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

NCT02092350 | Completed Phase 2 Results DMC

• 2 other identifiers: 5172-0522013-003858-25
• Study Type: interventional
• Target: 237
• Locations: 0 countries
• Sites: N/A

Brief 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%.

Conditions

Hepatitis C Virus

Outcome Measures

Primary Outcomes (3)

• 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)

• 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

• 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 Outcomes (2)

• Percentage of Participants With Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)

  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)

  Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment)

Study Arms (3)

Immediate Treatment

EXPERIMENTAL

Participants receive grazoprevir 100 mg tablet, orally, once per day (QD) + elbasvir 50 mg tablet, orally, QD, for 12 weeks.

Drug: Grazoprevir; Drug: Elbasvir

Deferred Treatment

EXPERIMENTAL

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; Drug: Elbasvir; Drug: Placebo to Grazoprevir; Drug: Placebo to Elbasvir

Intensive PK

EXPERIMENTAL

Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing.

Drug: Grazoprevir; Drug: Elbasvir

Interventions

Grazoprevir DRUG

Grazoprevir 100 mg tablet

Also known as: MK-5172

Deferred Treatment; Immediate Treatment; Intensive PK

Elbasvir DRUG

Elbasvir 50 mg tablet

Also known as: MK-8742

Deferred Treatment; Immediate Treatment; Intensive PK

Placebo to Grazoprevir DRUG

Placebo tablet matched to grazoprevir

Deferred Treatment

Placebo to Elbasvir DRUG

Placebo tablet matched to elbasvir

Deferred Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (6)

• Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, Martin P, Pol S, Londono 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 treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015 Oct 17;386(10003):1537-45. doi: 10.1016/S0140-6736(15)00349-9. Epub 2015 Oct 5.

  PMID: 26456905 RESULT

• Bruchfeld A, Roth D, Martin P, Nelson DR, Pol S, Londono 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 disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):585-594. doi: 10.1016/S2468-1253(17)30116-4. Epub 2017 May 30.

  PMID: 28576451 RESULT

• Prabhu AR, Rao IR, Nagaraju SP, Rajwar E, Venkatesh BT, Nair N S, Pai G, Reddy NP, Suvarna D. Interventions for dialysis patients with hepatitis C virus (HCV) infection. Cochrane Database Syst Rev. 2023 Apr 25;4(4):CD007003. doi: 10.1002/14651858.CD007003.pub3.

  PMID: 37096802 DERIVED

• Caro L, Wenning L, Feng HP, Guo Z, Du L, Bhagunde P, Fandozzi C, Panebianco D, Marshall WL, Butterton JR, Iwamoto M, Yeh WW. Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment. Eur J Clin Pharmacol. 2019 May;75(5):665-675. doi: 10.1007/s00228-018-2585-3. Epub 2019 Jan 25.

  PMID: 30680407 DERIVED

• Reau N, Robertson MN, Feng HP, Caro L, Yeh WW, Nguyen BT, Wahl J, Barr E, Hwang P, Klopfer SO. Concomitant proton pump inhibitor use does not reduce the efficacy of elbasvir/grazoprevir: A pooled analysis of 1,322 patients with hepatitis C infection. Hepatol Commun. 2017 Aug 22;1(8):757-764. doi: 10.1002/hep4.1081. eCollection 2017 Oct.

  PMID: 29404492 DERIVED

• Jacobson IM, Lawitz E, Kwo PY, Hezode C, Peng CY, Howe AYM, Hwang P, Wahl J, Robertson M, Barr E, Haber BA. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology. 2017 May;152(6):1372-1382.e2. doi: 10.1053/j.gastro.2017.01.050. Epub 2017 Feb 11.

  PMID: 28193518 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

grazoprevir; elbasvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2014
• First Posted: March 20, 2014
• Study Start: March 17, 2014
• Primary Completion: March 11, 2015
• Study Completion: September 2, 2015
• Last Updated: September 24, 2018
• Results First Posted: April 12, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share