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)

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01667081
• Other study ID #: 5172-017
• Secondary ID: 2012-002232-85
• Status: Completed
• Start date: October 17, 2012
• Est. completion date: March 31, 2021

Study information

• Verified date: March 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2438
• Est. completion date: March 31, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• Grazoprevir
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to ~60 months after enrollment in this study
Primary	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.	Up to ~60 months after enrollment in this study
Primary	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.	Up to ~60 months after enrollment in this study
Primary	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.	Up to ~60 months after enrollment in this study
Primary	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.	Up to ~ 60 months after enrollment in this study
Primary	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.	Up to ~60 months after enrollment in this study
Primary	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.	Up to ~60 months after enrollment in this study