MK-5172/MK-3682 with MK-8742 or MK-8408 in HCV GT1, GT2, and GT4 Infected Subjects

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2014-003304-73-ES
• Date of registration: 22/09/2014
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,
• Public title: MK-5172/MK-3682 with MK-8742 or MK-8408 in HCV GT1, GT2, and GT4 Infected Subjects
• Scientific title: A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-3682 with Either MK-8742 or MK-8408 in Subjects with Chronic HCV GT1, GT2, and GT4 Infection - MK-5172/MK-3682 with MK-8742 or MK-8408 in HCV GT1, GT2, and GT4 Infected Subjects
• Date of first enrolment: 21/11/2014
• Target sample size: 560
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003304-73
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: MK-8742 versus MK-8408; Number of treatment arms in the trial: 16
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Canada, Denmark, France, Germany, Israel, Italy, Lithuania, New Zealand, Poland, Puerto Rico, Spain, Sweden, Taiwan, United Kingdom, United States

Contacts

• Name: Investigación Clínica
• Affiliation: Merck Sharp & Dohme de España S.A.

• Name: Investigación Clínica
• Affiliation: Merck Sharp & Dohme de España S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
The following applies to Part A and Part B (unless otherwise specified):
1. be > or = to 18 years of age
2. HCV RNA (> or = to 10,000 IU/mL in peripheral blood) at the time of screening
3. have documented chronic HCV GT1, GT2, or GT4 (NOTE: GT4 infected subjects are only eligible for enrollment in Part B) (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.Be otherwise healthy as determined by the medical history, physical examination, ECG, and clinical laboratory measurements performed at the time of screening
5.have liver disease staging assessment as follows:
Absence of cirrhosis is defined as any one of the following (both Part A and Part B):
-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 < or = to 12.5 kPa
-A Fibrosure® (Fibrotest®) score of< or = to 0.48 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) of < or = to 1 during Screening
Compensated cirrhosis is defined as any one of the following (Part B only):
-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 with a result >12.5 kPa
-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.)
6.be HCV treatment naïve
(Read the rest in protocol)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 160

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 study or has a history of a clinically significant psychiatric disorder which 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.
3.For cirrhotics (Parts B and C only):
a.subjects that are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >5, must be excluded
4.coinfected with hepatitis B virus
5.coinfected with HIV (Part A only).
6.For subjects with HIV, has a history of opportunistic infection in the preceding 6 months prior to screening. A list of these events may be found in Appendix B of the following document: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm
7.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.
(Read the rest in protocol)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Chronic Hepatitis C infected patient

Intervention(s)

Product Name: MK-3682
Product Code: MK-3682
Pharmaceutical Form: Tablet
INN or Proposed INN: MK-3682
Other descriptive name: MK-3682
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Product Name: MK-5172
Product Code: MK-5172
Pharmaceutical Form: Tablet
INN or Proposed INN: MK-5172
Other descriptive name: MK-5172
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: MK-8408
Product Code: MK-8408
Pharmaceutical Form: Capsule
INN or Proposed INN: MK-8408
Other descriptive name: MK-8408
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: MK-8742
Product Code: MK-8742
Pharmaceutical Form: Tablet
INN or Proposed INN: MK-8742
Other descriptive name: MK-8742
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: Objective (1): To evaluate the efficacy of the combination regimens of MK-5172 and MK-3682 with either MK-8742 or MK-8408 as assessed by the proportion of subjects in each arm achieving SVR12 (Sustained Virologic Response 12 weeks after the end of all study therapy), defined as HCV RNA Objective (2): To evaluate the safety and tolerability of the combination regimens of MK-5172 and MK-3682 with either MK-8742 or MK-8408 to subjects in each arm.

Primary end point(s): The primary efficacy endpoint will be the proportion of subjects achieving SVR12 in each treatment arm.

Secondary Objective: Objective: To evaluate the efficacy of the combination regimens of MK-5172 and MK-3682 with either MK-8742 or MK-8408 as assessed by the proportion of subjects in each arm achieving SVR4 (Sustained Virologic Response 4 weeks after the end of all study therapy), defined as HCV RNA In Part B, the secondary objectives above will be evaluated within each subject population (HIV/HCV co-infected vs. mono-infected, and cirrhotic vs. non-cirrhotic) separately. In addition, the following objectives will also be evaluated for the HIV co-infected population:
Objective: To evaluate the proportion of subjects who develop HIV-1 virologic failure (HIV-1 RNA 200 copies/mL, confirmed on two consecutive tests at least 2 weeks apart, in subjects compliant with their HIV antiretroviral therapy [ART]).
(Read rest in the protocol)

Timepoint(s) of evaluation of this end point: 12 weeks after completion of therapy

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 4 weeks after completion of therapy

Secondary end point(s): The secondary objective of this study is to estimate the SVR4 rates for each of the treatment arms. A two-sided 95% confidence interval will be constructed for SVR4 for each arm separately.

Secondary ID(s)

MK-3682-011

2014-003304-73-SE

Source(s) of Monetary Support

Merck Sharp & Dhome Corp.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 14/12/2017
• Date Completed: 12/12/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-003304-73/results