Clinical trial 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)
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-08-17
Enrollment: 2438
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Time to Viral Relapse
timeFrame: Up to ~60 months after enrollment in this study
measure: Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections
timeFrame: Up to ~60 months after enrollment in this study
measure: Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections
timeFrame: Up to ~60 months after enrollment in this study
measure: Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections
timeFrame: Up to ~60 months after enrollment in this study
measure: Number of Participants Who Experienced a Drug-Related Adverse Event (AE) During the Long-Term Follow-Up
timeFrame: Up to ~ 60 months after enrollment in this study
measure: Number of Participants Who Experienced a Drug-Related Serious Adverse Event (SAE) During the Long-Term Follow-Up
timeFrame: Up to ~60 months after enrollment in this study
measure: Number of Participants Who Experienced an Event of Clinical Interest (ECI) During the Long-Term Follow-Up
timeFrame: Up to ~60 months after enrollment in this study
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.