A Study of Different Doses of Grazoprevir (MK-5172) Given With Pegylated Interferon Alfa-2b and Ribavirin to Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-038)

NCT01710501 | Completed Phase 2 Results

• 2 other identifiers: 5172-0382012-003333-42
• Study Type: interventional
• Target: 87
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a study designed to compare the safety and efficacy of 3 different doses of grazoprevir (MK-5172) combined with pegylated interferon alfa-2b (PEG-IFN) and ribavirin (RBV) in treatment-naïve participants with genotype 1 (GT1) chronic hepatitis C (CHC). Participants will receive 12 weeks of treatment with grazoprevir combined with Peg-IFN and RBV, and depending on response at Week 4 may go on to receive an additional 12 weeks of treatment with Peg-IFN and RBV.

Conditions

Chronic Hepatitis C (CHC)

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12)

  Hepatitis C virus ribonucleic acid (HCV RNA) was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR12 was defined as HCV RNA \<25 IU/mL (either target detected, unquantifiable or target not detected) 12 weeks after the end of all study therapy.

  12 weeks after end of treatment (up to 36 weeks total)

• Number of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days

  An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol -specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

  14 days following last dose of study drug (up to 26 weeks)

• Number of Participants Discontinued From Study Treatment Due to AEs During the Treatment Period and First 14 Follow-up Days

  An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol -specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

  Up to 24 weeks

Secondary Outcomes (5)

• Percentage of Participants Achieving Undetectable HCV RNA During Treatment by Time Point

  From Treatment Week (TW) 2 through end of treatment (up to 24 weeks)

• Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment by Time Point

  From TW 2 through end of treatment (up to 24 weeks)

• Percentage of Participants Achieving SVR4

  4 weeks after end of treatment (up to 28 weeks total)

• Percentage of Subjects Achieving SVR24

  24 weeks after end of treatment (up to 48 weeks total)

• Number of Participants Developing Post-baseline Antiviral Resistance to Grazoprevir Among Participants Not Achieving SVR24 Response

  From Day 1 up to Follow-up Week 24 (up to 48 weeks total)

Study Arms (3)

Grazoprevir 25 mg + PEG-IFN + RBV

EXPERIMENTAL

After a maximum of a 45 day screening window, randomized participants receive 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by Response Guided Therapy (RGT). Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their Hepatitis C virus ribonucleic acid (HCV RNA) level at Treatment Week (TW) 4.

Drug: Grazoprevir; Biological: pegylated interferon alfa-2b; Drug: Ribavirin; Drug: Placebo

Grazoprevir 50 mg + PEG-IFN + RBV

EXPERIMENTAL

After a maximum of a 45 day screening window, randomized participants receive 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4.

Drug: Grazoprevir; Biological: pegylated interferon alfa-2b; Drug: Ribavirin; Drug: Placebo

Grazoprevir 100 mg + PEG-IFN + RBV

EXPERIMENTAL

After a maximum of a 45 day screening window, randomized participants receive 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4.

Drug: Grazoprevir; Biological: pegylated interferon alfa-2b; Drug: Ribavirin; Drug: Placebo

Interventions

Grazoprevir DRUG

Grazoprevir tablet, orally, once per day at assigned dose

Also known as: MK-5172

Grazoprevir 100 mg + PEG-IFN + RBV; Grazoprevir 25 mg + PEG-IFN + RBV; Grazoprevir 50 mg + PEG-IFN + RBV

pegylated interferon alfa-2b BIOLOGICAL

1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection

Also known as: SCH 054031, PegIntron™, PEG-IFN

Grazoprevir 100 mg + PEG-IFN + RBV; Grazoprevir 25 mg + PEG-IFN + RBV; Grazoprevir 50 mg + PEG-IFN + RBV

Ribavirin DRUG

Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight

Also known as: Rebetol™, RBV

Grazoprevir 100 mg + PEG-IFN + RBV; Grazoprevir 25 mg + PEG-IFN + RBV; Grazoprevir 50 mg + PEG-IFN + RBV

Placebo DRUG

Placebo to match grazoprevir tablets to maintain dose blinding

Grazoprevir 100 mg + PEG-IFN + RBV; Grazoprevir 25 mg + PEG-IFN + RBV; Grazoprevir 50 mg + PEG-IFN + RBV

Eligibility Criteria

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

You may qualify if:

• Treatment naive
• Chronic, compensated HCV GT1 infection
• Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis
• No evidence of cirrhosis or hepatocellular carcinoma by biopsy or noninvasive testing (e.g. FibroScan and/or FibroTest)
• Must agree to use two acceptable methods of birth control from at least 2 weeks prior to first dose and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations

You may not qualify if:

• Non-GT1 HCV infection, including a mixed GT infection (with a non-GT1) or a non-typeable genotype.
• Documented to be Human Immunodeficiency Virus (HIV) positive or co-infected with hepatitis B virus
• Hepatocellular carcinoma (HCC) or under evaluation for HCC
• Participating in or has participated in a study with an investigational compound or device within 30 days of signing informed consent
• Diabetic and/or hypertensive with clinically significant ocular examination findings
• Current or history of central nervous system trauma, seizure disorder, stroke or transient ischemic attack
• Chronic pulmonary disease
• Current or history of any clinically significant cardiac abnormalities/dysfunction
• Active clinical gout within the last year
• History of gastric surgery or history of malabsorption disorders
• Active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin)
• Pregnant, lactating, expecting to conceive or donate eggs, or male participant planning to impregnate or provide sperm donation or with a female partner who is pregnant
• Current moderate or severe depression or history of depression associated with hospitalization, electroconvulsive therapy, or severe disruption of daily functions, or suicidal or homicidal ideation and/or attempt, or history of severe psychiatric disorders
• Evidence or history of chronic hepatitis not caused by HCV

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Lagging M, Brown A, Mantry PS, Ramji A, Weilert F, Vierling JM, Howe A, Gendrano IN 3rd, Hwang P, Zhang B, Wahl J, Robertson M, Mobashery N. Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial. J Viral Hepat. 2016 Feb;23(2):80-8. doi: 10.1111/jvh.12464. Epub 2015 Sep 10.

  PMID: 26353843 RESULT

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

grazoprevir; peginterferon alfa-2b; Ribavirin

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

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2012
• First Posted: October 19, 2012
• Study Start: December 7, 2012
• Primary Completion: November 25, 2013
• Study Completion: January 29, 2014
• Last Updated: February 4, 2021
• Results First Posted: March 4, 2016

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share