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Chronic Hepatitis CPhase 2/3NCT02115321

Study of Efficacy and Safety of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Chronic Hepatitis C Participants With Child-Pugh (CP)-B Hepatic Insufficiency (MK-5172-059)

A Phase 2/3 study testing Grazoprevir, Elbasvir and MK-5172A in people with Chronic Hepatitis C, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is being done to evaluate the efficacy and safety of the drug combination grazoprevir (GZR; MK-5172) + elbasvir (EBR; MK-8742) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infection and who have cirrhosis and Child-Pugh (CP) score 7-9 moderate hepatic insufficiency (CP-B). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Hepatitis C
What is being tested?
Grazoprevir, Elbasvir and MK-5172A
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
No sites listed yet
Study dates
9 May 2014to 16 Jun 2015
Phase
Phase 2/3
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 documented chronic HCV GT1 infection (for Arm 4 participants may have GT4 or GT6 infection) with no evidence of non-typable or mixed genotype infection
  • Has clinical evidence of hepatic cirrhosis with a score on the Child-Pugh scale from 7 to 9 and not anticipated to receive a liver transplant within the next 36 weeks (for Arm 1, Arm 3, and Arm 4)
  • Has no evidence of cirrhosis (only for Arm 2 )
  • Agrees to remain truly abstinent or use (or have their partner use) an acceptable method of birth control from at least 2 weeks prior to Day 1 and continue until at least 14 days after last dose of study drug, or longer if dictated by local regulations

Who cannot join

  • Is co-infected with hepatitis B virus or human immunodeficiency virus (HIV)
  • Has previously received direct-acting antiviral therapy for HCV
  • Has a history of malignancy <=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or under evaluation for other active or suspected malignancy
  • Has cirrhosis and liver imaging results within 4 weeks prior to screening 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
  • Has clinically-relevant drug or alcohol abuse within 12 months of screening
Show all 12Show fewer
  • Is pregnant or breast-feeding, or expecting to conceive or donate eggs or sperm from at least 2 weeks prior to Day 1 and continue throughout treatment and follow up, or longer if dictated by local regulations
  • Has received organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
  • Has poor venous access
  • Has a history of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorders (e.g., celiac sprue disease)
  • Requires, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
  • Has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis

About this study

Official title: A Phase II/III Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects With Chronic Hepatitis C Virus Infection With Advanced Cirrhosis and Child-Pugh (CP)-B Hepatic Insufficiency

This study is being done to evaluate the efficacy and safety of the drug combination grazoprevir (GZR; MK-5172) + elbasvir (EBR; MK-8742) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infection and who have cirrhosis and Child-Pugh (CP) score 7-9 moderate hepatic insufficiency (CP-B). The primary hypothesis is that the percentage of HCV-infected participants with hepatic insufficiency (the CP-B population) achieving sustained viral response (SVR) 12 weeks after the end of all treatment (SVR12) will be greater than 60%. Additionally, ten non-cirrhotic (NC) HCV-infected GT1 participants will also be given GZR + EBR at the beginning of the study; this will be done for the purpose of collecting plasma pharmacokinetic (PK) data in HCV GT1-infected participants who do not have hepatic insufficiency.

Read the detailed description

The study will be conducted sequentially in 3 Parts. Each participant will participate in only one Part.

Participants will be enrolled in either Part A, Part B, or Part C:

  • Part A: CP-B participants will receive GZR 50 mg+ EBR 50 mg; NC participants will receive GZR 100 mg/EBR 50 mg.
  • Part B: CP-B participants will receive GZR 100 mg + EBR 50 mg.
  • Part C: CP-B participants will receive either GZR 50 mg or 100 mg + EBR 50 mg. Study progression from Part A to Part B and from Part B to Part C will be based upon a review of safety and efficacy in Parts A and B, respectively. Depending upon safety and efficacy in Part A, the study may progress directly from Part A to Part C using GZR 50 mg + EBR 50 mg, without performing Part B.
Being tested
Grazoprevir, Elbasvir, MK-5172A
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.

  • GrazoprevirDrug

    Also called MK-5172

    GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.

  • ElbasvirDrug

    Also called MK-8742

    EBR was supplied as 50 mg tablets and was taken q.d. by mouth.

  • MK-5172ADrug

    MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.

Study groups in NCT02115321
Study groupRoleWhat they receive
Part A: CP-B GZR 50 mg + EBR 50 mgExperimentalCP-B participants take GZR 50 mg + EBR 50 mg once daily (q.d.) by mouth for 12 weeks.
Receives: Drug: Grazoprevir; Drug: Elbasvir
Part A: NC GZR 100 mg + EBR 50 mgExperimentalNC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Receives: Drug: Grazoprevir; Drug: Elbasvir; Drug: MK-5172A
Part B: CP-B GZR 100 mg + EBR 50 mgExperimentalCP-B participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Receives: Drug: Grazoprevir; Drug: Elbasvir; Drug: MK-5172A
Part C: CP-B GZR 50 mg or 100 mg + EBR 50 mgExperimentalCP-B participants take GZR 50 mg or GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks (GZR dose chosen based on results of Part A CP-B arm).
Receives: Drug: Grazoprevir; Drug: Elbasvir; Drug: MK-5172A

What is being measured

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

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

    SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels below the lower limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

    Measured: Week 24

  2. Number of Participants Experiencing an Adverse Event (AE) During Treatment and First 14 Follow-up Days

    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 14 weeks

  3. Number of Participants Discontinuing Study Drug 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 12 weeks

Secondary outcomes (5)

  1. Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants

    The MELD score provides an objective and granular assessment of liver improvement as a continuous variable. The calculation of MELD score is based on three biochemical variables (serum bilirubin, creatinine and international normalized ratio [INR] of prothrombin time). The MELD equation is as follows: 9.57 x ln(creatinine mg/dL) +3.78 x ln(bilirubin mg/dL) +11.2 x ln (INR) + 6.43. Scores are multiplied by 10 and rounded to the nearest whole number and range from 6 (less ill) to 40 (gravely ill). MELD scores were determined at Baseline (Day 1) and again at Week 12, Follow-up (FU) Week 12 (Week 24), and FU Week 24 (Week 36). Change from baseline in MELD score = Post-baseline MELD score - baseline MELD score.

    Measured: Baseline and Weeks 12, 24, and 36

  2. Percentage of Participants With HCV RNA Undetectable at Weeks 2, 4, and 12

    HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

    Measured: Week 2, 4, and 12

  3. Percentage of Participants With HCV RNA <LLoQ at Weeks 2, 4, and 12

    HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

    Measured: Weeks 2, 4, and 12

  4. Percentage of Participants Achieving Sustained Viral Response 4 Weeks After Completing Study Therapy (SVR4)

    SVR4 was defined as HCV RNA levels <LLoQ 4 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

    Measured: Week 16

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

    SVR24 was defined as HCV RNA levels <LLoQ 24 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

    Measured: Week 36

Timeline

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

  1. First posted16 Apr 2014 (estimated)
  2. Study start9 May 2014
  3. Primary completion5 Mar 2015
  4. Study completion16 Jun 2015

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 2/3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02115321
Sponsor's protocol ID
5172-059
Other IDs
2014-000672-25, 2014
Status last verified
Jun 2019
First submitted
14 Apr 2014
Last updated
26 Jun 2019
Data monitoring committee
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Jacobson IM, Poordad F, Firpi-Morell R, Everson GT, Verna EC, Bhanja S, Hwang P, Caro L, Robertson M, Charles ED, Platt H. Elbasvir/Grazoprevir in People With Hepatitis C Genotype 1 Infection and Child-Pugh Class B Cirrhosis: The C-SALT Study. Clin Transl Gastroenterol. 2019 Apr;10(4):e00007. doi: 10.14309/ctg.0000000000000007.

    PubMed 30939489

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Grazoprevir, Elbasvir and MK-5172A in people with Chronic 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 12 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 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 Mar 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 Achieving Sustained Viral Response 12 Weeks After Completing Study Therapy (SVR12) (time frame: Week 24). 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 NCT02115321, 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 26 Jun 2019.

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