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)

NCT ID: NCT02115321

Last Updated: 2019-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-09
• Study Completion Date: 2015-06-16

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.

Conditions

Chronic Hepatitis C

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: CP-B GZR 50 mg + EBR 50 mg

CP-B participants take GZR 50 mg + EBR 50 mg once daily (q.d.) by mouth for 12 weeks.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.

Elbasvir

Intervention Type: DRUG

EBR was supplied as 50 mg tablets and was taken q.d. by mouth.

Part A: NC GZR 100 mg + EBR 50 mg

NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.

Elbasvir

Intervention Type: DRUG

EBR was supplied as 50 mg tablets and was taken q.d. by mouth.

MK-5172A

Intervention Type: DRUG

MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.

Part B: CP-B GZR 100 mg + EBR 50 mg

CP-B participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.

Elbasvir

Intervention Type: DRUG

EBR was supplied as 50 mg tablets and was taken q.d. by mouth.

MK-5172A

Intervention Type: DRUG

MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.

Part C: CP-B GZR 50 mg or 100 mg + EBR 50 mg

CP-B participants take GZR 50 mg or GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks (GZR dose chosen based on results of Part A CP-B arm).

Group Type: EXPERIMENTAL

Grazoprevir

Intervention Type: DRUG

GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.

Elbasvir

Intervention Type: DRUG

EBR was supplied as 50 mg tablets and was taken q.d. by mouth.

MK-5172A

Intervention Type: DRUG

MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.

Interventions

Grazoprevir

GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.

Intervention Type: DRUG

Elbasvir

EBR was supplied as 50 mg tablets and was taken q.d. by mouth.

Intervention Type: DRUG

MK-5172A

MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.

Intervention Type: DRUG

Other Intervention Names

MK-5172; MK-8742

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 30939489 (View on PubMed)

Other Identifiers

2014-000672-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

5172-059

Identifier Type: -

Identifier Source: org_study_id