Hepatitis C VirusPhase 2NCT02105454

Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin in Participants With Chronic Hepatitis C Who Failed Prior Direct-Acting Antiviral Therapy (MK-5172-048)

A Phase 2 study testing Grazoprevir (GZR), Elbasvir (EBR) and Ribavirin (RBV) in people with Hepatitis C Virus, 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

In this study, participants with hepatitis C virus (HCV) genotype 1 (GT1) who failed prior direct-acting antiviral (DAA) therapy will receive Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin (RBV) to evaluate sustained virologic response (SVR) using this drug combination. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatitis C Virus
What is being tested?: Grazoprevir (GZR), Elbasvir (EBR) and Ribavirin (RBV)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 79 participants
Where: No sites listed yet
Study dates: 23 May 2014to 4 May 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

Documented chronic HCV GT1 infection (with no evidence of non-typable or mixed genotype)
Absence of cirrhosis, or cirrhosis with these criteria: METAVIR F4, or Fibroscan with result >12.5 kPa, or FibroSure® (Fibrotest®) score of >0.75 + aspartate aminotransferase (AST): platelet ratio index (APRI) of >2- Prior regimen containing an approved DAA (boceprevir, telaprevir, simeprevir, or sofosbuvir), pegylated interferon, and/or RBV
Participants of reproductive potential must agree to remain truly abstinent or use (or have their partner use) 2 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

Who cannot join

Received any HCV regimen containing a DAA with the exception of boceprevir, telaprevir, simeprevir, or sofosbuvir in combination with pegylated interferon and/or RBV
Evidence of decompensated liver disease or cirrhosis
Co-infected with hepatitis B virus or human immunodeficiency virus (HIV)
History of malignancy <=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or under evaluation for other active or suspected malignancy
Evidence of hepatocellular carcinoma (HCC) or under evaluation for HCC
Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study

Show all 15Show fewer

Clinically-relevant drug or alcohol abuse within 12 months of screening
Pregnant, breast-feeding, or expecting to conceive or donate eggs or sperm from at least 2 weeks prior to Day 1 and continue throughout treatment and follow up, or longer if dictated by local regulations
Male participant whose female partner (s) is/are pregnant
Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
Poor venous access
History of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorders (e.g., celiac sprue disease)
Hemoglobinopathy, including, but not limited to, thalassemia major
Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
Evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis

About this study

Official title: A Phase II Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 + MK-8742 + Ribavirin (R) in Subjects With Chronic Hepatitis C Virus Infection Who Failed Prior Direct Acting Antiviral Therapy

Conditions: Hepatitis C Virus
Being tested: Grazoprevir (GZR), Elbasvir (EBR), Ribavirin (RBV)
Medical subject headings: Hepatitis C

What participants receive

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

Grazoprevir (GZR)Drug
100 mg oral tablet (total daily dose)
Elbasvir (EBR)Drug
10 mg oral capsule (total daily dose = 5 capsules)
Ribavirin (RBV)Drug
200 mg oral capsule (total daily dose = 4-7 capsules)

Study groups in NCT02105454
Study group	Role	What they receive
GZR 100 mg + EBR 50 mg + RBV for 12 weeks	Experimental	Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks Receives: Drug: Grazoprevir (GZR); Drug: Elbasvir (EBR); Drug: Ribavirin (RBV)

What is being measured

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

Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12)
SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, <15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy.
Measured: Up to 24 weeks
Percentage of Participants Experiencing Adverse Events
Adverse event is 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.
Measured: Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug)
Percentage of Participants Discontinuing Study Drug Due to an Adverse Event
Adverse event is 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.
Measured: Up to 12 weeks

Secondary outcomes (1)

Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy
SVR12 is defined as participants having HCV RNA level lower than the LLoQ (<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy. Prior DAA therapy regimen included boceprevir, telaprevir, simeprevir, or sofosbuvir taken concomitantly with peginterferon and ribavirin. Below categories specify with our without resistance-associated variants (RAVs) of the hepatitis C virus.
Measured: Up to 24 weeks

Timeline

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

23 May 20144 May 2015

First posted7 Apr 2014 (estimated)
Study start23 May 2014
Primary completion4 May 2015
Study completion4 May 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 (3)Papers the sponsor has linked to this study.
Other trials for Hepatitis C VirusStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 79 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02105454
Sponsor's protocol ID: 5172-048
Other IDs: 2013-004213-41
Status last verified: Aug 2018
First submitted: 2 Apr 2014
Last updated: 24 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Forns X, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Buti M. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.
PubMed 25895428
Jacobson IM, Lawitz E, Kwo PY, Hezode C, Peng CY, Howe AYM, Hwang P, Wahl J, Robertson M, Barr E, Haber BA. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology. 2017 May;152(6):1372-1382.e2. doi: 10.1053/j.gastro.2017.01.050. Epub 2017 Feb 11.
PubMed 28193518
Buti M, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Forns X. Grazoprevir, Elbasvir, and Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection After Failure of Pegylated Interferon and Ribavirin With an Earlier-Generation Protease Inhibitor: Final 24-Week Results From C-SALVAGE. Clin Infect Dis. 2016 Jan 1;62(1):32-6. doi: 10.1093/cid/civ722. Epub 2015 Sep 14.
PubMed 26371152

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

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Study at a glance

From the registry record, last updated by the sponsor on 24 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 + MK-8742 + Ribavirin (R) in Subjects With Chronic Hepatitis C Virus Infection Who Failed Prior Direct Acting Antiviral Therapy
ClinicalTrials.gov ID: NCT02105454
Acronym / sponsor ID: 5172-048
Conditions: Hepatitis C Virus
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 79 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 23 May 2014 (actual)
Primary completion: 4 May 2015 (actual)
Study completion: 4 May 2015 (actual)
First posted: 7 Apr 2014 (estimated)
Results: Posted 4 Mar 2016

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: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
GZR 100 mg + EBR 50 mg + RBV for 12 weeks	Experimental	Drug: Grazoprevir (GZR), Drug: Elbasvir (EBR), Drug: Ribavirin (RBV)Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks

Who may qualify

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

Key inclusion criteria (3 listed)

Documented chronic HCV GT1 infection (with no evidence of non-typable or mixed genotype)
Absence of cirrhosis, or cirrhosis with these criteria: METAVIR F4, or Fibroscan with result >12.5 kPa, or FibroSure® (Fibrotest®) score of >0.75 + aspartate aminotransferase (AST): platelet ratio index (APRI) of >2- Prior regimen containing an approved DAA (boceprevir, telaprevir, simeprevir, or sofosbuvir), pegylated interferon, and/or RBV
Participants of reproductive potential must agree to remain truly abstinent or use (or have their partner use) 2 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

Key exclusion criteria (15 listed)

Received any HCV regimen containing a DAA with the exception of boceprevir, telaprevir, simeprevir, or sofosbuvir in combination with pegylated interferon and/or RBV
Evidence of decompensated liver disease or cirrhosis
Co-infected with hepatitis B virus or human immunodeficiency virus (HIV)
History of malignancy <=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or under evaluation for other active or suspected malignancy
Evidence of hepatocellular carcinoma (HCC) or under evaluation for HCC

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
Grazoprevir (GZR)100 mg oral tablet (total daily dose)	Drug	GZR 100 mg + EBR 50 mg + RBV for 12 weeks
Elbasvir (EBR)10 mg oral capsule (total daily dose = 5 capsules)	Drug	GZR 100 mg + EBR 50 mg + RBV for 12 weeks
Ribavirin (RBV)200 mg oral capsule (total daily dose = 4-7 capsules)	Drug	GZR 100 mg + EBR 50 mg + RBV for 12 weeks

Primary outcome

Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12)
Time frame: Up to 24 weeks
SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, <15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy.
Percentage of Participants Experiencing Adverse Events
Time frame: Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug)
Adverse event is 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.
Percentage of Participants Discontinuing Study Drug Due to an Adverse Event
Time frame: Up to 12 weeks
Adverse event is 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.

1 secondary outcome

Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy
Time frame: Up to 24 weeks

Results and safety

Results posted to the registry on 4 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
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks	79	78

Primary outcome: Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12)

Time frame: Up to 24 weeks. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	GZR 100 mg + EBR 50 mg + RBV for 12 Weeks n = 70
Value	97.1 (90.1 to 99.7)

Population analysed: Per protocol population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints.

Primary outcome: Percentage of Participants Experiencing Adverse Events

Time frame: Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug). Number. Unit: Percentage of participants

Measure	GZR 100 mg + EBR 50 mg + RBV for 12 Weeks n = 79
Value	79.7 (69.2 to 88.0)

Population analysed: All participants as treated population defined as all participants who received at least one dose of study medication.

Primary outcome: Percentage of Participants Discontinuing Study Drug Due to an Adverse Event

Time frame: Up to 12 weeks. Number. Unit: Percentage of participants

Measure	GZR 100 mg + EBR 50 mg + RBV for 12 Weeks n = 79
Value	1.3 (0.0 to 6.9)

Population analysed: All participants as treated population defined as all participants who received at least one dose of study medication.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks	6 of 79 (7.6%)	47 of 79 (59.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25895428Forns X, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Buti M. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.
Derived from this study: PubMed 28193518Jacobson IM, Lawitz E, Kwo PY, Hezode C, Peng CY, Howe AYM, Hwang P, Wahl J, Robertson M, Barr E, Haber BA. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology. 2017 May;152(6):1372-1382.e2. doi: 10.1053/j.gastro.2017.01.050. Epub 2017 Feb 11.
Derived from this study: PubMed 26371152Buti M, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Forns X. Grazoprevir, Elbasvir, and Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection After Failure of Pegylated Interferon and Ribavirin With an Earlier-Generation Protease Inhibitor: Final 24-Week Results From C-SALVAGE. Clin Infect Dis. 2016 Jan 1;62(1):32-6. doi: 10.1093/cid/civ722. Epub 2015 Sep 14.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Hepatitis C Virus

RecruitingObservational study
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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 (GZR), Elbasvir (EBR) and Ribavirin (RBV) in people with Hepatitis C Virus, 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 3 inclusion and 15 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 24 Sep 2018. 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 4 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 Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12) (time frame: Up to 24 weeks). 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 NCT02105454, which also lists 3 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 24 Sep 2018.