NCT01667081

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)

Completed Results posted Last updated 6 June 2022

What this trial tests

trial testing Grazoprevir in Hepatitis C in 2,438 participants. Completed in 31 March 2021.

Timeline

17 October 2012

Primary endpoint
31 March 2021

31 March 2021

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Status	Completed
Study type	OBSERVATIONAL
Enrollment	2,438
Start date	17 October 2012
Primary completion	31 March 2021
Estimated completion	31 March 2021

Drugs / interventions tested

• Grazoprevir (GRAZOPREVIR) — full drug profile →

Conditions studied

• Hepatitis C — all drugs for Hepatitis C →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

3 and older, any sex, with Hepatitis C. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Viral Relapse Primary · 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.

Group	Value	95% CI
GZR 100 mg + EBR 50 mg +/- RBV	NA	NA – NA
Other GZR Regimen	NA	NA – NA

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

Failure

Group	Value	95% CI
EBR/GZR +/- RBV: NS3 RASs	22
EBR/GZR +/- RBV: NS5A RASs	25
EBR/GZR +/-RBV: Both NS3 and NS5A RASs	18
GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs	11

24 weeks post failure

Group	Value	95% CI
EBR/GZR +/- RBV: NS3 RASs	10
EBR/GZR +/- RBV: NS5A RASs	25
EBR/GZR +/-RBV: Both NS3 and NS5A RASs	8
GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs	2

48 weeks post failure

Group	Value	95% CI
EBR/GZR +/- RBV: NS3 RASs	6
EBR/GZR +/- RBV: NS5A RASs	22
EBR/GZR +/-RBV: Both NS3 and NS5A RASs	4
GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs	2

96 weeks post failure

Group	Value	95% CI
EBR/GZR +/- RBV: NS3 RASs	4
EBR/GZR +/- RBV: NS5A RASs	15
EBR/GZR +/-RBV: Both NS3 and NS5A RASs	3
GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs	1

≥144 weeks post failure

Group	Value	95% CI
EBR/GZR +/- RBV: NS3 RASs	2
EBR/GZR +/- RBV: NS5A RASs	11
EBR/GZR +/-RBV: Both NS3 and NS5A RASs	1
GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs	1

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

Failure

Group	Value	95% CI
EBR/GZR+/- RBV: NS3 RASs	4
EBR/GZR +/- RBV: NS5A RASs	7
EBR/GZR +/-RVB: Both NS3 and NS5A RASs	2
GZR + RBV or PR: NS3 RASs	3

24 weeks post failure

Group	Value	95% CI
EBR/GZR+/- RBV: NS3 RASs	2
EBR/GZR +/- RBV: NS5A RASs	7
EBR/GZR +/-RVB: Both NS3 and NS5A RASs	0
GZR + RBV or PR: NS3 RASs	1

48 weeks post failure

Group	Value	95% CI
EBR/GZR+/- RBV: NS3 RASs	1
EBR/GZR +/- RBV: NS5A RASs	5
EBR/GZR +/-RVB: Both NS3 and NS5A RASs	0
GZR + RBV or PR: NS3 RASs	1

96 weeks post failure

Group	Value	95% CI
EBR/GZR+/- RBV: NS3 RASs	1
EBR/GZR +/- RBV: NS5A RASs	3
EBR/GZR +/-RVB: Both NS3 and NS5A RASs	0
GZR + RBV or PR: NS3 RASs	1

≥144 weeks post failure

Group	Value	95% CI
EBR/GZR+/- RBV: NS3 RASs	0
EBR/GZR +/- RBV: NS5A RASs	3
EBR/GZR +/-RVB: Both NS3 and NS5A RASs	0
GZR + RBV or PR: NS3 RASs	1

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

Failure

Group	Value	95% CI
EBR/GZR: NS3 RASs	2
EBR/GZR: NS5A RASs	4
EBR/GZR: Both NS3 and NS5A RASs	2

24 weeks post failure

Group	Value	95% CI
EBR/GZR: NS3 RASs	1
EBR/GZR: NS5A RASs	3
EBR/GZR: Both NS3 and NS5A RASs	1

48 weeks post failure

Group	Value	95% CI
EBR/GZR: NS3 RASs	1
EBR/GZR: NS5A RASs	2
EBR/GZR: Both NS3 and NS5A RASs	1

96 weeks post failure

Group	Value	95% CI
EBR/GZR: NS3 RASs	1
EBR/GZR: NS5A RASs	2
EBR/GZR: Both NS3 and NS5A RASs	1

≥144 weeks post failure

Group	Value	95% CI
EBR/GZR: NS3 RASs	1
EBR/GZR: NS5A RASs	2
EBR/GZR: Both NS3 and NS5A RASs	1

Number of Participants Who Experienced a Drug-Related Adverse Event (AE) During the Long-Term Follow-Up Primary · 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.

Group	Value	95% CI
GZR 100 mg + EBR 50 mg +/- RBV	1
Other GZR Regimen	1

Number of Participants Who Experienced a Drug-Related Serious Adverse Event (SAE) During the Long-Term Follow-Up Primary · 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 p

Group	Value	95% CI
GZR 100 mg + EBR 50 mg +/- RBV	1
Other GZR Regimen	1

Number of Participants Who Experienced an Event of Clinical Interest (ECI) During the Long-Term Follow-Up Primary · 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 transplant

Group	Value	95% CI
GZR 100 mg + EBR 50 mg +/- RBV	98
Other GZR Regimen	4

Adverse events — posted to ClinicalTrials.gov

Time frame: From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GZR 100 mg + EBR 50 mg +/- RBV

Serious: 100/1909 (5%)

Deaths: 44/1909

Other GZR Regimen

Serious: 4/526 (1%)

Deaths: 3/527

Non-GZR Regimen

Serious: 0

Deaths: 0/2

Serious adverse events (55 terms)

Reaction	System	GZR 100 mg + EBR 50 mg +/-…	Other GZR Regimen	Non-GZR Regimen
End stage renal disease	Renal and urinary disorders	—	—	—
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Death	General disorders	—	—	—
Chronic kidney disease	Renal and urinary disorders	—	—	—
Renal failure	Renal and urinary disorders	—	—	—
Glomerular filtration rate decreased	Investigations	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—
Transient ischaemic attack	Nervous system disorders	—	—	—
Acute coronary syndrome	Cardiac disorders	—	—	—
Myocardial ischaemia	Cardiac disorders	—	—	—
Ascites	Gastrointestinal disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Sepsis	Infections and infestations	—	—	—
Septic shock	Infections and infestations	—	—	—
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—
Ischaemic stroke	Nervous system disorders	—	—	—
Glomerulonephritis chronic	Renal and urinary disorders	—	—	—
Renal impairment	Renal and urinary disorders	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—
Angina pectoris	Cardiac disorders	—	—	—
Angina unstable	Cardiac disorders	—	—	—
Cardiac failure	Cardiac disorders	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—

Most-reported serious reactions: End stage renal disease, Hepatocellular carcinoma, Death, Chronic kidney disease, Renal failure, Glomerular filtration rate decreased, Cardiac arrest, Myocardial infarction.

Data from ClinicalTrials.gov NCT01667081 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.