Efficacy and Safety of Uprifosbuvir (MK-3682) + Ruzasvir (MK-8408) in Treating Hepatitis C Virus Infection Genotypes 1-6 (MK-3682-041)

Hepatitis C Clinical Trial

Official title:

A Phase 2, Open-Label Clinical Trial to Study the Efficacy and Safety of 12 Weeks of the Combination Regimen of MK-3682 + Ruzasvir in Subjects With Chronic Hepatitis C Virus (HCV) Genotype 1, 2, 3, 4, 5 or 6 Infection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02956629
• Other study ID #: 3682-041
• Secondary ID: 2016-003227-37MK
• Status: Terminated
• Phase: Phase 2
• Start date: November 16, 2016
• Est. completion date: March 5, 2018

Study information

• Verified date: January 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a nonrandomized, multi-site, open-label trial to evaluate a novel two-drug combination regimen (uprifosbuvir [MK-3682] 450 mg + ruzasvir [RZR; MK-8408] 180 mg once daily [q.d.] for 12 weeks) in male and female treatment-naïve (TN) or treatment-experienced (TE) participants with chronic hepatitis C virus (HCV) infection genotype (GT) GT1, GT2, GT3, GT4, GT5, or GT6 who have not previously received HCV direct-acting antiviral (DAA) therapy. Cirrhotic (C) and non-cirrhotic (NC) participants with and without human immunodeficiency virus (HIV) co-infection will be enrolled.

Description:

Any GT that meets virologic futility criteria will be given the option of extending treatment with uprifosbuvir + RZR to 16 weeks with ribavirin (RBV) added.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 282
• Est. completion date: March 5, 2018
• Est. primary completion date: December 22, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• has HCV ribonucleic acid (RNA) (=10,000 IU/mL in peripheral blood) at the time of screening

• has documented chronic HCV GT1, GT2, GT3, GT4, GT5, or GT6 (with no evidence of non-typeable or mixed GT)

• is a female who is not of reproductive potential, or is a female of reproductive potential who agrees to avoid becoming pregnant from two weeks prior to Day 1 through 14 days after the last dose of study drug via abstinence or use of two approved contraceptives

• is C or NC

• if coinfected with HIV, has documented HIV infection prior to Day 1, and either does not use an antiretroviral therapy (ART) or has well-controlled HIV on stable ART (at least 4 weeks prior to study entry)

Exclusion Criteria:

• has evidence of decompensated liver disease

• is C and is Child-Pugh Class B or C, or has a Child-Tucotte-Pugh score >6

• is coinfected with hepatitis B virus (hepatitis B surface antigen or hepatitis B core antibody positive)

• is coinfected with HIV and has a recent (within 6 months prior to screening) opportunistic infection

• has a history of malignancy other than adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ within 5 years of signing informed consent

• is C and has evidence (liver imaging within 6 months prior to Day 1) of hepatocellular carcinoma (HCC) or is under evaluation for HCC

• has participated in another investigational drug study within 30 days of signing informed consent

• is a female who is pregnant or breastfeeding or expecting to conceive or donate eggs from Day 1 through 6 months after the last dose of study drug or longer if dictated by local regulations, or is a male who is expecting to donate sperm from Day 1 through 14 days after the last dose of study drug or longer if dictated by local regulations, or is a male whose female partner(s) is/are pregnant or breastfeeding

• has clinically relevant alcohol or drug abuse within 12 months of screening

• has any of the following conditions: organ transplants other than cornea and hair; poor venous access; history of gastric surgery; clinically significant cardiac abnormality/dysfunction; any major medical condition which, in the opinion of the investigator, might interfere with participation; hospitalization within 3 months prior to enrollment; any condition that might require hospitalization; any condition requiring or likely to require chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or immunosuppressant drugs; a life-threatening SAE during screening; or hepatitis not caused by HCV

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• Uprifosbuvir
Participants take 3 tablets each containing 150 mg uprifosbuvir q.d. by mouth.
• Ruzasvir
Participants take 3 capsules each containing 60 mg RZR q.d. by mouth.
• Ribavirin
RBV 200 mg capsules will be taken according to package instructions for a maximum of 16 weeks for any GT that meets virologic futility rules on uprifosbuvir + RZR alone.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Lawitz E, Gane E, Feld JJ, Buti M, Foster GR, Rabinovitz M, Burnevich E, Katchman H, Tomasiewicz K, Lahser F, Jackson B, Shaughnessy M, Klopfer S, Yeh WW, Robertson MN, Hanna GJ, Barr E, Platt HL; C-BREEZE-2 Study Investigators. Efficacy and safety of a t — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Completing Study Therapy (SVR12)	Plasma levels of hepatitis C virus (HCV) ribonucleic acid (RNA) were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from participants. SVR12 is the absence of detectable RNA of the hepatitis C virus, (	12 weeks after completing study therapy (Week 24)
Primary	Percentage of Participants Experiencing an Adverse Event (AE)	An adverse event (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. An AE 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 infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.	Up to Week 14
Primary	Percentage of Participants Experiencing an AE of Clinical Importance (ECI)	Adverse events of clinical importance, excluding overdoses include, but is not limited to, significant changes in alanine aminotransferase, aspartate aminotransferase, blood creatinine, glomerular filtration rate or hepatitis B reactivation.	Up to Week 14
Primary	Percentage of Participants Experiencing a Serious Adverse Event (SAE)	A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is an other important medical event; is a cancer; is associated with an overdose.	Up to Week 14
Primary	Percentage of Participants Experiencing a Drug-related 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. An AE 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 infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. A drug-related AE is determined by the investigator to be related to the use of the drug.	Up to Week 14
Primary	Percentage of Participants Experiencing a Drug-related SAE	A SAE is any AE occurring at any dose or during any use of Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is an other important medical event; is a cancer; is associated with an overdose. A drug-related SAE is determined by the investigator to be related to the use of the drug.	Up to Week 14
Primary	Percentage of Participants Discontinuing Study Therapy 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. An AE 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 infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.	Up to Week 12
Secondary	Percentage of Participants With SVR 24 Weeks After Completing Study Therapy (SVR24)	Plasma levels of HCV RNA) were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from participants. SVR24 is the absence of detectable RNA of the hepatitis C virus (	24 weeks after completing study therapy (Week 36)
Secondary	Percentage of Participants With Virologic Failure	Virologic failure is the detection of HCV RNA among participants who do not discontinue study for non-treatment-related reasons, either due to on-treatment failure defined as either non-response where HCV RNA is detected at end of treatment without HCV RNA	Up to Week 24