Clinical Trials List
Protocol NumberMK5172-062
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 Open-Label 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, GT5, and GT6 Infection who are on Opiate Substitution Therapy
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
MERCK SHARP & DOHME (I.A.) LLC. TAIWAN BRANCH (U.S.A.).
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- TENG-YU LEE Digestive System Department
- CHUNG-HSIN CHANG Digestive System Department
- 葉宏仁 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Jee-Fu Huang Digestive System Department
- Chia-Yen Dai Digestive System Department
- Ming-Lun Yeh Digestive System Department
- Ming-Lung Yu Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 陳昇弘 Digestive System Department
- Hung-Yao Chen Digestive System Department
- 蘇文邦 Digestive System Department
- 黃介良 Division of Psychiatry
- Hsueh-Chou Lai Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Hepatitis C virus
Objectives
1) Objective: To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by the proportion of subjects 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 MK-8742 achieving SVR12 will be superior to 67%.
2) Objective: To evaluate the safety and tolerability of MK-5172 in combination with MK-8742.
Test Drug
MK-5172A
Active Ingredient
MK-5172+MK-8742
Dosage Form
Tablet
Dosage
100mg MK-5172+50mg MK-8742
Endpoints
The PK endpoints for MK-5172 and MK-8742 are C2hrand Ctrough. PK samples will be collected from all subjects on each visit as described in the Study Flow Chart (Section 6) and Table 6: Pharmacokinetic Sampling Timepoints – Population PK (All Subjects)(sparse,
population PK sampling scheme). These samples will be used to evaluate not only PK
concentrations, but also PK/PD and PK/AE relationships of MK-5172 and MK-8742, as
appropriate. The predose time points outlined were chosen in order to capture Ctrough for both compounds. The frequency of Ctrough collections will allow an assessment of both patient drug concentrations and drug compliance, should a breakthrough occur. In addition, the postdose time points, in conjunction with the other samples, may be used for PK-AE and PKefficacy modeling.
population PK sampling scheme). These samples will be used to evaluate not only PK
concentrations, but also PK/PD and PK/AE relationships of MK-5172 and MK-8742, as
appropriate. The predose time points outlined were chosen in order to capture Ctrough for both compounds. The frequency of Ctrough collections will allow an assessment of both patient drug concentrations and drug compliance, should a breakthrough occur. In addition, the postdose time points, in conjunction with the other samples, may be used for PK-AE and PKefficacy modeling.
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 GT 1, 4, 5, and 6 infection (with no evidence of GT 2 or
GT 3 or non typeable genotypes. Mixed genotypes are allowed but not if they include GT
2 or 3:
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 and 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. be on opiate substitution therapy (OST) for at least 3 months prior to screening.
Medications recognized as components of opiate substitution therapy include:
methadone, levamethadone, buprenorphine, naloxone, and naltrexone.
5. must have consistently kept at least 80% of scheduled appointments while on OST.
6. must have not missed any scheduled appointments between screening and study entry.
7. have liver disease staging assessment as follows:
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 GT 1, 4, 5, and 6 infection (with no evidence of GT 2 or
GT 3 or non typeable genotypes. Mixed genotypes are allowed but not if they include GT
2 or 3:
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 and 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. be on opiate substitution therapy (OST) for at least 3 months prior to screening.
Medications recognized as components of opiate substitution therapy include:
methadone, levamethadone, buprenorphine, naloxone, and naltrexone.
5. must have consistently kept at least 80% of scheduled appointments while on OST.
6. must have not missed any scheduled appointments between screening and study entry.
7. have liver disease staging assessment as follows:
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 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.
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 Child-Pugh 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)
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 is not available, imaging is required during screening.
6. is taking or plans to take (a) any HIV therapy that includes a ritonavir-boosted or
unboosted protease inhibitor, efavirenz or etravirine, (b) any other prohibited medications
listed in Section 5 of this protocol, or (c) 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. for subjects with HIV, uses HIV drugs other than a dual NRTI backbone of tenofovir or abacavir and either emtricitabine or lamivudine PLUS raltegravir [or dolutegravir or rilpivirine].
8. 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.
9. is currently using or intends to use barbiturates. Patients with positive urine tests for barbituates at screening or Day 1 will be excluded from the study.
10. 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.
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 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.
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 Child-Pugh 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)
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 is not available, imaging is required during screening.
6. is taking or plans to take (a) any HIV therapy that includes a ritonavir-boosted or
unboosted protease inhibitor, efavirenz or etravirine, (b) any other prohibited medications
listed in Section 5 of this protocol, or (c) 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. for subjects with HIV, uses HIV drugs other than a dual NRTI backbone of tenofovir or abacavir and either emtricitabine or lamivudine PLUS raltegravir [or dolutegravir or rilpivirine].
8. 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.
9. is currently using or intends to use barbiturates. Patients with positive urine tests for barbituates at screening or Day 1 will be excluded from the study.
10. 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.
The Estimated Number of Participants
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Taiwan
15 participants
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Global
300 participants
