Safety and Efficacy of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Participants With Chronic Hepatitis C and Chronic Kidney Disease (MK-5172-052)
- Conditions
- Hepatitis C Virus
- Interventions
- Registration Number
- NCT02092350
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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%.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 237
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Deferred Treatment Placebo to Grazoprevir 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. Deferred Treatment Placebo to Elbasvir 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. Immediate Treatment Grazoprevir Participants receive grazoprevir 100 mg tablet, orally, once per day (QD) + elbasvir 50 mg tablet, orally, QD, for 12 weeks. Immediate Treatment Elbasvir Participants receive grazoprevir 100 mg tablet, orally, once per day (QD) + elbasvir 50 mg tablet, orally, QD, for 12 weeks. Deferred Treatment Grazoprevir 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. Deferred Treatment Elbasvir 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. Intensive PK Elbasvir Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing. Intensive PK Grazoprevir Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12) 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.
Number of Participants Discontinuing Study Drug Due to AEs During the Initial Treatment Period 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.
Number of Participants Experiencing an Adverse Event (AE) During the Initial Treatment and 14-day Follow-up Periods 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.
- Secondary Outcome Measures
Name Time Method 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) 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.
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) 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.