PK) data, working towards identifying a minimally invasive, reproducible platform to measure liver PK. The study will be done in 2 parts. In Part 1, participants will be randomized to one of five FNA/core needle biopsy (CNB) time-point collection sequences. In Part 2, participants will be randomized to one of two possible doses of vaniprevir and will be assigned to one of five FNA/CNB time-point collection sequences; participants in Part 2 will also receive background therapy with pegylated interferon alpha-2b (Peg-IFN alpha-2b) and ribavirin (RBV). The primary hypothesis is that there is a greater than 80% posterior probability that vaniprevir concentrations are successfully obtained at least 60% of the time from FNA liver samples collected at 2 of 3 specified timepoints.

Conditions: Chronic Hepatitis C
Being tested: Vaniprevir 600 mg, Peg-IFN alfa-2b, Ribavirin, Liver samples from FNA, Vaniprevir 300 mg
Medical subject headings: Hepatitis C, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Vaniprevir 600 mgDrug
Also called MK-7009
Vaniprevir capsules, were administered orally, twice per day (BID) to achieve a final daily dose of 600 mg on Days 1 through 6; and a single dose of 600 mg, orally, on Day 7.
Peg-IFN alfa-2bBiological
Also called PegIntron™
Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21
RibavirinBiological
Also called Rebetol™
Ribavirin capsules were administered on Days 1-21, orally, twice daily for a total daily dose of 600 - 1400 mg, depending on the participant's weight
Liver samples from FNAProcedure or surgery
Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.
Vaniprevir 300 mgDrug
Also called MK-7009
Vaniprevir capsules were administered orally, twice per day to achieve a final daily dose of 300 mg on Days 1 through 6; and a single dose of 300 mg, orally, on Day 7.
Liver samples from CNBProcedure or surgery
Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.

Study groups in NCT01678131
Study group	Role	What they receive
Vaniprevir 600 mg	Experimental	Participants received 600 mg vaniprevir only on days 1-7, and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10. Receives: Drug: Vaniprevir 600 mg; Procedure: Liver samples from FNA; Procedure: Liver samples from CNB
Vaniprevir 600 mg + Peg-IFN + RBV	Experimental	Participants received 600 mg vaniprevir on Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10. Receives: Drug: Vaniprevir 600 mg; Biological: Peg-IFN alfa-2b; Biological: Ribavirin; Procedure: Liver samples from FNA; Procedure: Liver samples from CNB
Vaniprevir 300 mg + Peg-IFN + RBV	Experimental	Participants received 300 mg vaniprevir from Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10. Receives: Biological: Peg-IFN alfa-2b; Biological: Ribavirin; Procedure: Liver samples from FNA; Drug: Vaniprevir 300 mg; Procedure: Liver samples from CNB

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA
Liver samples were collected by FNA at 3 of 5 of the following specified postdose timepoints: 3, 12, 24, 48 and 72 hours after a single vaniprevir dose on Day 7. The technical success of the FNA procedure was established for a participant if vaniprevir was detected from at least 2 of the 3 FNA collection timepoints.
Measured: Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Oct 20122 Sep 2013

First posted3 Sep 2012 (estimated)
Study start30 Oct 2012
Primary completion27 Aug 2013
Study completion2 Sep 2013

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe 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 1
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01678131
Sponsor's protocol ID: 7009-048
Other IDs: 2012-003284-21
Status last verified: Aug 2022
First submitted: 30 Aug 2012
Last updated: 26 Aug 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Gao W, Webber AL, Maxwell J, Anderson M, Caro L, Chung C, Miltenburg AMM, Popa S, Van Dyck K, Wenning L, Mangin E, Fandozzi C, Railkar R, Shire NJ, Fraser I, Howell B, Talal AH, Stoch SA. Fine-Needle Aspiration for the Evaluation of Hepatic Pharmacokinetics of Vaniprevir: A Randomized Trial in Patients With Hepatitis C Virus Infection. Clin Pharmacol Ther. 2020 Jun;107(6):1325-1333. doi: 10.1002/cpt.1737. Epub 2020 Feb 8.
PubMed 31868916

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic

All Chronic Hepatitis C trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-7009 in Chronic Hepatitis C Patients
ClinicalTrials.gov ID: NCT01678131
Acronym / sponsor ID: 7009-048
Conditions: Chronic Hepatitis C
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 30 Oct 2012 (actual)
Primary completion: 27 Aug 2013 (actual)
Study completion: 2 Sep 2013 (actual)
First posted: 3 Sep 2012 (estimated)
Results: Posted 29 Sep 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Vaniprevir 600 mg	Experimental	Drug: Vaniprevir 600 mg, Procedure: Liver samples from FNA, Procedure: Liver samples from CNBParticipants received 600 mg vaniprevir only on days 1-7, and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.
Vaniprevir 600 mg + Peg-IFN + RBV	Experimental	Drug: Vaniprevir 600 mg, Biological: Peg-IFN alfa-2b, Biological: Ribavirin, Procedure: Liver samples from FNA, Procedure: Liver samples from CNBParticipants received 600 mg vaniprevir on Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.
Vaniprevir 300 mg + Peg-IFN + RBV	Experimental	Biological: Peg-IFN alfa-2b, Biological: Ribavirin, Procedure: Liver samples from FNA, Drug: Vaniprevir 300 mg, Procedure: Liver samples from CNBParticipants received 300 mg vaniprevir from Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Body Mass Index (BMI) ≥18.5 kg/m^2 and ≤32.0 kg/m^2
Under evaluation for treatment of chronic hepatitis C virus (HCV)
Chronic compensated, genotype 1 HCV infection
Treatment-naïve or previously treated and tolerated at least 12 weeks of continuous licensed interferon (including pegylated interferon) and ribavirin combination therapy with at least a partial response, or previously treated with investigational products and/or vaccines, other than HCV nonstructural proteins (NS) NS3/4A protease inhibitors, either alone or in combination with other licensed therapies
Able to avoid use of anticoagulants, nonsteroidal anti-inflammatory agents and aspirin for at least seven (7) days preceding the initial liver biopsy and continuing throughout the entire study

Key exclusion criteria (17 listed)

Pregnant, lactating, or intending to become pregnant or donate eggs, or intending to donate sperm
History of stroke, chronic seizures, or major neurological disorder
Did not achieve a viral response to prior treatment with licensed interferon-based therapy
Previously treated with an NS3/4A protease inhibitor (investigational or licensed)
Evidence or history of chronic hepatitis not caused by HCV infection including but not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced hepatitis or autoimmune hepatitis

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
Vaniprevir 600 mgAlso: MK-7009Vaniprevir capsules, were administered orally, twice per day (BID) to achieve a final daily dose of 600 mg on Days 1 through 6; and a single dose of 600 mg, orally, on Day 7.	Drug	Vaniprevir 600 mg, Vaniprevir 600 mg + Peg-IFN + RBV
Peg-IFN alfa-2bAlso: PegIntron™Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21	Biological	Vaniprevir 300 mg + Peg-IFN + RBV, Vaniprevir 600 mg + Peg-IFN + RBV
RibavirinAlso: Rebetol™Ribavirin capsules were administered on Days 1-21, orally, twice daily for a total daily dose of 600 - 1400 mg, depending on the participant's weight	Biological	Vaniprevir 300 mg + Peg-IFN + RBV, Vaniprevir 600 mg + Peg-IFN + RBV
Liver samples from FNALiver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.	Procedure or surgery	Vaniprevir 300 mg + Peg-IFN + RBV, Vaniprevir 600 mg, Vaniprevir 600 mg + Peg-IFN + RBV
Vaniprevir 300 mgAlso: MK-7009Vaniprevir capsules were administered orally, twice per day to achieve a final daily dose of 300 mg on Days 1 through 6; and a single dose of 300 mg, orally, on Day 7.	Drug	Vaniprevir 300 mg + Peg-IFN + RBV
Liver samples from CNBLiver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.	Procedure or surgery	Vaniprevir 300 mg + Peg-IFN + RBV, Vaniprevir 600 mg, Vaniprevir 600 mg + Peg-IFN + RBV

Primary outcome

Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA
Time frame: Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose
Liver samples were collected by FNA at 3 of 5 of the following specified postdose timepoints: 3, 12, 24, 48 and 72 hours after a single vaniprevir dose on Day 7. The technical success of the FNA procedure was established for a participant if vaniprevir was detected from at least 2 of the 3 FNA collection timepoints.

Results and safety

Results posted to the registry on 29 Sep 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
600 mg Vaniprevir	10	10
300 mg Vaniprevir + PegIFN/RBV	10	9
600 mg Vaniprevir + PegIFN/RBV	11	9

Primary outcome: Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA

Time frame: Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose. Number. Unit: Participants

Measure	600 mg Vaniprevir n = 10	300 mg Vaniprevir + PegIFN/RBV n = 9	600 mg Vaniprevir + PegIFN/RBV n = 10
Value	10	9	10

600 mg Vaniprevir vs 300 mg Vaniprevir + PegIFN/RBV vs 600 mg Vaniprevir + PegIFN/RBV: Posterior Percentage Probability: 100

Population analysed: Participants treated with vaniprevir who had hepatic FNA collected at 3 timepoints. One participant from the 300 mg Vaniprevir + Peg-IFN/RBV treatment group, and one participant from the 600 mg Vaniprevir + Peg-IFN/RBV treatment group discontinued treatment prior to collection of 3 FNAs, and were therefore excluded from the analysis.

Adverse events

Time frame: up to 14 days after last treatment with vaniprevir (up to approximately Day 21). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
600 mg Vaniprevir	0 of 10 (0%)	4 of 10 (40%)	Not reported
300 mg Vaniprevir + PegIFN/RBV	0 of 10 (0%)	10 of 10 (100%)	Not reported
600 mg Vaniprevir + PegIFN/RBV	0 of 11 (0%)	10 of 11 (90.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31868916Gao W, Webber AL, Maxwell J, Anderson M, Caro L, Chung C, Miltenburg AMM, Popa S, Van Dyck K, Wenning L, Mangin E, Fandozzi C, Railkar R, Shire NJ, Fraser I, Howell B, Talal AH, Stoch SA. Fine-Needle Aspiration for the Evaluation of Hepatic Pharmacokinetics of Vaniprevir: A Randomized Trial in Patients With Hepatitis C Virus Infection. Clin Pharmacol Ther. 2020 Jun;107(6):1325-1333. doi: 10.1002/cpt.1737. Epub 2020 Feb 8.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Chronic Hepatitis C

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic

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.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vaniprevir 600 mg, Peg-IFN alfa-2b and Ribavirin in people with Chronic Hepatitis C, run by Merck Sharp & Dohme LLC.

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 6 inclusion and 17 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: finished, as of the sponsor's last update on 26 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

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?

Yes. Results are posted in the registry (first posted 29 Sep 2014). 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?

Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA (time frame: Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01678131, which also lists 1 linked publication.

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 26 Aug 2022.