Hepatitis CNCT01667081

Durability of Virologic Response and/or Viral Resistance Patterns in Participants With Chronic Hepatitis C Who Have Been Previously Treated With Grazoprevir (MK-5172) (MK-5172-017)

An observational study of 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 3 years and older
Conditions the study is for: Hepatitis C
What is being tested?: Grazoprevir
How many people: 2,438 participants
Where: No sites listed yet
Study dates: 17 Oct 2012to 31 Mar 2021
Phase: Observational
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 3 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Study population: Adult and pediatric participants previously treated with a grazoprevir-containing regimen while enrolled in a Merck study. All participants enrolled having failed therapy from prior studies (except MK-5172-052 [NCT02092350]) will be followed for 3 years in the current follow-up study, and all participants enrolled from MK-5172-052 (irrespective of prior response) will be followed for 5 years in the current follow-up study.

Who may be able to join

Previously participated in a HCV treatment protocol that included grazoprevir in the treatment regimen
Must enroll in the present study within three months of the last study visit of their previous protocol in which they received a grazoprevir-containing regimen
For Amendment 03: Adult participants must have received a grazoprevir-containing regimen in a prior trial and have been identified as having failed therapy in that study
For Amendment 04: Pediatric participants must have received at least 1 dose of a grazoprevir-containing regimen and experienced virologic failure with 1 or more associated treatment-emergent RASs at Follow-up Week 12 in MK-5172-079 (NCT03379506)

Who cannot join

Has received HCV therapy after completion of the protocol-defined grazoprevir treatment trial regimen and before or after entry into this follow-up study
For Amendment 03: Has failed therapy due to re-infection, defined as an HCV RNA sample with a different genotype than the baseline genotype in the prior treatment study, or an HCV RNA sample determined to be reinfection by phylogenetic analysis with comparison to the baseline sequence in the prior treatment study
For Amendment 03: Has failed therapy and received retreatment with HCV therapy, except in the case where they were re-treated in a Merck-sponsored protocol

About this study

Official title: A Long-Term Follow-Up Study to Evaluate the Durability of Virologic Response and/or Viral Resistance Patterns of Subjects With Chronic Hepatitis C Who Have Been Previously Treated With MK-5172 in a Prior Clinical Trial

This is a three-year (except for participants with chronic kidney disease [CKD] or cirrhosis) multicenter study to follow participants who received at least one dose of grazoprevir (MK-5172) in a previous study to determine whether they remain hepatitis C virus (HCV)-Ribonucleic acid (RNA) negative over time, and to determine if they have developed antiviral resistance. The study will also evaluate long-term adverse events in this population. Participants from MK-5172-052 (NCT02092350) with CKD or cirrhosis will be followed for five years.

Read the detailed description

As of Amendment 03, the study design is revised such that continued enrollment will only be for participants who failed prior therapy with a grazoprevir regimen. Participants with CKD enrolled from MK-5172-052 (NCT02092350) will continue enrollment regardless of prior treatment-response and remain in this study for five years, while participants enrolled from all other studies with HCV RNA less than the lower limit of quantitation (LLOQ) will be discontinued and end their participation after the next scheduled visit. In addition, participants who receive other HCV treatments concurrent with this follow-up study or received other HCV treatments prior to this study will be discontinued and their data excluded from analysis.

As of Amendment 04, the protocol has been updated to include enrollment of pediatric participants from protocol MK-5172-079 (NCT03379506). Enrollment is limited to participants who experienced virologic failure associated with 1 or more treatment-emergent resistant associated substitutions (RASs) present at 12 weeks after receiving grazoprevir treatment in prior treatment study MK-5172-079 (NCT03379506).

Conditions: Hepatitis C
Being tested: Grazoprevir
Medical subject headings: Hepatitis C

What participants receive

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

GrazoprevirDrug
Participants previously received study treatment with grazoprevir at the dose and frequency specified in the study protocol. Grazoprevir was not administered to participants in the course of this follow-up study.

Study groups in NCT01667081
Study group	Role	What they receive
Grazoprevir		Participants who previously received grazoprevir as study treatment on a prior study. Receives: Drug: Grazoprevir

What is being measured

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

Time to Viral Relapse
Viral relapse is defined as any participant who has confirmed HCV Ribonucleic acid (RNA) ≥ Lower limit of quantification (LLoQ) of 15 IU/mL and had achieved sustained virologic response (SVR) in the follow up in the prior treatment study. Time to relapse is defined as the time from last dose of study therapy taken in the prior treatment study until the date where HCV RNA is ≥LLoQ.
Measured: Up to ~60 months after enrollment in this study
Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections
In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time.
Measured: Up to ~60 months after enrollment in this study
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections
In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time.
Measured: Up to ~60 months after enrollment in this study
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections
In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time.
Measured: Up to ~60 months after enrollment in this study
Number of Participants Who Experienced a Drug-Related Adverse Event (AE) During the Long-Term Follow-Up
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The study investigator determined whether the adverse event was drug-related.
Measured: Up to ~ 60 months after enrollment in this study
Number of Participants Who Experienced a Drug-Related Serious Adverse Event (SAE) During the Long-Term Follow-Up
A serious adverse event (SAE) is any adverse experience occurring at any dose that either results in death, is life threatening, results in a persistent or significant disability/incapacity, results in or prolongs an existing inpatient hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose (whether accidental or intentional), or other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious adverse experience when, based upon appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed previously. The study investigator determined whether the adverse event was drug-related.
Measured: Up to ~60 months after enrollment in this study
Number of Participants Who Experienced an Event of Clinical Interest (ECI) During the Long-Term Follow-Up
An ECI includes spontaneous bacterial peritonitis, variceal bleeding, ascites, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, liver transplant, cardiovascular disease limited to angina and myocardial infarction, neurologic disorders limited to transient ischemic attack (TIA) or stroke, graft rejection in participants who have undergone liver or kidney transplant, or one of the following in participants from the MK-5172-052 (NCT02092350) base study: kidney transplant, decreased estimated glomerular filtration rate (eGFR), new onset diabetes, cryoglobulinemia, or post transplantation glomerulonephritis.
Measured: Up to ~60 months after enrollment in this study

Timeline

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

17 Oct 201231 Mar 2021

First posted17 Aug 2012 (estimated)
Study start17 Oct 2012
Primary completion31 Mar 2021
Study completion31 Mar 2021

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 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: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 2,438 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01667081
Sponsor's protocol ID: 5172-017
Other IDs: 2012-002232-85
Status last verified: Mar 2022
First submitted: 14 Aug 2012
Last updated: 6 Jun 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Lahser F, Galloway A, Hwang P, Palcza J, Brunhofer J, Wahl J, Robertson M, Barr E, Black T, Asante-Appiah E, Haber B. Interim analysis of a 3-year follow-up study of NS5A and NS3 resistance-associated substitutions after treatment with grazoprevir-containing regimens in participants with chronic HCV infection. Antivir Ther. 2018;23(7):593-603. doi: 10.3851/IMP3253. Epub 2018 Jul 24.
PubMed 30038064

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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All Hepatitis C trials

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: A Long-Term Follow-Up Study to Evaluate the Durability of Virologic Response and/or Viral Resistance Patterns of Subjects With Chronic Hepatitis C Who Have Been Previously Treated With MK-5172 in a Prior Clinical Trial
ClinicalTrials.gov ID: NCT01667081
Acronym / sponsor ID: 5172-017
Conditions: Hepatitis C
Study type: Observational
Recruitment status: Completed
Enrolment: 2,438 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 17 Oct 2012 (actual)
Primary completion: 31 Mar 2021 (actual)
Study completion: 31 Mar 2021 (actual)
First posted: 17 Aug 2012 (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.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Grazoprevir	–	Drug: GrazoprevirParticipants who previously received grazoprevir as study treatment on a prior study.

Who may qualify

Ages: 3 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult
Study population: Adult and pediatric participants previously treated with a grazoprevir-containing regimen while enrolled in a Merck study. All participants enrolled having failed therapy from prior studies (except MK-5172-052 [NCT02092350]) will be followed for 3 years in the current follow-up study, and all participants enrolled from MK-5172-052 (irrespective of prior response) will be followed for 5 years in the current follow-up study.

Key inclusion criteria (4 listed)

Previously participated in a HCV treatment protocol that included grazoprevir in the treatment regimen
Must enroll in the present study within three months of the last study visit of their previous protocol in which they received a grazoprevir-containing regimen
For Amendment 03: Adult participants must have received a grazoprevir-containing regimen in a prior trial and have been identified as having failed therapy in that study
For Amendment 04: Pediatric participants must have received at least 1 dose of a grazoprevir-containing regimen and experienced virologic failure with 1 or more associated treatment-emergent RASs at Follow-up Week 12 in MK-5172-079 (NCT03379506)

Key exclusion criteria (3 listed)

Has received HCV therapy after completion of the protocol-defined grazoprevir treatment trial regimen and before or after entry into this follow-up study
For Amendment 03: Has failed therapy due to re-infection, defined as an HCV RNA sample with a different genotype than the baseline genotype in the prior treatment study, or an HCV RNA sample determined to be reinfection by phylogenetic analysis with comparison to the baseline sequence in the prior treatment study
For Amendment 03: Has failed therapy and received retreatment with HCV therapy, except in the case where they were re-treated in a Merck-sponsored protocol

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
GrazoprevirParticipants previously received study treatment with grazoprevir at the dose and frequency specified in the study protocol. Grazoprevir was not administered to participants in the course of this follow-up study.	Drug	Grazoprevir

Primary outcome

Time to Viral Relapse
Time frame: Up to ~60 months after enrollment in this study
Viral relapse is defined as any participant who has confirmed HCV Ribonucleic acid (RNA) ≥ Lower limit of quantification (LLoQ) of 15 IU/mL and had achieved sustained virologic response (SVR) in the follow up in the prior treatment study. Time to relapse is defined as the time from last dose of study therapy taken in the prior treatment study until the date where HCV RNA is ≥LLoQ.
Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections
Time frame: Up to ~60 months after enrollment in this study
In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time.
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections
Time frame: Up to ~60 months after enrollment in this study
In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time.
Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections
Time frame: Up to ~60 months after enrollment in this study
In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time.
Number of Participants Who Experienced a Drug-Related Adverse Event (AE) During the Long-Term Follow-Up
Time frame: Up to ~ 60 months after enrollment in this study
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The study investigator determined whether the adverse event was drug-related.
Number of Participants Who Experienced a Drug-Related Serious Adverse Event (SAE) During the Long-Term Follow-Up
Time frame: Up to ~60 months after enrollment in this study
A serious adverse event (SAE) is any adverse experience occurring at any dose that either results in death, is life threatening, results in a persistent or significant disability/incapacity, results in or prolongs an existing inpatient hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose (whether accidental or intentional), or other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious adverse experience when, based upon appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed previously. The study investigator determined whether the adverse event was drug-related.
Number of Participants Who Experienced an Event of Clinical Interest (ECI) During the Long-Term Follow-Up
Time frame: Up to ~60 months after enrollment in this study
An ECI includes spontaneous bacterial peritonitis, variceal bleeding, ascites, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, liver transplant, cardiovascular disease limited to angina and myocardial infarction, neurologic disorders limited to transient ischemic attack (TIA) or stroke, graft rejection in participants who have undergone liver or kidney transplant, or one of the following in participants from the MK-5172-052 (NCT02092350) base study: kidney transplant, decreased estimated glomerular filtration rate (eGFR), new onset diabetes, cryoglobulinemia, or post transplantation glomerulonephritis.

Results and safety

Results posted to the registry on 6 Jun 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Grazoprevir (GZR) 100 mg + Elbasvir (EBR) 50 mg +/- Ribavirin (RBV)	1,909	132
Other GZR Regimen	526	169

Primary outcome: Time to Viral Relapse

Time frame: Up to ~60 months after enrollment in this study. Median (Inter-Quartile Range). Unit: Months

Measure	GZR 100 mg + EBR 50 mg +/- RBV n = 1837	Other GZR Regimen n = 495
Value	NA (NA to NA)	NA (NA to NA)

Population analysed: All participants who achieved SVR during the follow-up period of the prior treatment study and did not start any new HCV therapy between the end of the prior treatment study and entry in this study

Primary outcome: Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections

Time frame: Up to ~60 months after enrollment in this study. Count of participants. Unit: Participants

Measure	EBR/GZR +/- RBV: NS3 RASs n = 31	EBR/GZR +/- RBV: NS5A RASs n = 31	EBR/GZR +/-RBV: Both NS3 and NS5A RASs n = 31	GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs n = 16
Failure	22	25	18	11
24 weeks post failure	10	25	8	2
48 weeks post failure	6	22	4	2
96 weeks post failure	4	15	3	1
≥144 weeks post failure	2	11	1	1

Population analysed: Participants met the criteria of virologic failure either in the prior base study or had HCV RNA Target detected, quantifiable \[TD(q)\] at entry in current study. Participants did not receive new HCV therapy between the end of the prior base study and entry into this study. Only HCV genotype infections that had adequate reference information were included.

Primary outcome: Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections

Time frame: Up to ~60 months after enrollment in this study. Count of participants. Unit: Participants

Measure	EBR/GZR+/- RBV: NS3 RASs n = 9	EBR/GZR +/- RBV: NS5A RASs n = 9	EBR/GZR +/-RVB: Both NS3 and NS5A RASs n = 9	GZR + RBV or PR: NS3 RASs n = 5
Failure	4	7	2	3
24 weeks post failure	2	7	0	1
48 weeks post failure	1	5	0	1
96 weeks post failure	1	3	0	1
≥144 weeks post failure	0	3	0	1

Population analysed: Participants met the criteria of virologic failure either in the prior base study or had HCV RNA TD(q) at entry in current study. Participants did not receive new HCV therapy between the end of the prior base study and entry into this study. Only HCV genotype infections that had adequate reference information were included.

Primary outcome: Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections

Time frame: Up to ~60 months after enrollment in this study. Count of participants. Unit: Participants

Measure	EBR/GZR: NS3 RASs n = 5	EBR/GZR: NS5A RASs n = 5	EBR/GZR: Both NS3 and NS5A RASs n = 5
Failure	2	4	2
24 weeks post failure	1	3	1
48 weeks post failure	1	2	1
96 weeks post failure	1	2	1
≥144 weeks post failure	1	2	1

Adverse events

Time frame: From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GZR 100 mg + EBR 50 mg +/- RBV	100 of 1,909 (5.2%)	0 of 1,909 (0%)	44 of 1,909
Other GZR Regimen	4 of 526 (0.8%)	0 of 526 (0%)	3 of 527
Non-GZR Regimen	0 of 0	0 of 0	0 of 2

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.
Background: PubMed 30038064Lahser F, Galloway A, Hwang P, Palcza J, Brunhofer J, Wahl J, Robertson M, Barr E, Black T, Asante-Appiah E, Haber B. Interim analysis of a 3-year follow-up study of NS5A and NS3 resistance-associated substitutions after treatment with grazoprevir-containing regimens in participants with chronic HCV infection. Antivir Ther. 2018;23(7):593-603. doi: 10.3851/IMP3253. Epub 2018 Jul 24.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/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?

An observational study of 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 4 inclusion and 3 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 6 Jun 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.

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?

Time to Viral Relapse (time frame: Up to ~60 months after enrollment in this study). The study lists 7 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 NCT01667081, 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 6 Jun 2022.