Clinical Trials List
Protocol NumberMK5172-067
2014-12-01 - 2017-06-30
Phase III
Terminated6
Study ended1
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 GT 1, GT 4 and GT 6 Infection in the Asia Pacific
-
Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
-
Sponsor
Merck Sharp & Dohme Corp.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chiu Hung Chiu Division of General Internal Medicine
- 邱彥程 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chun-Yen Lin Division of General Internal Medicine
- Chien-Hao Huang Division of General Internal Medicine
- 陳威廷 Division of General Internal Medicine
- Wen-Juei Jeng Division of General Internal Medicine
- Yi-Cheng Chen Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- CHUNG-HSIN CHANG Division of General Internal Medicine
- 葉宏仁 Division of General Internal Medicine
- TENG-YU LEE Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ming-Lung Yu Digestive System Department
- Jee-Fu Huang Digestive System Department
- Ming-Lun Yeh Digestive System Department
- Chia-Yen Dai Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 黃惠君 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 曾柏霖 Division of General Internal Medicine
- 林明宗 Division of General Internal Medicine
- 洪肇宏 Division of General Internal Medicine
- 紀廣明 Division of General Internal Medicine
- 陳建宏 Division of General Internal Medicine
- 顏毅豪 Division of General Internal Medicine
- Jing-Houng Wang Division of General Internal Medicine
- 張國欽 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Hsueh-Chou Lai Digestive System Department
- 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
12 Study ended
Condition/Disease
Chronic HCV GT 1, GT 4 and GT 6 Infection
Objectives
Primary Objective(s)
(1) Objective: To evaluate the efficacy of MK-5172A 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.
(2) Objective: To evaluate the safety and tolerability of MK-5172A.
Test Drug
MK-5172A
Active Ingredient
MK-5172A
Dosage Form
tablet
Dosage
100mg MK-5172+50mg MK-8742
Endpoints
The primary measurement for efficacy in this trial is the plasma HCV RNA level. Long term
suppression of HCV RNA, typically reported as Sustained Virologic Response (SVR), has
been associated with improved outcomes in patients with chronic hepatitis C infection as
measured by biochemical and histological remission of liver disease. Most available data
suggest that SVR following antiviral therapy reduces the risk of progression to cirrhosis and
may prevent the development of severe liver complications and improve survival [25].
The primary evaluation of efficacy in this trial is based on SVR12 (Sustained Virologic
Response 12 weeks after the end of all study therapy), the same endpoint used for approval
of simeprevir and sofosbuvir. Since a high degree of concordance has been observed
between SVR12 and SVR24 [31], SVR12 is now being used as the primary endpoint for
registration of DAAs in the US and Europe; SVR24 will be a key secondary efficacy
endpoint, and the concordance between SVR12 and SVR24 will be further assessed.
Another secondary evaluation of efficacy is based on SVR4 (Sustained Virologic Response 4
weeks after the end of all study therapy).
Safety Endpoints
The safety and tolerability of MK-5172 in combination with MK-8742 (MK-5172A) is
assessed by a clinical evaluation of adverse events and inspection of other trial parameters
including vital signs, physical examinations, 12-lead ECGs, and standard laboratory safety
tests at appropriate time points as specified in the Trial Flow Chart. Adverse events are
graded and recorded according to Section 7.2. Subjects may be asked to return for
unscheduled visits in order to perform additional safety monitoring.
suppression of HCV RNA, typically reported as Sustained Virologic Response (SVR), has
been associated with improved outcomes in patients with chronic hepatitis C infection as
measured by biochemical and histological remission of liver disease. Most available data
suggest that SVR following antiviral therapy reduces the risk of progression to cirrhosis and
may prevent the development of severe liver complications and improve survival [25].
The primary evaluation of efficacy in this trial is based on SVR12 (Sustained Virologic
Response 12 weeks after the end of all study therapy), the same endpoint used for approval
of simeprevir and sofosbuvir. Since a high degree of concordance has been observed
between SVR12 and SVR24 [31], SVR12 is now being used as the primary endpoint for
registration of DAAs in the US and Europe; SVR24 will be a key secondary efficacy
endpoint, and the concordance between SVR12 and SVR24 will be further assessed.
Another secondary evaluation of efficacy is based on SVR4 (Sustained Virologic Response 4
weeks after the end of all study therapy).
Safety Endpoints
The safety and tolerability of MK-5172 in combination with MK-8742 (MK-5172A) is
assessed by a clinical evaluation of adverse events and inspection of other trial parameters
including vital signs, physical examinations, 12-lead ECGs, and standard laboratory safety
tests at appropriate time points as specified in the Trial Flow Chart. Adverse events are
graded and recorded according to Section 7.2. Subjects may be asked to return for
unscheduled visits in order to perform additional safety monitoring.
Inclution Criteria
1. Be ≥18 years of age on day of signing informed consent
2. Have HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time of screening
3. Have documented chronic HCV GT1, GT4, or GT6 (with no evidence of non -
typeable 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 [39][40]:
A liver biopsy performed prior to Day 1 of this trial showing cirrhosis (F4)
Fibroscan performed within 12 calendar months of Day 1 of this trial showing
cirrhosis with result >12.5 kPa [40]*
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 trial showing
absence of cirrhosis
Fibroscan performed within 12 months of Day 1 of this trial with a result of
≤12.5 kPa [40]*
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®
.
5. Have the following HCV treatment status:
Treatment naïve: Naïve to interferon, ribavirin and/or direct-acting
antivirals used to treat HCV infection.
NOTE: Includes subjects who are treatment naïve who are ineligible to take
IFN. See Section 7.1.2.1 for more details and definitions.
6. Meet one of the following categories:
a) The subject is a male.
b) The subject is a female who is not of reproductive potential, defined as a female
who either: (1) is postmenopausal (defined as at least 12 months with no menses
in women ≥45 years of age); (2) has had a hysterectomy and/or bilateral
oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at
least 6 weeks prior to screening; OR (3) has a congenital or acquired condition
that prevents childbearing.
c) The subject is a female who is of reproductive potential and agrees to avoid
becoming pregnant for at least 2 weeks prior to Day 1 and continue for 14 days
after the last dose of study drug by complying with one of the following: (1)
practice abstinence from heterosexual activity OR (2) use (or have her partner
use) acceptable contraception during heterosexual activity. Acceptable methods
of contraception are:
Single method (one of the following is acceptable):
• intrauterine device (IUD)
• vasectomy of a female subject’s male partner
• contraceptive rod implanted into the skin
Combination method (requires use of two of the following):
• diaphragm with spermicide (cannot be used in conjunction with cervical
cap/spermicide)
• cervical cap with spermicide (nulliparous women only)
• contraceptive sponge (nulliparous women only)
• male condom or female condom (cannot be used together)
• hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or
progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or
subcutaneous contraceptive injection
Abstinence (relative to heterosexual activity) can be used as the sole method of
contraception if it is consistently employed as the subject’s preferred and usual
lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs.
Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation
methods, etc.) and withdrawal are not acceptable methods of contraception.
If a contraceptive method listed above is restricted by local regulations/guidelines,
then it does not qualify as an acceptable method of contraception for subjects
participating at sites in this country/region.
7. Understand the trial procedures, alternative treatments available, risks involved with
the trial, and voluntarily agrees to participate by giving written informed consent.
8. Provide written informed consent for the trial. The subject may also provide consent
for Future Biomedical Research. However, the subject may participate in the main
trial without participating in Future Biomedical Research.
2. Have HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time of screening
3. Have documented chronic HCV GT1, GT4, or GT6 (with no evidence of non -
typeable 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 [39][40]:
A liver biopsy performed prior to Day 1 of this trial showing cirrhosis (F4)
Fibroscan performed within 12 calendar months of Day 1 of this trial showing
cirrhosis with result >12.5 kPa [40]*
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 trial showing
absence of cirrhosis
Fibroscan performed within 12 months of Day 1 of this trial with a result of
≤12.5 kPa [40]*
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®
.
5. Have the following HCV treatment status:
Treatment naïve: Naïve to interferon, ribavirin and/or direct-acting
antivirals used to treat HCV infection.
NOTE: Includes subjects who are treatment naïve who are ineligible to take
IFN. See Section 7.1.2.1 for more details and definitions.
6. Meet one of the following categories:
a) The subject is a male.
b) The subject is a female who is not of reproductive potential, defined as a female
who either: (1) is postmenopausal (defined as at least 12 months with no menses
in women ≥45 years of age); (2) has had a hysterectomy and/or bilateral
oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at
least 6 weeks prior to screening; OR (3) has a congenital or acquired condition
that prevents childbearing.
c) The subject is a female who is of reproductive potential and agrees to avoid
becoming pregnant for at least 2 weeks prior to Day 1 and continue for 14 days
after the last dose of study drug by complying with one of the following: (1)
practice abstinence from heterosexual activity OR (2) use (or have her partner
use) acceptable contraception during heterosexual activity. Acceptable methods
of contraception are:
Single method (one of the following is acceptable):
• intrauterine device (IUD)
• vasectomy of a female subject’s male partner
• contraceptive rod implanted into the skin
Combination method (requires use of two of the following):
• diaphragm with spermicide (cannot be used in conjunction with cervical
cap/spermicide)
• cervical cap with spermicide (nulliparous women only)
• contraceptive sponge (nulliparous women only)
• male condom or female condom (cannot be used together)
• hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or
progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or
subcutaneous contraceptive injection
Abstinence (relative to heterosexual activity) can be used as the sole method of
contraception if it is consistently employed as the subject’s preferred and usual
lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs.
Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation
methods, etc.) and withdrawal are not acceptable methods of contraception.
If a contraceptive method listed above is restricted by local regulations/guidelines,
then it does not qualify as an acceptable method of contraception for subjects
participating at sites in this country/region.
7. Understand the trial procedures, alternative treatments available, risks involved with
the trial, and voluntarily agrees to participate by giving written informed consent.
8. Provide written informed consent for the trial. The subject may also provide consent
for Future Biomedical Research. However, the subject may participate in the main
trial without participating in Future Biomedical Research.
Exclusion Criteria
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 trial or has a history of a clinically significant psychiatric disorder
which, in the opinion of the investigator, would interfere with the trial 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
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 shows evidence of
hepatocellular carcinoma (HCC) or is under evaluation for HCC.
6. Is taking or plans to take any of the prohibited medications listed in Section 5 of this
protocol, or taking or medication or herbal preparations with known hepatotoxic
potential, or taking herbal supplements, including but not limited to, St. John’s Wort
(Hypericum perforatum) within 2 weeks of Day 1.
7. Is currently participating or has participated in a trial with an investigational
compound within 30 days of signing informed consent and is not willing to refrain
from participating in another such trial during the course of this trial.
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 Day 1 and continue throughout treatment, and 14 days after the last dose of
study medication or longer if dictated by local regulations.
10. Has any of the following conditions:
a. Organ transplants (including hematopoietic stem cell transplants) other than
cornea and hair.
b. Poor venous access that precludes routine peripheral blood sampling required for
this trial.
c. History of gastric surgery (e.g., stapling, bypass) or a history of malabsorption
disorders (e.g., celiac sprue disease).
d. History of a medical/surgical condition that resulted in hospitalization within the
3 months prior to enrollment, other than for minor elective procedures.
e. Medical/surgical conditions that may result in a need for hospitalization during
the period of the trial.
f. Any medical condition requiring, or likely to require, chronic systemic
administration of corticosteroids, TNF antagonists, or other immunosuppressant
drugs during the course of the trial.
11. Has any condition, prestudy laboratory abnormality, ECG abnormality, or history of
any illness, which, in the opinion of the investigator, might confound the results of
the trial or pose additional risk in administering the study drugs to the subject.
12. Has a life-threatening SAE during the screening period.
13. Has a history of chronic hepatitis not caused by HCV, including but not limited to
nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune
hepatitis.
emotional problems at the time of pre-study screening visit or expected during the
conduct of the trial or has a history of a clinically significant psychiatric disorder
which, in the opinion of the investigator, would interfere with the trial 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
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 shows evidence of
hepatocellular carcinoma (HCC) or is under evaluation for HCC.
6. Is taking or plans to take any of the prohibited medications listed in Section 5 of this
protocol, or taking or medication or herbal preparations with known hepatotoxic
potential, or taking herbal supplements, including but not limited to, St. John’s Wort
(Hypericum perforatum) within 2 weeks of Day 1.
7. Is currently participating or has participated in a trial with an investigational
compound within 30 days of signing informed consent and is not willing to refrain
from participating in another such trial during the course of this trial.
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 Day 1 and continue throughout treatment, and 14 days after the last dose of
study medication or longer if dictated by local regulations.
10. Has any of the following conditions:
a. Organ transplants (including hematopoietic stem cell transplants) other than
cornea and hair.
b. Poor venous access that precludes routine peripheral blood sampling required for
this trial.
c. History of gastric surgery (e.g., stapling, bypass) or a history of malabsorption
disorders (e.g., celiac sprue disease).
d. History of a medical/surgical condition that resulted in hospitalization within the
3 months prior to enrollment, other than for minor elective procedures.
e. Medical/surgical conditions that may result in a need for hospitalization during
the period of the trial.
f. Any medical condition requiring, or likely to require, chronic systemic
administration of corticosteroids, TNF antagonists, or other immunosuppressant
drugs during the course of the trial.
11. Has any condition, prestudy laboratory abnormality, ECG abnormality, or history of
any illness, which, in the opinion of the investigator, might confound the results of
the trial or pose additional risk in administering the study drugs to the subject.
12. Has a life-threatening SAE during the screening period.
13. Has a history of chronic hepatitis not caused by HCV, including but not limited to
nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune
hepatitis.
The Estimated Number of Participants
-
Taiwan
80 participants
-
Global
353 participants
