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Hepatitis C, ChronicPhase 2NCT02759315

Efficacy and Safety of Uprifosbuvir (MK-3682) With Ruzasvir (MK-8408) in Adults With Chronic Hepatitis C Genotype 1, 2, 3, 4, 5 or 6 Infection (MK-3682-035)

A Phase 2 study testing Uprifosbuvir 450 mg and Ruzasvir 60 mg in people with Hepatitis C, Chronic, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is an open-label, multi-center trial to evaluate the novel 2-drug regimen of uprifosbuvir (MK-3682) 450 mg and ruzasvir (MK-8408) 60 mg in participants with chronic hepatitis C virus (HCV) genotype (GT)1, GT2, GT3, GT4, GT5, or GT6 infection. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatitis C, Chronic
What is being tested?
Uprifosbuvir 450 mg and Ruzasvir 60 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
No sites listed yet
Study dates
3 May 2016to 16 Nov 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has hepatitis C virus (HCV) ribonucleic acid (RNA) at the time of screening
  • Has documented chronic HCV genotype (GT)1, GT2, GT3, GT4, GT5, or GT6 with no evidence of non-typeable or mixed GT infection
  • Is otherwise healthy as determined by the medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements performed at the time of screening
  • Has absence of cirrhosis or has compensated cirrhosis
  • Is HCV treatment-naïve or has experienced virologic failure after completing a prior interferon-containing regimen
  • Is of non-childbearing potential or agrees to avoid becoming pregnant or impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug and for 14 days after the last dose of study drug
  • For human immunodeficiency virus (HIV) co-infected participants: is not currently on antiretroviral therapy (ART) and has no plans to initiate ART treatment while participating in this study Or has well-controlled HIV on ART

Who cannot join

  • Is mentally or legally incapacitated, has significant emotional problems (at screening or expected during the study) or has a history of a clinically significant psychiatric disorder that would interfere with the study procedures.
  • Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease
  • Is Child-Pugh Class B or C or has a Pugh-Turcotte (CPT) score >6 if cirrhotic
  • Is co-infected with Hepatitis B Virus
  • Has a history of opportunistic infection in the preceding 6 months prior to screening if co-infected with HIV
  • Has a history of malignancy ≤5 years prior to study start (except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ) or is under evaluation for other active or suspected malignancy
Show all 17Show fewer
  • Has cirrhosis and liver imaging within 6 months prior to study start showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
  • Is taking any medications or herbal supplements restricted by the study entry criteria in the period from ≤2 weeks prior to study start through 2 weeks after the last dose of study drug
  • Has clinically-relevant drug or alcohol abuse within 12 months of study start
  • Has participated in any clinical study of an investigational product within 30 days prior to the first dose of study drug
  • Is female and is pregnant or breastfeeding, or expecting to conceive or donate eggs from at least 2 weeks prior to study start and 14 days after the last dose of study drug
  • Is male and is expecting to donate sperm from at least 2 weeks prior to Day 1 until 14 days after the last dose of study drug
  • Has or has had any of the following: organ transplants (including hematopoietic stem cell transplants) other than cornea and hair; poor venous access; history of gastric surgery; or history of malabsorption disorders
  • Has any cardiac abnormalities/dysfunction including but not limited to: unstable angina; unstable congestive heart failure; or unstable arrhythmia
  • Has a history of a medical/surgical condition that resulted in hospitalization within 3 months prior to study start, other than for minor elective procedures
  • Has any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the study
  • Has evidence of history of chronic hepatitis not caused by HCV

About this study

Official title: A Phase II, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-3682 + MK-8408 in Subjects With Chronic HCV Genotype 1, 2, 3, 4, 5 or 6 Infection

This study is an open-label, multi-center trial to evaluate the novel 2-drug regimen of uprifosbuvir (MK-3682) 450 mg and ruzasvir (MK-8408) 60 mg in participants with chronic hepatitis C virus (HCV) genotype (GT)1, GT2, GT3, GT4, GT5, or GT6 infection. The impact of the study treatment regimen on the percentage of participants with undetectable HCV ribonucleic acid [RNA] 12 weeks after completing study treatment (SVR12) will be evaluated.

Being tested
Uprifosbuvir 450 mg, Ruzasvir 60 mg
Medical subject headings
Hepatitis C, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Uprifosbuvir 450 mgDrug

    Also called MK-3682

    450 mg administered as 3 x 150 mg oral tablets

  • Ruzasvir 60 mgDrug

    Also called MK-8408

    60 mg administered as 6 x 10 mg oral capsules

Study groups in NCT02759315
Study groupRoleWhat they receive
GT1: Uprifosbuvir 450 mg + Ruzasvir 60 mgExperimentalParticipants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT1 Arm is sub-divided into GT1a and GT1b Arms. GT1a Arm will enroll approximately 35 participants including up to 10 participants who are compensated cirrhotics and GT1b Arm will enroll approximately 15 participants including up to 5 participants who are compensated cirrhotics.
Receives: Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg
GT2: Uprifosbuvir 450 mg + Ruzasvir 60 mgExperimentalParticipants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT2 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.
Receives: Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg
GT3: Uprifosbuvir 450 mg + Ruzasvir 60 mgExperimentalParticipants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT3 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.
Receives: Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg
GT4: Uprifosbuvir 450 mg + Ruzasvir 60 mgExperimentalParticipants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT4 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.
Receives: Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg
GT5: Uprifosbuvir 450 mg + Ruzasvir 60 mgExperimentalParticipants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT5 Arm of the study will enroll approximately 25 participants including both non- cirrhotics and compensated cirrhotics.
Receives: Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg
GT6: Uprifosbuvir 450 mg + Ruzasvir 60 mgExperimentalParticipants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT6 Arm of the study will enroll approximately 25 participants including both non- cirrhotics and compensated cirrhotics.
Receives: Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)

    The percentage of participants in each arm achieving SVR12 was determined. SVR12 was defined as HCV ribonucleic acid (RNA) levels in plasma < lower limit of quantification (LLOQ) 12 weeks after completing study treatment. Plasma levels of HCV RNA were measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.

    Measured: Week 24 (12 weeks after completing study therapy)

  2. Percentage of Participants With ≥1 Adverse Events (AEs)

    The percentage of participants experiencing an AE during the treatment period and first 2 weeks of follow-up was determined. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measured: Up to Week 14 (up to 2 weeks after completing study therapy)

  3. Percentage of Participants Withdrawing From Study Therapy Due to an AE

    The percentage of participants discontinuing from study therapy during the treatment period was determined. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measured: Up to Week 12

  4. Percentage of Participants With ≥1 Events of Clinical Interest (ECIs)

    The percentage of participants with ECIs was determined. ECIs were defined as the following: 1) an overdose of study drug; 2) first instance of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >500 IU/L; 3) first instance of ALT or AST >3x nadir and >3x upper limit of normal (ULN); 4) first instance of estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2; or 4) first instance of serum creatinine >1.3x ULN and elevated from baseline.

    Measured: Up to Week 14 (up to 2 weeks after completing study therapy)

Secondary outcomes (3)

  1. Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)

    The percentage of participants in each arm achieving SVR24 was determined. SVR24 was defined as HCV RNA levels in plasma < LLOQ 24 weeks after completing study treatment. Plasma levels of HCV RNA were measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL. For SVR24, participants with GT1 infection were separated into GT1a or GT1b infection.

    Measured: Week 36 (24 weeks after completing study therapy)

  2. Percentage of Participants With Virologic Failure (VF)

    The percentage of participants in each arm experiencing VF was determined. VF was defined as: 1) non-response (HCV RNA detected at end of treatment without HCV RNA < LLOQ while on treatment); 2) rebound (>1 log 10 IU/mL increase in HCV RNA from nadir while on treatment); 3) virologic breakthrough (HCV RNA ≥LLOQ after being <LLOQ on treatment); or 4) relapse (HCV RNA ≥LLOQ after end of all study therapy after being undetectable at end of treatment); virologic failure could occur either on-treatment or relapse post-treatment. For VF, participants with GT1 infection were separated into GT1a or GT1b infection

    Measured: 12 weeks after the end of all study therapy (24 weeks)

  3. Percentage of Participants With Baseline Resistance-Associated Substitutions (RAS) Achieving SVR12

    The percentage of participants in each arm with baseline RAS achieving SVR12 was determined. Analysis of RAS in NS5A or NS5B at baseline was determined. SVR12 was defined as HCV RNA levels in plasma < LLOQ 24 weeks after completing study treatment. Plasma levels of HCV RNA were measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.

    Measured: 12 weeks after the end of all study therapy (24 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2016 (estimated)
  2. Study start3 May 2016
  3. Primary completion27 Jul 2017
  4. Study completion16 Nov 2017

Why it stopped: The study was terminated based on review of Phase 2 efficacy data

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
160 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02759315
Sponsor's protocol ID
3682-035
Other IDs
MK-3682-035
Status last verified
Jun 2019
First submitted
29 Apr 2016
Last updated
26 Jun 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Lawitz E, Poordad F, Anderson LJ, Vesay M, Kelly MM, Liu H, Gao W, Fernsler D, Asante-Appiah E, Robertson MN, Hanna GJ, Barr E, Butterton J, Kowdley KV, Hassanein T, Sahota A, Gordon SC, Yeh WW. Efficacy and safety of ruzasvir 60 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis C virus genotype 1, 2, 3, 4 or 6 infection. J Viral Hepat. 2019 Jun;26(6):675-684. doi: 10.1111/jvh.13079. Epub 2019 Mar 12.

    PubMed 30739366

  • 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 two-drug direct-acting antiviral agent regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis C virus genotype 1, 2, 3, 4, 5 or 6. J Viral Hepat. 2019 Sep;26(9):1127-1138. doi: 10.1111/jvh.13132. Epub 2019 Jul 11.

    PubMed 31108015

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Uprifosbuvir 450 mg and Ruzasvir 60 mg in people with Hepatitis C, Chronic, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12) (time frame: Week 24 (12 weeks after completing study therapy)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02759315, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2019.

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