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)

NCT02115321 | Completed Phase 2 Results

• 2 other identifiers: 5172-0592014-000672-25
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Hepatitis C

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Achieving Sustained Viral Response 12 Weeks After Completing Study Therapy (SVR12)

  SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels below the lower limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

  Week 24

• Number of Participants Experiencing an Adverse Event (AE) During Treatment and First 14 Follow-up Days

  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.

  Up to 14 weeks

• Number of Participants Discontinuing Study Drug Due to an AE

  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.

  Up to 12 weeks

Secondary Outcomes (5)

• Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants

  Baseline and Weeks 12, 24, and 36

• Percentage of Participants With HCV RNA Undetectable at Weeks 2, 4, and 12

  Week 2, 4, and 12

• Percentage of Participants With HCV RNA <LLoQ at Weeks 2, 4, and 12

  Weeks 2, 4, and 12

• Percentage of Participants Achieving Sustained Viral Response 4 Weeks After Completing Study Therapy (SVR4)

  Week 16

• Percentage of Participants Achieving Sustained Viral Response 24 Weeks After Completing Study Therapy (SVR24)

  Week 36

Study Arms (4)

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

EXPERIMENTAL

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

Drug: Grazoprevir; Drug: Elbasvir

Part A: NC GZR 100 mg + EBR 50 mg

EXPERIMENTAL

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

Drug: Grazoprevir; Drug: Elbasvir; Drug: MK-5172A

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

EXPERIMENTAL

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

Drug: Grazoprevir; Drug: Elbasvir; Drug: MK-5172A

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

EXPERIMENTAL

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).

Drug: Grazoprevir; Drug: Elbasvir; Drug: MK-5172A

Interventions

Grazoprevir 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.

Also known as: MK-5172

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

Elbasvir DRUG

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

Also known as: MK-8742

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

MK-5172A DRUG

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

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

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 30939489 RESULT

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

grazoprevir; elbasvir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

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

ClinicalTrialsDisclosure@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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2014
• First Posted: April 16, 2014
• Study Start: May 9, 2014
• Primary Completion: March 5, 2015
• Study Completion: June 16, 2015
• Last Updated: June 26, 2019
• Results First Posted: March 17, 2016

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share