- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02115321
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)
June 11, 2019 updated by: Merck Sharp & Dohme LLC
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Phase 2
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion criteria:
- 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
Exclusion criteria:
- 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
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Part A: CP-B GZR 50 mg + EBR 50 mg
CP-B participants take GZR 50 mg + EBR 50 mg once daily (q.d.) by mouth for 12 weeks.
|
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.
Other Names:
EBR was supplied as 50 mg tablets and was taken q.d. by mouth.
Other Names:
|
EXPERIMENTAL: Part A: NC GZR 100 mg + EBR 50 mg
NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
|
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.
Other Names:
EBR was supplied as 50 mg tablets and was taken q.d. by mouth.
Other Names:
MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.
|
EXPERIMENTAL: Part B: CP-B GZR 100 mg + EBR 50 mg
CP-B participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
|
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.
Other Names:
EBR was supplied as 50 mg tablets and was taken q.d. by mouth.
Other Names:
MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.
|
EXPERIMENTAL: Part C: CP-B GZR 50 mg or 100 mg + EBR 50 mg
CP-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).
|
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.
Other Names:
EBR was supplied as 50 mg tablets and was taken q.d. by mouth.
Other Names:
MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants Achieving Sustained Viral Response 12 Weeks After Completing Study Therapy (SVR12)
Time Frame: Week 24
|
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.
|
Week 24
|
Number of Participants Experiencing an Adverse Event (AE) During Treatment and First 14 Follow-up Days
Time Frame: Up to 14 weeks
|
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.
|
Up to 14 weeks
|
Number of Participants Discontinuing Study Drug Due to an AE
Time Frame: Up to 12 weeks
|
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.
|
Up to 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants
Time Frame: Baseline and Weeks 12, 24, and 36
|
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.
|
Baseline and Weeks 12, 24, and 36
|
Percentage of Participants With HCV RNA Undetectable at Weeks 2, 4, and 12
Time Frame: Week 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.
|
Week 2, 4, and 12
|
Percentage of Participants With HCV RNA <LLoQ at Weeks 2, 4, and 12
Time Frame: 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.
|
Weeks 2, 4, and 12
|
Percentage of Participants Achieving Sustained Viral Response 4 Weeks After Completing Study Therapy (SVR4)
Time Frame: Week 16
|
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.
|
Week 16
|
Percentage of Participants Achieving Sustained Viral Response 24 Weeks After Completing Study Therapy (SVR24)
Time Frame: Week 36
|
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.
|
Week 36
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
May 9, 2014
Primary Completion (ACTUAL)
March 5, 2015
Study Completion (ACTUAL)
June 16, 2015
Study Registration Dates
First Submitted
April 14, 2014
First Submitted That Met QC Criteria
April 14, 2014
First Posted (ESTIMATE)
April 16, 2014
Study Record Updates
Last Update Posted (ACTUAL)
June 26, 2019
Last Update Submitted That Met QC Criteria
June 11, 2019
Last Verified
June 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Enterovirus Infections
- Picornaviridae Infections
- Liver Failure
- Hepatic Insufficiency
- Hepatitis
- Hepatitis A
- Hepatitis C
- Hepatitis, Chronic
- Hepatitis C, Chronic
- Anti-Infective Agents
- Antiviral Agents
- Grazoprevir
Other Study ID Numbers
- 5172-059
- 2014-000672-25 (EUDRACT_NUMBER)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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