Hepatitis C, ChronicPhase 2NCT01353911

Grazoprevir (MK-5172) Administered With Peginterferon and Ribavirin in Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-003)

A Phase 2 study testing Grazoprevir, Boceprevir and Peg-interferon alfa-2b in people with Hepatitis C, Chronic, 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

This study will evaluate the safety, tolerability, and antiviral activity of grazoprevir (MK-5172) when administered in combination with peginterferon alfa-2b (Peg-IFN) and ribavirin (RBV) in treatment-naïve (TN) participants with chronic hepatitis C. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatitis C, Chronic
What is being tested?: Grazoprevir, Boceprevir and Peg-interferon alfa-2b
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 368 participants
Where: No sites listed yet
Study dates: 27 Jun 2011to 10 Mar 2015
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Has previously documented chronic hepatitis C genotype 1 (CHC GT 1) infection
Has hepatitis C virus (HCV) ribonucleic acid (RNA value) ≥10,000 IU/mL
Body weight ≥40 kg (88 lbs) and ≤125 kg (275 lbs)
Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs and symptoms of decompensated liver disease
Had a liver biopsy within 3 years of screening or between screening and Day 1 with histology consistent with CHC and no evidence of cirrhosis or hepatocellular carcinoma or no other cause for chronic liver disease (for participants with compensated cirrhosis, any liver biopsy demonstrating cirrhosis regardless of length of time since biopsy)
Female of childbearing potential or a male with female sexual partner who is of childbearing potential agrees to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations
For participants with compensated cirrhosis, evidence of cirrhosis without evidence of hepatocellular carcinoma (confirmed by ultrasound within 4 weeks prior)

Who cannot join

Is pregnant, breastfeeding, or plans to become pregnant or donate eggs
Is human immunodeficiency virus (HIV) positive or known to be co-infected with hepatitis B virus
Has received prior approved or investigational treatment for hepatitis C
Has evidence of hepatocellular carcinoma or is under evaluation for hepatocellular carcinoma
For participants with compensated cirrhosis: alphafetoprotein level of ≥100 ng/mL
Has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years

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Has evidence or history of chronic hepatitis not caused by HCV
Is diabetic and/or hypertensive with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality
Has any known medical condition that could interfere with participation in and completion of the study
Pre-existing psychiatric condition including but not limited to moderate or severe depression, suicidal or homicidal ideation or attempt, schizophrenia, psychosis, bipolar disorder, post traumatic stress disorder, or mania
Is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent
Member or family member of study staff

About this study

Official title: A Randomized, Active-Controlled, Dose-Ranging Estimation Study to Evaluate the Safety, Tolerability, and Efficacy of Different Regimens of MK-5172 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Treatment-Naïve Patients With Chronic Genotype 1 Hepatitis C Virus Infection

Read the detailed description

Amendment 4 unblinded treatment after an interim analysis for all subsequently enrolled TN participants (the Second Cohort) who were receiving grazoprevir 400 or 800 mg daily, and they were down-dosed to 100 mg daily between Treatment Week (TW) 3 and TW12 for the remainder of the 12-week treatment course.

Amendment 5 allowed treatment-naïve participants with chronic hepatitis C and compensated cirrhosis to be enrolled and receive open-label grazoprevir 100 mg in combination with Peg-IFN and RBV, without a corresponding control arm.

Conditions: Hepatitis C, Chronic
Being tested: Grazoprevir, Boceprevir, Placebo for Grazoprevir, Placebo for Boceprevir, Peg-interferon alfa-2b
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.

GrazoprevirDrug
Orally once daily in AM. Blinded or open-label depending on treatment arm.
BoceprevirDrug
Also called Victrelis
Four 200 mg capsules orally three times daily.
Placebo for GrazoprevirDrug
Orally once daily in AM.
Placebo for BoceprevirDrug
Four capsules orally three times daily.
Peg-interferon alfa-2bDrug
Also called PegIntron, Peg-IFN alfa-2b
1.5 μg/kg/week subcutaneous injection.
RibavirinDrug
Also called Rebetol
300 mg to 700 mg orally twice daily.

Study groups in NCT01353911
Study group	Role	What they receive
Grazoprevir 100 mg	Experimental	TN non-cirrhotic (NC) participants receive Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. Receives: Drug: Grazoprevir; Drug: Placebo for Boceprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin
Grazoprevir 200 mg	Experimental	TN NC participants receive Grazoprevir 200 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. Receives: Drug: Grazoprevir; Drug: Placebo for Boceprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin
Grazoprevir 400 mg	Experimental	TN NC participants receive Grazoprevir 400 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. Receives: Drug: Grazoprevir; Drug: Placebo for Boceprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin
Grazoprevir 800 mg	Experimental	TN NC participants receive Grazoprevir 800 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. Receives: Drug: Grazoprevir; Drug: Placebo for Boceprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin
Boceprevir 800 mg	Active comparator	TN NC participants start a 4 week lead-in with Peg-IFN + RBV, then receive Boceprevir 800 mg + Peg-IFN + RBV for 24 weeks followed by 0 or 20 weeks of Peg-IFN + RBV, based on response guided therapy. Receives: Drug: Boceprevir; Drug: Placebo for Grazoprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin
Grazoprevir 400 mg/100 mg	Experimental	As the result of an interim analysis, TN NC participants assigned to the 400 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study. Receives: Drug: Grazoprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin
Grazoprevir 800 mg/100 mg	Experimental	As the result of an interim analysis, TN NC participants assigned to the 800 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study. Receives: Drug: Grazoprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin
OL Grazoprevir 100 mg	Experimental	TN cirrhotic participants receive open-label Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. Receives: Drug: Grazoprevir; Drug: Peg-interferon alfa-2b; Drug: Ribavirin

What is being measured

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

Percentage of Participants Achieving Complete Early Viral Response (cEVR)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). cEVR was defined as undetectable HCV RNA (target not detected [TND]) at Week 12. 95% confidence intervals provided based on the Clopper-Pearson method.
Measured: After 12 weeks of treatment with grazoprevir/boceprevir
Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
Measured: Treatment period plus the first 14 days of follow-up (up to 50 weeks)
Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
Measured: Treatment period plus the first 14 days of follow-up (up to 50 weeks)

Secondary outcomes (5)

Median Time to First Achievement of Undetectable HCV RNA During Treatment
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Undetectable HCV RNA (target not detected [TND]) was defined as below the 9.3 IU/ml limit of detection. Kaplan Meier summary statistics were calculated for each treatment arm.
Measured: From first dose of study medication until first achievement of undetectable HCV RNA (up to 48 weeks of treatment)
Percentage of Participants Achieving Rapid Viral Response (RVR)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). RVR was defined as undetectable (TND) HCV RNA at Week 4 of study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
Measured: After 4 weeks of treatment with grazoprevir/boceprevir
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR12 was defined as undetectable (TND) HCV RNA at 12 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
Measured: 12 weeks after the end of all treatment (up to 60 weeks)
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24)
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR24 was defined as undetectable (TND) HCV RNA at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
Measured: 24 weeks after the end of all treatment (up to 72 weeks)
Percentage of Participants Achieving Undetectable HCV RNA at Week 72
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Undetectable HCV RNA (target not detected [TND]) was defined as below the 9.3 IU/ml limit of detection. 95% confidence intervals provided based on the Clopper-Pearson method.
Measured: Week 72

Timeline

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

27 Jun 201110 Mar 2015

First posted16 May 2011 (estimated)
Study start27 Jun 2011
Primary completion20 Jan 2013
Study completion10 Mar 2015

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 (2)Papers the sponsor has linked to this study.
Other trials for Hepatitis C, ChronicStudies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 368 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01353911
Sponsor's protocol ID: 5172-003
Other IDs: 2011-000759-18
Status last verified: May 2024
First submitted: 12 May 2011
Last updated: 22 May 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Manns MP, Vierling JM, Bacon BR, Bruno S, Shibolet O, Baruch Y, Marcellin P, Caro L, Howe AY, Fandozzi C, Gress J, Gilbert CL, Shaw PM, Cooreman MP, Robertson MN, Hwang P, Dutko FJ, Wahl J, Mobashery N. The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis C virus genotype 1 infection without cirrhosis. Gastroenterology. 2014 Aug;147(2):366-76.e6. doi: 10.1053/j.gastro.2014.04.006. Epub 2014 Apr 12.
PubMed 24727022
Howe AY, Black S, Curry S, Ludmerer SW, Liu R, Barnard RJ, Newhard W, Hwang PM, Nickle D, Gilbert C, Caro L, DiNubile MJ, Mobashery N. Virologic resistance analysis from a phase 2 study of MK-5172 combined with pegylated interferon/ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection. Clin Infect Dis. 2014 Dec 15;59(12):1657-65. doi: 10.1093/cid/ciu696. Epub 2014 Sep 28.
PubMed 25266289

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 Hepatitis C, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 22 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Active-Controlled, Dose-Ranging Estimation Study to Evaluate the Safety, Tolerability, and Efficacy of Different Regimens of MK-5172 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Treatment-Naïve Patients With Chronic Genotype 1 Hepatitis C Virus Infection
ClinicalTrials.gov ID: NCT01353911
Acronym / sponsor ID: 5172-003
Conditions: Hepatitis C, Chronic
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 368 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 27 Jun 2011 (actual)
Primary completion: 20 Jan 2013 (actual)
Study completion: 10 Mar 2015 (actual)
First posted: 16 May 2011 (estimated)
Results: Posted 2 Mar 2016

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 8

Arm	Type	Receives
Grazoprevir 100 mg	Experimental	Drug: Grazoprevir, Drug: Placebo for Boceprevir, Drug: Peg-interferon alfa-2b, Drug: RibavirinTN non-cirrhotic (NC) participants receive Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.
Grazoprevir 200 mg	Experimental	Drug: Grazoprevir, Drug: Placebo for Boceprevir, Drug: Peg-interferon alfa-2b, Drug: RibavirinTN NC participants receive Grazoprevir 200 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.
Grazoprevir 400 mg	Experimental	Drug: Grazoprevir, Drug: Placebo for Boceprevir, Drug: Peg-interferon alfa-2b, Drug: RibavirinTN NC participants receive Grazoprevir 400 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.
Grazoprevir 800 mg	Experimental	Drug: Grazoprevir, Drug: Placebo for Boceprevir, Drug: Peg-interferon alfa-2b, Drug: RibavirinTN NC participants receive Grazoprevir 800 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.
Boceprevir 800 mg	Active comparator	Drug: Boceprevir, Drug: Placebo for Grazoprevir, Drug: Peg-interferon alfa-2b, Drug: RibavirinTN NC participants start a 4 week lead-in with Peg-IFN + RBV, then receive Boceprevir 800 mg + Peg-IFN + RBV for 24 weeks followed by 0 or 20 weeks of Peg-IFN + RBV, based on response guided therapy.
Grazoprevir 400 mg/100 mg	Experimental	Drug: Grazoprevir, Drug: Peg-interferon alfa-2b, Drug: RibavirinAs the result of an interim analysis, TN NC participants assigned to the 400 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study.
Grazoprevir 800 mg/100 mg	Experimental	Drug: Grazoprevir, Drug: Peg-interferon alfa-2b, Drug: RibavirinAs the result of an interim analysis, TN NC participants assigned to the 800 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study.
OL Grazoprevir 100 mg	Experimental	Drug: Grazoprevir, Drug: Peg-interferon alfa-2b, Drug: RibavirinTN cirrhotic participants receive open-label Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.

Who may qualify

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

Key inclusion criteria (7 listed)

Has previously documented chronic hepatitis C genotype 1 (CHC GT 1) infection
Has hepatitis C virus (HCV) ribonucleic acid (RNA value) ≥10,000 IU/mL
Body weight ≥40 kg (88 lbs) and ≤125 kg (275 lbs)
Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs and symptoms of decompensated liver disease
Had a liver biopsy within 3 years of screening or between screening and Day 1 with histology consistent with CHC and no evidence of cirrhosis or hepatocellular carcinoma or no other cause for chronic liver disease (for participants with compensated cirrhosis, any liver biopsy demonstrating cirrhosis regardless of length of time since biopsy)

Key exclusion criteria (12 listed)

Is pregnant, breastfeeding, or plans to become pregnant or donate eggs
Is human immunodeficiency virus (HIV) positive or known to be co-infected with hepatitis B virus
Has received prior approved or investigational treatment for hepatitis C
Has evidence of hepatocellular carcinoma or is under evaluation for hepatocellular carcinoma
For participants with compensated cirrhosis: alphafetoprotein level of ≥100 ng/mL

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
GrazoprevirOrally once daily in AM. Blinded or open-label depending on treatment arm.	Drug	Grazoprevir 100 mg, Grazoprevir 200 mg, Grazoprevir 400 mg, Grazoprevir 400 mg/100 mg, Grazoprevir 800 mg, Grazoprevir 800 mg/100 mg, OL Grazoprevir 100 mg
BoceprevirAlso: VictrelisFour 200 mg capsules orally three times daily.	Drug	Boceprevir 800 mg
Placebo for GrazoprevirOrally once daily in AM.	Drug	Boceprevir 800 mg
Placebo for BoceprevirFour capsules orally three times daily.	Drug	Grazoprevir 100 mg, Grazoprevir 200 mg, Grazoprevir 400 mg, Grazoprevir 800 mg
Peg-interferon alfa-2bAlso: PegIntron, Peg-IFN alfa-2b1.5 μg/kg/week subcutaneous injection.	Drug	Boceprevir 800 mg, Grazoprevir 100 mg, Grazoprevir 200 mg, Grazoprevir 400 mg, Grazoprevir 400 mg/100 mg, Grazoprevir 800 mg, Grazoprevir 800 mg/100 mg, OL Grazoprevir 100 mg
RibavirinAlso: Rebetol300 mg to 700 mg orally twice daily.	Drug	Boceprevir 800 mg, Grazoprevir 100 mg, Grazoprevir 200 mg, Grazoprevir 400 mg, Grazoprevir 400 mg/100 mg, Grazoprevir 800 mg, Grazoprevir 800 mg/100 mg, OL Grazoprevir 100 mg

Primary outcome

Percentage of Participants Achieving Complete Early Viral Response (cEVR)
Time frame: After 12 weeks of treatment with grazoprevir/boceprevir
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). cEVR was defined as undetectable HCV RNA (target not detected [TND]) at Week 12. 95% confidence intervals provided based on the Clopper-Pearson method.
Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days
Time frame: Treatment period plus the first 14 days of follow-up (up to 50 weeks)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days
Time frame: Treatment period plus the first 14 days of follow-up (up to 50 weeks)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.

5 secondary outcomes

Median Time to First Achievement of Undetectable HCV RNA During Treatment
Time frame: From first dose of study medication until first achievement of undetectable HCV RNA (up to 48 weeks of treatment)
Percentage of Participants Achieving Rapid Viral Response (RVR)
Time frame: After 4 weeks of treatment with grazoprevir/boceprevir
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of Study Therapy (SVR12)
Time frame: 12 weeks after the end of all treatment (up to 60 weeks)
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR24)
Time frame: 24 weeks after the end of all treatment (up to 72 weeks)
Percentage of Participants Achieving Undetectable HCV RNA at Week 72
Time frame: Week 72

Results and safety

Results posted to the registry on 2 Mar 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
OL Grazoprevir 100 mg	36	28
Grazoprevir 100 mg	66	57
Grazoprevir 200 mg	68	59
Grazoprevir 400 mg	24	22
Grazoprevir 800 mg	29	23
Grazoprevir 400 mg/100 mg	43	36
Grazoprevir 800 mg/100 mg	36	30
Boceprevir 800 mg	66	51

Primary outcome: Percentage of Participants Achieving Complete Early Viral Response (cEVR)

Time frame: After 12 weeks of treatment with grazoprevir/boceprevir. Number (95% Confidence Interval). Unit: percentage of participants

Measure	OL Grazoprevir 100 mg n = 36	Grazoprevir 100 mg n = 66	Grazoprevir 200 mg n = 68	Grazoprevir 400 mg n = 24	Grazoprevir 800 mg n = 29	Grazoprevir 400 mg/100 mg n = 43	Grazoprevir 800 mg/100 mg n = 36	Boceprevir 800 mg n = 66
Value	94.4 (81.3 to 99.9)	80.3 (68.7 to 89.1)	85.3 (74.6 to 92.7)	87.5 (67.6 to 97.3)	75.9 (56.5 to 89.7)	86.0 (72.1 to 94.7)	86.1 (70.5 to 95.3)	69.7 (57.1 to 80.4)

Population analysed: FAS; all randomized/enrolled participants who received ≥1 dose of study treatment. A Missing = Failure approach was used for missing data. Results for participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens.

Primary outcome: Number of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days

Time frame: Treatment period plus the first 14 days of follow-up (up to 50 weeks). Number. Unit: participants

Measure	OL Grazoprevir 100 mg n = 36	Grazoprevir 100 mg n = 66	Grazoprevir 200 mg n = 68	Grazoprevir 400 mg n = 24	Grazoprevir 800 mg n = 29	Grazoprevir 400 mg/100 mg n = 43	Grazoprevir 800 mg/100 mg n = 36	Boceprevir 800 mg n = 66
Value	34	65	66	23	28	42	35	64

Population analysed: All Participants as Treated (APaT) population; all randomized/enrolled who received ≥1 dose of study treatment according to treatment actually received. Participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens.

Primary outcome: Number of Participants Who Discontinued Study Medication Due to AEs During the Treatment Period and First 14 Follow-up Days

Time frame: Treatment period plus the first 14 days of follow-up (up to 50 weeks). Number. Unit: participants

Measure	OL Grazoprevir 100 mg n = 36	Grazoprevir 100 mg n = 66	Grazoprevir 200 mg n = 68	Grazoprevir 400 mg n = 24	Grazoprevir 800 mg n = 29	Grazoprevir 400 mg/100 mg n = 43	Grazoprevir 800 mg/100 mg n = 36	Boceprevir 800 mg n = 66
Value	2	3	4	2	3	4	2	9

Population analysed: APaT population; all randomized/enrolled who received ≥1 dose of study treatment according to treatment actually received. Participants who received grazoprevir 400 or 800 mg and were then down-dosed to receive grazoprevir 100 mg are reported separately from participants who completed the 400 mg and 800 mg regimens.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of study medication up to 72 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cirr: OL Grazoprevir 100 mg	3 of 36 (8.3%)	34 of 36 (94.4%)	Not reported
Non-cirr: Grazoprevir 100 mg	6 of 66 (9.1%)	64 of 66 (97%)	Not reported
Non-cirr: Grazoprevir 200 mg	9 of 68 (13.2%)	65 of 68 (95.6%)	Not reported
Non-cirr: Grazoprevir 400 mg	2 of 24 (8.3%)	23 of 24 (95.8%)	Not reported
Non-cirr: Grazoprevir 800 mg	2 of 29 (6.9%)	27 of 29 (93.1%)	Not reported
Non-cirr: Grazoprevir 400 mg/100 mg	5 of 43 (11.6%)	42 of 43 (97.7%)	Not reported
Non-cirr: Grazoprevir 800 mg/100 mg	4 of 36 (11.1%)	36 of 36 (100%)	Not reported
Non-cirr: Boceprevir 800 mg	5 of 66 (7.6%)	64 of 66 (97%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 24727022Manns MP, Vierling JM, Bacon BR, Bruno S, Shibolet O, Baruch Y, Marcellin P, Caro L, Howe AY, Fandozzi C, Gress J, Gilbert CL, Shaw PM, Cooreman MP, Robertson MN, Hwang P, Dutko FJ, Wahl J, Mobashery N. The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis C virus genotype 1 infection without cirrhosis. Gastroenterology. 2014 Aug;147(2):366-76.e6. doi: 10.1053/j.gastro.2014.04.006. Epub 2014 Apr 12.
Derived from this study: PubMed 25266289Howe AY, Black S, Curry S, Ludmerer SW, Liu R, Barnard RJ, Newhard W, Hwang PM, Nickle D, Gilbert C, Caro L, DiNubile MJ, Mobashery N. Virologic resistance analysis from a phase 2 study of MK-5172 combined with pegylated interferon/ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection. Clin Infect Dis. 2014 Dec 15;59(12):1657-65. doi: 10.1093/cid/ciu696. Epub 2014 Sep 28.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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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.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Grazoprevir, Boceprevir and Peg-interferon alfa-2b in people with Hepatitis C, Chronic, 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 7 inclusion and 12 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 22 May 2024. 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 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 2 Mar 2016). 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?

Percentage of Participants Achieving Complete Early Viral Response (cEVR) (time frame: After 12 weeks of treatment with grazoprevir/boceprevir). The study lists 3 primary outcomes in all. 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 NCT01353911, which also lists 2 linked publications.

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 22 May 2024.