Hepatitis CPhase 2NCT02133131
Efficacy and Safety of Grazoprevir (MK-5172), Elbasvir (MK-8742), and Sofosbuvir for Chronic Infection With Hepatitis C Virus Genotypes 1 and 3 (MK-5172-074)
A Phase 2 study testing Grazoprevir/Elbasvir FDC and Sofosbuvir in people with Hepatitis C, run by Merck Sharp & Dohme LLC.
Trial summary
This is a study of grazoprevir (MK-5172) + elbasvir (MK-8742) and sofosbuvir (SOF) in treatment-naive participants with chronic hepatitis C (HCV) genotype (GT) 1 or GT3. The objective is to determine the proportion of participants achieving sustained virologic response 12 weeks after ending study treatment (SVR12). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Grazoprevir/Elbasvir FDC and Sofosbuvir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- No sites listed yet
- Study dates
- 13 Jun 2014to 1 Feb 2016
- 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 HCV RNA ≥10,000 IU/mL in peripheral blood at the time of screening
- has documented chronic HCV GT1 or GT3 infection
- has either negative or positive history of liver cirrhosis based on liver biopsy, Fibroscan, or FibroSure ® (Fibrotest®)
- is treatment naïve to all anti-HCV treatment
Who cannot join
- has evidence of decompensated liver disease
- is coinfected with hepatitis B virus (e.g. hepatitis B surface antigen positive) or human immunodeficiency virus
- has a history of malignancy ≤5 years prior to signing informed consent, 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
- has clinically-relevant drug or alcohol abuse within 12 months of screening
- has any of the following conditions: organ transplants other than cornea and hair, poor venous access that precludes routine peripheral blood sampling, history of gastric surgery or malabsorption disorders, or any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
- has a 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-5172, MK-8742, and Sofosbuvir in Treatment-Naïve Subjects With Chronic HCV GT1 or GT3 Infection
This is a study of grazoprevir (MK-5172) + elbasvir (MK-8742) and sofosbuvir (SOF) in treatment-naive participants with chronic hepatitis C (HCV) genotype (GT) 1 or GT3. The objective is to determine the proportion of participants achieving sustained virologic response 12 weeks after ending study treatment (SVR12).
Read the detailed description
The study is an open-label, single-center, multiple-arm investigation of a fixed-dose combination [FDC] of grazoprevir 100mg + elbasvir 50mg, and SOF 400mg, in treatment-naive participants with chronic HCV GT1 or GT3. The impact of study treatment regimens of varying duration on SVR12 (undetectable HCV ribonucleic acid [RNA] 12 weeks after ending study treatment) in cirrhotic (C) participants and non-cirrhotic (NC) participants will be determined (Part A). Any HCV GT1 participant from study Arms 1-4 in Part A who experienced virologic relapse will be offered retreatment consisting of 12 additional weeks of treatment with MK-5172/MK-8742 + SOF + ribavirin and 24 weeks of follow-up in Part B.
- Conditions
- Hepatitis C
- Being tested
- Grazoprevir/Elbasvir FDC, Sofosbuvir
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Grazoprevir/Elbasvir FDCDrug
Also called MK-5172A, Zepatier
FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth.
SofosbuvirDrug
Sofosbuvir 400mg tablet taken q.d. by mouth.
| Study group | Role | What they receive |
|---|---|---|
| GT1:NC Grazoprevir/Elbasvir+SOF 4wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned). Receives: Drug: Grazoprevir/Elbasvir FDC; Drug: Sofosbuvir |
| GT1:NC Grazoprevir/Elbasvir+SOF 6wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned). Receives: Drug: Grazoprevir/Elbasvir FDC; Drug: Sofosbuvir |
| GT1:C Grazoprevir/Elbasvir+SOF 6wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned). Receives: Drug: Grazoprevir/Elbasvir FDC; Drug: Sofosbuvir |
| GT1:C Grazoprevir/Elbasvir+SOF 8wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned). Receives: Drug: Grazoprevir/Elbasvir FDC; Drug: Sofosbuvir |
| GT3:NC Grazoprevir/Elbasvir+SOF 8wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned). Receives: Drug: Grazoprevir/Elbasvir FDC; Drug: Sofosbuvir |
| GT3:NC Grazoprevir/Elbasvir+SOF 12wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned). Receives: Drug: Grazoprevir/Elbasvir FDC; Drug: Sofosbuvir |
| GT3:C Grazoprevir/Elbasvir+SOF 12wk | Experimental | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned). Receives: Drug: Grazoprevir/Elbasvir FDC; Drug: Sofosbuvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12)
The percentage of participants achieving SVR12, defined as HCV ribonucleic acid (RNA) <15 IU/mL 12 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0.
Measured: Up to 24 weeks
Number of Participants Experiencing at Least 1 Adverse Event (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.
Measured: Up to Week 14
Number 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.
Measured: Up to Week 12
Secondary outcomes (1)
Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4)
The percentage of participants achieving SVR4, defined as HCV ribonucleic acid (RNA) <15 IU/mL 4 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0.
Measured: Up to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2014 (estimated)
- Study start13 Jun 2014
- Primary completion2 Nov 2015
- Study completion1 Feb 2016
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 Hepatitis CStudies 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
- 143 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
- NCT02133131
- Sponsor's protocol ID
- 5172-074
- Status last verified
- Jan 2021
- First submitted
- 5 May 2014
- Last updated
- 5 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Lawitz E, Poordad F, Gutierrez JA, Wells JT, Landaverde CE, Evans B, Howe A, Huang HC, Li JJ, Hwang P, Dutko FJ, Robertson M, Wahl J, Barr E, Haber B. Short-duration treatment with elbasvir/grazoprevir and sofosbuvir for hepatitis C: A randomized trial. Hepatology. 2017 Feb;65(2):439-450. doi: 10.1002/hep.28877. Epub 2016 Dec 19.
PubMed 27770561
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172, MK-8742, and Sofosbuvir in Treatment-Naïve Subjects With Chronic HCV GT1 or GT3 Infection
- ClinicalTrials.gov ID
- NCT02133131
- Acronym / sponsor ID
- 5172-074
- Conditions
- Hepatitis C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2014 (actual)
- Primary completion
- 2 Nov 2015 (actual)
- Study completion
- 1 Feb 2016 (actual)
- First posted
- 7 May 2014 (estimated)
- Results
- Posted 17 Nov 2016
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 study of grazoprevir (MK-5172) + elbasvir (MK-8742) and sofosbuvir (SOF) in treatment-naive participants with chronic hepatitis C (HCV) genotype (GT) 1 or GT3. The objective is to determine the proportion of participants achieving sustained virologic response 12 weeks after ending study treatment (SVR12).
Detailed description
The study is an open-label, single-center, multiple-arm investigation of a fixed-dose combination [FDC] of grazoprevir 100mg + elbasvir 50mg, and SOF 400mg, in treatment-naive participants with chronic HCV GT1 or GT3. The impact of study treatment regimens of varying duration on SVR12 (undetectable HCV ribonucleic acid [RNA] 12 weeks after ending study treatment) in cirrhotic (C) participants and non-cirrhotic (NC) participants will be determined (Part A). Any HCV GT1 participant from study Arms 1-4 in Part A who experienced virologic relapse will be offered retreatment consisting of 12 additional weeks of treatment with MK-5172/MK-8742 + SOF + ribavirin and 24 weeks of follow-up in Part B.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| GT1:NC Grazoprevir/Elbasvir+SOF 4wk | Experimental | Drug: Grazoprevir/Elbasvir FDC, Drug: SofosbuvirParticipants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned). |
| GT1:NC Grazoprevir/Elbasvir+SOF 6wk | Experimental | Drug: Grazoprevir/Elbasvir FDC, Drug: SofosbuvirParticipants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned). |
| GT1:C Grazoprevir/Elbasvir+SOF 6wk | Experimental | Drug: Grazoprevir/Elbasvir FDC, Drug: SofosbuvirParticipants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned). |
| GT1:C Grazoprevir/Elbasvir+SOF 8wk | Experimental | Drug: Grazoprevir/Elbasvir FDC, Drug: SofosbuvirParticipants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned). |
| GT3:NC Grazoprevir/Elbasvir+SOF 8wk | Experimental | Drug: Grazoprevir/Elbasvir FDC, Drug: SofosbuvirParticipants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned). |
| GT3:NC Grazoprevir/Elbasvir+SOF 12wk | Experimental | Drug: Grazoprevir/Elbasvir FDC, Drug: SofosbuvirParticipants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned). |
| GT3:C Grazoprevir/Elbasvir+SOF 12wk | Experimental | Drug: Grazoprevir/Elbasvir FDC, Drug: SofosbuvirParticipants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- has HCV RNA ≥10,000 IU/mL in peripheral blood at the time of screening
- has documented chronic HCV GT1 or GT3 infection
- has either negative or positive history of liver cirrhosis based on liver biopsy, Fibroscan, or FibroSure ® (Fibrotest®)
- is treatment naïve to all anti-HCV treatment
Key exclusion criteria (7 listed)
- has evidence of decompensated liver disease
- is coinfected with hepatitis B virus (e.g. hepatitis B surface antigen positive) or human immunodeficiency virus
- has a history of malignancy ≤5 years prior to signing informed consent, 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
- has clinically-relevant drug or alcohol abuse within 12 months of screening
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 |
|---|---|---|
| Grazoprevir/Elbasvir FDCAlso: MK-5172A, ZepatierFDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth. | Drug | GT1:C Grazoprevir/Elbasvir+SOF 6wk, GT1:C Grazoprevir/Elbasvir+SOF 8wk, GT1:NC Grazoprevir/Elbasvir+SOF 4wk, GT1:NC Grazoprevir/Elbasvir+SOF 6wk, GT3:C Grazoprevir/Elbasvir+SOF 12wk, GT3:NC Grazoprevir/Elbasvir+SOF 12wk, GT3:NC Grazoprevir/Elbasvir+SOF 8wk |
| SofosbuvirSofosbuvir 400mg tablet taken q.d. by mouth. | Drug | GT1:C Grazoprevir/Elbasvir+SOF 6wk, GT1:C Grazoprevir/Elbasvir+SOF 8wk, GT1:NC Grazoprevir/Elbasvir+SOF 4wk, GT1:NC Grazoprevir/Elbasvir+SOF 6wk, GT3:C Grazoprevir/Elbasvir+SOF 12wk, GT3:NC Grazoprevir/Elbasvir+SOF 12wk, GT3:NC Grazoprevir/Elbasvir+SOF 8wk |
Primary outcome
Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12)
Time frame: Up to 24 weeks
The percentage of participants achieving SVR12, defined as HCV ribonucleic acid (RNA) <15 IU/mL 12 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0.
Number of Participants Experiencing at Least 1 Adverse Event (AE)
Time frame: Up to Week 14
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.
Number of Participants Discontinuing Study Therapy Due to an AE
Time frame: Up to Week 12
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.
1 secondary outcome
Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4)
Time frame: Up to 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27770561Lawitz E, Poordad F, Gutierrez JA, Wells JT, Landaverde CE, Evans B, Howe A, Huang HC, Li JJ, Hwang P, Dutko FJ, Robertson M, Wahl J, Barr E, Haber B. Short-duration treatment with elbasvir/grazoprevir and sofosbuvir for hepatitis C: A randomized trial. Hepatology. 2017 Feb;65(2):439-450. doi: 10.1002/hep.28877. Epub 2016 Dec 19.
- 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 Grazoprevir/Elbasvir FDC and Sofosbuvir in people with 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 4 inclusion and 7 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: finished, as of the sponsor's last update on 5 Feb 2021. 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 17 Nov 2016). 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 With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) (time frame: Up to 24 weeks). The study lists 3 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 NCT02133131, 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 5 Feb 2021.