Clinical Trials List
Protocol NumberMK5172-060
NCT Number(ClinicalTrials.gov Identfier)NCT02105467
2014-06-01 - 2016-04-30
Phase III
Terminated3
ICD-10B17.10
Acute hepatitis C without hepatic coma
ICD-10B19.20
Unspecified viral hepatitis C without hepatic coma
ICD-9070.51
Hepatitis C without mention of hepatic coma, acute or unspecified
A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naïve Subjects with Chronic HCV GT1, GT4, and GT6 Infection.
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Jee-Fu Huang Digestive System Department
- Ming-Lun Yeh Digestive System Department
- Ming-Lung Yu Digestive System Department
- Chia-Yen Dai Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 陳昇弘 Digestive System Department
- 蘇文邦 Digestive System Department
- Hung-Yao Chen Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chen-Hua Liu Division of General Internal Medicine
- PEI-JER CHEN Division of General Internal Medicine
- 蘇東弘 Division of General Internal Medicine
- Chun-Jen Liu Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Hepatitis C Virus
Objectives
Primary Objective(s) & Hypothesis(es)
(1) Objective: To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by the proportion of subjects in the immediate treatment arm achieving SVR12 (Sustained Virologic Response 12 weeks after the end of all study therapy), defined as HCV RNA < LLOQ (either TD[u] or TND) 12 weeks after the end of all study therapy.
Hypothesis: The proportion of subjects receiving MK-5172 in combination with MK8742 in the immediate treatment arm achieving SVR12 will be superior to 73%.
(2) Objective: To evaluate the safety and tolerability of MK-5172 in combination with MK8742.
3.2 Secondary Objective(s) & Hypothesis(es)
(1) Objective: To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by the proportion of subjects in the immediate treatment arm achieving SVR24 (Sustained Virologic Response 24 weeks after the end of all study therapy), defined as HCV RNA < LLOQ (either TD(u) or TND) 24 weeks after the end of all study therapy.
Other Objectives (e.g., Tertiary, Exploratory, etc.)
(1) Objective: To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by the proportion of subjects in the immediate treatment arm achieving undetectable (TND) HCV RNA and HCV RNA < LLOQ at Week 2, 4, 12 and FollowUp Week 4 (SVR 4).
(2) Objective: To describe and compare patient-reported outcomes related to health-related quality of life, fatigue, and work productivity/activity impairment before, during, and after treatment with MK-5172 and MK-8742 versus placebo.
(3) Objective: To evaluate the emergence of viral resistance-associated variants (RAVs) to MK-5172 or MK-8742 when administered as part of a combination regimen.
(4) Objective: To evaluate the pharmacokinetics (PK) of MK-5172 and MK-8742.
(5) Objective: To explore the relationship between genetic variation and subject response to the treatment(s) administered.
Test Drug
MK-5172A
Active Ingredient
MK-5172
MK-8742
MK-8742
Dosage Form
Tablet
Dosage
100
50
50
Endpoints
Hypothesis: The proportion of subjects receiving MK-5172 in combination with MK8742 in the immediate treatment arm achieving SVR12 will be superior to 73%.
Inclution Criteria
Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. be ≥18 years of age on day of signing informed consent
2. HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time of screening
3. have documented chronic HCV GT1, GT4, GT5 or GT6 (with no evidence of nontypeable or mixed genotype) infection:
Positive for anti-HCV antibody, HCV RNA, or any of the above HCV genotypes at least 6 months before screening, or Positive for anti-HCV antibody or HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of CHC disease, such as the presence of fibrosis)
4. have liver disease staging assessment as follows:
Cirrhosis is defined as any one of the following [28, 29]:
A liver biopsy performed prior to Day 1 of this study showing cirrhosis (F4) Fibroscan performed within 12 calendar months of Day 1 of this study showing cirrhosis with result >12.5 kPa [29]* A FibroSure® (Fibrotest® ) performed during Screening with a score of >0.75 and an aspartate aminotransferase (AST): platelet ratio index (APRI) of >2. APRI formula:
AST÷lab upper limit of normal (ULN) for AST x 100÷ {platelet count÷100} (APRI
calculation to be provided by the central laboratory.)
Absence of cirrhosis is defined as any one of the following:
Liver biopsy performed within 24 months of Day 1 of this study showing absence of
cirrhosis
Fibroscan performed within 12 months of Day 1 of this study with a result of ≤12.5
kPa [29]*
A Fibrosure®
(Fibrotest®
) score of ≤0.48 and Aspartate Aminotransferase to Platelet
Ratio Index (APRI) of ≤1 during Screening
* Fibroscan cut-off of 12.5 kPa has a positive predictive value of 90% and a sensitivity of 95% for
≥F3. Based on box and whisker plot of interquartile distribution >12.5 kPa will exclude the majority
of subjects with metavir F3 fibrosis.
In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy is required. Liver biopsy results supersede the results obtained by Fibroscan® or Fibrosure®.
In order to be eligible for participation in this trial, the subject must:
1. be ≥18 years of age on day of signing informed consent
2. HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time of screening
3. have documented chronic HCV GT1, GT4, GT5 or GT6 (with no evidence of nontypeable or mixed genotype) infection:
Positive for anti-HCV antibody, HCV RNA, or any of the above HCV genotypes at least 6 months before screening, or Positive for anti-HCV antibody or HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of CHC disease, such as the presence of fibrosis)
4. have liver disease staging assessment as follows:
Cirrhosis is defined as any one of the following [28, 29]:
A liver biopsy performed prior to Day 1 of this study showing cirrhosis (F4) Fibroscan performed within 12 calendar months of Day 1 of this study showing cirrhosis with result >12.5 kPa [29]* A FibroSure® (Fibrotest® ) performed during Screening with a score of >0.75 and an aspartate aminotransferase (AST): platelet ratio index (APRI) of >2. APRI formula:
AST÷lab upper limit of normal (ULN) for AST x 100÷ {platelet count÷100} (APRI
calculation to be provided by the central laboratory.)
Absence of cirrhosis is defined as any one of the following:
Liver biopsy performed within 24 months of Day 1 of this study showing absence of
cirrhosis
Fibroscan performed within 12 months of Day 1 of this study with a result of ≤12.5
kPa [29]*
A Fibrosure®
(Fibrotest®
) score of ≤0.48 and Aspartate Aminotransferase to Platelet
Ratio Index (APRI) of ≤1 during Screening
* Fibroscan cut-off of 12.5 kPa has a positive predictive value of 90% and a sensitivity of 95% for
≥F3. Based on box and whisker plot of interquartile distribution >12.5 kPa will exclude the majority
of subjects with metavir F3 fibrosis.
In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy is required. Liver biopsy results supersede the results obtained by Fibroscan® or Fibrosure®.
Exclusion Criteria
Subject Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. is under the age of legal consent, is mentally or legally ncapacitated, 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
2. 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. For cirrhotics, subjects that are ChildPugh Class B or C or who have a Pugh-Turcotte (CPT) score >6, must be excluded
NOTE: To calculate the Child-Pugh score, refer to the following website:
http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality.
3. is coinfected with hepatitis B virus (e.g. HBsAg positive) or HIV.
4. 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 is under evaluation for other active or suspected malignancy.
5. has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.
NOTE: If liver imaging within 6 months of Day 1 not available, imaging is required during screening
6. is taking or plans to take any of the prohibited medications listed in Section 5 of this protocol or taking herbal supplements, including but not limited to St. John’s Wort (Hypericum perforatum) within 2 weeks of Day 1. Only silymarin (Milk Thistle, Silybum marianum) is permitted during the trial.
7. 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.
8. has a clinically-relevant drug or alcohol abuse within 12 months of screening.
9. is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 and continue throughout treatment and follow up, or longer if dictated by local regulations.
10. has any of the following conditions:
Organ transplants (including hematopoietic stem cell transplants) other than
cornea and hair.
Poor venous access that precludes routine peripheral blood sampling required for
this trial.
Subject with a history of gastric surgery (e.g., stapling, bypass) or subject with a
history of malabsorption disorders (e.g., celiac sprue disease).
Any medical condition requiring, or likely to require, chronic systemic
administration of corticosteroids during the course of the trial.
11. has any condition or prestudy laboratory abnormality, or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the subject.
12. had a life-threatening SAE during the screening period.
13. has evidence of history of chronic hepatitis not caused by HCV, including but not
limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis.
NOTE: Subjects with history of acute non-HCV-related hepatitis, which resolved >6 months before study entry, can be enrolled.
14. has exclusionary laboratory values as listed below.
NOTE: If any of the laboratory exclusion criteria below in Table 3 are met, the site may have the abnormal value retested one time.
The subject must be excluded from participating in the trial if the subject:
1. is under the age of legal consent, is mentally or legally ncapacitated, 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
2. 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. For cirrhotics, subjects that are ChildPugh Class B or C or who have a Pugh-Turcotte (CPT) score >6, must be excluded
NOTE: To calculate the Child-Pugh score, refer to the following website:
http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality.
3. is coinfected with hepatitis B virus (e.g. HBsAg positive) or HIV.
4. 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 is under evaluation for other active or suspected malignancy.
5. has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.
NOTE: If liver imaging within 6 months of Day 1 not available, imaging is required during screening
6. is taking or plans to take any of the prohibited medications listed in Section 5 of this protocol or taking herbal supplements, including but not limited to St. John’s Wort (Hypericum perforatum) within 2 weeks of Day 1. Only silymarin (Milk Thistle, Silybum marianum) is permitted during the trial.
7. 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.
8. has a clinically-relevant drug or alcohol abuse within 12 months of screening.
9. is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 and continue throughout treatment and follow up, or longer if dictated by local regulations.
10. has any of the following conditions:
Organ transplants (including hematopoietic stem cell transplants) other than
cornea and hair.
Poor venous access that precludes routine peripheral blood sampling required for
this trial.
Subject with a history of gastric surgery (e.g., stapling, bypass) or subject with a
history of malabsorption disorders (e.g., celiac sprue disease).
Any medical condition requiring, or likely to require, chronic systemic
administration of corticosteroids during the course of the trial.
11. has any condition or prestudy laboratory abnormality, or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the subject.
12. had a life-threatening SAE during the screening period.
13. has evidence of history of chronic hepatitis not caused by HCV, including but not
limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis.
NOTE: Subjects with history of acute non-HCV-related hepatitis, which resolved >6 months before study entry, can be enrolled.
14. has exclusionary laboratory values as listed below.
NOTE: If any of the laboratory exclusion criteria below in Table 3 are met, the site may have the abnormal value retested one time.
The Estimated Number of Participants
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Taiwan
20 participants
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Global
400 participants
