MK-3682B (MK-5172 + MK-3682 + MK-8408 Fixed Dose Combination (FDC)) in HCV GT1 or GT3 DAA Failures
- Conditions
- Hepatitis C infectionTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2015-001483-19-ES
- Lead Sponsor
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
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 or HCV GT3 infection (with no evidence of non-typeable or mixed genotype)
4. have documented relapse, defined as having HCV RNA target not detected at end-oftreatment, but HCV RNA quantifiable (=LLOQ) during follow-up, after treatment with one of the following direct-acting antiretroviral (DAA) regimens either by approved dosage and duration or by completion of a clinical trial:
GT1:
-SOF/LDV ± RBV
-MK-5172/MK-8742 ± RBV
GT3:
-SOF + RBV
-SOF + PR
-SOF + DCV ± RBV
-SOF/LDV ± RBV
5. be otherwise healthy as determined by the medical history, physical examination, ECG, and clinical laboratory measurements performed at the time of screening
6. have liver disease staging assessment as follows:
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
-A Fibrosure® (Fibrotest®) score of = 0.48 and Aspartate Aminotransferase to
Platelet Ratio Index (APRI) of = during Screening
Compensated cirrhosis is defined as any one of the following:
-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.)
7. meet one of the following categories:
a. The subject is a male who is not of reproductive potential, defined as a male
who has azoospermia (whether due to having had a vasectomy or due to an
underlying medical condition).
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) and have a documented follicle
stimulating hormone (FSH) level in the postmenopausal range at pretrial
(screening); (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 or a male who is of reproductive potential and agrees
to avoid becoming pregnant or impregnating a partner beginning at least 2
weeks prior to administration of the initial dose of study drug, through 6
months after taking the last dose of study drug (or longer if dictated by local
regulations), by complying with one of the following: (1) practice
abstinence† from heterosexual activity OR (2) use (or have their partner use)
two forms of acceptable contraception during heterosexual activity.
8. understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
9. 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.
Refer to protocol for a complete list
Are
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 previously received a DAA containing regimen other than the permitted regimens listed in Inclusion Criterion nº4. Examples of exclusionary regimens include, but are not limited to:
-SOF + PR or SOF + RBV for GT1
-SIM + SOF ± RBV
-OBV/PTV/r and DSV ± RBV
3. did not complete their prior DAA therapy due to intolerance to the DAA regimen or who discontinued the DAA regimen for reasons other than virologic failure (e.g., non-compliance, lost to follow-up, withdrew consent).
NOTE: The trial is limited to those who have documented virologic relapse with a properly administered DAA regimen.
4. 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.
5. 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.
6. is coinfected with hepatitis B virus (e.g. HBsAg positive).
7. 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
8. 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.
9. 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.
10. is taking or plans to take any of the prohibited medications listed in the protocol or is taking herbal supplements, including but not limited to St. John´s Wort (Hypericum perforatum) from 2 weeks prior to Day 1 through 2 weeks after the study treatment period.
11. 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. (Subjects participating in MK-5172 Protocol 017 may be enrolled in this study, MK- 3682 Protocol 021).
12. has clinically-relevant drug or alcohol abuse within 12 months of screening
13. is a female and is pregnant or breastfeeding or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 through at least 6 months after last dose of study drug, or longer if dictated by local regulations, OR is a male subject who is expecting to donate sperm or planning to impregnate female partner(s) from at least two weeks prior to Day 1 through at least 6 months after last dose of study drug, or longer if dictated by local regulations.
NOTE: After randomization, those female subjects randomized to a regimen that
does not contain ribaviri
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method