HepatitisPhase 2NCT02613403
Efficacy and Safety of Grazoprevir (+) Uprifosbuvir (+) Ruzasvir (MK-3682B) (MK-5172 + MK-3682 + MK-8408) Fixed Dose Combination in Chronic HCV Participants Failing Prior Antiviral Treatment (MK-3682-021)
A Phase 2 study testing MK-3682B and Ribavirin in people with Hepatitis and Hepatitis C, run by Merck Sharp & Dohme LLC.
Trial summary
This is a randomized, multicenter, 2-part, open-label trial of the combination regimen of grazoprevir (GZR [MK-5172]; 100mg), uprifosbuvir (UPR [MK-3682]; 450 mg) and ruzasvir (RZR [MK-8408]; 60 mg) with and without Ribavirin (RBV) in cirrhotic (C) or non-cirrhotic (NC) participants infected with hepatitis C virus… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis, Hepatitis C, Digestive System Diseases
- What is being tested?
- MK-3682B and Ribavirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- No sites listed yet
- Study dates
- 10 Dec 2015to 27 Mar 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
- Part A
- Has documented chronic HCV GT1 or HCV GT3 infection with no evidence of non-typeable or mixed genotype.
- Has documented relapse, defined as having HCV RNA target not detected at end-of-treatment, but HCV RNA quantifiable during follow-up, after treatment with one of the following DAA regimens either by approved dosage and duration or by completion of a clinical trial: GT1: SOF/LDV ± RBV; GT1: GZR/EBR ± RBV; GT3: SOF + RBV; GT3: SOF + PR; GT3: SOF + DCV ± RBV; GT3: SOF/LDV ± RBV.
- Is otherwise healthy.
- If male, be not of reproductive potential or agree to avoid impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug, through 6 months after taking the last dose of study drug (or longer if dictated by local regulations), by complying with one of the following: (1) practice abstinence from heterosexual activity or (2) use (or have their partner use) two forms of acceptable contraception during heterosexual activity which may include oral contraceptives.
- Part B
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- Has documented chronic HCV GT1, GT2, GT3, GT4, GT5, GT6 infection with no evidence of non-typeable or mixed genotype.
- Has documented virologic failure, defined as having quantifiable HCV RNA at any time after completion of HCV therapy with a DAA regimen either by approved dosage and duration or by completion of a clinical trial that was not attributed to re-infection: GT1, GT2, GT4, GT5, or GT6: any prior all-oral DAA regimens; GT3: any prior all-oral DAA regimen or SOF/PR. Participants [Parts A and B] who previously failed PR treatment, with or without simepravir (SIM), boceprevir (BOC), or telaprevir (TPV), prior to receiving DAA therapy, may also be enrolled.
- Parts A and B
- Has HCV RNA ≥ 10,000 IU/mL in peripheral blood at enrollment.
- Has either absence of cirrhosis or presence of compensated cirrhosis.
- If female, be not of reproductive potential or agree to avoid becoming pregnant beginning at least 2 weeks prior to administration of the initial dose of study drug, through either 6 months [Part A] or 14 days [Part B] after taking the last dose of study drug (or longer if dictated by local regulations), by complying with one of the following: (1) practice abstinence from heterosexual activity or (2) use (or have their partner use) two forms of acceptable contraception during heterosexual activity which may include oral contraceptives.
- For HIV co-infected participants: 1) have documented HIV-1 infection [Part A] or HIV infection [Part B]; 2) either not be currently on antiretroviral therapy (ART) with no plans to initiate ART while participating in this study or have well controlled HIV on ART; and 3) have at least one viable antiretroviral regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of anti-retroviral drug resistance [Part A].
Who cannot join
- Part A
- Has previously received a DAA containing regimen other than the permitted regimens listed above.
- Did not complete their prior DAA therapy due to intolerance to the DAA regimen or who failed the DAA regimen for reasons other than relapse (e.g., virologic breakthrough, rebound or non-response, non-compliance, lost to follow-up, withdrew consent).
- Is a male whose female partner(s) is/are pregnant or is a male who is expecting to donate sperm or planning to impregnate female partner(s) from at least two weeks prior to Day 1 through at least 6 months after last dose of study drug, or longer if dictated by local regulations.
- Has personal or family history of Torsade de pointes.
- Has chronic pulmonary disease.
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- Has an hemoglobinopathy.
- Has central nervous system (CNS) trauma requiring intubation, intracranial pressure monitoring, brain meningeal or skull surgery, or resulting in seizure, coma, permanent neurologic deficits, abnormal brain imaging, or cerebral spinal fluid (CSF) leak; prior brain hemorrhage and/or intracranial aneurysms (whether adequately repaired or not).
- Has current or history of seizure disorder unless seizure was >10 years ago, a single isolated event, no history of or current use of anti-seizure medications, and a documented normal neurological examination at Day 1.
- Has history of stroke or transient ischemic attack.
- Part B
- Did not complete their prior DAA therapy due to intolerance to the DAA regimen or who failed the DAA regimen for reasons other than virologic failure.
- Has any major medical condition, clinically-significant illness (other than HCV), pretrial laboratory or ECG abnormality, or history of any illness that might interfere with treatment, assessment, compliance or pose additional risk in administering study drug to the participant.
- Parts A and B
- Is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, 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.
- Has cirrhosis classified as Child-Pugh Class B or C or has a Pugh-Turcotte score >6
- Is co-infected with hepatitis B virus (HBV)
- For participants with HIV, has a history of opportunistic infection in the 6 months prior to screening.
- Has a history of malignancy ≤5 years prior to enrollment 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.
- Has cirrhosis and liver imaging within 6 months of Day 1 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 (trial treatment period). Participants participating in MK-5172-017 (NCT01667081) may be enrolled in this study, MK- 3682-021.
- Has clinically-relevant drug or alcohol abuse within 12 months of screening
- Is a female and is pregnant or breastfeeding or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 through at least 6 months [Part A] or 14 days [Part B] after last dose of study drug, or longer if dictated by local regulations.
- Has organ transplants (including hematopoietic stem cell transplants) other than cornea and hair.
- Has history of gastric surgery or history of malabsorption disorders.
- Has current or history of any clinically significant cardiac abnormalities/dysfunction.
- Has medical/surgical conditions that may result in a need for hospitalization during the period of the study.
- Has a medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the study
- Has evidence of history of chronic hepatitis not caused by HCV. Participants with history of acute non-HCV-related hepatitis, that resolved >6 months before study entry, may be enrolled.
About this study
Official title: A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-3682B (MK-5172 + MK-3682 + MK-8408 Fixed Dose Combination (FDC)) in Subjects With Chronic HCV GT1 or GT3 Infection Who Have Failed a Direct Acting Antiviral Regimen
This is a randomized, multicenter, 2-part, open-label trial of the combination regimen of grazoprevir (GZR [MK-5172]; 100mg), uprifosbuvir (UPR [MK-3682]; 450 mg) and ruzasvir (RZR [MK-8408]; 60 mg) with and without Ribavirin (RBV) in cirrhotic (C) or non-cirrhotic (NC) participants infected with hepatitis C virus (HCV) previously failing a direct-acting antiviral regimen (DAA). The combination regimen, referred to as MK-3682B, will be administered as two fixed-dose combination (FDC) tablets, given once-daily. The study will evaluate the efficacy of MK-3682B with or without RBV as assessed by the proportion of participants achieving Sustained Virologic Response 12 weeks (SVR12) after the end of all study therapy.
Read the detailed description
This trial was divided into Part A and Part B. In Part A, comprised of 4 treatment arms, C or NC participants with HCV genotype (GT) 1 infection previously failing a DAA regimen of either sofosbuvir (SOF)/ledipasvir (LDV) [Arms 1 and 2] or elbasvir (EBR)/GZR [Arms 3 and 4] were randomized to receive either one of the following: 1) MK-3682B + RBV for 16 weeks [Arms 1 and 3]; or 2) MK-3682B for 24 weeks [Arms 2 and 4]. Study Part A was completed as planned per study protocol. In Part B, C or NC participants with GT1 through GT6 infection previously failing any all-oral DAA regimen (GT1-6) or SOF/pegylated interferon and ribavirin (PR) regimen (GT 3 only) were to receive MK-3682B for 16 weeks. However, the trial was terminated prior to participant enrollment for study Part B.
Participants in MK-5172-017 (NCT01667081) were eligible for enrollment in the study.
- Conditions
- Hepatitis, Hepatitis C, Digestive System Diseases, Flaviviridae Infections, Hepatitis, Viral, Human, Liver Diseases
- Being tested
- MK-3682B, Ribavirin
- Medical subject headings
- Hepatitis, Hepatitis C, Digestive System Diseases, Flaviviridae Infections, Hepatitis, Viral, Human, Liver Diseases, RNA Virus Infections, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-3682BDrug
Two MK- 3682B 1,136 mg FDC tablets each containing 50 mg MK-5172 (GZR), 225 mg MK-3682 (UPR, formerly IDX21437), and 30 mg MK-8408 (RZR) taken once daily by mouth.
RibavirinDrug
Ribavirin 200 mg capsules, taken twice daily by mouth as part of a weight-based dosing regimen. Depending on participant body weight, total daily dose of Ribavirin may be 800, 1000, 1200 or 1400 mg per day.
| Study group | Role | What they receive |
|---|---|---|
| [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV | Experimental | C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. Receives: Drug: MK-3682B; Drug: Ribavirin |
| [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B | Experimental | C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks. Receives: Drug: MK-3682B |
| [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV | Experimental | C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. Receives: Drug: MK-3682B; Drug: Ribavirin |
| [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B | Experimental | C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks. Receives: Drug: MK-3682B |
| [Part B] Prior DAA (GT1-6) or SOF/PR (GT3) Failure: MK-3682B | Experimental | C or NC HCV participants previously failing any all-oral DAA regimen (GT1-6) or SOF/PR regimen (GT 3 only) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 16 weeks. Receives: Drug: MK-3682B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After The End of Study Therapy (SVR12)
The percentage of participants achieving SVR12 was determined, defined as having a plasma HCV ribonucleic acid (RNA) level below the lower limit of quantification (LLOQ) 12 weeks after the end of study therapy. Plasma HCV RNA level was measured using the Roche COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay with a LLOQ of 15 IU/mL.
Measured: 12 weeks following final dose of study treatment ([MK-3682B + RBV Groups]: Study Week 28; [MK-3682B Groups]: Study Week 36)
Number of Participants Who Experienced an Adverse Event
The number of participants experiencing an adverse event (AE) was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.
Measured: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
The number of participants discontinuing study drug due to an AE was assessed.
Measured: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced a Serious Adverse Event
The number of participants experiencing a serious adverse event (SAE) was assessed. An SAE is an adverse event that: results in death; is life threatening; results in persistent or significant disability or incapacity; results in or prolongs a hospitalization; is a congenital anomaly or birth defect; is a cancer; or may jeopardize the participant, potentially require medical or surgical intervention.
Measured: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced a Drug-Related Adverse Event
The number of participants experiencing a drug-related AE was assessed. A drug-related AE was an AE thought to be possibly, probably, or definitely related to the study drug as determined by the investigator.
Measured: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced a Serious and Drug-Related Adverse Event
The number of participants experiencing a serious and drug-related AE was assessed.
Measured: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced an Accidental or Intentional Overdose Without Adverse Effect
The number of participants experiencing an accidental or intentional overdose without adverse effect was determined. Per study protocol, any occurrence of a participant receiving either MK-3682B or RBV at any dose higher than prescribed was considered an overdose. If this definition of overdose was met without any associated clinical symptoms or abnormal laboratory results, this occurrence of overdose was reported as an accidental or intentional overdose without adverse effect.
Measured: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced a Non-Overdose Event of Clinical Interest
The number of participants experiencing a non-overdose event of clinical interest (ECI) was determined. Non-overdose ECIs, assessed from initiation of study therapy through 14 days following study treatment cessation, included the following: 1) aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >500 IU/L; or 2) AST or ALT >3x nadir value and >3X upper limit normal (ULN).
Measured: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced AST/ALT >5x Upper Limit Normal (ULN)
The number of participants experiencing AST / ALT >5 times ULN from study week 4 until 2 weeks following completion of study therapy was determined.
Measured: From Study Week 4 up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2015 (estimated)
- Study start10 Dec 2015
- Primary completion9 Jan 2017
- Study completion27 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HepatitisStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02613403
- Sponsor's protocol ID
- 3682-021
- Other IDs
- MK-3682-021, 2015-001483-19, 2015
- Status last verified
- May 2024
- First submitted
- 20 Nov 2015
- Last updated
- 22 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Wyles D, Wedemeyer H, Ben-Ari Z, Gane EJ, Hansen JB, Jacobson IM, Laursen AL, Luetkemeyer A, Nahass R, Pianko S, Zeuzem S, Jumes P, Huang HC, Butterton J, Robertson M, Wahl J, Barr E, Joeng HK, Martin E, Serfaty L; C-CREST Part C and C-SURGE Investigators. Grazoprevir, ruzasvir, and uprifosbuvir for hepatitis C virus after NS5A treatment failure. Hepatology. 2017 Dec;66(6):1794-1804. doi: 10.1002/hep.29358. Epub 2017 Oct 30.
PubMed 28688129
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-3682B (MK-5172 + MK-3682 + MK-8408 Fixed Dose Combination (FDC)) in Subjects With Chronic HCV GT1 or GT3 Infection Who Have Failed a Direct Acting Antiviral Regimen
- ClinicalTrials.gov ID
- NCT02613403
- Acronym / sponsor ID
- 3682-021
- Conditions
- Hepatitis, Hepatitis C, Digestive System Diseases, Flaviviridae Infections, Hepatitis, Viral, Human, Liver Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 10 Dec 2015 (actual)
- Primary completion
- 9 Jan 2017 (actual)
- Study completion
- 27 Mar 2017 (actual)
- First posted
- 24 Nov 2015 (estimated)
- Results
- Posted 20 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, multicenter, 2-part, open-label trial of the combination regimen of grazoprevir (GZR [MK-5172]; 100mg), uprifosbuvir (UPR [MK-3682]; 450 mg) and ruzasvir (RZR [MK-8408]; 60 mg) with and without Ribavirin (RBV) in cirrhotic (C) or non-cirrhotic (NC) participants infected with hepatitis C virus (HCV) previously failing a direct-acting antiviral regimen (DAA). The combination regimen, referred to as MK-3682B, will be administered as two fixed-dose combination (FDC) tablets, given once-daily. The study will evaluate the efficacy of MK-3682B with or without RBV as assessed by the proportion of participants achieving Sustained Virologic Response 12 weeks (SVR12) after the end of all study therapy.
Detailed description
This trial was divided into Part A and Part B. In Part A, comprised of 4 treatment arms, C or NC participants with HCV genotype (GT) 1 infection previously failing a DAA regimen of either sofosbuvir (SOF)/ledipasvir (LDV) [Arms 1 and 2] or elbasvir (EBR)/GZR [Arms 3 and 4] were randomized to receive either one of the following: 1) MK-3682B + RBV for 16 weeks [Arms 1 and 3]; or 2) MK-3682B for 24 weeks [Arms 2 and 4]. Study Part A was completed as planned per study protocol. In Part B, C or NC participants with GT1 through GT6 infection previously failing any all-oral DAA regimen (GT1-6) or SOF/pegylated interferon and ribavirin (PR) regimen (GT 3 only) were to receive MK-3682B for 16 weeks. However, the trial was terminated prior to participant enrollment for study Part B.
Participants in MK-5172-017 (NCT01667081) were eligible for enrollment in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV | Experimental | Drug: MK-3682B, Drug: RibavirinC or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. |
| [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B | Experimental | Drug: MK-3682BC or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks. |
| [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV | Experimental | Drug: MK-3682B, Drug: RibavirinC or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. |
| [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B | Experimental | Drug: MK-3682BC or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks. |
| [Part B] Prior DAA (GT1-6) or SOF/PR (GT3) Failure: MK-3682B | Experimental | Drug: MK-3682BC or NC HCV participants previously failing any all-oral DAA regimen (GT1-6) or SOF/PR regimen (GT 3 only) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 16 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Part A
- Has documented chronic HCV GT1 or HCV GT3 infection with no evidence of non-typeable or mixed genotype.
- Has documented relapse, defined as having HCV RNA target not detected at end-of-treatment, but HCV RNA quantifiable during follow-up, after treatment with one of the following DAA regimens either by approved dosage and duration or by completion of a clinical trial: GT1: SOF/LDV ± RBV; GT1: GZR/EBR ± RBV; GT3: SOF + RBV; GT3: SOF + PR; GT3: SOF + DCV ± RBV; GT3: SOF/LDV ± RBV.
- Is otherwise healthy.
- If male, be not of reproductive potential or agree to avoid impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug, through 6 months after taking the last dose of study drug (or longer if dictated by local regulations), by complying with one of the following: (1) practice abstinence from heterosexual activity or (2) use (or have their partner use) two forms of acceptable contraception during heterosexual activity which may include oral contraceptives.
Key exclusion criteria (30 listed)
- Part A
- Has previously received a DAA containing regimen other than the permitted regimens listed above.
- Did not complete their prior DAA therapy due to intolerance to the DAA regimen or who failed the DAA regimen for reasons other than relapse (e.g., virologic breakthrough, rebound or non-response, non-compliance, lost to follow-up, withdrew consent).
- Is a male whose female partner(s) is/are pregnant or is a male who is expecting to donate sperm or planning to impregnate female partner(s) from at least two weeks prior to Day 1 through at least 6 months after last dose of study drug, or longer if dictated by local regulations.
- Has personal or family history of Torsade de pointes.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-3682BTwo MK- 3682B 1,136 mg FDC tablets each containing 50 mg MK-5172 (GZR), 225 mg MK-3682 (UPR, formerly IDX21437), and 30 mg MK-8408 (RZR) taken once daily by mouth. | Drug | [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV, [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B, [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV, [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B, [Part B] Prior DAA (GT1-6) or SOF/PR (GT3) Failure: MK-3682B |
| RibavirinRibavirin 200 mg capsules, taken twice daily by mouth as part of a weight-based dosing regimen. Depending on participant body weight, total daily dose of Ribavirin may be 800, 1000, 1200 or 1400 mg per day. | Drug | [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV, [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV |
Primary outcome
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After The End of Study Therapy (SVR12)
Time frame: 12 weeks following final dose of study treatment ([MK-3682B + RBV Groups]: Study Week 28; [MK-3682B Groups]: Study Week 36)
The percentage of participants achieving SVR12 was determined, defined as having a plasma HCV ribonucleic acid (RNA) level below the lower limit of quantification (LLOQ) 12 weeks after the end of study therapy. Plasma HCV RNA level was measured using the Roche COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay with a LLOQ of 15 IU/mL.
Number of Participants Who Experienced an Adverse Event
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
The number of participants experiencing an adverse event (AE) was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
The number of participants discontinuing study drug due to an AE was assessed.
Number of Participants Who Experienced a Serious Adverse Event
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
The number of participants experiencing a serious adverse event (SAE) was assessed. An SAE is an adverse event that: results in death; is life threatening; results in persistent or significant disability or incapacity; results in or prolongs a hospitalization; is a congenital anomaly or birth defect; is a cancer; or may jeopardize the participant, potentially require medical or surgical intervention.
Number of Participants Who Experienced a Drug-Related Adverse Event
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
The number of participants experiencing a drug-related AE was assessed. A drug-related AE was an AE thought to be possibly, probably, or definitely related to the study drug as determined by the investigator.
Number of Participants Who Experienced a Serious and Drug-Related Adverse Event
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
The number of participants experiencing a serious and drug-related AE was assessed.
Number of Participants Who Experienced an Accidental or Intentional Overdose Without Adverse Effect
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
The number of participants experiencing an accidental or intentional overdose without adverse effect was determined. Per study protocol, any occurrence of a participant receiving either MK-3682B or RBV at any dose higher than prescribed was considered an overdose. If this definition of overdose was met without any associated clinical symptoms or abnormal laboratory results, this occurrence of overdose was reported as an accidental or intentional overdose without adverse effect.
Number of Participants Who Experienced a Non-Overdose Event of Clinical Interest
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
The number of participants experiencing a non-overdose event of clinical interest (ECI) was determined. Non-overdose ECIs, assessed from initiation of study therapy through 14 days following study treatment cessation, included the following: 1) aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >500 IU/L; or 2) AST or ALT >3x nadir value and >3X upper limit normal (ULN).
Number of Participants Who Experienced AST/ALT >5x Upper Limit Normal (ULN)
Time frame: From Study Week 4 up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
The number of participants experiencing AST / ALT >5 times ULN from study week 4 until 2 weeks following completion of study therapy was determined.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28688129Wyles D, Wedemeyer H, Ben-Ari Z, Gane EJ, Hansen JB, Jacobson IM, Laursen AL, Luetkemeyer A, Nahass R, Pianko S, Zeuzem S, Jumes P, Huang HC, Butterton J, Robertson M, Wahl J, Barr E, Joeng HK, Martin E, Serfaty L; C-CREST Part C and C-SURGE Investigators. Grazoprevir, ruzasvir, and uprifosbuvir for hepatitis C virus after NS5A treatment failure. Hepatology. 2017 Dec;66(6):1794-1804. doi: 10.1002/hep.29358. Epub 2017 Oct 30.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MK-3682B and Ribavirin in people with Hepatitis and Hepatitis C, 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 13 inclusion and 30 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 22 May 2024. 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 20 Mar 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 The End of Study Therapy (SVR12) (time frame: 12 weeks following final dose of study treatment ([MK-3682B + RBV Groups]: Study Week 28; [MK-3682B Groups]: Study Week 36)). The study lists 9 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 NCT02613403, which also lists 1 linked publication.
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 22 May 2024.