Clinical trial NCT02115321: Study of Efficacy and Safety of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Chronic Hepatitis C Participants With Child-Pugh (CP)-B Hepatic Insufficiency (MK-5172-059)
Official title: A Phase II/III 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 With Advanced Cirrhosis and Child-Pugh (CP)-B Hepatic Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Chronic Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-04-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is being done to evaluate the efficacy and safety of the drug combination grazoprevir (GZR; MK-5172) + elbasvir (EBR; MK-8742) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infection and who have cirrhosis and Child-Pugh (CP) score 7-9 moderate hepatic insufficiency (CP-B). The primary hypothesis is that the percentage of HCV-infected participants with hepatic insufficiency (the CP-B population) achieving sustained viral response (SVR) 12 weeks after the end of all treatment (SVR12) will be greater than 60%. Additionally, ten non-cirrhotic (NC) HCV-infected GT1 participants will also be given GZR + EBR at the beginning of the study; this will be done for the purpose of collecting plasma pharmacokinetic (PK) data in HCV GT1-infected participants who do not have hepatic insufficiency.

Detailed description: The study will be conducted sequentially in 3 Parts. Each participant will participate in only one Part.

Participants will be enrolled in either Part A, Part B, or Part C:

* Part A: CP-B participants will receive GZR 50 mg+ EBR 50 mg; NC participants will receive GZR 100 mg/EBR 50 mg.
* Part B: CP-B participants will receive GZR 100 mg + EBR 50 mg.
* Part C: CP-B participants will receive either GZR 50 mg or 100 mg + EBR 50 mg. Study progression from Part A to Part B and from Part B to Part C will be based upon a review of safety and efficacy in Parts A and B, respectively. Depending upon safety and efficacy in Part A, the study may progress directly from Part A to Part C using GZR 50 mg + EBR 50 mg, without performing Part B.

Eligibility criteria: Inclusion criteria:

* Has documented chronic HCV GT1 infection (for Arm 4 participants may have GT4 or GT6 infection) with no evidence of non-typable or mixed genotype infection
* Has clinical evidence of hepatic cirrhosis with a score on the Child-Pugh scale from 7 to 9 and not anticipated to receive a liver transplant within the next 36 weeks (for Arm 1, Arm 3, and Arm 4)
* Has no evidence of cirrhosis (only for Arm 2 )
* Agrees to remain truly abstinent or use (or have their partner use) an acceptable method of birth control from at least 2 weeks prior to Day 1 and continue until at least 14 days after last dose of study drug, or longer if dictated by local regulations

Exclusion criteria:

* Is co-infected with hepatitis B virus or human immunodeficiency virus (HIV)
* Has previously received direct-acting antiviral therapy for HCV
* Has a history of malignancy \<=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or under evaluation for other active or suspected malignancy
* Has cirrhosis and liver imaging results within 4 weeks prior to screening showing evidence of hepatocellular carcinoma (HCC), or is under evaluation for HCC
* Is currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study
* Has clinically-relevant drug or alcohol abuse within 12 months of screening
* Is pregnant or breast-feeding, or expecting to conceive or donate eggs or sperm from at least 2 weeks prior to Day 1 and continue throughout treatment and follow up, or longer if dictated by local regulations
* Has received organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
* Has poor venous access
* Has a history of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorders (e.g., celiac sprue disease)
* Requires, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
* Has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis

Primary outcomes:
measure: Percentage of Participants Achieving Sustained Viral Response 12 Weeks After Completing Study Therapy (SVR12)
timeFrame: Week 24
measure: Number of Participants Experiencing an Adverse Event (AE) During Treatment and First 14 Follow-up Days
timeFrame: Up to 14 weeks
measure: Number of Participants Discontinuing Study Drug Due to an AE
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants
timeFrame: Baseline and Weeks 12, 24, and 36
measure: Percentage of Participants With HCV RNA Undetectable at Weeks 2, 4, and 12
timeFrame: Week 2, 4, and 12
measure: Percentage of Participants With HCV RNA <LLoQ at Weeks 2, 4, and 12
timeFrame: Weeks 2, 4, and 12
measure: Percentage of Participants Achieving Sustained Viral Response 4 Weeks After Completing Study Therapy (SVR4)
timeFrame: Week 16
measure: Percentage of Participants Achieving Sustained Viral Response 24 Weeks After Completing Study Therapy (SVR24)
timeFrame: Week 36
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Jacobson IM, Poordad F, Firpi-Morell R, Everson GT, Verna EC, Bhanja S, Hwang P, Caro L, Robertson M, Charles ED, Platt H. Elbasvir/Grazoprevir in People With Hepatitis C Genotype 1 Infection and Child-Pugh Class B Cirrhosis: The C-SALT Study. Clin Transl Gastroenterol. 2019 Apr;10(4):e00007. doi: 10.14309/ctg.0000000000000007.