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

Hepatitis C Virus Clinical Trial

— C-SURFER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02092350
• Other study ID #: 5172-052
• Secondary ID: 2013-003858-25
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 17, 2014
• Est. completion date: September 2, 2015

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 237
• Est. completion date: September 2, 2015
• Est. primary completion date: March 11, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Grazoprevir
Grazoprevir 100 mg tablet
• Elbasvir
Elbasvir 50 mg tablet
• Placebo to Grazoprevir
Placebo tablet matched to grazoprevir
• Placebo to Elbasvir
Placebo tablet matched to elbasvir

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (2)

Bruchfeld A, Roth D, Martin P, Nelson DR, Pol S, Londoño MC, Monsour H Jr, Silva M, Hwang P, Arduino JM, Robertson M, Nguyen BY, Wahl J, Barr E, Greaves W. Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney — View Citation

Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, Martin P, Pol S, Londoño MC, Hassanein T, Zamor PJ, Zuckerman E, Wan S, Jackson B, Nguyen BY, Robertson M, Barr E, Wahl J, Greaves W. Grazoprevir plus elbasvir in treatment-naive and treat — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)	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)
Primary	Number of Participants Experiencing an Adverse Event (AE) During the Initial Treatment and 14-day Follow-up Periods	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
Primary	Number of Participants Discontinuing Study Drug Due to AEs During the Initial Treatment Period	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	Percentage of Participants With Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)	SVR24 was defined as HCV RNA	Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment)
Secondary	Percentage of Participants With Sustained Virologic Response 4 Weeks After Completing Study Therapy (SVR4)	SVR4 was defined as HCV RNA	Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment)