Safety and Efficacy of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Participants With Chronic Hepatitis C and Chronic Kidney Disease (MK-5172-052) (C-SURFER)

August 23, 2018 updated by: Merck Sharp & Dohme LLC

A Phase II/III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects With Chronic Hepatitis C Virus Infection and Chronic Kidney Disease

This study will evaluate the safety and efficacy of combination treatment with grazoprevir (MK-5172) + elbasvir (MK-8742) for cirrhotic and non-cirrhotic participants with chronic Genotype 1 (GT1) hepatitis C virus (HCV) infection and chronic kidney disease (CKD). The primary study hypothesis is that the proportion of HCV GT1-infected CKD participants within the Immediate Treatment and Intensive Pharmacokinetics (PK) groups achieving a sustained viral response 12 weeks after the end of all study treatment (SVR12) will be >45%.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
237

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Documented chronic (at least 6 months) HCV GT 1 infection (with no evidence of mixed genotypes or genotype that cannot be assigned a type)
  • Evidence or no evidence of liver cirrhosis based on one of the following:
  • Liver biopsy performed within 24 months of Day 1 (if participant is cirrhotic then there is no time restriction on biopsy)
  • Fibroscan performed within 12 months of Day 1 of this study
  • Fibrosure™ (Fibrotest™) plus aspartate aminotransferase to platelet Ratio Index [APRI] obtained during the screening period)
  • Has HCV status that is one of the following:
  • Treatment naïve
  • Prior interferon or pegylated interferon with or without ribavarin failures (null responder, partial responder, or relapser)
  • Intolerant to prior interferon or pegylated intereferon with or without ribavarin regimen
  • Chronic kidney disease (defined as glomerular filtration rate [eGFR] <=29) non-dialysis dependent or on hemodialysis for at least 3 months, including individuals awaiting kidney transplant and those with failed kidney transplants but no longer on immunosuppressant therapy)
  • Female participant of reproductive potential must agree to remain abstinent or use (or have their partner use) 2 acceptable methods of contraception from at least 2 weeks prior to Day 1 through 14 days after the last dose of study drugs, or longer if dictated by local regulations

Exclusion Criteria:

  • Evidence of decompensated liver disease
  • On peritoneal dialysis for management of kidney disease
  • Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
  • History of malignancy <=5 years prior to signing informed consent
  • Clinical diagnosis of substance abuse
  • Pregnant, breast-feeding, expecting to conceive or donate eggs, or donate sperm from Day 1 through 14 days after the last study dose, or longer if dictated by local regulations
  • Organ transplant (including hematopoietic stem cell transplant) other than kidney, cornea, and hair
  • Conditions requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
  • Uncontrolled or poorly controlled hypertension
  • Significant cardiovascular disorder (e.g. myocardial infarction or unstable angina) or cardiovascular procedure within 3 months prior to signing informed consent
  • New or worsening signs or symptoms of congestive heart failure within 3 months of signing informed consent
  • Severe active peripheral vascular disease
  • Recent (within 3 months prior to signing informed consent) episode or recurrence of stroke, transient ischemic attack (TIA) or neurological disorder, including but not limited to seizures
  • Evidence or history of chronic hepatitis not caused by HCV

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Immediate Treatment
Participants receive grazoprevir 100 mg tablet, orally, once per day (QD) + elbasvir 50 mg tablet, orally, QD, for 12 weeks.
Drug: Grazoprevir
Grazoprevir 100 mg tablet
Other Names:
  • MK-5172
Drug: Elbasvir
Elbasvir 50 mg tablet
Other Names:
  • MK-8742
Experimental: Deferred Treatment
Participants receive placebos to both grazoprevir and elbasvir for 12 weeks, and after a 4-week break, grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks.
Drug: Grazoprevir
Grazoprevir 100 mg tablet
Other Names:
  • MK-5172
Drug: Elbasvir
Elbasvir 50 mg tablet
Other Names:
  • MK-8742
Drug: Placebo to Grazoprevir
Placebo tablet matched to grazoprevir
Drug: Placebo to Elbasvir
Placebo tablet matched to elbasvir
Experimental: Intensive PK
Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing.
Drug: Grazoprevir
Grazoprevir 100 mg tablet
Other Names:
  • MK-5172
Drug: Elbasvir
Elbasvir 50 mg tablet
Other Names:
  • MK-8742

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)
Time Frame: Week 24 (Immediate Treatment + Intensive PK) or Week 40 (Deferred Treatment)
SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) lower than the limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
Week 24 (Immediate Treatment + Intensive PK) or Week 40 (Deferred Treatment)
Number of Participants Experiencing an Adverse Event (AE) During the Initial Treatment and 14-day Follow-up Periods
Time Frame: Up to Week 14
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
Up to Week 14
Number of Participants Discontinuing Study Drug Due to AEs During the Initial Treatment Period
Time Frame: Up to Week 12
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
Up to Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)
Time Frame: Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment)
SVR24 was defined as HCV RNA <LLoQ 24 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment)
Percentage of Participants With Sustained Virologic Response 4 Weeks After Completing Study Therapy (SVR4)
Time Frame: Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment)
SVR4 was defined as HCV RNA <LLoQ 4 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 17, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 11, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 2, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 20, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 24, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 5172-052
  • 2013-003858-25 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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